472 results on '"Jones, P Simon"'
Search Results
2. Frontotemporal lobar degeneration changes neuronal beta-frequency dynamics during the mismatch negativity response
- Author
-
Perry, Alistair, Hughes, Laura E., Adams, Natalie E., Naessens, Michelle, Kloosterman, Niels A., Rouse, Matthew A., Murley, Alexander G., Street, Duncan, Jones, P. Simon, and Rowe, James B.
- Published
- 2024
- Full Text
- View/download PDF
3. Structural correlates of survival in progressive supranuclear palsy
- Author
-
Street, Duncan, Bevan-Jones, W Richard, Malpetti, Maura, Jones, P Simon, Passamonti, Luca, Ghosh, Boyd CP., Rittman, Timothy, Coyle-Gilchrist, Ian TS., Allinson, Kieren, Dawson, Catherine E., and Rowe, James B.
- Published
- 2023
- Full Text
- View/download PDF
4. Temporal lobe perceptual predictions for speech are instantiated in motor cortex and reconciled by inferior frontal cortex
- Author
-
Cope, Thomas E., Sohoglu, Ediz, Peterson, Katie A., Jones, P. Simon, Rua, Catarina, Passamonti, Luca, Sedley, William, Post, Brechtje, Coebergh, Jan, Butler, Christopher R., Garrard, Peter, Abdel-Aziz, Khaled, Husain, Masud, Griffiths, Timothy D., Patterson, Karalyn, Davis, Matthew H., and Rowe, James B.
- Published
- 2023
- Full Text
- View/download PDF
5. The neurophysiological effect of NMDA-R antagonism of frontotemporal lobar degeneration is conditional on individual GABA concentration
- Author
-
Perry, Alistair, Hughes, Laura E., Adams, Natalie, Naessens, Michelle, Murley, Alexander G., Rouse, Matthew A., Street, Duncan, Jones, P. Simon, Cope, Thomas E., Kocagoncu, Ece, and Rowe, James B.
- Published
- 2022
- Full Text
- View/download PDF
6. Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes
- Author
-
Murley, Alexander G., Tsvetanov, Kamen A., Rouse, Matthew A., Jones, P. Simon, Sværke, Katrine, Li, Win, Carpenter, Adrian, and Rowe, James B.
- Published
- 2022
- Full Text
- View/download PDF
7. Peripheral inflammatory markers relate to central inflammation and survival in syndromes associated with frontotemporal lobar degeneration
- Author
-
Malpetti, Maura, primary, Swann, Peter, additional, Tsvetanov, Kamen A, additional, Chouliaras, Leonidas, additional, Strauss, Alexandra, additional, Chikaura, Tanatswa, additional, Murley, Alexander G, additional, Ashton, Nicholas, additional, Barker, Peter, additional, Jones, P Simon, additional, Fryer, Tim D., additional, Hong, Young T., additional, Cope, Thomas E, additional, Savulich, George, additional, Street, Duncan, additional, Bevan-Jones, W Richard, additional, Rittman, Timothy, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, Aigbirhio, Franklin I., additional, O’Brien, John T., additional, and Rowe, James B., additional
- Published
- 2024
- Full Text
- View/download PDF
8. Altered network stability in progressive supranuclear palsy
- Author
-
Whiteside, David J, Jones, P. Simon, Ghosh, Boyd C P, Coyle-Gilchrist, Ian, Gerhard, Alexander, Hu, Michele T., Klein, Johannes C, Leigh, P. Nigel, Church, Alistair, Burn, David J, Morris, Huw R, Rowe, James B, and Rittman, Timothy
- Published
- 2021
- Full Text
- View/download PDF
9. In vivo coupling of dendritic complexity with presynaptic density in primary tauopathies
- Author
-
Mak, Elijah, Holland, Negin, Jones, P. Simon, Savulich, George, Low, Audrey, Malpetti, Maura, Kaalund, Sanne S, Passamonti, Luca, Rittman, Timothy, Romero-Garcia, Rafael, Manavaki, Roido, Williams, Guy B., Hong, Young T., Fryer, Tim D., Aigbirhio, Franklin I., O'Brien, John T, and Rowe, James B
- Published
- 2021
- Full Text
- View/download PDF
10. Imaging tau burden in dementia with Lewy bodies using [18F]-AV1451 positron emission tomography
- Author
-
Mak, Elijah, Nicastro, Nicolas, Malpetti, Maura, Savulich, George, Surendranathan, Ajenthan, Holland, Negin, Passamonti, Luca, Jones, P Simon, Carter, Stephen F., Su, Li, Hong, Young T., Fryer, Tim D., Williams, Guy B., Aigbirhio, Franklin, Rowe, James B., and O'Brien, John T.
- Published
- 2021
- Full Text
- View/download PDF
11. Proximity to dementia onset and multi-modal neuroimaging changes: The prevent-dementia study
- Author
-
Mak, Elijah, Dounavi, Maria-Eleni, Low, Audrey, Carter, Stephen F., McKiernan, Elizabeth, Williams, Guy B, Jones, P Simon, Carriere, Isabelle, Muniz, Graciela Terrera, Ritchie, Karen, Ritchie, Craig, Su, Li, and O'Brien, John T
- Published
- 2021
- Full Text
- View/download PDF
12. An in vivo probabilistic atlas of the human locus coeruleus at ultra-high field
- Author
-
Ye, Rong, Rua, Catarina, O'Callaghan, Claire, Jones, P. Simon, Hezemans, Frank H., Kaalund, Sanne S., Tsvetanov, Kamen A., Rodgers, Christopher T., Williams, Guy, Passamonti, Luca, and Rowe, James B.
