Author: "Sylvia Villeneuve" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Sylvia Villeneuve"' showing total 138 results

Start Over Author "Sylvia Villeneuve"

138 results on '"Sylvia Villeneuve"'

1. Genetic and clinical correlates of two neuroanatomical AI dimensions in the Alzheimer’s disease continuum

Author: Junhao Wen, Zhijian Yang, Ilya M. Nasrallah, Yuhan Cui, Guray Erus, Dhivya Srinivasan, Ahmed Abdulkadir, Elizabeth Mamourian, Gyujoon Hwang, Ashish Singh, Mark Bergman, Jingxuan Bao, Erdem Varol, Zhen Zhou, Aleix Boquet-Pujadas, Jiong Chen, Arthur W. Toga, Andrew J. Saykin, Timothy J. Hohman, Paul M. Thompson, Sylvia Villeneuve, Randy Gollub, Aristeidis Sotiras, Katharina Wittfeld, Hans J. Grabe, Duygu Tosun, Murat Bilgel, Yang An, Daniel S. Marcus, Pamela LaMontagne, Tammie L. Benzinger, Susan R. Heckbert, Thomas R. Austin, Lenore J. Launer, Mark Espeland, Colin L. Masters, Paul Maruff, Jurgen Fripp, Sterling C. Johnson, John C. Morris, Marilyn S. Albert, R. Nick Bryan, Susan M. Resnick, Luigi Ferrucci, Yong Fan, Mohamad Habes, David Wolk, Li Shen, Haochang Shou, and Christos Davatzikos
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Alzheimer’s disease (AD) is associated with heterogeneous atrophy patterns. We employed a semi-supervised representation learning technique known as Surreal-GAN, through which we identified two latent dimensional representations of brain atrophy in symptomatic mild cognitive impairment (MCI) and AD patients: the “diffuse-AD” (R1) dimension shows widespread brain atrophy, and the “MTL-AD” (R2) dimension displays focal medial temporal lobe (MTL) atrophy. Critically, only R2 was associated with widely known sporadic AD genetic risk factors (e.g., APOE ε4) in MCI and AD patients at baseline. We then independently detected the presence of the two dimensions in the early stages by deploying the trained model in the general population and two cognitively unimpaired cohorts of asymptomatic participants. In the general population, genome-wide association studies found 77 genes unrelated to APOE differentially associated with R1 and R2. Functional analyses revealed that these genes were overrepresented in differentially expressed gene sets in organs beyond the brain (R1 and R2), including the heart (R1) and the pituitary gland, muscle, and kidney (R2). These genes were enriched in biological pathways implicated in dendritic cells (R2), macrophage functions (R1), and cancer (R1 and R2). Several of them were “druggable genes” for cancer (R1), inflammation (R1), cardiovascular diseases (R1), and diseases of the nervous system (R2). The longitudinal progression showed that APOE ε4, amyloid, and tau were associated with R2 at early asymptomatic stages, but this longitudinal association occurs only at late symptomatic stages in R1. Our findings deepen our understanding of the multifaceted pathogenesis of AD beyond the brain. In early asymptomatic stages, the two dimensions are associated with diverse pathological mechanisms, including cardiovascular diseases, inflammation, and hormonal dysfunction—driven by genes different from APOE—which may collectively contribute to the early pathogenesis of AD. All results are publicly available at https://labs-laboratory.com/medicine/ .
Published: 2024
Full Text: View/download PDF

2. Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status

Author: Alfie Wearn, Stéfanie A. Tremblay, Christine L. Tardif, Ilana R. Leppert, Claudine J. Gauthier, Giulia Baracchini, Colleen Hughes, Patrick Hewan, Jennifer Tremblay-Mercier, Pedro Rosa-Neto, Judes Poirier, Sylvia Villeneuve, Taylor W. Schmitz, Gary R. Turner, R. Nathan Spreng, and PREVENT-AD Research Group
Subjects: Science
Abstract: Abstract The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer’s disease (AD). They project broadly throughout the brain’s white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.
Published: 2024
Full Text: View/download PDF

3. The neurophysiological brain-fingerprint of Parkinson’s diseaseResearch in context

Author: Jason da Silva Castanheira, Alex I. Wiesman, Justine Y. Hansen, Bratislav Misic, Sylvain Baillet, John Breitner, Judes Poirier, Pierre Bellec, Véronique Bohbot, Mallar Chakravarty, Louis Collins, Pierre Etienne, Alan Evans, Serge Gauthier, Rick Hoge, Yasser Ituria-Medina, Gerhard Multhaup, Lisa-Marie Münter, Natasha Rajah, Pedro Rosa-Neto, Jean-Paul Soucy, Etienne Vachon-Presseau, Sylvia Villeneuve, Philippe Amouyel, Melissa Appleby, Nicholas Ashton, Daniel Auld, Gülebru Ayranci, Christophe Bedetti, Marie-Lise Beland, Kaj Blennow, Ann Brinkmalm Westman, Claudio Cuello, Mahsa Dadar, Leslie-Ann Daoust, Samir Das, Marina Dauar-Tedeschi, Louis De Beaumont, Doris Dea, Maxime Descoteaux, Marianne Dufour, Sarah Farzin, Fabiola Ferdinand, Vladimir Fonov, Julie Gonneaud, Justin Kat, Christina Kazazian, Anne Labonté, Marie-Elyse Lafaille-Magnan, Marc Lalancette, Jean-Charles Lambert, Jeannie-Marie Leoutsakos, Laura Mahar, Axel Mathieu, Melissa McSweeney, Pierre-François Meyer, Justin Miron, Jamie Near, Holly NewboldFox, Nathalie Nilsson, Pierre Orban, Cynthia Picard, Alexa Pichet Binette, Jean-Baptiste Poline, Sheida Rabipour, Alyssa Salaciak, Matthew Settimi, Sivaniya Subramaniapillai, Angela Tam, Christine Tardif, Louise Théroux, Jennifer Tremblay-Mercier, Stephanie Tullo, Irem Ulku, Isabelle Vallée, Henrik Zetterberg, Vasavan Nair, Jens Pruessner, Paul Aisen, Elena Anthal, Alan Barkun, Thomas Beaudry, Fatiha Benbouhoud, Jason Brandt, Leopoldina Carmo, Charles Edouard Carrier, Laksanun Cheewakriengkrai, Blandine Courcot, Doris Couture, Suzanne Craft, Christian Dansereau, Clément Debacker, René Desautels, Sylvie Dubuc, Guerda Duclair, Mark Eisenberg, Rana El-Khoury, Anne-Marie Faubert, David Fontaine, Josée Frappier, Joanne Frenette, Guylaine Gagné, Valérie Gervais, Renuka Giles, Renee Gordon, Clifford Jack, Benoit Jutras, Zaven Khachaturian, David Knopman, Penelope Kostopoulos, Félix Lapalme, Tanya Lee, Claude Lepage, Illana Leppert, Cécile Madjar, David Maillet, Jean-Robert Maltais, Sulantha Mathotaarachchi, Ginette Mayrand, Diane Michaud, Thomas Montine, John Morris, Véronique Pagé, Tharick Pascoal, Sandra Peillieux, Mirela Petkova, Galina Pogossova, Pierre Rioux, Mark Sager, Eunice Farah Saint-Fort, Mélissa Savard, Reisa Sperling, Shirin Tabrizi, Pierre Tariot, Eduard Teigner, Ronald Thomas, Paule-Joanne Toussaint, Miranda Tuwaig, Vinod Venugopalan, Sander Verfaillie, Jacob Vogel, Karen Wan, Seqian Wang, Elsa Yu, Isabelle Beaulieu-Boire, Pierre Blanchet, Sarah Bogard, Manon Bouchard, Sylvain Chouinard, Francesca Cicchetti, Martin Cloutier, Alain Dagher, Clotilde Degroot, Alex Desautels, Marie Hélène Dion, Janelle Drouin-Ouellet, Anne-Marie Dufresne, Nicolas Dupré, Antoine Duquette, Thomas Durcan, Lesley K. Fellows, Edward Fon, Jean-François Gagnon, Ziv Gan-Or, Angela Genge, Nicolas Jodoin, Jason Karamchandani, Anne-Louise Lafontaine, Mélanie Langlois, Etienne Leveille, Martin Lévesque, Calvin Melmed, Oury Monchi, Jacques Montplaisir, Michel Panisset, Martin Parent, Minh-Thy Pham-An, Ronald Postuma, Emmanuelle Pourcher, Trisha Rao, Jean Rivest, Guy Rouleau, Madeleine Sharp, Valérie Soland, Michael Sidel, Sonia Lai Wing Sun, Alexander Thiel, and Paolo Vitali
Subjects: Movement disorders, Parkinson’s disease, Neural dynamics, Oscillations, Arrhythmic brain activity, Magnetoencephalography, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).
Published: 2024
Full Text: View/download PDF

4. Resting-state MRI functional connectivity as a neural correlate of multidomain lifestyle adherence in older adults at risk for Alzheimer’s disease

Author: Meishan Ai, Timothy P. Morris, Jiahe Zhang, Adrián Noriega de la Colina, Jennifer Tremblay-Mercier, Sylvia Villeneuve, Susan Whitfield-Gabrieli, Arthur F. Kramer, Maiya R. Geddes, and for the PREVENT-AD Research Group
Subjects: Medicine, Science
Abstract: Abstract Prior research has demonstrated the importance of a healthy lifestyle to protect brain health and diminish dementia risk in later life. While a multidomain lifestyle provides an ecological perspective to voluntary engagement, its association with brain health is still under-investigated. Therefore, understanding the neural mechanisms underlying multidomain lifestyle engagement, particularly in older adults at risk for Alzheimer’s disease (AD), gives valuable insights into providing lifestyle advice and intervention for those in need. The current study included 139 healthy older adults with familial risk for AD from the Prevent-AD longitudinal aging cohort. Self-reported exercise engagement, cognitive activity engagement, healthy diet adherence, and social activity engagement were included to examine potential phenotypes of an individual’s lifestyle adherence. Two adherence profiles were discovered using data-driven clustering methodology [i.e., Adherence to healthy lifestyle (AL) group and Non-adherence to healthy lifestyle group]. Resting-state functional connectivity matrices and grey matter brain features obtained from magnetic resonance imaging were used to classify the two groups using a support vector machine (SVM). The SVM classifier was 75% accurate in separating groups. The features that show consistently high importance to the classification model were functional connectivity mainly between nodes located in different prior-defined functional networks. Most nodes were located in the default mode network, dorsal attention network, and visual network. Our results provide preliminary evidence of neurobiological characteristics underlying multidomain healthy lifestyle choices.
Published: 2023
Full Text: View/download PDF

5. Day‐to‐day sleep variability with Alzheimer's biomarkers in at‐risk elderly

Author: Andrée‐Ann Baril, Cynthia Picard, Anne Labonté, Erlan Sanchez, Catherine Duclos, Béry Mohammediyan, Nicholas J. Ashton, Henrik Zetterberg, Kaj Blennow, John C. S. Breitner, Sylvia Villeneuve, Judes Poirier, and PREVENT‐AD Research Group
Subjects: accelerometry, amyloid, APOE ε4, apolipoprotein, atrophy, bedtime, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract INTRODUCTION Measuring day‐to‐day sleep variability might reveal unstable sleep‐wake cycles reflecting neurodegenerative processes. We evaluated the association between Alzheimer's disease (AD) fluid biomarkers with day‐to‐day sleep variability. METHODS In the PREVENT‐AD cohort, 203 dementia‐free participants (age: 68.3 ± 5.4; 78 males) with a parental history of sporadic AD were tested with actigraphy and fluid biomarkers. Day‐to‐day variability (standard deviations over a week) was assessed for sleep midpoint, duration, efficiency, and nighttime activity count. RESULTS Lower cerebrospinal fluid (CSF) ApoE, higher CSF p‐tau181/amyloid‐β (Aβ)42, and higher plasma p‐tau231/Aβ42 were associated with higher variability of sleep midpoint, sleep duration, and/or activity count. The associations between fluid biomarkers with greater sleep duration variability were especially observed in those that carried the APOE4 allele, mild cognitive impairment converters, or those with gray matter atrophy. DISCUSSION Day‐to‐day sleep variability were associated with biomarkers of AD in at‐risk individuals, suggesting that unstable sleep promotes neurodegeneration or, conversely, that AD neuropathology disrupts sleep‐wake cycles.
Published: 2024
Full Text: View/download PDF

6. Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease

Author: Dániel Veréb, Mite Mijalkov, Yu-Wei Chang, Anna Canal-Garcia, Emiliano Gomez-Ruis, Anne Maass, Sylvia Villeneuve, Giovanni Volpe, and Joana B. Pereira
Subjects: Alzheimer’s disease, Cognitive aging, fMRI, Cerebrospinal fluid markers, Apolipoprotein E, Memory, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background The medial parietal cortex is an early site of pathological protein deposition in Alzheimer’s disease (AD). Previous studies have identified different subregions within this area; however, these subregions are often heterogeneous and disregard individual differences or subtle pathological alterations in the underlying functional architecture. To address this limitation, here we measured the continuous connectivity gradients of the medial parietal cortex and assessed their relationship with cerebrospinal fluid (CSF) biomarkers, ApoE ε4 carriership and memory in asymptomatic individuals at risk to develop AD. Methods Two hundred sixty-three cognitively normal participants with a family history of sporadic AD who underwent resting-state and task-based functional MRI using encoding and retrieval tasks were included from the PREVENT-AD cohort. A novel method for characterizing spatially continuous patterns of functional connectivity was applied to estimate functional gradients in the medial parietal cortex during the resting-state and task-based conditions. This resulted in a set of nine parameters that described the appearance of the gradient across different spatial directions. We performed correlation analyses to assess whether these parameters were associated with CSF biomarkers of phosphorylated tau181 (p-tau), total tau (t-tau), and amyloid-ß1-42 (Aß). Then, we compared the spatial parameters between ApoE ε4 carriers and noncarriers, and evaluated the relationship between these parameters and memory. Results Alterations involving the superior part of the medial parietal cortex, which was connected to regions of the default mode network, were associated with higher p-tau, t-tau levels as well as lower Aß/p-tau levels during the resting-state condition (p
Published: 2023
Full Text: View/download PDF

7. Trait Mindfulness Is Associated With Less Amyloid, Tau, and Cognitive Decline in Individuals at Risk for Alzheimer’s Disease