- Published
- 2021
- Full Text
- View/download PDF
13. Differential Synaptic Loss in β‐Amyloid Positive Versus β‐Amyloid Negative Corticobasal Syndrome.
- Author
-
Holland, Negin, Savulich, George, Jones, P. Simon, Whiteside, David J., Street, Duncan, Swann, Peter, Naessens, Michelle, Malpetti, Maura, Hong, Young T., Fryer, Tim D., Rittman, Timothy, Mulroy, Eoin, Aigbirhio, Franklin I., Bhatia, Kailash P., O'Brien, John T., and Rowe, James B.
- Abstract
Background/Objective: The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4‐repeat‐tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to β‐amyloid status. Methods: Twenty‐five people with CBS, and 32 age‐/sex‐/education‐matched healthy controls participated. Regional synaptic density was estimated by [11C]UCB‐J non‐displaceable binding potential (BPND), AD‐tau pathology by [18F]AV‐1451 BPND, and gray matter volume by T1‐weighted magnetic resonance imaging. Participants with CBS had β‐amyloid imaging with 11C‐labeled Pittsburgh Compound‐B ([11C]PiB) positron emission tomography. Symptom severity was assessed with the progressive supranuclear palsy‐rating‐scale, the cortical basal ganglia functional scale, and the revised Addenbrooke's Cognitive Examination. Regional differences in BPND and gray matter volume between groups were assessed by ANOVA. Results: Compared to controls, patients with CBS had higher [18F]AV‐1451 uptake, gray matter volume loss, and reduced synaptic density. Synaptic loss was more severe and widespread in the β‐amyloid negative group. Asymmetry of synaptic loss was in line with the clinically most affected side. Discussion: Distinct patterns of [11C]UCB‐J and [18F]AV‐1451 binding and gray matter volume loss, indicate differences in the pathogenic mechanisms of CBS according to whether it is associated with the presence of Alzheimer's disease or not. This highlights the potential for different therapeutic strategies in CBSs. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
14. Multi‐modal MR and synaptic PET changes in dementia with Lewy bodies
- Author
-
Mak, Elijah, primary, Carter, Stephen F, additional, Savulich, George, additional, Holland, Negin, additional, Swann, Peter, additional, McKiernan, Elizabeth, additional, Chouliaras, Leonidas, additional, Malpetti, Maura, additional, Su, Li, additional, Jones, P Simon, additional, Rowe, James B., additional, and O'Brien, John T, additional
- Published
- 2023
- Full Text
- View/download PDF
15. Apoe ε4 exacerbates age‐dependent decline of cortical microstructural changes in cognitively normal midlife individuals: the PREVENT‐Dementia and ALFA studies
- Author
-
Mak, Elijah, primary, Dounavi, Maria‐Eleni, additional, Operto, Grégory, additional, Ziukelis, Elina T, additional, Jones, P Simon, additional, Low, Audrey, additional, Swann, Peter, additional, Newton, Coco, additional, Muniz‐Terrera, Graciela, additional, Malhotra, Paresh A, additional, Koychev, Ivan, additional, Falcon, Carles, additional, Mackay, Clare, additional, Lawlor, Brian, additional, Naci, Lorina, additional, Wells, Katie, additional, Ritchie, Craig W, additional, Ritchie, Karen, additional, Su, Li, additional, Gispert, Juan Domingo, additional, and O'Brien, John T, additional
- Published
- 2023
- Full Text
- View/download PDF
16. Functional connectivity moderates the impact of synaptic loss on behaviour in frontotemporal lobar degeneration syndromes
- Author
-
Whiteside, David J, primary, Holland, Negin, additional, Tsvetanov, Kamen A, additional, Malpetti, Maura, additional, Savulich, George, additional, Jones, P Simon, additional, Naessens, Michelle, additional, Fryer, Tim D, additional, Hong, Young T, additional, Aigbirhio, Franklin I, additional, Mulroy, Eoin, additional, Bhatia, Kailash, additional, Rittman, Timothy, additional, O'Brien, John T, additional, and Rowe, James B., additional
- Published
- 2023
- Full Text
- View/download PDF
17. Peripheral and central markers of inflammation increased in frontotemporal dementia and related conditions
- Author
-
Malpetti, Maura, primary, Swann, Peter, additional, Chouliaras, Leonidas, additional, Tsvetanov, Kamen A, additional, Jones, P Simon, additional, Cope, Thomas E, additional, Bevan‐Jones, W Richard, additional, Savulich, George, additional, Street, Duncan, additional, Whiteside, David J, additional, Rittman, Timothy, additional, Murley, Alexander G, additional, Stockton, Katherine, additional, Hong, Young T, additional, Fryer, Tim D, additional, Aigbirhio, Franklin I, additional, O'Brien, John T, additional, and Rowe, James B., additional
- Published
- 2023
- Full Text
- View/download PDF
18. The Surfer’s Shoulder: A Systematic Review of Current Literature and Potential Pathophysiological Explanations of Chronic Shoulder Complaints in Wave Surfers
- Author
-
Langenberg, Lisette Charlotte, Vieira Lima, Guilherme, Heitkamp, Sebastiaan Emanuel, Kemps, Floortje Lutgart Arnoldus Maria, Jones, Matthew Simon, Moreira, Miguel António de Almeida Garcia, and Eygendaal, Denise
- Published
- 2021
- Full Text
- View/download PDF
19. Metabolomic changes associated with frontotemporal lobar degeneration syndromes
- Author
-
Murley, Alexander G., Jones, P. Simon, Coyle Gilchrist, Ian, Bowns, Lucy, Wiggins, Julie, Tsvetanov, Kamen A., and Rowe, James B.
- Published
- 2020
- Full Text
- View/download PDF
20. Locus Coeruleus Integrity Is Linked to Response Inhibition Deficits in Parkinson's Disease and Progressive Supranuclear Palsy
- Author
-
Ye, Rong, primary, Hezemans, Frank H., additional, O'Callaghan, Claire, additional, Tsvetanov, Kamen A., additional, Rua, Catarina, additional, Jones, P. Simon, additional, Holland, Negin, additional, Malpetti, Maura, additional, Murley, Alexander G., additional, Barker, Roger A., additional, Williams-Gray, Caroline H., additional, Robbins, Trevor W., additional, Passamonti, Luca, additional, and Rowe, James B., additional
- Published
- 2023
- Full Text
- View/download PDF
21. Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome
- Author
-
Whiteside, David J, Street, Duncan, Murley, Alexander G, Jones, P Simon, Malpetti, Maura, Ghosh, Boyd CP, Coyle-Gilchrist, Ian, Gerhard, Alexander, Hu, Michele T, Klein, Johannes C, Leigh, P Nigel, Church, Alistair, Burn, David J, Morris, Huw R, Rowe, James B, Rittman, Timothy, Whiteside, David J [0000-0002-5890-9220], Klein, Johannes C [0000-0002-8553-2801], Apollo - University of Cambridge Repository, Whiteside, David J. [0000-0002-5890-9220], and Klein, Johannes C. [0000-0002-8553-2801]
- Subjects
Corticobasal Degeneration ,connectivity ,tauopathies ,fMRI ,Medizin ,Humans ,Neurodegenerative Diseases ,corticobasal syndrome ,prediction ,progressive supranuclear palsy ,Supranuclear Palsy, Progressive ,Prognosis ,survival - Abstract
in press; CA extern There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson-plus and the UK National PSP Research Network (PROSPECT-MR). Resting-state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large-scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between-network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five-fold cross-validation. In PSP and CBS, between-network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between-network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics.
- Published
- 2023
22. Longitudinal Synaptic Loss in Primary Tauopathies: An In Vivo [11 C] UCB‐J Positron Emission Tomography Study
- Author
-
Holland, Negin, primary, Jones, P. Simon, additional, Savulich, George, additional, Naessens, Michelle, additional, Malpetti, Maura, additional, Whiteside, David J., additional, Street, Duncan, additional, Swann, Peter, additional, Hong, Young T., additional, Fryer, Tim D., additional, Rittman, Timothy, additional, Mulroy, Eoin, additional, Aigbirhio, Franklin I., additional, Bhatia, Kailash P., additional, O'Brien, John T., additional, and Rowe, James B., additional
- Published
- 2023
- Full Text
- View/download PDF
23. Artificial grammar learning in vascular and progressive non-fluent aphasias
- Author
-
Cope, Thomas E., Wilson, Benjamin, Robson, Holly, Drinkall, Rebecca, Dean, Lauren, Grube, Manon, Jones, P. Simon, Patterson, Karalyn, Griffiths, Timothy D., Rowe, James B., and Petkov, Christopher I.
- Published
- 2017
- Full Text
- View/download PDF
24. Early-stage 11C-Flumazenil PET predicts day-14 selective neuronal loss in a rodent model of transient focal cerebral ischemia
- Author
-
Hughes, Jessica L, Beech, John S, Jones, P Simon, Wang, Dechao, Menon, David K, Aigbirhio, Franklin I, Fryer, Tim D, and Baron, Jean-Claude
- Published
- 2020
- Full Text
- View/download PDF
25. Temporal lobe perceptual predictions for speech are instantiated in motor cortex and reconciled by inferior frontal cortex
- Author
-
Cope, Thomas E, Sohoglu, Ediz, Peterson, Katie A, Jones, P Simon, Rua, Catarina, Passamonti, Luca, Sedley, William, Post, Brechtje, Coebergh, Jan, Butler, Christopher R, Garrard, Peter, Abdel-Aziz, Khaled, Husain, Masud, Griffiths, Timothy D, Patterson, Karalyn, Davis, Matthew H, Rowe, James B, Cope, Thomas E [0000-0002-4751-1786], and Apollo - University of Cambridge Repository
- Subjects
motor speech ,Brain Mapping ,language ,speech ,Motor Cortex ,Brain ,7T fMRI ,prediction ,nfvPPA ,Magnetic Resonance Imaging ,General Biochemistry, Genetics and Molecular Biology ,aphasia ,Temporal Lobe ,Frontal Lobe ,Broca's area ,CP: Neuroscience ,MVPA ,Humans ,predictive coding - Abstract
Humans use predictions to improve speech perception, especially in noisy environments. Here we use 7-T functional MRI (fMRI) to decode brain representations of written phonological predictions and degraded speech signals in healthy humans and people with selective frontal neurodegeneration (non-fluent variant primary progressive aphasia [nfvPPA]). Multivariate analyses of item-specific patterns of neural activation indicate dissimilar representations of verified and violated predictions in left inferior frontal gyrus, suggestive of processing by distinct neural populations. In contrast, precentral gyrus represents a combination of phonological information and weighted prediction error. In the presence of intact temporal cortex, frontal neurodegeneration results in inflexible predictions. This manifests neurally as a failure to suppress incorrect predictions in anterior superior temporal gyrus and reduced stability of phonological representations in precentral gyrus. We propose a tripartite speech perception network in which inferior frontal gyrus supports prediction reconciliation in echoic memory, and precentral gyrus invokes a motor model to instantiate and refine perceptual predictions for speech.