Author: Cherie Strikwerda-Brown, Hazal Ozlen, Alexa Pichet Binette, Marianne Chapleau, Natalie L. Marchant, John C.S. Breitner, and Sylvia Villeneuve
Subjects: Alzheimer’s disease, Amyloid, Cognition, Mindfulness, Prevention, Tau, Psychiatry, RC435-571
Abstract: Background: Mindfulness, defined as nonjudgmental awareness of the present moment, has been associated with an array of mental and physical health benefits. Mindfulness may also represent a protective factor for Alzheimer’s disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in older adults at risk for AD dementia. Methods: Measures of trait mindfulness, longitudinal cognitive assessments, and amyloid-β (Aβ) and tau positron emission tomography scans were collected in 261 nondemented older adults with a family history of AD dementia from the PREVENT-AD (Pre-symptomatic Evaluation of Experimental or Novel Treatments for AD) observational cohort study. Multivariate partial least squares analyses were used to examine relationships between combinations of different facets of trait mindfulness and 1) cognitive decline, 2) Aβ, and 3) tau. Results: Higher levels of mindful nonjudgment, describing, and nonreactivity were associated with less cognitive decline in attention, global cognition, and immediate and delayed memory. Higher levels of mindful nonjudgment and nonreactivity were related to less Aβ positron emission tomography signal in bilateral medial and lateral temporoparietal and frontal regions. Higher levels of mindful acting with awareness, describing, nonjudgment, and nonreactivity were associated with less tau positron emission tomography signal in bilateral medial and lateral temporal regions. Conclusions: Trait mindfulness was associated with less cognitive decline and less Aβ and tau in the brain in older adults at risk for AD dementia. Longitudinal studies examining the temporal relationship between trait mindfulness and AD markers, along with mindfulness intervention studies, will be important for further clarifying the potential protective benefits of mindfulness on AD risk.
Published: 2023
Full Text: View/download PDF

8. Sex differences in longitudinal changes of episodic memory-related brain activity and cognition in cognitively unimpaired older adults with a family history of Alzheimer’s disease

Author: Alexandria D. Samson, Sricharana Rajagopal, Stamatoula Pasvanis, Sylvia Villeneuve, Anthony R. McIntosh, and M. Natasha Rajah
Subjects: Sex differences, Episodic memory, Family history of Alzheimer’s disease, Task-related functional MRI, Cognition, Longitudinal study, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Episodic memory decline is an early symptom of Alzheimer’s disease (AD) – a neurodegenerative disease that has a higher prevalence rate in older females compared to older males. However, little is known about why these sex differences in prevalence rate exist. In the current longitudinal task fMRI study, we explored whether there were sex differences in the patterns of memory decline and brain activity during object-location (spatial context) encoding and retrieval in a large sample of cognitively unimpaired older adults from the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD) program who are at heightened risk of developing AD due to having a family history (+FH) of the disease. The goal of the study was to gain insight into whether there are sex differences in the neural correlates of episodic memory decline, which may advance knowledge about sex-specific patterns in the natural progression to AD. Our results indicate that +FH females performed better than +FH males at both baseline and follow-up on neuropsychological and task fMRI measures of episodic memory. Moreover, multivariate data-driven task fMRI analysis identified generalized patterns of longitudinal decline in medial temporal lobe activity that was paralleled by longitudinal increases in lateral prefrontal cortex, caudate and midline cortical activity during successful episodic retrieval and novelty detection in +FH males, but not females. Post-hoc analyses indicated that higher education had a stronger effect on +FH females neuropsychological scores compared to +FH males. We conclude that higher educational attainment may have a greater neuroprotective effect in older +FH females compared to +FH males.
Published: 2023
Full Text: View/download PDF

9. Social isolation is linked to classical risk factors of Alzheimer's disease-related dementias.

Author: Kimia Shafighi, Sylvia Villeneuve, Pedro Rosa Neto, AmanPreet Badhwar, Judes Poirier, Vaibhav Sharma, Yasser Iturria Medina, Patricia P Silveira, Laurette Dube, David Glahn, and Danilo Bzdok
Subjects: Medicine, Science
Abstract: Alzheimer's disease and related dementias is a major public health burden-compounding over upcoming years due to longevity. Recently, clinical evidence hinted at the experience of social isolation in expediting dementia onset. In 502,506 UK Biobank participants and 30,097 participants from the Canadian Longitudinal Study of Aging, we revisited traditional risk factors for developing dementia in the context of loneliness and lacking social support. Across these measures of subjective and objective social deprivation, we have identified strong links between individuals' social capital and various indicators of Alzheimer's disease and related dementias risk, which replicated across both population cohorts. The quality and quantity of daily social encounters had deep connections with key aetiopathological factors, which represent 1) personal habits and lifestyle factors, 2) physical health, 3) mental health, and 4) societal and external factors. Our population-scale assessment suggest that social lifestyle determinants are linked to most neurodegeneration risk factors, highlighting them as promising targets for preventive clinical action.
Published: 2023
Full Text: View/download PDF

10. APOE alleles are associated with sex-specific structural differences in brain regions affected in Alzheimer's disease and related dementia.

Author: Chloé Savignac, Sylvia Villeneuve, AmanPreet Badhwar, Karin Saltoun, Kimia Shafighi, Chris Zajner, Vaibhav Sharma, Sarah A Gagliano Taliun, Sali Farhan, Judes Poirier, and Danilo Bzdok
Subjects: Biology (General), QH301-705.5
Abstract: Alzheimer's disease is marked by intracellular tau aggregates in the medial temporal lobe (MTL) and extracellular amyloid aggregates in the default network (DN). Here, we examined codependent structural variations between the MTL's most vulnerable structure, the hippocampus (HC), and the DN at subregion resolution in individuals with Alzheimer's disease and related dementia (ADRD). By leveraging the power of the approximately 40,000 participants of the UK Biobank cohort, we assessed impacts from the protective APOE ɛ2 and the deleterious APOE ɛ4 Alzheimer's disease alleles on these structural relationships. We demonstrate ɛ2 and ɛ4 genotype effects on the inter-individual expression of HC-DN co-variation structural patterns at the population level. Across these HC-DN signatures, recurrent deviations in the CA1, CA2/3, molecular layer, fornix's fimbria, and their cortical partners related to ADRD risk. Analyses of the rich phenotypic profiles in the UK Biobank cohort further revealed male-specific HC-DN associations with air pollution and female-specific associations with cardiovascular traits. We also showed that APOE ɛ2/2 interacts preferentially with HC-DN co-variation patterns in estimating social lifestyle in males and physical activity in females. Our structural, genetic, and phenotypic analyses in this large epidemiological cohort reinvigorate the often-neglected interplay between APOE ɛ2 dosage and sex and link APOE alleles to inter-individual brain structural differences indicative of ADRD familial risk.
Published: 2022
Full Text: View/download PDF

11. Accelerated functional brain aging in pre-clinical familial Alzheimer’s disease

Author: Julie Gonneaud, Alex T. Baria, Alexa Pichet Binette, Brian A. Gordon, Jasmeer P. Chhatwal, Carlos Cruchaga, Mathias Jucker, Johannes Levin, Stephen Salloway, Martin Farlow, Serge Gauthier, Tammie L. S. Benzinger, John C. Morris, Randall J. Bateman, John C. S. Breitner, Judes Poirier, Etienne Vachon-Presseau, Sylvia Villeneuve, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Dominantly Inherited Alzheimer Network (DIAN) Study Group, and Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer’s Disease (PREVENT-AD) Research Group
Subjects: Science
Abstract: Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.
Published: 2021
Full Text: View/download PDF

12. White matter lesions may be an early marker for age-related cognitive decline

Author: Cassandra Morrison, Mahsa Dadar, Sylvia Villeneuve, and D. Louis Collins
Subjects: Cognitively normal older adults, Magnetic resonance imaging, White matter lesions, Cognitive decline, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: Research suggests that cerebral small vessel disease (CSVD), amyloid, and pTau contribute to age-related cognitive decline. It remains unknown how these factors relate to one another and how they jointly contribute to cognitive decline in normal aging. This project examines the association between these factors and their relationship to cognitive decline in cognitively unimpaired older adults without subjective cognitive decline. Methods: A total of 230 subjects with cerebrospinal fluid (CSF) Aß42, CSF pTau181, white matter lesions (WMLs) used as a proxy of CSVD, and cognitive scores from the Alzheimer’s Disease Neuroimaging Initiative were included. Associations between each factor and cognitive score were investigated using regression models. Furthermore, relationships between the three pathologies were also examined using regression models. Results: At baseline, there was an inverse association between WML load and Aß42 (t = −4.20, p
Published: 2022
Full Text: View/download PDF

13. Regional brain atrophy and cognitive decline depend on definition of subjective cognitive decline

Author: Cassandra Morrison, Mahsa Dadar, Neda Shafiee, Sylvia Villeneuve, and D. Louis Collins
Subjects: Subjective cognitive decline, Magnetic resonance imaging, Deformation based morphometry, Cognitive decline, Alzheimer’s disease, Regional atrophy, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: People with subjective cognitive decline (SCD) may be at increased risk for Alzheimer’s disease (AD). However, not all studies have observed this increased risk. This project examined whether four common methods of defining SCD yields different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+ ) and without SCD (SCD−). Methods: Data from 273 Alzheimer’s Disease Neuroimaging Initiative cognitively normal older adults were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry. Voxel-based logistic regressions were applied to deformation-based morphology results to determine if regional atrophy between SCD− and SCD+ differed by SCD definition. Linear mixed-effects models were used to evaluate differences in future cognitive decline. Results: Results varied between the four methods of defining SCD. Left hippocampal grading was more similar to AD in SCD+ than SCD− when using the CCI (p = .041) and Worry (p = .021) definitions. The right (p=.008) and left (p=.003) superior temporal regions had smaller volumes in SCD+ than SCD−, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer’s Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment. Conclusion: These findings suggest that the various methods used to differentiate between SCD− and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.
Published: 2022
Full Text: View/download PDF

14. Vascular risk factors are associated with a decline in resting-state functional connectivity in cognitively unimpaired individuals at risk for Alzheimer's disease

Author: Theresa Köbe, Alexa Pichet Binette, Jacob W. Vogel, Pierre-François Meyer, John C.S. Breitner, Judes Poirier, and Sylvia Villeneuve
Subjects: β-Amyloid, Global functional connectivity, Default-mode network, Longitudinal resting-state functional connectivity, tau, Vascular risk factors, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Resting-state functional connectivity is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. However, evidence is lacking regarding longitudinal changes in functional connectivity. This study includes 247 cognitively unimpaired individuals with a family history of sporadic AD (185 women/ 62 men; mean [SD] age of 63 [5.3] years). Plasma total-, HDL-, and LDL-cholesterol and systolic and diastolic blood pressure were measured at baseline. Global (whole-brain) brain functional connectivity and connectivity from canonical functional networks were computed from resting-state functional MRI obtained at baseline and ~3.5 years of annual follow-ups, using a predefined functional parcellation. A subsample underwent Aβ- and tau-PET (n=91). Linear mixed-effects models demonstrated that global functional connectivity increased over time across the entire sample. In contrast, higher total-cholesterol and LDL-cholesterol levels were associated with greater reduction of functional connectivity in the default-mode network over time. In addition, higher diastolic blood pressure was associated with global functional connectivity reduction. The associations were similar when the analyses were repeated using two other functional brain parcellations. Aβ and tau deposition in the brain were not associated with changes in functional connectivity over time in the subsample. These findings provide evidence that vascular burden is associated with a decrease in functional connectivity over time in older adults with elevated risk for AD. Future studies are needed to determine if the impact of vascular risk factors on functional brain changes precede the impact of AD pathology on functional brain changes.
Published: 2021
Full Text: View/download PDF

15. Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer’s disease

Author: Alexa Pichet Binette, Guillaume Theaud, François Rheault, Maggie Roy, D Louis Collins, Johannes Levin, Hiroshi Mori, Jae Hong Lee, Martin Rhys Farlow, Peter Schofield, Jasmeer P Chhatwal, Colin L Masters, Tammie Benzinger, John Morris, Randall Bateman, John CS Breitner, Judes Poirier, Julie Gonneaud, Maxime Descoteaux, Sylvia Villeneuve, DIAN Study Group, and PREVENT-AD Research Group
Subjects: PET, diffusion MRI, free-water, uncinate fasciculus, cingulum, Medicine, Science, Biology (General), QH301-705.5
Abstract: Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer’s disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focused on free-water-corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.
Published: 2021
Full Text: View/download PDF

16. Open science datasets from PREVENT-AD, a longitudinal cohort of pre-symptomatic Alzheimer’s disease

Author: Jennifer Tremblay-Mercier, Cécile Madjar, Samir Das, Alexa Pichet Binette, Stephanie O.M. Dyke, Pierre Étienne, Marie-Elyse Lafaille-Magnan, Jordana Remz, Pierre Bellec, D. Louis Collins, M. Natasha Rajah, Veronique Bohbot, Jeannie-Marie Leoutsakos, Yasser Iturria-Medina, Justin Kat, Richard D. Hoge, Serge Gauthier, Christine L. Tardif, M. Mallar Chakravarty, Jean-Baptiste Poline, Pedro Rosa-Neto, Alan C. Evans, Sylvia Villeneuve, Judes Poirier, and John C.S. Breitner
Subjects: Pre-symptomatic Alzheimer Disease, Biomarkers, Observational cohort, Open Science, Neuroimaging, Cerebrospinal Fluid proteins, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: To move Alzheimer Disease (AD) research forward it is essential to collect data from large cohorts, but also make such data available to the global research community. We describe the creation of an open science dataset from the PREVENT-AD (PResymptomatic EValuation of Experimental or Novel Treatments for AD) cohort, composed of cognitively unimpaired older individuals with a parental or multiple-sibling history of AD. From 2011 to 2017, 386 participants were enrolled (mean age 63 years old ± 5) for sustained investigation among whom 349 have retrospectively agreed to share their data openly. Repositories are findable through the unified interface of the Canadian Open Neuroscience Platform and contain up to five years of longitudinal imaging data, cerebral fluid biochemistry, neurosensory capacities, cognitive, genetic, and medical information. Imaging data can be accessed openly at https://openpreventad.loris.ca while most of the other information, sensitive by nature, is accessible by qualified researchers at https://registeredpreventad.loris.ca. In addition to being a living resource for continued data acquisition, PREVENT-AD offers opportunities to facilitate understanding of AD pathogenesis.
Published: 2021
Full Text: View/download PDF

17. Regional correlations between [11C]PIB PET and post-mortem burden of amyloid-beta pathology in a diverse neuropathological cohort

Author: Sang Won Seo, Nagehan Ayakta, Lea T. Grinberg, Sylvia Villeneuve, Manja Lehmann, Bruce Reed, Charles DeCarli, Bruce L. Miller, Howard J. Rosen, Adam L. Boxer, James P. O’Neil, Lee-Way Jin, William W. Seeley, William J. Jagust, and Gil D. Rabinovici
Subjects: Imaging, Pathology, Amyloid, Alzheimer’s disease, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Imaging-pathological correlation studies show that in vivo amyloid-β (Aβ) positron emission tomography (PET) strongly predicts the presence of significant Aβ pathology at autopsy. We sought to determine whether regional PiB-PET uptake would improve sensitivity for amyloid detection in comparison with global measures (experiment 1), and to estimate the relative contributions of different Aβ aggregates to in vivo PET signal (experiment 2). In experiment 1, 54 subjects with [11C] PiB-PET during life and postmortem neuropathologic examination (85.2% with dementia, interval from PET to autopsy 3.1 ± 1.9 years) were included. We assessed Thal amyloid phase (N = 36) and CERAD score (N = 54) versus both global and regional PiB SUVRs. In experiment 2 (N = 42), PiB SUVR and post-mortem amyloid β burden was analyzed in five customized regions of interest matching regions sampled at autopsy. We assessed the relative contribution of neuritic plaques (NPs), diffuse plaques (DPs) and cerebral amyloid angiopathy (CAA) to regional PIB SUVR using multi-linear regression. In experiment 1, there were no differences in Area Under the Curve for amyloid phase ≥ A2 and CERAD score ≥ C2 between global and highest regional PiB SUVR (p = 0.186 and 0.230). In experiment 2, when NPs, DPs, and/or CAA were included in the same model, moderate to severe NPs were independently correlated with PiB SUVR in all regions except for the inferior temporal and calcarine ROI (β = 0.414–0.804, p
Published: 2017
Full Text: View/download PDF