- Published
- 2023
26. Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials
- Author
-
Street, Duncan, primary, Jabbari, Edwin, additional, Costantini, Alyssa, additional, Jones, P Simon, additional, Holland, Negin, additional, Rittman, Timothy, additional, Jensen, Marte T, additional, Chelban, Viorica, additional, Goh, Yen Y, additional, Guo, Tong, additional, Heslegrave, Amanda J, additional, Roncaroli, Federico, additional, Klein, Johannes C, additional, Ansorge, Olaf, additional, Allinson, Kieren S J, additional, Jaunmuktane, Zane, additional, Revesz, Tamas, additional, Warner, Thomas T, additional, Lees, Andrew J, additional, Zetterberg, Henrik, additional, Russell, Lucy L, additional, Bocchetta, Martina, additional, Rohrer, Jonathan D, additional, Burn, David J, additional, Pavese, Nicola, additional, Gerhard, Alexander, additional, Kobylecki, Christopher, additional, Leigh, P Nigel, additional, Church, Alistair, additional, Hu, Michele T M, additional, Houlden, Henry, additional, Morris, Huw, additional, and Rowe, James B, additional
- Published
- 2023
- Full Text
- View/download PDF
27. Microglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia
- Author
-
Malpetti, Maura, primary, Cope, Thomas E, additional, Street, Duncan, additional, Jones, P Simon, additional, Hezemans, Frank H, additional, Mak, Elijah, additional, Tsvetanov, Kamen A, additional, Rittman, Timothy, additional, Bevan-Jones, W Richard, additional, Patterson, Karalyn, additional, Passamonti, Luca, additional, Fryer, Tim D, additional, Hong, Young T, additional, Aigbirhio, Franklin I, additional, O’Brien, John T, additional, and Rowe, James B, additional
- Published
- 2023
- Full Text
- View/download PDF
28. Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia
- Author
-
Whiteside, David J., Malpetti, Maura, Jones, P. Simon, Ghosh, Boyd C.P., Coyle-Gilchrist, Ian, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Ber, Isabelle Le, Gerhard, Alexander, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, Bouzigues, Arabella, Russell, Lucy L., Rohrer, Jonathan D., Rowe, James B., Rittman, Timothy, Whiteside, David J., Malpetti, Maura, Jones, P. Simon, Ghosh, Boyd C.P., Coyle-Gilchrist, Ian, van Swieten, John C., Seelaar, Harro, Jiskoot, Lize, Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R., Santana, Isabel, Ber, Isabelle Le, Gerhard, Alexander, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, Bouzigues, Arabella, Russell, Lucy L., Rohrer, Jonathan D., Rowe, James B., and Rittman, Timothy
- Abstract
Introduction: We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). Methods: For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. Results: We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. Discussion: Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. Highlights: We investigated brain network predictors of dementia symptom onset Frontotemporal dementia results in characteristic dynamic network patterns Alterations in network dynamics are associated with neuropsychological impairment Network dynamic changes predict symptomatic conversion in presymptomatic carriers Network dynamic changes are associated with longitudinal cognitive decline.
- Published
- 2023
29. Carrots and sticks fail to change behavior in cocaine addiction
- Author
-
Ersche, Karen D., Gillan, Claire M., Jones, P. Simon, Williams, Guy B., Ward, Laetitia H. E., Luijten, Maartje, de Wit, Sanne, Sahakian, Barbara J., Bullmore, Edward T., and Robbins, Trevor W.
- Published
- 2016
30. Progression of atypical parkinsonian syndromes:PROSPECT-M-UK study implications for clinical trials
- Author
-
Street, Duncan, Jabbari, Edwin, Costantini, Alyssa, Jones, P Simon, Holland, Negin, Rittman, Timothy, Jensen, Marte T, Chelban, Viorica, Goh, Yen Y, Guo, Tong, Heslegrave, Amanda J, Roncaroli, Federico, Klein, Johannes C, Ansorge, Olaf, Allinson, Kieren SJ, Jaunmuktane, Zane, Revesz, Tamas, Warner, Thomas T, Lees, Andrew J, Zetterberg, Henrik, Russell, Lucy L, Bocchetta, Martina, Rohrer, Jonathan D, Burn, David J, Pavese, Nicola, Gerhard, Alexander, Kobylecki, Christopher, Leigh, P Nigel, Church, Alistair, Hu, Michele TM, Houlden, Henry, Morris, Huw, Rowe, James B, Street, Duncan [0000-0003-2168-2242], Jabbari, Edwin [0000-0001-6844-882X], Rittman, Timothy [0000-0003-1063-6937], Chelban, Viorica [0000-0002-7797-0756], Warner, Thomas T [0000-0001-6195-6995], Lees, Andrew J [0000-0002-2476-4385], Bocchetta, Martina [0000-0003-1814-5024], Gerhard, Alexander [0000-0002-8071-6062], Houlden, Henry [0000-0002-2866-7777], Morris, Huw [0000-0002-5473-3774], and Apollo - University of Cambridge Repository
- Subjects
clinical trials ,multiple system atrophy ,progressive supranuclear palsy ,corticobasal syndrome ,Neurology (clinical) ,sample size - Abstract
Supplementary data is available online at https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awad105/7091433#supplementary-data . Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout. Copyright © The Author(s) 2023. The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, PSP-subcortical (PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (PSP-frontal, PSP-speech and language and PSP-CBS subtypes), MSA-parkinsonism, MSA-cerebellar, CBS with and without evidence of Alzheimer’s disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling and sample sizes for clinical trials of disease-modifying agents, according to group and assessment type. Two hundred forty-three people were recruited [117 PSP, 68 CBS, 42 MSA and 16 indeterminate; 138 (56.8%) male; age at recruitment 68.7 ± 8.61 years]. One hundred and fifty-nine completed the 6-month assessment (82 PSP, 27 CBS, 40 MSA and 10 indeterminate) and 153 completed the 12-month assessment (80 PSP, 29 CBS, 35 MSA and nine indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for 1-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease-specific. In conclusion, phenotypic variance within PSP, CBS and MSA is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial end points, from potential functional, cognitive, clinical or