18. Influence of Abdominal Obesity on the Lipid-Lipoprotein Profile in Apoprotein E2/4 Carriers: The Effect of an Apparent Duality

Author: Sylvia Villeneuve, Diane Brisson, and Daniel Gaudet
Subjects: Physiology, QP1-981, Biochemistry, QD415-436
Abstract: Background. Apolipoprotein (Apo) E plays a key role in the handling of lipoprotein particles with ApoE2 and ApoE4 frequently having opposite effects compared to ApoE3. Some individuals simultaneously carry both E2 and E4 alleles. The impact of the ApoE2/4 genotype on lipid concentrations and its consequences on health remain poorly documented. Objective. This study compared the lipid profile between ApoE2/4 carriers and other ApoE genotypes in relation to the waist circumference. Methods. Cholesterol, triglyceride (TG), and ApoB concentrations were measured among 2,680 Caucasians. Multivariate logistic regression models were used to estimate the contribution of ApoE2/4 to various dyslipidemic profiles associated with abdominal obesity. Results. In presence of abdominal obesity, the lipid profile was as deteriorated in ApoE2/4 carriers as in carriers of other ApoE genotypes. There was a more pronounced effect on TG-rich lipoproteins, particularly in ApoE2/2 (a feature of type III dysbetalipoproteinemia), and non-high-density lipoprotein (HDL) cholesterol in ApoE4/4. Compared to ApoE2/2, ApoE2/4 carriers presented lower very-low-density lipoprotein (VLDL) cholesterol concentrations and VLDL-cholesterol/TG ratios, with or without obesity, and higher low-density lipoprotein (LDL) cholesterol concentrations. Conclusion. In presence of abdominal obesity, the influence of the ApoE2 allele could be less pronounced than that of ApoE4 among ApoE2/4 individuals.
Published: 2015
Full Text: View/download PDF

19. Associations between white matter hyperintensities and β amyloid on integrity of projection, association, and limbic fiber tracts measured with diffusion tensor MRI.

Author: Linda L Chao, Charles Decarli, Stephen Kriger, Diana Truran, Yu Zhang, Joel Laxamana, Sylvia Villeneuve, William J Jagust, Nerses Sanossian, Wendy J Mack, Helena C Chui, and Michael W Weiner
Subjects: Medicine, Science
Abstract: The goal of this study was to assess the relationship between Aβ deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0-0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between Aβ deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. Aβ deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where Aβ deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ε4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue.
Published: 2013
Full Text: View/download PDF

20. Functional connectome fingerprinting across the lifespan

Author: Frédéric St-Onge, Mohammadali Javanray, Alexa Pichet Binette, Cherie Strikwerda-Brown, Jordana Remz, R. Nathan Spreng, Golia Shafiei, Bratislav Misic, Étienne Vachon-Presseau, and Sylvia Villeneuve
Subjects: Artificial Intelligence, Applied Mathematics, General Neuroscience, Computer Science Applications
Abstract: Systematic changes have been observed in the functional architecture of the human brain with advancing age. However, functional connectivity (FC) is also a powerful feature to detect unique “connectome fingerprints”, allowing identification of individuals among their peers. Although fingerprinting has been robustly observed in samples of young adults, the reliability of this approach has not been demonstrated across the lifespan. We applied the fingerprinting framework to the Cambridge Centre for Aging and Neuroscience cohort (n = 483 aged 18 to 89 years). We found that individuals are “fingerprintable” (i.e., identifiable) across independent functional MRI scans throughout the lifespan. We observed a U-shape distribution in the strength of “self-identifiability” (within-individual correlation across modalities), and “others-identifiability” (between-individual correlation across modalities), with a decrease from early adulthood into middle-age, before improving in older age. FC edges contributing to self-identifiability were not restricted to specific brain networks and were different between individuals across the lifespan sample. Self-identifiability was additionally associated with regional brain volume. These findings indicate that individual participant-level identification is preserved across the lifespan despite the fact that its components are changing non-linearly.
Published: 2023

21. White matter hyperintensity load varies depending on subjective cognitive decline criteria

Author: Cassandra Morrison, Mahsa Dadar, Sylvia Villeneuve, Simon Ducharme, and D. Louis Collins
Subjects: Aging, Original Article, Geriatrics and Gerontology
Abstract: Increased age and cognitive impairment is associated with an increase in cerebrovascular pathology often measured as white matter hyperintensities (WMHs) on MRI. Whether WMH burden differs between cognitively unimpaired older adults with subjective cognitive decline (SCD +) and without subjective cognitive decline (SCD −) remains conflicting, and could be related to the methods used to identify SCD. Our goal was to examine if four common SCD classification methods are associated with different WMH accumulation patterns between SCD + and SCD − . A total of 535 cognitively unimpaired older adults with 1353 time points from the Alzheimer’s Disease Neuroimaging Initiative were included in this study. SCD was operationalized using four different methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry. Linear mixed-effects models were used to investigate the associations between SCD and overall and regional WMH burden. Overall temporal WMH burden differences were only observed with the Worry questionnaire. Higher WMH burden change over time was observed in SCD + compared to SCD − in the temporal and parietal regions using the CCI (temporal, p = .01; parietal p = .02) and ECog (temporal, p = .02; parietal p = .01). For both the ECog + Worry and Worry questionnaire, change in WMH burden over time was increased in SCD + compared to SCD − for overall, frontal, temporal, and parietal WMH burden (p
Published: 2022

22. Midlife Physical Activity Engagement is Associated with Later-Life Cognition and Brain Health

Author: Meishan Ai, Timothy P. Morris, Adrián Noriega de la Colina, Nagashree Thovinakere, Jennifer Tremblay-Mercier, Sylvia Villeneuve, Arthur F. Kramer, and Maiya R. Geddes
Published: 2023

23. White matter hyperintensities are an early marker for cognitive decline in cognitively healthy older adults

Author: Cassandra Morrison, Mahsa Dadar, Sylvia Villeneuve, and Louis D Collins
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022

24. Associations between psychological factors, grey matter volume, and resistance and resilience to tau pathology in cognitively unimpaired older adults

Author: Cherie Strikwerda‐Brown, Frederic St‐Onge, Yara Yakoub, Hazal Ozlen, Alexa Pichet Binette, John Breitner, Sylvia Villeneuve, and PREVENT‐AD Research Group
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022

25. Electrophysiological markers of early Alzheimer’s Disease proteinopathy in the human brain

Author: Jonathan E Gallego Rudolf, Alex I Wiesman, Alexa Pichet Binette, Sylvia Villeneuve, and Sylvain Baillet
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022

26. Characterization of the contactin 5 protein and its risk-associated polymorphic variant throughout the Alzheimer's disease spectrum

Author: Marina Tedeschi Dauar, Anne Labonté, Cynthia Picard, Justin Miron, Pedro Rosa‐Neto, Henrik Zetterberg, Kaj Blennow, Sylvia Villeneuve, and Judes Poirier
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Abstract: We investigate the CNTN5 rs1461684 G variant and the contactin 5 protein in sporadic Alzheimer's disease (sAD).Contactin 5, sAD biomarkers, and synaptic markers were measured in the cerebrospinal fluid (CSF). Amyloid and tau deposition were assessed using positron emission tomography. Contactin 5 protein and mRNA levels were measured in brain tissue.CSF contactin 5 increases progressively in cognitively unimpaired individuals and is decreased in mild cognitive impairment and sAD. CSF contactin 5 correlates with sAD biomarkers and with synaptic markers. The rs1461684 G variant associates with faster disease progression in cognitively unimpaired subjects. Cortical full-length and isoform 3 CNTN5 mRNAs are decreased in the presence of the G allele and as a function of Consortium to Establish a Registry for Alzheimer's Disease stages.The newly identified rs1461684 G variant associates with sAD risk, rate of disease progression, and gene expression. Contactin 5 protein and mRNA are affected particularly in the early stages of the disease.
Published: 2022

27. The impact of demographic, clinical, genetic, and imaging variables on tau PET status

Author: Olof Strandberg, Chul Hyoung Lyoo, Adam L. Boxer, Renaud La Joie, Michael J. Pontecorvo, Erik Stormrud, Michael D. Devous, Young Hoon Ryu, Jonas Jögi, Ruben Smith, Edilio Borroni, Oskar Hansson, David N Soleimani-Meigooni, Jae Yong Choi, Rik Ossenkoppele, Hanna Cho, Bruce L. Miller, Tomas Olsson, Gregory Klein, Antoine Leuzy, Niklas Mattsson-Carlgren, Sebastian Palmqvist, Leonardo Iaccarino, Gil D. Rabinovici, Maria Luisa Gorno-Tempini, Sylvia Villeneuve, Carole H. Sudre, Neurology, Amsterdam Neuroscience - Neurodegeneration, and Radiology and nuclear medicine
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Neurology, tau Proteins, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, mental disorders, medicine, Clinical genetic, Dementia, Humans, Radiology, Nuclear Medicine and imaging, Cognitive Dysfunction, Cognitive impairment, Pathological, Demography, Aβ, Amyloid beta-Peptides, business.industry, General Medicine, Entorhinal cortex, medicine.disease, Hyperintensity, MCI, 030104 developmental biology, PET, Positron-Emission Tomography, Original Article, Tau, business, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract: Purpose A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. Methods We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model. Results Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan. Conclusion We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.
Published: 2021

28. Tau PET Imaging in Neurodegenerative Disorders

Author: Colin Groot, Sylvia Villeneuve, Ruben Smith, Oskar Hansson, Rik Ossenkoppele, Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Cross-Sectional Studies, Tauopathies, Alzheimer Disease, Positron-Emission Tomography, mental disorders, Humans, Radiology, Nuclear Medicine and imaging, Neurodegenerative Diseases, tau Proteins, United States
Abstract: The advent of PET ligands that bind tau pathology has enabled the quantification and visualization of tau pathology in aging and in Alzheimer disease (AD). There is strong evidence from neuropathologic studies that the most widely used tau PET tracers (i.e., 18F-flortaucipir, 18F-MK6240, 18F-RO948, and 18F-PI2620) bind tau aggregates formed in AD in the more advanced (i.e., ≥IV) Braak stages. However, tracer binding in most non-AD tauopathies is weaker and overlaps to a large extent with known off-target binding regions, limiting the quantification and visualization of non-AD tau pathology in vivo. Off-target binding is generally present in the substantia nigra, basal ganglia, pituitary, choroid plexus, longitudinal sinuses, meninges, or skull in a tracer-specific manner. Most cross-sectional studies use the inferior aspect of the cerebellar gray matter as a reference region, whereas for longitudinal analyses, an eroded white matter reference region is sometimes selected. No consensus has yet been reached on whether to use partial-volume correction of tau PET data. Although an increased neocortical tau PET signal is rare in cognitively unimpaired individuals, even in amyloid-β-positive cases, such a signal holds important prognostic information because preliminary data suggest that an elevated tau PET signal predicts cognitive decline over time. Also, in symptomatic stages of AD (i.e., mild cognitive impairment or AD dementia), tau PET shows great potential as a prognostic marker because an elevated baseline tau PET retention forecasts future cognitive decline and brain atrophy. For differential diagnostic use, the primary utility of tau PET is to differentiate AD dementia from other neurodegenerative diseases, as is in line with the conditions for the approval of 18F-flortaucipir by the U.S. Food and Drug Administration for clinical use. The differential diagnostic performance drops substantially at the mild-cognitive-impairment stage of AD, and there is no sufficient evidence for detection of sporadic non-AD primary tauopathies at the individual level for any of the currently available tau PET tracers. In conclusion, while the field is currently addressing outstanding methodologic issues, tau PET is gradually moving toward clinical application as a diagnostic and possibly prognostic marker in dementia expert centers and as a tool for selecting participants, assessing target engagement, and monitoring treatment effects in clinical trials.
Published: 2022

29. Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer’s Disease

Author: Alexa Pichet Binette, Étienne Vachon-Presseau, John Morris, Randall Bateman, Tammie Benzinger, D. Louis Collins, Judes Poirier, John C.S. Breitner, Sylvia Villeneuve, Ricardo Allegri, Fatima Amtashar, Randy Bateman, Sarah Berman, Courtney Bodge, Susan Brandon, William (Bill) Brooks, Jill Buck, Virginia Buckles, Sochenda Chea, Jasmeer Chhatwal, Patricio Chrem, Helena Chui, Jake Cinco, Jack Clifford, Carlos Cruchaga, Mirelle D‘Mello, Tamara Donahue, Jane Douglas, Noelia Edigo, Nilufer Erekin-Taner, Anne Fagan, Marty Farlow, Angela Farrar, Howard Feldman, Gigi Flynn, Nick Fox, Erin Franklin, Hisako Fujii, Cortaiga Gant, Samantha Gardener, Bernardino Ghetti, Alison Goate, Jill Goldman, Brian Gordon, Neill Graff-Radford, Julia Gray, Jenny Gurney, Jason Hassenstab, Mie Hirohara, David Holtzman, Russ Hornbeck, Siri Houeland DiBari, Takeshi Ikeuchi, Snezana Ikonomovic, Gina Jerome, Mathias Jucker, Celeste Karch, Kensaku Kasuga, Takeshi Kawarabayashi, William (Bill) Klunk, Robert Koeppe, Elke Kuder-Buletta, Christoph Laske, Jae-Hong Lee, Johannes Levin, Daniel Marcus, Ralph Martins, Neal Scott Mason, Colin Masters, Denise Maue-Dreyfus, Eric McDade, Lucy Montoya, Hiroshi Mori, Akem Nagamatsu, Katie Neimeyer, James Noble, Joanne Norton, Richard Perrin, Marc Raichle, John Ringman, Jee Hoon Roh, Stephen Salloway, Peter Schofield, Hiroyuki Shimada, Tomoyo Shiroto, Mikio Shoji, Wendy Sigurdson, Hamid Sohrabi, Paige Sparks, Kazushi Suzuki, Laura Swisher, Kevin Taddei, Jen Wang, Peter Wang, Mike Weiner, Mary Wolfsberger, Chengjie Xiong, Xiong Xu, Angela Tam, Anne Labonté, Anne-Marie Faubert, Axel Mathieu, Cécile Madjar, Charles Edouard Carrier, Christian Dansereau, Christina Kazazian, Claude Lepage, Cynthia Picard, David Maillet, Diane Michaud, Doris Couture, Doris Dea, Claudio Cuello, Alan Barkun, Alan Evans, Blandine Courcot, Christine Tardif, Clément Debacker, Clifford R. Jack, David Fontaine, David S. Knopman, Gerhard Maultaup, Jamie Near, Jeannie-Marie Leoutsakos, Jean-Robert Maltais, Jason Brandt, Jens Pruessner, John C. Morris, Laksanun Cheewakriengkrai, Lisa-Marie Münter, Louis Collins, Mallar Chakravarty, Mark A. Sager, Marina Dauar-Tedeschi, Mark Eisenberg, Natasha Rajah, Paul Aisen, Joanne Toussaint, Pedro Rosa-Neto, Pierre Bellec, Penelope Kostopoulos, Pierre Etienne, Pierre N. Tariot, Pierre Orban, Reisa A. Sperling, Rick Hoge, Ronald G. Thomas, Serge Gauthier, Suzanne Craft, Thomas J. Montine, Vasavan Nair, Véronique Bohbot, Vinod Venugopalan, Vladimir Fonov, Yasser Ituria-Medina, Zaven S. Khachaturian, Eduard Teigner, Elena Anthal, Elsa Yu, Fabiola Ferdinand, Galina Pogossova, Ginette Mayrand, Guerda Duclair, Guylaine Gagné, Holly Newbold-Fox, Illana Leppert, Isabelle Vallée, Jacob W. Vogel, Jennifer Tremblay-Mercier, Joanne Frenette, Josée Frappier, Justin Kat, Justin Miron, Karen Wan, Laura Mahar, Leopoldina Carmo, Louise Théroux, Mahsa Dadar, Marianne Dufour, Marie-Elyse Lafaille-Magnan, Melissa Appleby, Mélissa Savard, Miranda Tuwaig, Mirela Petkova, Pierre Rioux, Pierre-François Meyer, Rana El-Khoury, Renee Gordon, Renuka Giles, Samir Das, Seqian Wang, Shirin Tabrizi, Sulantha Mathotaarachchi, Sylvie Dubuc, Tanya Lee, Thomas Beaudry, Valérie Gervais, Véronique Pagé, Julie Gonneaud, Gülebru Ayranci, Tharick A. Pascoal, René Desautels, Fatiha Benbouhoud, Eunice Farah Saint-Fort, Sander C.J. Verfaillie, Sarah Farzin, Alyssa Salaciak, Stephanie Tullo, Etienne Vachon-Presseau, Leslie-Ann Daoust, Theresa Köbe, Nathan Spreng, Melissa McSweeney, Nathalie Nilsson, Morteza Pishnamazi, and Christophe Bedetti
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, tau Proteins, Disease, Article, 03 medical and health sciences, Cognition, 0302 clinical medicine, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Dementia, Big Five personality traits, Family history, Life Style, Biological Psychiatry, Aged, Amyloid beta-Peptides, Extraversion and introversion, business.industry, medicine.disease, Neuroticism, 3. Good health, 030104 developmental biology, Positron-Emission Tomography, Cohort, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract: Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.
Published: 2021

30. Social isolation is linked to classical risk factors of Alzheimer’s disease-related dementias

Author: Sylvia Villeneuve, Kimia Shafighi, Pedro Rosa-Neto, Judes Poirier, Patrícia Pelufo Silveira, Danilo Bzdok, David C. Glahn, AmanPreet Badhwar, Vaibhav Sharma, Laurette Dubé, and Yasser Iturria-Medina
Subjects: Gerontology, medicine.medical_specialty, education.field_of_study, Multidisciplinary, Public health, Population, Loneliness, Disease, medicine.disease, Social support, Social deprivation, medicine, Dementia, Social isolation, medicine.symptom, education, Psychology
Abstract: Alzheimer’s disease and related dementias is a major public health burden – compounding over upcoming years due to longevity. Recently, clinical evidence hinted at the experience of social isolation in expediting dementia onset. In 502,506 UK Biobank participants and 30,097 participants from the Canadian Longitudinal Study of Aging, we revisited traditional risk factors for developing dementia in the context of loneliness and lacking social support. Across these measures of subjective and objective social deprivation, we have identified strong links between individuals’ social capital and various indicators of Alzheimer’s disease and related dementias risk, which replicated across both population cohorts. The quality and quantity of daily social encounters had deep connections with key aetiopathological factors, which represent 1) personal habits and lifestyle factors, 2) physical health, 3) mental health, and 4) societal and external factors. Our population-scale assessment suggest that social lifestyle determinants are linked to most neurodegeneration risk factors, highlighting them promising targets for preventive clinical action.
Published: 2023