neuroimaging measures of disease progression. The Progressive Supranuclear Palsy–Corticobasal Syndrome–Multiple System Atrophy (PROSPECT-M-UK) study is supported by grants for PROSPECT, cerebrospinal fluid biomarker measurements, and PROSPECT magnetic resonance imaging and Sara Koe Fellowship grants from the PSP Association UK, CBD Solutions, the MSA Trust, the Wellcome Trust (103838; 220258); the NIHR Cambridge Biomedical Research Centre and Cambridge Brain Bank (BRC 1215-20014; NIHR203312: The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care); Cambridge Centre for Parkinson-Plus; Medical Research Council (SUAG/092 116768); and the NIHR UCLH Biomedical Research Centre. Queen Square Brain Bank is supported by the Reta Lila Weston Institute for Neurological Studies and the MRC. The fluid biomarker measurements were supported in part by the UK Dementia Research Institute at UCL and a multiuser equipment grant from Wellcome Trust. The Cambridge Brain Bank is part of the Cambridge Human research Tissue Bank funded by the Biomedical Research Council. The Oxford Brain Bank is supported by the MRC, Brains for Dementia Research (Alzheimer’s Society and Alzheimer’s Research UK), and the NIHR Oxford Biomedical Research Centre. In addition, this study was supported by the Medical Research Council (MRC 548211) (Dr Jabbari); the Association of British Neurologists Clinical Research Training Fellowships (Dr Holland, Dr Goh and Dr Chelban); the MSA Trust (Dr Chelban, Dr Goh); Guarantors of Brain (Dr Chelban); CBD Solutions (Dr Revesz, and Dr Morris); the NIHR Oxford Health Clinical Research Facility (Dr Klein); the NIHR Queen Square Biomedical Research Centre based at UCLH (Dr Revesz and Dr Jaunmuktane) a Wallenberg Academy fellowship (Dr Zetterberg); the Monument Trust Discovery Award from Parkinson’s UK (Dr Hu). Dr Bocchetta is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). Dr Bocchetta’s work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. Professor Rohrer is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). Professor Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), European Union Joint Program for Neurodegenerative Disorders (JPND2021-00694), and the UK Dementia Research Institute at UCL. Professor Roncaroli’s work is supported by The Manchester Brain Bank, which is part of BDR, jointly funded by Alzheimer’s Society and Alzheimer’s Research UK. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission, under a Creative Commons Attribution 4.0 International License.
- Published
- 2023
31. Microglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia
- Author
-
Malpetti, Maura, Cope, Thomas E, Street, Duncan, Jones, P Simon, Hezemans, Frank H, Mak, Elijah, Tsvetanov, Kamen A, Rittman, Timothy, Bevan-Jones, W Richard, Patterson, Karalyn, Passamonti, Luca, Fryer, Tim D, Hong, Young T, Aigbirhio, Franklin I, O'Brien, John T, Rowe, James B, Malpetti, Maura [0000-0001-8923-9656], Mak, Elijah [0000-0002-6437-8024], Rittman, Timothy [0000-0003-1063-6937], Patterson, Karalyn [0000-0003-1927-7424], O'Brien, John T [0000-0002-0837-5080], and Apollo - University of Cambridge Repository
- Subjects
PET ,Neurology (clinical) ,prognosis ,microglial activation ,frontotemporal dementia - Abstract
Frontotemporal dementia is clinically and neuropathologically heterogeneous, but neuroinflammation, atrophy and cognitive impairment occur in all of its principal syndromes. Across the clinical spectrum of frontotemporal dementia, we assess the predictive value of in vivo neuroimaging measures of microglial activation and grey-matter volume on the rate of future cognitive decline. We hypothesized that inflammation is detrimental to cognitive performance, in addition to the effect of atrophy. Thirty patients with a clinical diagnosis of frontotemporal dementia underwent a baseline multimodal imaging assessment, including [11C]PK11195 PET to index microglial activation and structural MRI to quantify grey-matter volume. Ten people had behavioural variant frontotemporal dementia, 10 had the semantic variant of primary progressive aphasia and 10 had the non-fluent agrammatic variant of primary progressive aphasia. Cognition was assessed at baseline and longitudinally with the revised Addenbrooke's Cognitive Examination, at an average of 7-month intervals (for an average of ∼2 years, up to ∼5 years). Regional [11C]PK11195 binding potential and grey-matter volume were determined, and these were averaged within four hypothesis-driven regions of interest: bilateral frontal and temporal lobes. Linear mixed-effect models were applied to the longitudinal cognitive test scores, with [11C]PK11195 binding potentials and grey-matter volumes as predictors of cognitive performance, with age, education and baseline cognitive performance as covariates. Faster cognitive decline was associated with reduced baseline grey-matter volume and increased microglial activation in frontal regions, bilaterally. In frontal regions, microglial activation and grey-matter volume were negatively correlated, but provided independent information, with inflammation the stronger predictor of the rate of cognitive decline. When clinical diagnosis was included as a factor in the models, a significant predictive effect was found for [11C]PK11195 BPND in the left frontal lobe (−0.70, P = 0.01), but not for grey-matter volumes (P > 0.05), suggesting that inflammation severity in this region relates to cognitive decline regardless of clinical variant. The main results were validated by two-step prediction frequentist and Bayesian estimation of correlations, showing significant associations between the estimated rate of cognitive change (slope) and baseline microglial activation in the frontal lobe. These findings support preclinical models in which neuroinflammation (by microglial activation) accelerates the neurodegenerative disease trajectory. We highlight the potential for immunomodulatory treatment strategies in frontotemporal dementia, in which measures of microglial activation may also improve stratification for clinical trials.
- Published
- 2023
32. Locus Coeruleus Integrity Is Linked to Response Inhibition Deficits in Parkinson's Disease and Progressive Supranuclear Palsy.
- Author
-
Rong Ye, Hezemans, Frank H., O'Callaghan, Claire, Tsvetanov, Kamen A., Rua, Catarina, Jones, P. Simon, Holland, Negin, Malpetti, Maura, Murley, Alexander G., Barker, Roger A., Williams-Gray, Caroline H., Robbins, Trevor W., Passamonti, Luca, and Rowe, James B.
- Subjects
LOCUS coeruleus ,PROGRESSIVE supranuclear palsy ,PARKINSON'S disease ,RESPONSE inhibition ,DISEASE progression ,PARKINSONIAN disorders ,PARTIAL least squares regression - Abstract
Parkinson's disease (PD) and progressive supranuclear palsy (PSP) both impair response inhibition, exacerbating impulsivity. Inhibitory control deficits vary across individuals and are linked with worse prognosis, and lack improvement on dopaminergic therapy. Motor and cognitive control are associated with noradrenergic innervation of the cortex, arising from the locus coeruleus (LC) noradrenergic system. Here we test the hypothesis that structural variation of the LC explains response inhibition deficits in PSP and PD. Twenty-four people with idiopathic PD, 14 with PSP-Richardson's syndrome, and 24 age- and sex-matched controls undertook a stop-signal task and ultrahigh field 7T magnetization-transfer-weighted imaging of the LC. Parameters of "race models" of go-versus stop-decisions were estimated using hierarchical Bayesian methods to quantify the cognitive processes of response inhibition. We tested the multivariate relationship between LC integrity and model parameters using partial least squares. Both disorders impaired response inhibition at the group level. PSP caused a distinct pattern of abnormalities in inhibitory control with a paradoxically reduced threshold for go responses, but longer nondecision times, and more lapses of attention. The variation in response inhibition correlated with the variability of LC integrity across participants in both clinical groups. Structural imaging of the LC, coupled with behavioral modeling in parkinsonian disorders, confirms that LC integrity is associated with response inhibition and LC degeneration contributes to neurobehavioral changes. The noradrenergic system is therefore a promising target to treat impulsivity in these conditions. The optimization of noradrenergic treatment is likely to benefit from stratification according to LC integrity. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
33. Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome.
- Author
-
Whiteside, David J., Street, Duncan, Murley, Alexander G., Jones, P. Simon, Malpetti, Maura, Ghosh, Boyd C. P., Coyle‐Gilchrist, Ian, Gerhard, Alexander, Hu, Michele T., Klein, Johannes C., Leigh, P. Nigel, Church, Alistair, Burn, David J., Morris, Huw R., Rowe, James B., and Rittman, Timothy
- Subjects
PROGRESSIVE supranuclear palsy ,PARTIAL least squares regression ,INDEPENDENT component analysis ,MAGNETIC resonance imaging ,FUNCTIONAL magnetic resonance imaging ,CEREBRAL atrophy - Abstract
There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson‐plus and the UK National PSP Research Network (PROSPECT‐MR). Resting‐state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large‐scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between‐network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five‐fold cross‐validation. In PSP and CBS, between‐network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between‐network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
34. Synaptic loss in behavioural variant of frontotemporal dementia:an in vivo [ 11 C]UCB‐J PET study
- Author
-
Malpetti, Maura, primary, Jones, P Simon, additional, Cope, Thomas E, additional, Holland, Negin, additional, Naessens, Michelle, additional, Rouse, Matthew A, additional, Savulich, George, additional, Fryer, Tim D, additional, Hong, Young T, additional, Milicevic‐Sephton, Selena, additional, Aigbirhio, Franklin I, additional, O'Brien, John T, additional, and Rowe, James B, additional
- Published
- 2022
- Full Text
- View/download PDF
35. Synaptic Loss in Frontotemporal Dementia Revealed by [11 C] UCB‐J Positron Emission Tomography
- Author
-
Malpetti, Maura, primary, Jones, P. Simon, additional, Cope, Thomas E., additional, Holland, Negin, additional, Naessens, Michelle, additional, Rouse, Matthew A., additional, Rittman, Timothy, additional, Savulich, George, additional, Whiteside, David J., additional, Street, Duncan, additional, Fryer, Tim D., additional, Hong, Young T., additional, Milicevic Sephton, Selena, additional, Aigbirhio, Franklin I., additional, O′Brien, John T., additional, and Rowe, James B., additional
- Published
- 2022
- Full Text
- View/download PDF
36. An open-label study to assess the feasibility and tolerability of rilmenidine for the treatment of Huntington’s disease
- Author
-
Underwood, Benjamin R., Green-Thompson, Zeyn W., Pugh, Peter J., Lazic, Stanley E., Mason, Sarah L., Griffin, Jules, Jones, P. Simon, Rowe, James B., Rubinsztein, David C., and Barker, Roger A.