31. Brain charts for the human lifespan

Author: Armin Raznahan, Eric Courchesne, Andrea Parolin Jackowski, Kamen A. Tsvetanov, Cameron T. Ellis, R.C. Gur, Bin Bae J, Park Mtm, Pedro A. Valdes-Sosa, Simon N. Vandekar, Jacob W. Vogel, Juan Zhou, Machteld Marcelis, Kiho Im, Patricia Ellen Grant, Minhui Ouyang, Blesa Cabez M, Michael V. Lombardo, Sarah E. Morgan, James P. Boardman, Adamson C, Calhoun Vd, Delarue M, James H. Cole, Pichet Binette A, Roberto Toro, David H. Rowitch, Nynke A. Groenewold, Kevin M. Anderson, David T.W. Jones, Michael Schöll, Wang Ys, Aiden Corvin, R.E. Gur, Damien A. Fair, Gareth Ball, Herma Lina Schaare, Andrew Zalesky, Evdokia Anagnostou, Michael J. Meaney, Taki Y, Gareth J. Sullivan, Warrier, Petra E. Vértes, Chixiang Chen, Lisa T. Eyler, Wei Liao, Tomáš Paus, Jeremy A. Elman, Phillip McGuire, Hisham Ziauddeen, William S. Kremen, Etienne Vachon-Presseau, E.T. Bullmore, Christophe Tzourio, White, Hammill Cf, Mothersill D, Richard N. Henson, Jiang Qiu, Duncan E. Astle, Fabrice Crivello, Paul C. Fletcher, Chertavian C, Kim K, Jennifer Crosbie, Russell Schachar, Gabriel A. Devenyi, Manfred G. Kitzbichler, Tianye Jia, Trey Hedden, Sang Jae Lee, Ross D. Markello, Silke Kern, Ian M. Goodyer, Keith A. Johnson, Frauke Beyer, Bernard Mazoyer, A. Heinz, Sylvane Desrivières, Rosenberg, Gary Donohoe, Ong Mq, Alexander D. Edwards, Dan J. Stein, Nenad Medic, Zuo Xn, Travis T. Mallard, Peter Fonagy, Lindsay W. Victoria, Ingmar Skoog, Avram J. Holmes, Jason P. Lerch, Jed T. Elison, Jianfu Li, John H. Gilmore, Rosemary Holt, Caitlin K. Rollins, Carol E. Franz, Pedro Mario Pan, Saashi A Bedford, Yang N, Jonathan C Ipser, Richard A. I. Bethlehem, Tuulari Jj, Stolicyn A, Hua Huang, Bratislav Misic, Conor Liston, Ayub M, Lisa Ronan, Yeo Bt, Sophie Adler, Charles J. Lynch, Faith M. Gunning, Konrad Wagstyl, M. Mallar Chakravarty, John Suckling, Theodore D. Satterthwaite, Bharath Holla, Yap Seng Chong, Jinglei Lv, Jakob Seidlitz, Niall J Bourke, Xinlei Qian, Simon Baron-Cohen, Cynthia M. Ortinau, Deirel Paz Linares, Thyreau B, René S. Kahn, Aaron P. Schultz, Vanessa Cropley, Eric Westman, Mitchell Valdés-Sosa, Rik Ossenkoppele, André Zugman, Hasse Karlsson, Sylvia Villeneuve, Katja Heuer, Di Biase Ma, Margaret L. Westwater, Sofie L. Valk, David J. Sharp, Brigitte Landeau, Matthew Borzage, Kirsten A. Donald, Timothy Rittman, Richard Beare, Giovanni Abrahão Salum, Gunter Schumann, Ryuta Kawashima, Romero-Garcia R, John Blangero, Yun Hj, Russel T. Shinohara, Nicolas Crossley, Simon K. Warfield, Karen Pierce, George S. Alexopoulos, Katharine Dunlop, David C. Glahn, Francois Lalonde, Anqi Qiu, Lana Vasung, Gaël Chételat, Lídice Galán-García, Clifford R. Jack, Reisa A. Sperling, Anna Zettergren, Elizabeth Kelley, Arno Villringer, Andrea Mechelli, Benegal, Aaron Alexander-Bloch, Nicholas B. Turk-Browne, van Amelsvoort T, John D. Lewis, Heather C. Whalley, A. V. Witte, Zdenka Pausova, Joel T. Nigg, Heather J. Zar, Raymond J. Dolan, Christopher D. Smyser, Jay N. Giedd, Lena Palaniyappan, Ali Gholipour, Areces-Gonzalez A, Peter B. Jones, Jacqueline Hoare, Oskar Hansson, Linnea Karlsson, C Pantelis, Paly L, Bonnie Auyeung, Jorge Bosch-Bayard, Bethlehem, Richard [0000-0002-0714-0685], White, Simon [0000-0001-8642-7037], Astle, Duncan [0000-0002-7042-5392], Baron-Cohen, Simon [0000-0001-9217-2544], Henson, Rik [0000-0002-0712-2639], Jones, Peter [0000-0002-0387-880X], Kitzbichler, Manfred [0000-0002-4494-0753], Rittman, Timothy [0000-0003-1063-6937], Rowitch, David [0000-0002-0079-0060], Tsvetanov, Kamen A. [0000-0002-3178-6363], Westwater-Wozniak, Margaret [0000-0002-2918-0979], Ziauddeen, Hisham [0000-0003-4044-1719], Apollo - University of Cambridge Repository, British Academy, Autism Research Trust, National Institute of Mental Health (US), UK Research and Innovation, Medical Research Council (UK), National Institute for Health and Care Research (US), Wellcome Trust, University of Cambridge, Cambridge Biomedical Research Centre, University of Cambridge [UK] (CAM), University of Pennsylvania, Yale University [New Haven], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neuroscience - Department of Neuroscience, Centre de Recherche Interdisciplinaire / Center for Research and Interdisciplinarity [Paris, France] (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Med Staf Spec Psychiatrie (9), Neurology, Amsterdam Neuroscience - Neurodegeneration, 3R-BRAIN, AIBL, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s Disease Repository Without Borders Investigators, CALM Team, Cam-CAN, CCNP, COBRE, cVEDA, ENIGMA Developmental Brain Age Working Group, Developing Human Connectome Project, FinnBrain, Harvard Aging Brain Study, IMAGEN, KNE96, The Mayo Clinic Study of Aging, NSPN, POND, The PREVENT-AD Research Group, VETSA, [Bethlehem, R. A. I.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Auyeung, B.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Baron-Cohen, S.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Bedford, S. A.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Holt, R.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Lombardo, M. V.] Univ Cambridge, Dept Psychiat, Autism Res Ctr, Cambridge, England, [Bethlehem, R. A. I.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England, [Kitzbichler, M. G.] Univ Cambridge, Dept Psychiat, Brain Mapping Unit, Cambridge, England, [Seidlitz, J.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Vogel, J. W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Gur, R. E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Gur, R. C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Jackowski, A. P.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Satterthwaite, T. D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Alexander-Bloch, A. F.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA, [Seidlitz, J.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA, [Alexander-Bloch, A. F.] Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat & Behav Sci, Philadelphia, PA 19104 USA, [Seidlitz, J.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Chertavian, C.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Gur, R. E.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Gur, R. C.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [Alexander-Bloch, A. F.] Childrens Hosp Philadelphia & Penn Med, Lifespan Brain Inst, Philadelphia, PA USA, [White, S. R.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Goodyer, I. M.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Henson, R. N.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Jones, P. B.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Kitzbichler, M. G.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Medic, N.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Morgan, S. E.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Romero-Garcia, R.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Ronan, L.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Suckling, J.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Vertes, P. E.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Warrier, V.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Westwater, M. L.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Ziauddeen, H.] Univ Cambridge, Dept Psychiat, Cambridge, England, [Bullmore, E. T.] Univ Cambridge, Dept Psychiat, Cambridge, England, [White, S. R.] Univ Cambridge, MRC Biostat Unit, Cambridge, England, [Vogel, J. W.] Univ Penn, Lifespan Informat & Neuroimaging Ctr, Philadelphia, PA 19104 USA, [Satterthwaite, T. D.] Univ Penn, Lifespan Informat & Neuroimaging Ctr, Philadelphia, PA 19104 USA, [Anderson, K. M.] Yale Univ, Dept Psychol, New Haven, CT USA, [Ellis, C. T.] Yale Univ, Dept Psychol, New Haven, CT USA, [Turk-Browne, N. B.] Yale Univ, Dept Psychol, New Haven, CT USA, [Adamson, C.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Ball, G.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Beare, R.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Jackowski, A. P.] Murdoch Childrens Res Inst, Dev Imaging, Melbourne, Vic, Australia, [Adamson, C.] Monash Univ, Dept Med, Melbourne, Vic, Australia, [Beare, R.] Monash Univ, Dept Med, Melbourne, Vic, Australia, [Adler, S.] UCL Great Ormond St Inst Child Hlth, London, England, [Alexopoulos, G. S.] Weill Cornell Med, Dept Psychiat, Weill Cornell Inst Geriatr Psychiat, New York, NY USA, [Anagnostou, E.] Univ Toronto, Dept Pediat, Toronto, ON, Canada, [Anagnostou, E.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada, [Pierce, K.] Holland Bloorview Kids Rehabil Hosp, Toronto, ON, Canada, [Areces-Gonzalez, A.] Univ Elect Sci & Technol China, MOE Key Lab NeuroInformat, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Paz-Linares, D.] Univ Elect Sci & Technol China, MOE Key Lab NeuroInformat, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Areces-Gonzalez, A.] Univ Pinar del Rio Hermanos Saiz Montes de Oca, Pinar Del Rio, Cuba, [Astle, D. E.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Henson, R. N.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Whalley, H. C.] Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England, [Auyeung, B.] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, Edinburgh, Midlothian, Scotland, [Pausova, Z.] Univ Edinburgh, Sch Philosophy Psychol & Language Sci, Dept Psychol, Edinburgh, Midlothian, Scotland, [Ayub, M.] Queens Univ, Dept Psychiat, Ctr Neurosci Studies, Kingston, ON, Canada, [Ayub, M.] UCL, Mental Hlth Neurosci Res Dept, Div Psychiat, London, England, [Bae, J.] Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Seongnam, South Korea, [Ball, G.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia, [Baron-Cohen, S.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge Lifetime Asperger Syndrome Serv CLASS, Cambridge, England, [Benegal, V.] Natl Inst Mental Hlth & Neurosci NIMHANS, Ctr Addict Med, Bengaluru, India, [Beyer, F.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Villringer, A.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Witte, A. V.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany, [Blangero, J.] Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Dept Human Genet, Edinburg, TX USA, [Blesa Cabez, M.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Boardman, J. P.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Sullivan, G.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland, [Borzage, M.] Univ Southern Calif, Childrens Hosp Los Angeles, Keck Sch Med, Fetal & Neonatal Inst,Div Neonatol,Dept Pediat, Los Angeles, CA 90007 USA, [Bosch-Bayard, J. F.] Montreal Neurol Inst, Ludmer Ctr Neuroinformat & Mental Hlth, McGill Ctr Integrat Neurosci, Montreal, PQ, Canada, [Bosch-Bayard, J. F.] McGill Univ, Montreal, PQ, Canada, [Chakravarty, M. M.] McGill Univ, Montreal, PQ, Canada, [Bourke, N.] Imperial Coll London, Dept Brain Sci, London, England, [Sharp, D.] Imperial Coll London, Dept Brain Sci, London, England, [Alexander-Bloch, A. F.] Imperial Coll London, Dept Brain Sci, London, England, [Bourke, N.] Dementia Res Inst, Care Res & Technol Ctr, London, England, [Calhoun, V. D.] Georgia State Univ, Triinst Ctr Translat Res Neuroimaging & Data Sci, Georgia Inst Technol, Atlanta, GA 30303 USA, [Calhoun, V. D.] Emory Univ, Atlanta, GA 30322 USA, [Chakravarty, M. M.] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Comp Brain Anat CoBrA Lab, Montreal, PQ, Canada, [Chen, C.] Univ Penn, Penn Stat Imaging & Visualizat Ctr, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA, [Shinohara, R. T.] Univ Penn, Penn Stat Imaging & Visualizat Ctr, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA, [Chetelat, G.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Delarue, M.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Landeau, B.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Paly, L.] Normandie Univ, PhIND Physiopathol & Imaging Neurol Disorders, Inst Blood & Brain Caen Normandie, UNICAEN,INSERM,U1237, Caen, France, [Chong, Y. S.] Agcy Sci Technol & Res, Singapore Inst Clin Sci, Singapore, Singapore, [Chong, Y. S.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynaecol, Singapore, Singapore, [Cole, J. H.] UCL, Ctr Med Image Comp CMIC, London, England, [Cole, J. H.] UCL, Dementia Res Ctr DRC, London, England, [Corvin, A.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland, [Costantino, M.] Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Verdun, PQ, Canada, [Costantino, M.] McGill Univ, Undergrad Program Neurosci, Montreal, PQ, Canada, [Courchesne, E.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA, [Courchesne, E.] Univ Calif San Diego, Autism Ctr Excellence, San Diego, CA 92103 USA, [Crivello, F.] Univ Bordeaux, Inst Neurodegenerat Disorders, CNRS UMR5293, CEA, Bordeaux, France, [Mazoyer, B.] Univ Bordeaux, Inst Neurodegenerat Disorders, CNRS UMR5293, CEA, Bordeaux, France, [Cropley, V. L.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Di Biase, M. A.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Lv, J.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Zalesky, A.] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia, [Hammill, C. F.] Hosp Sick Children, Toronto, ON, Canada, [Schachar, R. J.] Hosp Sick Children, Toronto, ON, Canada, [Crossley, N.] Pontificia Univ Catolica Chile, Sch Med, Dept Psychiat, Santiago, Chile, [Crossley, N.] Kings Coll London, Dept Psychosis Studies, Inst Psychiat Psychol & Neurosci, London, England, [McGuire, P.] Kings Coll London, Dept Psychosis Studies, Inst Psychiat Psychol & Neurosci, London, England, [Crossley, N.] Inst Milenio Intelligent Healthcare Engn, Santiago, Chile, [Delorme, R.] Robert Debre Univ Hosp, AP HP, Child & Adolescent Psychiat Dept, Paris, France, [Delorme, R.] Inst Pasteur, Human Genet & Cognit Funct, Paris, France, [Desrivieres, S.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England, [Devenyi, G. A.] Douglas Mental Hlth Univ Inst, McGill Dept Psychiat, Cerebral Imaging Ctr, Montreal, PQ, Canada, [Devenyi, G. A.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada, [Di Biase, M. A.] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA, [Dolan, R.] UCL, Max Planck UCL Ctr Computat Psychiat & Ageing Res, London, England, [Dolan, R.] Wellcome Ctr Human Neuroimaging, London, England, [Wagstyl, K.] Wellcome Ctr Human Neuroimaging, London, England, [Donald, K. A.] Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Div Dev Paediat, Cape Town, South Africa, [Donald, K. A.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Groenewold, N. A.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Donohoe, G.] Natl Univ Ireland Galway, Sch Psychol, Ctr Neuroimaging Cognit & Genom NICOG, Galway, Ireland, [Dunlop, K.] Weill Cornell Med, Dept Psychiat, Weil Family Brain & Mind Res Inst, New York, NY USA, [Lynch, C.] Weill Cornell Med, Dept Psychiat, Weil Family Brain & Mind Res Inst, New York, NY USA, [Edwards, A. D.] Kings Coll London, Ctr Dev Brain, London, England, [Edwards, A. D.] Evelina London Childrens Hosp, London, England, [Edwards, A. D.] MRC Ctr Neurodev Disorders, London, England, [Elison, J. T.] Univ Minnesota, Mason Inst Dev Brain, Dept Pediat, Inst Child Dev, Minneapolis, MN USA, [Fair, D. A.] Univ Minnesota, Mason Inst Dev Brain, Dept Pediat, Inst Child Dev, Minneapolis, MN USA, [Feczko, E.] Univ Minnesota, Mason Inst Dev Brain, Dept Pediat, Inst Child Dev, Minneapolis, MN USA, [Ellis, C. T.] Haskins Labs Inc, New Haven, CT USA, [Elman, J. A.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genet Aging, La Jolla, CA 92093 USA, [Franz, C. E.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genet Aging, La Jolla, CA 92093 USA, [Kremen, W. S.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genet Aging, La Jolla, CA 92093 USA, [Eyler, L.] VA San Diego Healthcare, Desert Pacific Mental Illness Res Educ & Clin Ctr, San Diego, CA USA, [Eyler, L.] Univ Calif San Diego, Dept Psychiat, Los Angeles, CA USA, [Fletcher, P. C.] Univ Cambridge, Dept Psychiat, Cambridge Biomed Campus, Cambridge, England, [Fletcher, P. C.] Wellcome Trust MRC Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England, [Fletcher, P. C.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England, [Jones, P. B.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England, [Suckling, J.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England, [Ziauddeen, H.] Cambridgeshire & Peterborough NHS Fdn Trust, Cambridge, England, [Fonagy, P.] UCL, Dept Clin Educ & Hlth Psychol, London, England, [Fonagy, P.] Anna Freud Natl Ctr Children & Families, London, England, [Galan-Garcia, L.] Cuban Ctr Neurosci, Havana, Cuba, [Valdes-Sosa, M. J.] Cuban Ctr Neurosci, Havana, Cuba, [Gholipour, A.] Boston Childrens Hosp, Computat Radiol Lab, Boston, MA USA, [Warfield, S. K.] Boston Childrens Hosp, Computat Radiol Lab, Boston, MA USA, [Giedd, J.] Univ Calif San Diego, Dept Child & Adolescent Psychiat, San Diego, CA 92103 USA, [Giedd, J.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA, [Gilmore, J. H.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA, [Glahn, D. C.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA, [Im, K.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA, [Mathias, S. R.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA, [Rodrigue, A.] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA, [Glahn, D. C.] Harvard Med Sch, Boston, MA 02115 USA, [Im, K.] Harvard Med Sch, Boston, MA 02115 USA, [Johnson, K. A.] Harvard Med Sch, Boston, MA 02115 USA, [Mathias, S. R.] Harvard Med Sch, Boston, MA 02115 USA, [Rodrigue, A.] Harvard Med Sch, Boston, MA 02115 USA, [Schultz, A. P.] Harvard Med Sch, Boston, MA 02115 USA, [Sperling, R. A.] Harvard Med Sch, Boston, MA 02115 USA, [Grant, P. E.] Harvard Med Sch, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Div Newborn Med & Neuroradiol, Boston, MA 02115 USA, [Groenewold, N. A.] Univ Cape Town, SA MRC Unit Child & Adolescent Hlth, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa, [Zar, H. J.] Univ Cape Town, SA MRC Unit Child & Adolescent Hlth, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa, [Gunning, F. M.] Weill Cornell Med, Dept Psychiat, Weill Cornell Inst Geriatr Psychiat, New York, NY USA, [Victoria, L. W.] Weill Cornell Med, Dept Psychiat, Weill Cornell Inst Geriatr Psychiat, New York, NY USA, [Hammill, C. F.] Mouse Imaging Ctr, Toronto, ON, Canada, [Hansson, O.] Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Malmo, Sweden, [Hansson, O.] Skane Univ Hosp, Memory Clin, Malmo, Sweden, [Hedden, T.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA, [Hedden, T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02115 USA, [Heinz, A.] Charite Univ Med Berlin, Charite Campus Mitte, Berlin, Germany, [Heinz, A.] Free Univ Berlin, Charite Campus Mitte, Berlin, Germany, [Heinz, A.] Humboldt Univ, Dept Psychiat & Psychotherapy, Charite Campus Mitte, Berlin, Germany, [Heuer, K.] Max Planck Inst Human Cognit & Brain Sci, Dept Neuropsychol, Leipzig, Germany, [Heuer, K.] Univ Paris, Paris, France, [Toro, R.] Univ Paris, Paris, France, [Hoare, J.] Univ Cape Town, Dept Psychiat, Cape Town, South Africa, [Holla, B.] NIMHANS, Dept Integrat Med, Bengaluru, India, [Holla, B.] NIMHANS, Dept Psychiat, Accelerator Program Discovery Brain Disorders Usi, Bengaluru, India, [Holmes, A. J.] Yale Univ, Dept Psychol, New Haven, CT USA, [Villeneuve, S.] Yale Univ, Dept Psychol, New Haven, CT USA, [Holmes, A. J.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA, [Villeneuve, S.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA, [Huang, H.] Childrens Hosp Philadelphia, Radiol Res, Philadelphia, PA 19104 USA, [Ouyang, M.] Childrens Hosp Philadelphia, Radiol Res, Philadelphia, PA 19104 USA, [Huang, H.] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA, [Ipser, J.] Univ Cape Town, Dept Psychiat & Mental Hlth, Clin Neurosci Inst, Cape Town, South Africa, [Jack, C. R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA, [Jones, D. T.] Mayo Clin, Dept Radiol, Rochester, MN USA, Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil, [Jackowski, A. P.] Natl Inst Dev Psychiat, Beijing, Peoples R China, [Jia, T.] Fudan Univ, Inst Sci & Technol Brain Inspired Intelligence, Shanghai, Peoples R China, [Jia, T.] Fudan Univ, Minist Educ, Key Lab Computat Neurosci & Brain Inspired Intell, Shanghai, Peoples R China, [Jia, T.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Ctr Populat Neurosci & Precis Med PONS, SGDP Ctr, London, England, [Johnson, K. A.] Massachusetts Gen Hosp, Dept Neurol, Harvard Aging Brain Study, Boston, MA 02114 USA, [Schultz, A. P.] Massachusetts Gen Hosp, Dept Neurol, Harvard Aging Brain Study, Boston, MA 02114 USA, [Sperling, R. A.] Massachusetts Gen Hosp, Dept Neurol, Harvard Aging Brain Study, Boston, MA 02114 USA, [Johnson, K. A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA, [Sperling, R. A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA, [Johnson, K. A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA, [Jones, D. T.] Mayo Clin, Dept Neurol, Rochester, MN USA, [3R-BRAIN] Mayo Clin, Dept Neurol, Rochester, MN USA, [Kahn, R. S.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA, [Karlsson, H.] Univ Turku, Dept Psychiat, Dept Clin Med, Turku, Finland, [Karlsson, L.] Univ Turku, Dept Psychiat, Dept Clin Med, Turku, Finland, [Tuulari, J. J.] Univ Turku, Dept Psychiat, Dept Clin Med, Turku, Finland, [Karlsson, H.] Univ Turku, FinnBrain Birth Cohort Study, Turku Brain & Mind Ctr, Turku, Finland, [Karlsson, L.] Univ Turku, FinnBrain Birth Cohort Study, Turku Brain & Mind Ctr, Turku, Finland, [Tuulari, J. J.] Univ Turku, FinnBrain Birth Cohort Study, Turku Brain & Mind Ctr, Turku, Finland, [Karlsson, H.] Turku Univ Hosp, Turku, Finland, [Karlsson, L.] Turku Univ Hosp, Turku, Finland, [Tuulari, J. J.] Turku Univ Hosp, Turku, Finland, [Karlsson, H.] Turku Univ Hosp, Ctr Populat Hlth Res, Turku, Finland, [Karlsson, L.] Turku Univ Hosp, Ctr Populat Hlth Res, Turku, Finland, [Karlsson, H.] Univ Turku, Turku, Finland, [Karlsson, L.] Univ Turku, Turku, Finland, [Kawashima, R.] Tohoku Univ, Inst Dev Aging & Canc, Aoba Ku, Sendai, Miyagi, Japan, [Taki, Y.] Tohoku Univ, Inst Dev Aging & Canc, Aoba Ku, Sendai, Miyagi, Japan, [Thyreau, B.] Tohoku Univ, Inst Dev Aging & Canc, Aoba Ku, Sendai, Miyagi, Japan, [Kelley, E. A.] Queens Univ, Ctr Neurosci Studies, Dept Psychol, Kingston, ON, Canada, [Kelley, E. A.] Queens Univ, Ctr Neurosci Studies, Dept Psychiat, Kingston, ON, Canada, [Kern, S.] Univ Gothenburg, Neuropsychiat Epidemiol Unit, Dept Psychiat & Neurochem,Sahlgrenska Acad, Ctr Ageing & Hlth AGECAP,Inst Neurosci & Physiol, Gothenburg, Sweden, [Skoog, I.] Univ Gothenburg, Neuropsychiat Epidemiol Unit, Dept Psychiat & Neurochem,Sahlgrenska Acad, Ctr Ageing & Hlth AGECAP,Inst Neurosci & Physiol, Gothenburg, Sweden, [Zettergren, A.] Univ Gothenburg, Neuropsychiat Epidemiol Unit, Dept Psychiat & Neurochem,Sahlgrenska Acad, Ctr Ageing & Hlth AGECAP,Inst Neurosci & Physiol, Gothenburg, Sweden, [Kern, S.] Sahlgrens Univ Hosp, Psychiat Cognit & Old Age Psychiat Clin, Reg Vastra Gotaland, Gothenburg, Sweden, [Skoog, I.] Sahlgrens Univ Hosp, Psychiat Cognit & Old Age Psychiat Clin, Reg Vastra Gotaland, Gothenburg, Sweden, [Kim, K. W.] Seoul Natl Univ, Dept Brain & Cognit Sci, Coll Nat Sci, Seoul, South Korea, [Kim, K. W.] Seoul Natl Univ, Bundang Hosp, Dept Neuropsychiat, Seongnam, South Korea, [Kim, K. W.] Seoul Natl Univ, Dept Psychiat, Coll Med, Seoul, South Korea, [Kim, K. W.] SNU MRC, Inst Human Behav Med, Seoul, South Korea, [Lalonde, F.] NIMH, Sect Dev Neurogenom, Human Genet Branch, Bethesda, MD 20892 USA, [Raznahan, A.] NIMH, Sect Dev Neurogenom, Human Genet Branch, Bethesda, MD 20892 USA, [Lee, S.] Seoul Natl Univ, Coll Nat Sci, Dept Brain & Cognit Sci, Seoul, South Korea, [Lerch, J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada, [Lerch, J.] Univ Oxford, Nuffield Dept Clin Neurosci, FMRIB, Wellcome Ctr Integrat Neuroimaging, Oxford, England, [Lewis, J. D.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada, [Li, J.] Univ Elect Sci & Technol China, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Liao, W.] Univ Elect Sci & Technol China, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Valdes-Sosa, P. A.] Univ Elect Sci & Technol China, Clin Hosp, Chengdu Brain Sci Inst, Chengdu, Peoples R China, [Liston, C.] Weill Cornell Med, Dept Psychiat, New York, NY USA, [Liston, C.] Weill Cornell Med, Brain & Mind Res Inst, New York, NY USA, [Lombardo, M. V.] Ist Italiano Tecnol, Ctr Neurosci & Cognit Syst UniTn, Lab Autism & Neurodev Disorders, Rovereto, Italy, [Lv, J.] Univ Sydney, Sch Biomed Engn, Sydney, NSW, Australia, [Lv, J.] Univ Sydney, Brain & Mind Ctr, Sydney, NSW, Australia, [Mallard, T. T.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA, [Marcelis, M.] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, EURON,Med Ctr, Maastricht, Netherlands, [Marcelis, M.] Inst Mental Hlth Care Eindhoven GGzE, Eindhoven, Netherlands, [Markello, R. D.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada, [Misic, B.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada, [Vasung, L.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada, [Mazoyer, B.] Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinformat & Mental Hlth, Montreal, PQ, Canada, [Meaney, M. J.] Douglas Mental Hlth Univ Inst, Ludmer Ctr Neuroinformat & Mental Hlth, Montreal, PQ, Canada, [Meaney, M. J.] Singapore Inst Clin Sci, Singapore, Singapore, [Mechelli, A.] Bordeaux Univ Hosp, Bordeaux, France, [Morgan, S. E.] Univ Cambridge, Dept Comp Sci & Technol, Cambridge, England, [Morgan, S. E.] Alan Turing Inst, London, England, [Vertes, P. E.] Alan Turing Inst, London, England, [Mothersill, D.] Natl Coll Ireland, Sch Business, Dept Psychol, Dublin, Ireland, [Mothersill, D.] Natl Univ Ireland Galway, Sch Psychol, Galway, Ireland, [Mothersill, D.] Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom, Galway, Ireland, [Mothersill, D.] Trinity Coll Dublin, Dept Psychiat, Dublin, Ireland, [Nigg, J.] Oregon Hlth & Sci Univ, Dept Psychiat, Sch Med, Portland, OR 97201 USA, [Ong, M. Q. W.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Qian, X.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Zhou, J. H.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Ortinau, C.] Washington Univ, Dept Pediat, St Louis, MO 63130 USA, [Ossenkoppele, R.] Vrije Univ Amsterdam, Alzheimer Ctr Amsterdam, Amsterdam UMC, Dept Neurol,Amsterdam Neurosci, Amsterdam, Netherlands, [Ossenkoppele, R.] Lund Univ, Clin Memory Res Unit, Lund, Sweden, [Palaniyappan, L.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada, [Palaniyappan, L.] Univ Western Ontario, Brain & Mind Inst, London, ON, Canada, [Pan, P. M.] Fed Univ Sao Poalo UNIFESP, Dept Psychiat, Sao Poalo, Brazil, [Pan, P. M.] Natl Inst Dev Psychiat Children & Adolescents INP, Sao Poalo, Brazil, [Zugman, A.] Natl Inst Dev Psychiat Children & Adolescents INP, Sao Poalo, Brazil, [Pantelis, C.] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Carlton, Vic, Australia, [Pantelis, C.] Melbourne Hlth, Carlton, Vic, Australia, [Pantelis, C.] Univ Melbourne, Melbourne Sch Engn, Parkville, Vic, Australia, [Pantelis, C.] Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia, [Park, M. M.] Western Univ, Schulich Sch Med & Dent, Dept Psychiat, London, ON, Canada, [Rollins, C. K.] Univ Montreal, Dept Psychiat, Fac Med, Montreal, PQ, Canada, [Rollins, C. K.] Univ Montreal, CHU St Justine, Montreal, PQ, Canada, [Romero-Garcia, R.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada, [Romero-Garcia, R.] Univ Toronto, Dept Psychol, Toronto, ON, Canada, [Rosenberg, M. D.] Univ Toronto, Dept Physiol, Toronto, ON, Canada, [Rosenberg, M. D.] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada, [Paz-Linares, D.] Cuban Neurosci Ctr, Havana, Cuba, [Pichet Binette, A.] McGill Univ, Fac Med, Dept Psychiat, Montreal, PQ, Canada, [Villeneuve, S.] McGill Univ, Fac Med, Dept Psychiat, Montreal, PQ, Canada, [Pichet Binette, A.] Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada, [Villeneuve, S.] Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada, [Qiu, J.] Southwest Univ, Sch Psychol, Chongqing, Peoples R China, [Qiu, A.] Natl Univ Singapore, N1 Inst Hlth, Dept Biomed Engn, Singapore, Singapore, [Rittman, T.] Univ Cambridge, Dept Clin Neurosci, Cambridge, England, [Tsvetanov, K. A.] Univ Cambridge, Dept Clin Neurosci, Cambridge, England, [Rollins, C. K.] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA, [Rollins, C. K.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA, [Romero-Garcia, R.] Univ Seville, Dpto Fisiol Med & Biofis, Inst Biomed Sevilla IBiS HUVR CSIC, Seville, Spain, [Rosenberg, M. D.] Univ Chicago, Dept Psychol, 5848 S Univ Ave, Chicago, IL 60637 USA, [Rosenberg, M. D.] Univ Chicago, Inst Neurosci, Chicago, IL USA, [Rowitch, D. H.] Univ Cambridge, Dept Paediat, Cambridge, England, [Rowitch, D. H.] Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England, [Salum, G. A.] Univ Fed Rio Grande Sul UFRGS, Hosp Clin Porto Alegre, Dept Psychiat, Porto Alegre, RS, Brazil, [Salum, G. A.] Natl Inst Dev Psychiat INPD, Sao Paulo, Brazil, [Schaare, H. L.] Max Planck Inst Human Cognit & Brain Sci, Otto Hahn Grp Cognit Neurogenet, Leipzig, Germany, [Schaare, H. L.] Res Ctr Juelich, Inst Neurosci & Med INM 7 Brain & Behav, Julich, Germany, [Schultz, A. P.] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA, [Schumann, G.] Fudan Univ, Inst Sci & Technol Brain Inspired Intelligence, Ctr Populat Neurosci & Stratified Med PONS, Shanghai, Peoples R China, [Schumann, G.] Charite Campus Mitte, Dept Psychiat & Psychotherapy, Charite Mental Hlth, PONS Ctr, Berlin, Germany, [Scholl, M.] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden, [Scholl, M.] Univ Gothenburg, Dept Psychiat & Neurochem, Gothenburg, Sweden, [Scholl, M.] UCL, Queens Sq Inst Neurol, Dementia Res Ctr, London, England, [Sharp, D.] UK Dementia Res Inst, Care Res & Technol Ctr, London, England, [Shinohara, R. T.] Univ Penn, Perelman Sch Med, Dept Radiol, Ctr Biomed Image Comp & Analyt, Philadelphia, PA 19104 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA, [Smyser, C. D.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA, [Stein, D. J.] Univ Cape Town, Dept Psychiat, SA MRC Unit Risk & Resilience Mental Disorders, Cape Town, South Africa, [Stein, D. J.] Univ Cape Town, Neurosci Inst, Cape Town, South Africa, [Stolicyn, A.] Univ Edinburgh, Ctr Clin Brain Sci, Div Psychiat, Edinburgh, Midlothian, Scotland, [Whalley, H. C.] Univ Edinburgh, Ctr Clin Brain Sci, Div Psychiat, Edinburgh, Midlothian, Scotland, [Toro, R.] Inst Pasteur, Dept Neurosci, Paris, France, [Traut, N.] Inst Pasteur, Dept Neurosci, Paris, France, [Traut, N.] Univ Paris 05, Ctr Res & Interdisciplinar CRI, Paris, France, [Tsvetanov, K. A.] Univ Cambridge, Dept Psychol, Cambridge, England, [Turk-Browne, N. B.] Yale Univ, Wu Tsai Inst, New Haven, CT USA, [Tuulari, J. J.] Univ Turku, Dept Clin Med, Turku, Finland, [Tuulari, J. J.] Univ Turku, Turku Coll Sci Med & Technol, Turku, Finland, [Tzourio, C.] Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, CHU Bordeaux, U1219,INSERM, Bordeaux, France, [Vachon-Presseau, E.] McGill Univ, Fac Dent Med & Oral Hlth Sci, Montreal, PQ, Canada, [Valdes-Sosa, P. A.] McGill Univ, Alan Edwards Ctr Res Pain AECRP, Montreal, PQ, Canada, [Valk, S. L.] Forschungszentrum Julich, Inst Neurosci & Med 7, Julich, Germany, [Valk, S. L.] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany, [van Amelsvoort, T.] Maastricht Univ, Dept Psychiat & Neurosychol, Maastricht, Netherlands, [Vandekar, S. N.] Vanderbilt Univ, Dept Biostat, 221 Kirkland Hall, Nashville, TN 37235 USA, [Villeneuve, S.] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA, [Villringer, A.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Witte, A. V.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Zuo, X. N.] Univ Leipzig, Clin Cognit Neurol, Med Ctr, Leipzig, Germany, [Wang, Y. S.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Yang, N.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Yeo, B.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Zuo, X. N.] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing, Peoples R China, [Wang, Y. S.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Yang, N.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Zuo, X. N.] Beijing Normal Univ, IDG McGovern Inst Brain Res, Dev Populat Neuroscience Res Ctr, Beijing, Peoples R China, [Wang, Y. S.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Yang, N.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Zuo, X. N.] Natl Basic Sci Data Ctr, Beijing, Peoples R China, [Wang, Y. S.] Chinese Acad Sci, Res Ctr Lifespan Dev Brain & Mind, Inst Psychol, Beijing, Peoples R China, [Yang, N.] Chinese Acad Sci, Res Ctr Lifespan Dev Brain & Mind, Inst Psychol, Beijing, Peoples R China, [Westman, E.] Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden, [Witte, A. V.] Univ Leipzig, CRC 1052 Obes Mech, Fac Med, Leipzig, Germany, [Zhou, J. H.] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Sleep & Cognit, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Translat MR Res, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, N1 Inst Hlth, Singapore, Singapore, [Yeo, B.] Natl Univ Singapore, Inst Digital Med, Singapore, Singapore, [Yun, H.] Natl Univ Singapore, Integrat Sci & Engn Programme ISEP, Singapore, Singapore, [Zar, H. J.] Univ Melbourne, Dept Biomed Engn, Melbourne, Vic, Australia, [Zhou, J. H.] Natl Univ Singapore, Yong Loo Lin Sch Med, Ctr Translat Magnet Resonance Res, Singapore, Singapore, [Ziauddeen, H.] Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Cambridge, England, [Zugman, A.] NIMH, NIH, Bethesda, MD 20892 USA, [Zugman, A.] Escola Paulista Med, Dept Psychiat, Sao Paulo, Brazil, [Zuo, X. N.] Nanning Normal Univ, Sch Educ Sci, Key Lab Brain & Educ, Nanning, Peoples R China, British Academy Postdoctoral fellowship, NIMH, UKRI Medical Research Council, NIHR Cambridge Biomedical Research Centre, NIHR Senior Investigator award, MRC research infrastructure award, Commonwealth Scientific and Industrial Research Organisation (CSIRO), and Ontario Brain Institute
Subjects: 631/378/2649, OpenPain Project, KNE96, Growth, Psychiatric-disorders, DISEASE, 3R-BRAIN, Brain charts, MRI Brain, OASIS-3, Disease, CCNP, 631/378/2571, UMN BCP, Multidisciplinary, medicine.diagnostic_test, PSYCHIATRIC-DISORDERS, article, Brain, Human brain, ASSOCIATION, Magnetic Resonance Imaging, Harvard Aging Brain Study, The Mayo Clinic Study of Aging, NSPN, medicine.anatomical_structure, GROWTH, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:500, BURDEN, WHITE-MATTER, FinnBrain, Harvard Aging Brain Study, Organization, Mri, MRI, medicine.medical_specialty, Concurrent validity, MODELS, Cam-CAN, Longevity, CALM Team, POND, Neuroimaging, Burden, ORGANIZATION, AIBL, The PREVENT-AD Research Group, VETSA, Cortical thickness, Association, Physical medicine and rehabilitation, FinnBrain, IMAGEN, KNE96, White-matter, medicine, Humans, ASRB, 631/378/1689, COBRE, business.industry, 631/378/2611, Brain morphometry, Neurosciences, Alzheimer’s Disease Repository Without Borders Investigators, Magnetic resonance imaging, Alzheimer’s Disease Neuroimaging Initiative, Anthropometry, Body Height, Brain growth, Birth, 59/57, Normative, IMAGEN, ENIGMA Developmental Brain Age working group, NSPN, business, CCNP, 3R-BRAIN, CORTICAL THICKNESS, Developing Human Connectome Project, ENIGMA Developmental Brain Age working group, The PREVENT-AD Research Group, VETSA, Bullmore, E.T
Abstract: Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.
Published: 2022

32. APOE ɛ2 vs APOE ɛ4 dosage shows sex-specific links to hippocampus-default network subregion co-variation

Author: Chloé Savignac, Sylvia Villeneuve, AmanPreet Badhwar, Karin Saltoun, Kimia Shafighi, Chris Zajner, Vaibhav Sharma, Sarah A Gagliano Taliun, Sali Farhan, Judes Poirier, and Danilo Bzdok
Abstract: Alzheimer’s disease and related dementias (ADRD) are marked by intracellular tau aggregates in the medial-temporal lobe (MTL) and extracellular amyloid aggregates in the default network (DN). Here, we sought to clarify ADRD-related co-dependencies between the MTL’s most vulnerable structure, the hippocampus (HC), and the highly associative DN at a subregion resolution. We confronted the effects of APOE ɛ2 and ɛ4, rarely investigated together, with their impact on HC-DN co-variation regimes at the population level. In a two-pronged decomposition of structural brain scans from ∼40,000 UK Biobank participants, we located co-deviating structural patterns in HC and DN subregions as a function of ADRD family risk. Across the disclosed HC-DN signatures, recurrent deviations in the CA1, CA2/3, molecular layer, fornix’s fimbria, and their cortical partners related to ADRD risk. Phenome-wide profiling of HC-DN co- variation expressions from these population signatures revealed male-specific associations with air-pollution, and female-specific associations with cardiovascular traits. We highlighted three main factors associated with brain-APOE associations across the different gene variants: happiness, and satisfaction with friendships, and with family. We further showed that APOE ɛ2/2 interacts preferentially with HC-DN co-variation patterns in estimating social lifestyle in males and physical activity in females. Our findings reinvigorate the often-neglected interplay between APOE ɛ2 dosage and sex, which we have linked to fine-grained structural divergences indicative of ADRD susceptibility.
Published: 2022