- Published
- 2017
- Full Text
- View/download PDF
37. Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia
- Author
-
Whiteside, David J, Malpetti, Maura, Jones, P Simon, Ghosh, Boyd CP, Coyle‐Gilchrist, Ian, van Swieten, John C, Seelaar, Harro, Jiskoot, Lize, Borroni, Barbara, Sanchez‐Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Masellis, Mario, Tartaglia, Maria Carmela, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Butler, Chris R, Santana, Isabel, Ber, Isabelle Le, Gerhard, Alexander, Ducharme, Simon, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Pasquier, Florence, Bouzigues, Arabella, Russell, Lucy L, Rohrer, Jonathan D, Rowe, James B, Rittman, Timothy, Esteve, Aitana Sogorb, Nelson, Annabel, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang‐Wai, David, Rogaeva, Ekaterina, Castelo‐Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego‐Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, Simões do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa‐Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl‐Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas‐Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Whiteside, David [0000-0002-5890-9220], Apollo - University of Cambridge Repository, GENFI Consortium, Repositório da Universidade de Lisboa, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, Simões do Couto, Frederico, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Russell, Lucy L, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, and Neurology
- Subjects
Epidemiology ,FEATURED ARTICLE ,Medizin ,Clinical Neurology ,NETWORK CONNECTIVITY ,frontotemporal dementia ,disease progression ,functional magnetic resonance imaging (fMRI) ,network dynamics ,presymptomatic ,DISEASE ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,SDG 3 - Good Health and Well-being ,Humans ,Cognitive Dysfunction ,ddc:610 ,BRAIN ,BATTERY ,Science & Technology ,Health Policy ,Brain ,FUNCTIONAL CONNECTIVITY ,Magnetic Resonance Imaging ,STATE ,TIME ,Psychiatry and Mental health ,COMPENSATION ,Frontotemporal Dementia ,Mutation ,FEATURED ARTICLES ,Neurology (clinical) ,Human medicine ,Neurosciences & Neurology ,Geriatrics and Gerontology ,Life Sciences & Biomedicine - Abstract
© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Introduction: We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). Methods: For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. Results: We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. Discussion: Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. Highlights: We investigated brain network predictors of dementia symptom onset Frontotemporal dementia results in characteristic dynamic network patterns Alterations in network dynamics are associated with neuropsychological impairment Network dynamic changes predict symptomatic conversion in presymptomatic carriers Network dynamic changes are associated with longitudinal cognitive decline., GENFI was funded by the Medical Research Council UK (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX grant (by DLR/BMBF 2019-02248) and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). The study was co-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge (BRC-1215-20014), the Cambridge Centre for Parkinson-plus (RG95450); the Wellcome Trust (220258); the Evelyn Trust (17/09) and Medical Research Council (SUAG/092 116768).
- Published
- 2022
38. Synaptic loss in frontotemporal dementia revealed by [11 C]UCB-J PET
- Author
-
Malpetti, Maura, Jones, P Simon, Cope, Thomas E, Holland, Negin, Naessens, Michelle, Rouse, Matthew A, Rittman, Timothy, Savulich, George, Whiteside, David J, Street, Duncan, Fryer, Tim D, Hong, Young T, Sephton, Selena Milicevic, Aigbirhio, Franklin I, O'Brien, John T, Rowe, James B, Malpetti, Maura [0000-0001-8923-9656], Holland, Negin [0000-0003-3813-0882], and Apollo - University of Cambridge Repository
- Subjects
Pick Disease of the Brain ,Frontotemporal Dementia ,Positron-Emission Tomography ,Humans ,Brain ,Neurodegenerative Diseases ,Frontal Lobe - Abstract
OBJECTIVE: Synaptic loss is an early feature of neurodegenerative disease models, and is severe in post mortem clinical studies, including frontotemporal dementia. Positron emission tomography (PET) with radiotracers that bind to synaptic vesicle glycoprotein 2A enables quantification of synaptic density in vivo. This study used [11 C]UCB-J PET in participants with behavioural variant frontotemporal dementia (bvFTD), testing the hypothesis that synaptic loss is severe and related to clinical severity. METHODS: Eleven participants with clinically probable bvFTD and 25 age- and sex-matched healthy controls were included. Participants underwent dynamic [11 C]UCB-J PET, structural MRI and a neuropsychological battery, including the Addenbrooke's Cognitive Examination (ACE-R), and INECO frontal screening (IFS). General linear models compared [11 C]UCB-J binding potential maps and grey-matter volume between groups, and assessed associations between synaptic density and clinical severity in patients. Analyses were also performed using partial-volume corrected [11 C]UCB-J binding potential from regions of interest (ROIs). RESULTS: Patients with bvFTD showed severe synaptic loss compared to controls. [11 C]UCB-J binding was reduced bilaterally in medial and dorsolateral frontal regions, inferior frontal gyri, anterior and posterior cingulate gyrus, insular cortex and medial temporal lobe. Synaptic loss in the frontal and cingulate regions correlated significantly with cognitive impairments. Synaptic loss was more severe than atrophy. Results from ROI-based analyses mirrored the voxel-wise results. INTERPRETATION: In accordance with preclinical models, and human post mortem evidence, there is widespread frontotemporal loss of synapses in symptomatic bvFTD, in proportion to severity. [11 C]UCB-J PET could support translational studies and experimental medicine strategies for new disease-modifying treatments for neurodegeneration. This article is protected by copyright. All rights reserved.
- Published
- 2022
- Full Text
- View/download PDF
39. Locus Coeruleus Integrity from 7 T MRI Relates to Apathy and Cognition in Parkinsonian Disorders
- Author
-
Ye, Rong, O'Callaghan, Claire, Rua, Catarina, Hezemans, Frank H, Holland, Negin, Malpetti, Maura, Jones, P Simon, Barker, Roger A, Williams-Gray, Caroline H, Robbins, Trevor W, Passamonti, Luca, Rowe, James, Ye, Rong [0000-0003-2529-7755], O'Callaghan, Claire [0000-0001-5698-6364], Rua, Catarina [0000-0002-0404-4399], Malpetti, Maura [0000-0001-8923-9656], Williams-Gray, Caroline H [0000-0002-2648-9743], Passamonti, Luca [0000-0002-7937-0615], Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository
- Subjects
cognition ,Parkinsonian Disorders ,locus coeruleus ,magnetization-transfer imaging ,Parkinson's disease ,Apathy ,noradrenaline ,Humans ,Parkinson Disease ,Supranuclear Palsy, Progressive ,7 T magnetic resonance imaging ,progressive supranuclear palsy ,Magnetic Resonance Imaging - Abstract
BACKGROUND: Neurodegeneration in the locus coeruleus (LC) contributes to neuropsychiatric symptoms in both Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Spatial precision of LC imaging is improved with ultrahigh field 7 T magnetic resonance imaging. OBJECTIVES: This study aimed to characterize the spatial patterns of LC pathological change in PD and PSP and the transdiagnostic relationship between LC signals and neuropsychiatric symptoms. METHODS: Twenty-five people with idiopathic PD, 14 people with probable PSP-Richardson's syndrome, and 24 age-matched healthy controls were recruited. Participants underwent clinical assessments and high-resolution (0.08 mm3 ) 7 T-magnetization-transfer imaging to measure LC integrity in vivo. Spatial patterns of LC change were obtained using subregional mean contrast ratios and significant LC clusters; we further correlated the LC contrast with measures of apathy and cognition, using both mixed-effect models and voxelwise analyses. RESULTS: PSP and PD groups showed significant LC degeneration in the caudal subregion relative to controls. Mixed-effect models revealed a significant interaction between disease-group and apathy-related correlations with LC degeneration (β = 0.46, SE [standard error] = 0.17, F(1, 35) = 7.46, P = 0.01), driven by a strong correlation in PSP (β = -0.58, SE = 0.21, t(35) = -2.76, P = 0.009). Across both disease groups, voxelwise analyses indicated that lower LC integrity was associated with worse cognition and higher apathy scores. CONCLUSIONS: The relationship between LC and nonmotor symptoms highlights a role for noradrenergic dysfunction across both PD and PSP, confirming the potential for noradrenergic therapeutic strategies to address transdiagnostic cognitive and behavioral features in neurodegenerative disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- Published
- 2022
40. [11C]PK11195 binding in Alzheimer disease and progressive supranuclear palsy
- Author
-
Passamonti, Luca, Rodríguez, Patricia Vázquez, Hong, Young T., Allinson, Kieren S.J., Bevan-Jones, W. Richard, Williamson, David, Jones, P. Simon, Arnold, Robert, Borchert, Robin J., Surendranathan, Ajenthan, Mak, Elijah, Su, Li, Fryer, Tim D., Aigbirhio, Franklin I., OʼBrien, John T., and Rowe, James B.
- Published
- 2018
- Full Text
- View/download PDF
41. White matter change with apathy and impulsivity in frontotemporal lobar degeneration syndromes
- Author
-
Lansdall, Claire J., Coyle-Gilchrist, Ian T.S., Jones, P. Simon, Vázquez Rodríguez, Patricia, Wilcox, Alicia, Wehmann, Eileen, Dick, Katrina M., Robbins, Trevor W., and Rowe, James B.
- Published
- 2018
- Full Text
- View/download PDF
42. Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy
- Author
-
Cope, Thomas E, Rittman, Timothy, Borchert, Robin J, Jones, P Simon, Vatansever, Deniz, Allinson, Kieren, Passamonti, Luca, Vazquez Rodriguez, Patricia, Bevan-Jones, W Richard, OʼBrien, John T, and Rowe, James B
- Published
- 2018
- Full Text
- View/download PDF
43. Longitudinal Synaptic Loss in Primary Tauopathies: An In Vivo [11C]UCB‐J Positron Emission Tomography Study.
- Author
-
Holland, Negin, Jones, P. Simon, Savulich, George, Naessens, Michelle, Malpetti, Maura, Whiteside, David J., Street, Duncan, Swann, Peter, Hong, Young T., Fryer, Tim D., Rittman, Timothy, Mulroy, Eoin, Aigbirhio, Franklin I., Bhatia, Kailash P., O'Brien, John T., and Rowe, James B.
- Abstract
Background: Synaptic loss is characteristic