33. Repetitive negative thinking is associated with amyloid, tau, and cognitive decline

Author: Eider M. Arenaza-Urquijo, Alexa Pichet Binette, Julie Gonneaud, Gaël Chételat, Rebecca M. Jones, Sylvia Villeneuve, Lise R Lovland, Natalie L. Marchant, CHETELAT, Gaëlle, University College of London [London] (UCL), Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, and PREVENT-AD Research Group
Subjects: cognition, Epidemiology, Neuropsychological Tests, 0302 clinical medicine, Risk Factors, worry, tau, 030212 general & internal medicine, Cognitive decline, Depression (differential diagnoses), media_common, Aged, 80 and over, Health Policy, Confounding, amyloid, Cognition, Middle Aged, Alzheimer's disease, Temporal Lobe, Pessimism, Psychiatry and Mental health, Memory, Short-Term, depression, Cohort, Anxiety, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Worry, repetitive negative thinking, Clinical psychology, media_common.quotation_subject, tau Proteins, 03 medical and health sciences, Cellular and Molecular Neuroscience, Developmental Neuroscience, Alzheimer Disease, medicine, Humans, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Amyloid beta-Peptides, business.industry, rumination, Positron-Emission Tomography, Rumination, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: International audience; Introduction: The Cognitive Debt hypothesis proposes that repetitive negative thinking(RNT), a modifiable process common to many psychological risk factors for Alzheimer’sdisease (AD) may itself increase risk. We sought to empirically examine relationshipsbetween RNT and markers of AD, compared with anxiety and depression symptoms.Methods: Two hundred and ninety-two older adults with longitudinal cognitive assessments, including 113 with amyloid-positron emission tomography (PET) and tau-PETscans, from the PREVENT-AD cohort and 68 adults with amyloid-PET scans from theIMAP+ cohort were included. All participants completed RNT, anxiety, and depressionquestionnaires.Results: RNT was associated with decline in global cognition (P = .02); immediate (P =.03) and delayed memory (P = .04); and global amyloid (PREVENT-AD: P = .01; IMAP+:P = .03) and entorhinal tau (P = .02) deposition. Relationships remained after adjustingfor potential confounders.Discussion: RNT was associated with decline in cognitive domains affected early inAD and with neuroimaging AD biomarkers. Future research could investigate whethermodifying RNT reduces AD risk.
Published: 2020

34. Intermediate flortaucipir uptake is associated with Aβ-PET and CSF tau in asymptomatic adults

Author: Julie Gonneaud, Alexa Pichet Binette, Pierre-François Meyer, Pedro Rosa-Neto, Judes Poirier, John C.S. Breitner, Christophe Bedetti, Hazal Ozlen, Anne Labonté, Sylvia Villeneuve, and Melissa McSweeney
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, tau Proteins, Standardized uptake value, Asymptomatic, Temporal lobe, Correlation, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Humans, Effects of sleep deprivation on cognitive performance, Family history, Aged, business.industry, Brain, Middle Aged, medicine.disease, 030104 developmental biology, Positron-Emission Tomography, Cohort, Female, Neurology (clinical), Radiopharmaceuticals, medicine.symptom, Alzheimer's disease, business, 030217 neurology & neurosurgery, Carbolines
Abstract: ObjectiveTo investigate relationships between flortaucipir (FTP) uptake, age, and established Alzheimer disease (AD) markers in asymptomatic adults at increased risk of AD.MethodsOne-hundred nineteen individuals with a family history of AD (Presymptomatic Evaluation of Experimental or Novel Treatments of Alzheimer’s Disease [PREVENT-AD] cohort, mean age 67 ± 5 years) underwent tau-PET ([18F]FTP), β-amyloid (Aβ)-PET ([18F]NAV4694 [NAV]), and cognitive assessment. Seventy-four participants also had CSF phosphorylated tau and total tau data available. We investigated the association between age and FTP in this relatively young cohort of older adults. We also investigated regional FTP standardized uptake value ratio (SUVR) differences between Aβ-positive and Aβ-negative individuals and regional correlations between FTP and NAV retention. In cortical regions showing consistent associations across analyses, we assessed whether FTP was in addition related to CSF tau and cognitive performance. Lastly, we identified the lowest FTP value at which associations with Aβ-PET, CSF, and cognition were detectable.ResultsIncreased age was associated only with amygdala and transverse temporal lobe FTP retention. Aβ-positive individuals had higher FTP SUVR values in several brain regions, further showing correlation with NAV load through the cortex. Increased FTP SUVRs in medial temporal regions were associated with increased CSF tau values and worse cognition. The SUVRs at which associations between entorhinal FTP SUVR and other AD markers were first detected differed by modality, with a detection point of 1.12 for CSF values, 1.2 for Aβ-PET, and 1.4 for cognition.ConclusionsRelatively low FTP-PET SUVRs are associated with pathologic markers of AD in the preclinical phase of the disease. Adjustment in the tau threshold should be considered, depending on the purpose of the tau classification.
Published: 2020

35. Plasma p-tau231, p-tau181, PET Biomarkers, and Cognitive Change in Older Adults

Author: Pierre-François, Meyer, Nicholas J, Ashton, Thomas K, Karikari, Cherie, Strikwerda-Brown, Theresa, Köbe, Julie, Gonneaud, Alexa, Pichet Binette, Hazal, Ozlen, Yara, Yakoub, Joel, Simrén, Josef, Pannee, Juan, Lantero-Rodriguez, Anne, Labonté, Suzanne L, Baker, Michael, Schöll, Eugeen, Vanmechelen, John C S, Breitner, Henrik, Zetterberg, Kaj, Blennow, Judes, Poirier, and Sylvia, Villeneuve
Subjects: Amyloid beta-Peptides, Cognition, Neurology, Alzheimer Disease, Positron-Emission Tomography, Humans, Cognitive Dysfunction, tau Proteins, Neurology (clinical), Biomarkers, Aged
Abstract: The objective of this study was to evaluate novel plasma p-tau231 and p-tau181, as well as AβIn a cohort of 244 older adults at risk of Alzheimer's disease (AD) owing to a family history of AD dementia, we measured single molecule array (Simoa)-based plasma tau biomarkers (p-tau231 and p-tau181), AβPlasma p-tau biomarkers correlated with flortaucipir binding in medial temporal, parietal, and inferior temporal regions. P-tau231 showed further associations in lateral parietal and occipital cortices. Plasma AβPlasma p-tau231 showed more robust associations with PET biomarkers than p-tau181 in presymptomatic individuals. The combination of p-tau and Aβ
Published: 2022

36. CSF apolipoprotein B levels predict future visuospatial cognitive decline and synaptic pathology in cognitively unimpaired healthy elderly with a parental history of Alzheimer’s disease

Author: Judes Poirier, Nathalie I.V. Nilsson, Anne Labonté, Pedro Rosa‐Neto, Nicholas J. Ashton, Henrik Zetterberg, Kaj Blennow, John Breitner, Sylvia Villeneuve, Cynthia Picard, and Prevent‐AD Research Group
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021

37. Plasma p‐tau231 in the Alzheimer’s disease continuum: A multi‐cohort evaluation of diagnostic performance, detection of Aβ pathology and preclinical application

Author: Nicholas J. Ashton, Thomas K. Karikari, Juan Lantero Rodriguez, Andréa Lessa Benedet, Anniina Snellman, Tharick A. Pascoal, Serge Gauthier, Pedro Rosa‐Neto, Clifford R. Jack, Ronald C. Petersen, Michelle M. Mielke, Pratishtha Chatterjee, Ralph N. Martins, Madhav Thambisetty, Vijay R. Varma, Susan M. Resnick, Nick C. Fox, Antoinette O'Connor, Agathe Vrillon, Claire Paquet, Sylvia Villeneuve, Judes Poirier, Prevent‐AD Research Group, Doug R. Galasko, Marta Milà‐Alomà, Carolina Minguillón, Karine Fauria, Marc Suarez‐Calvet, Eugeen Vanmechelen, Henrik Zetterberg, and Kaj Blennow
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021

38. Cognitive differences between healthy monolingual and bilingual anglophones on the English version of the Dépistage Cognitif de Québec: A new screening tool for atypical dementia

Author: Marianne Lévesque, Marie-Christine Ouellet, Synthia Meilleur-Durand, Brandy L. Callahan, David Bergeron, Ging-Yuek Hsiung, Louis Verret, Marie-Pierre Fortin, Mario Masellis, Pamela Jarrett, Serge Gauthier, Stéphane Poulin, Stephen C. Cunnane, Sylvia Villeneuve, Joël Macoir, Rémi W. Bouchard, and Robert Laforce
Subjects: Linguistics and Language, Language and Linguistics, Education
Abstract: Aims and Objectives: Cognitive abilities between monolingual and bilingual individuals may differ, making it an important factor to consider during the administration of cognitive screening tools. Otherwise, assessments could be subject to misinterpretation, leading to possible inaccurate diagnoses. The current project aimed to compare cognitive performance of healthy older monolingual and bilingual anglophones on the English version of a new cognitive screening test designed for better recognition of atypical dementia: the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org ). Design: The DCQ was administered by qualified psychometricians to 85 native English-speaking participants aged 50 years and over, in various sites across Canada. Language proficiency was established using the Language Experience and Proficiency Questionnaire (LEAP-Q). The Montreal Cognitive Assessment (MoCA) was used to exclude individuals with cognitive impairments. Data and Analysis: Amid the anglophone participants recruited, 30 monolingual anglophones and 29 bilingual anglophones (English and French) met inclusion criteria. Groups had similar age, education, and MoCA scores. Monolinguals and bilinguals were compared on their total DCQ scores and each of the five DCQ indexes: Memory, Visuospatial, Executive, Language, and Behavioural. Findings: The bilingual participants performed better on the Language Index, which contributed to the significant bilingual advantage for the overall DCQ scores. When applying a Bonferroni correction, the differences between groups were, however, not maintained. No differences were found on any of the other indexes. Originality: This study is the first to explore psychometric properties of the DCQ in older monolingual and bilingual participants tested in their native language. Implications: Results highlight the importance of identifying and characterizing linguistic diversity before using new screening tools in clinical settings. The potential cognitive advantages of bilingualism should be considered when interpreting test data and explicitly discussed in neuropsychological reports.
Published: 2022

39. White matter hyperintensities may be an early marker for age-related cognitive decline

Author: Mahsa Dadar, C. Morrison, Sylvia Villeneuve, and D.L. Collins
Subjects: Age-related cognitive decline, medicine.medical_specialty, business.industry, Cognition, Disease, Audiology, medicine.disease, Hyperintensity, Neuroimaging, Cohort, Medicine, Alzheimer's disease, Cognitive decline, business
Abstract: BackgroundResearch suggests that cerebral small vessel disease (CSVD), amyloid, and pTau contribute to age-related cognitive decline. It remains unknown how these factors relate to one another, nor how they jointly contribute to cognitive decline in normal aging. This project examines the association between these pathologies and their relationship to cognitive decline in cognitively normal older adults without subjective cognitive decline.MethodsA total of 230 subjects with CSF Aß42, CSF pTau181, white matter hyperintensities (WMHs) used as a proxy of CSVD and cognitive scores from the Alzheimer’s Disease Neuroimaging Initiative were included. Associations between each pathology and cognitive score were investigated using regression models. Furthermore, relationships between the three pathologies were also examined using regression models.ResultsAt baseline, there was an inverse association between WMH load and Aß42 (t=-4.20, pt=0.51, p=.61). Correcting for age, sex and education, baseline WMH load was associated with baseline ADAS-13 scores (t=2.59, p=.01) and lower follow-up executive functioning (t= -2.84, p=.005). Baseline Aß42 was associated with executive function at baseline (t=3.58, p<.004) but not at follow-up (t=1.05, p=0.30), nor with ADAS-13 at baseline (t=-0.24, p0.81) or follow-up (t=0.09, p=0.93). Finally, baseline pTau was not associated with any cognitive measure at baseline or follow-up.ConclusionBoth baseline Aß42 and WMH load are associated with some baseline cognition scores, but only baseline WMH load is associated with follow-up executive functioning, indicating that it may be one of the earliest pathologies that contributes to future cognitive decline, in cognitively healthy older adults. Given that healthy older adults with WMH pathology exhibit declines in cognitive functioning, they may be less resilient to future pathology increasing their risk for cognitive impairment due to dementia than those without WMHs.
Published: 2021

40. Association of Elevated Amyloid and Tau Positron Emission Tomography Signal With Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment

Author: Cherie, Strikwerda-Brown, Diana A, Hobbs, Julie, Gonneaud, Frédéric, St-Onge, Alexa Pichet, Binette, Hazal, Ozlen, Karine, Provost, Jean-Paul, Soucy, Rachel F, Buckley, Tammie L S, Benzinger, John C, Morris, Victor L, Villemagne, Vincent, Doré, Reisa A, Sperling, Keith A, Johnson, Christopher C, Rowe, Brian A, Gordon, Judes, Poirier, John C S, Breitner, Sylvia, Villeneuve, and Pierrick, Bourgeat
Subjects: Amyloid beta-Peptides, Alzheimer Disease, Positron-Emission Tomography, Humans, Cognitive Dysfunction, Female, tau Proteins, Amyloidosis, Longitudinal Studies, Neurology (clinical), Middle Aged, Biomarkers, Aged
Abstract: ImportanceNational Institute on Aging–Alzheimer’s Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD).ObjectiveTo assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD.Design, Setting, and ParticipantsThis longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years.ExposuresBased on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T−, A−T+, A−T−). Presence (+) or absence (−) of neurodegeneration (N) was assessed using temporal cortical thickness.Main Outcomes and MeasuresEach cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups.ResultsAmong 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable.Conclusions and RelevanceThe clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years.
Published: 2022

41. Spatial Extent of Amyloid-β Levels and Associations with Alzheimer’s Disease Biomarkers

Author: Sylvia Villeneuve, Judes Poirier, Theresa Köbe, Alexa Pichet Binette, Pierre-François Meyer, John C.S. Breitner, and Hazal Ozlen
Subjects: Amyloid β, business.industry, mental disorders, Immunology, Alzheimer's disease biomarkers, Medicine, business, Spatial extent
Abstract: Objective: To investigate the biological and clinical correlates of Aβ spatial extent deposition levels in cognitively unimpaired older adults.Methods: We included cognitively unimpaired older adults from three cohorts, totalling 529 participants (PREVENT-AD, n=129; ADNI, n=400 and HABS, n=288) who underwent Aβ positron emission tomography (PET). We used Gaussian-mixture models to identify region-specific thresholds of Aβ positivity in seven brain regions prone to early Aβ accumulation. Individuals were classified as having “widespread” Aβ deposition if they were positive in all seven regions, “regional” Aβ deposition if they were positive in one to six regions, or Aβ negative if negative in all regions. We compared demographics, genetics, tau-PET binding, and cognitive performance and decline between the three groups.Results: In all cohorts, most participants with regional Aβ-PET binding did not meet the cohort-specific criteria for Aβ-positivity (79% for PREVENT-AD, 57% for ADNI, and 100% for HABS). Regional Aβ groups had normal baseline cognition and relatively normal tau-PET binding, but a greater proportion of APOE ε4 carriers, decreased CSF Aβ1-42 levels, and greater amount of longitudinal Aβ-PET binding accumulation (only available in ADNI and HABS) when compared with the Negative Aβ groups. Widespread Aβ groups had lower baseline cognitive performance (PREVENT-AD only), faster cognitive decline (all cohorts) and greater amount of longitudinal tau binding than the other groups (only available in ADNI and HABS). Conclusions: Individuals with regional Aβ deposition might be the best candidate for preventive trials since they do not yet have widespread tau and cognitive decline. Widespread levels of Aβ seem to be needed for tau spreading.
Published: 2021

42. Trait mindfulness is associated with less amyloid, tau, and cognitive decline in individuals at risk for Alzheimer’s disease

Author: Pichet Binette A, Breitner Jcs, Natalie L. Marchant, Strikwerda-Brown C, Hazal Ozlen, Chapleau M, and Sylvia Villeneuve
Subjects: Mindfulness, medicine, Protective factor, Trait, Dementia, Brain Structure and Function, Cognition, Cognitive skill, Cognitive decline, medicine.disease, Psychology, Clinical psychology
Abstract: BACKGROUND AND OBJECTIVESMindfulness, defined as non-judgmental awareness of the present moment, has been associated with an array of mental and physical health benefits, including improved cognitive functioning and changes to brain structure and function. Mindfulness may also represent a protective factor for Alzheimer’s disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in older adults at risk for AD dementia.METHODSTwo hundred sixty-one nondemented older adults with a family history of AD dementia were included from the PREVENT-AD observational cohort study, including 124 with Aβ- and tau-positron emission tomography (PET) scans. All participants completed measures of trait mindfulness and longitudinal cognitive assessments. Multivariate partial least squares analyses were used to examine relationships between combinations of different facets of trait mindfulness and (1) cognitive decline, (2) Aβ, and (3) tau.RESULTSHigher levels of mindful nonjudgment, describing, and nonreactivity were associated with less cognitive decline in attention, global cognition, and immediate and delayed memory. Higher levels of mindful nonjudgment and nonreactivity were related to less Aβ-PET signal in bilateral medial and lateral temporoparietal and frontal regions. Higher levels of mindful acting with awareness, describing, nonjudgment, and nonreactivity were associated with less tau-PET signal in bilateral temporal regions, namely entorhinal cortex, amygdala, and parahippocampal, fusiform, and inferior temporal gyri. These relationships remained significant when additional demographic (age, sex, education and APOE status) and psychological (personality traits and neuropsychiatric symptoms) were included in analyses. When mindfulness, personality traits, and neuropsychiatric symptoms were entered into the same model, mindful nonjudgment showed the strongest association with cognitive decline and Aβ.DISCUSSIONTrait mindfulness is associated with less cognitive decline and less Aβ and tau in the brain in older adults at risk for AD dementia. In addition to its other health benefits, trait mindfulness may also represent a psychological protective factor for AD dementia. Longitudinal studies examining the temporal relationship between trait mindfulness and AD markers, along with mindfulness intervention studies with cognition and pathology as outcome variables, will be important for further clarifying the potential protective benefits of mindfulness on AD risk.
Published: 2021

43. Vascular risk factors are associated with a decline in resting-state functional connectivity in cognitively unimpaired individuals at risk for Alzheimer's disease

Author: Alexa Pichet Binette, Judes Poirier, Sylvia Villeneuve, Pierre-François Meyer, Theresa Köbe, Jacob W. Vogel, and John C.S. Breitner
Subjects: medicine.medical_specialty, Longitudinal resting-state functional connectivity, Cognitive Neuroscience, Neurosciences. Biological psychiatry. Neuropsychiatry, Disease, Vascular risk, 050105 experimental psychology, Functional networks, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 0501 psychology and cognitive sciences, tau, Family history, Default mode network, Resting state fMRI, business.industry, Functional connectivity, 05 social sciences, Blood pressure, Neurology, Default-mode network, Vascular risk factors, Cardiology, Global functional connectivity, business, β-Amyloid, 030217 neurology & neurosurgery, RC321-571
Abstract: Resting-state functional connectivity is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. However, evidence is lacking regarding longitudinal changes in functional connectivity. This study includes 247 cognitively unimpaired individuals with a family history of sporadic AD (185 women/ 62 men; mean [SD] age of 63 [5.3] years). Plasma total-, HDL-, and LDL-cholesterol and systolic and diastolic blood pressure were measured at baseline. Global (whole-brain) brain functional connectivity and connectivity from canonical functional networks were computed from resting-state functional MRI obtained at baseline and ~3.5 years of annual follow-ups, using a predefined functional parcellation. A subsample underwent Aβ- and tau-PET (n=91). Linear mixed-effects models demonstrated that global functional connectivity increased over time across the entire sample. In contrast, higher total-cholesterol and LDL-cholesterol levels were associated with greater reduction of functional connectivity in the default-mode network over time. In addition, higher diastolic blood pressure was associated with global functional connectivity reduction. The associations were similar when the analyses were repeated using two other functional brain parcellations. Aβ and tau deposition in the brain were not associated with changes in functional connectivity over time in the subsample. These findings provide evidence that vascular burden is associated with a decrease in functional connectivity over time in older adults with elevated risk for AD. Future studies are needed to determine if the impact of vascular risk factors on functional brain changes precede the impact of AD pathology on functional brain changes.
Published: 2021

44. Regional atrophy and cognitive decline depend on definition of subjective cognitive decline

Author: Morrison C, Neda Shafiee, Mahsa Dadar, Sylvia Villeneuve, and Collins Dl
Subjects: medicine.medical_specialty, business.industry, media_common.quotation_subject, Montreal Cognitive Assessment, Cognition, Disease, Audiology, Logistic regression, medicine.disease, Atrophy, Neuroimaging, medicine, Worry, Cognitive decline, business, media_common
Abstract: BackgroundPeople with subjective cognitive decline (SCD) may be at increased risk for Alzheimer’s disease (AD). However, not all studies have observed this increased risk. Inconsistencies may be related to different methods used to define SCD. The current project examined whether four methods of defining SCD (applied to the same sample) results in different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+) and without SCD (SCD-).MethodsMRI scans and questionnaire data for 273 cognitively normal older adults from Alzheimer’s Disease Neuroimaging Initiative were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry only. A previously validated MRI analysis method (SNIPE) was used to measure hippocampal volume and grading. Deformation-based morphometry was performed to examine volume at regions known to be vulnerable to AD. Logistic regressions were completed to determine whether diagnostic method was associated with volume differences between SCD- and SCD+. Linear mixed effects models were performed to examine the relationship between the definitions of SCD and future cognitive decline.ResultsResults varied between the four methods of defining SCD. Left hippocampal grading was lower in SCD+ than SCD-when using the CCI (p=.041) and Worry (p=.021) definitions. The right (p=.008) and left (p=.003) superior temporal regions were smaller in SCD+ than SCD-, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer’s Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment.ConclusionThe current findings suggest that the various methods used to differentiate between SCD- and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.
Published: 2021

45. Author response: Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer’s disease

Author: Randall J. Bateman, Hiroshi Mori, Judes Poirier, Colin L. Masters, Tammie L.S. Benzinger, Jasmeer P. Chhatwal, Maxime Descoteaux, Martin R. Farlow, D. Louis Collins, Guillaume Theaud, John C. Morris, Alexa Pichet Binette, Peter R. Schofield, Julie Gonneaud, John C.S. Breitner, François Rheault, Jae-Hong Lee, Sylvia Villeneuve, Maggie Roy, and Johannes Levin
Subjects: Pathology, medicine.medical_specialty, Tau pathology, business.industry, medicine, Disease, business, White matter microstructure
Published: 2021

46. Open science datasets from PREVENT-AD, a longitudinal cohort of pre-symptomatic Alzheimer’s disease

Author: Alan C. Evans, Sylvia Villeneuve, Marie-Elyse Lafaille-Magnan, Jean-Baptiste Poline, Yasser Iturria-Medina, Stephanie O.M. Dyke, Pedro Rosa-Neto, Justin Kat, Pierre Etienne, Samir Das, Judes Poirier, M. Natasha Rajah, Pierre Bellec, Jennifer Tremblay-Mercier, D. Louis Collins, Cécile Madjar, Jordana Remz, Véronique D. Bohbot, Alexa Pichet Binette, John C.S. Breitner, Jeannie Marie S. Leoutsakos, Serge Gauthier, Christine L. Tardif, M. Mallar Chakravarty, and Richard D. Hoge
Subjects: Gerontology, Canada, Open science, Cognitive Neuroscience, Computer applications to medicine. Medical informatics, R858-859.7, tau Proteins, Neuroimaging, Disease, 050105 experimental psychology, Pre-symptomatic Alzheimer Disease, 03 medical and health sciences, 0302 clinical medicine, Open Science, Alzheimer Disease, Humans, Medicine, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Longitudinal cohort, RC346-429, Observational cohort, Retrospective Studies, Amyloid beta-Peptides, business.industry, 05 social sciences, Regular Article, Cognition, Middle Aged, Longitudinal imaging, medicine.disease, Cerebrospinal Fluid proteins, Neurology, Cohort, Neurology (clinical), Neurology. Diseases of the nervous system, Alzheimer's disease, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Highlights • PREVENT-AD is openly releasing datasets to the neuroscience community. • PREVENT-AD is a longitudinal study of older adults at-risk of Alzheimer disease. • Data include imaging, genetics, fluid biochemistry, neurosensory, cognition and more. • Data collection methods and data sharing plans for open science are described., To move Alzheimer Disease (AD) research forward it is essential to collect data from large cohorts, but also make such data available to the global research community. We describe the creation of an open science dataset from the PREVENT-AD (PResymptomatic EValuation of Experimental or Novel Treatments for AD) cohort, composed of cognitively unimpaired older individuals with a parental or multiple-sibling history of AD. From 2011 to 2017, 386 participants were enrolled (mean age 63 years old ± 5) for sustained investigation among whom 349 have retrospectively agreed to share their data openly. Repositories are findable through the unified interface of the Canadian Open Neuroscience Platform and contain up to five years of longitudinal imaging data, cerebral fluid biochemistry, neurosensory capacities, cognitive, genetic, and medical information. Imaging data can be accessed openly at https://openpreventad.loris.ca while most of the other information, sensitive by nature, is accessible by qualified researchers at https://registeredpreventad.loris.ca. In addition to being a living resource for continued data acquisition, PREVENT-AD offers opportunities to facilitate understanding of AD pathogenesis.
Published: 2021

47. ApoE4 associated with higher tau accumulation independent of amyloid burden

Author: Alexa Pichet Binette, Sylvia Villeneuve, Anna Rubinski, Nicolai Franzmeier, Judes Poirier, Michael Ewers, and Julia Neitzel
Subjects: Pathology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Neuropathology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Medicine, Amyloid burden, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2020

48. Cognitive differences between healthy monolingual and bilingual anglophones on the English version of the Dépistage Cognitif de Québec: A new screening tool for atypical dementia

Author: Rémi W. Bouchard, Synthia Meilleur-Durand, Mario Masellis, Ging-Yuek Robin Hsiung, Yannick Nadeau, Pamela Jarrett, Marie-Pierre Fortin, Stéphanie Caron, Robert Laforce, Brandy L. Callahan, Pierre Molin, Marianne Lévesque, Louis Verret, Carol Hudon, Serge Gauthier, Sylvia Villeneuve, Stephen C. Cunnane, and Marie-Christine Ouellet
Subjects: Epidemiology, Health Policy, Cognition, medicine.disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, English version, medicine, Dementia, Screening tool, Neurology (clinical), Geriatrics and Gerontology, Psychology, Clinical psychology
Published: 2020

49. Evaluation of a retinal deep phenotyping platform to detect the likely cerebral amyloid PET status in humans

Author: Claudia Chevrefils, Sylvain Beaulieu, Tharick A. Pascoal, Hossam El Shahawy, Ziad S Nasreddine, David S. Knopman, Sam Osseiran, Peter J. Kertes, Frédéric Lesage, Sandra E. Black, John J Chen, Sylvia Villeneuve, Jean-Philippe Sylvestre, Céline Chayer, Marc-André Rhéaume, Jean Daniel Arbour, Val J. Lowe, Pedro Rosa-Neto, Alain Robillard, Serge Gauthier, and Jean-Paul Soucy
Subjects: Pathology, medicine.medical_specialty, Epidemiology, business.industry, Health Policy, Amyloid pet, Retinal, Psychiatry and Mental health, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Developmental Neuroscience, chemistry, medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2020

50. Bundle-specific associations between white matter microstructure and Aβ and tau pathology at their connecting cortical endpoints in older adults at risk of Alzheimer’s disease

Author: Guillaume Theaud, Alexa Pichet Binette, Judes Poirier, François Rheault, Maggie Roy, D. Louis Collins, Maxime Descoteaux, John C.S. Breitner, and Sylvia Villeneuve
Subjects: business.industry, Fornix, Fractional anisotropy, Cingulum (brain), Uncinate fasciculus, Medicine, Degeneration (medical), Disease, business, behavioral disciplines and activities, Pathological, Neuroscience, White matter microstructure
Abstract: Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer’s disease (AD), are believed to spread through connected regions. Combining diffusion imaging and positron emission tomography, we investigated associations between Aβ, tau and white matter microstructure specifically in bundles connecting brain regions in which AD pathology accumulates. In 126 cognitively normal elderly at risk of AD, we focussed on free-water corrected diffusion measures in the cingulum, posterior cingulum, fornix and uncinate fasciculus. We found higher tissue fractional anisotropy and lower mean and radial diffusivity related to increased Aβ at the cortical endpoints of the cingulum and fornix. We observed similar but stronger associations in the uncinate fasciculus, but with increased Aβ and tau at the endpoints of this bundle. This consistent pattern of associations, with opposite directionality to the usual degeneration pattern in symptomatic individuals, suggests more restricted diffusion in bundles vulnerable to preclinical AD pathology.
Published: 2020

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

138 results on '"Sylvia Villeneuve"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources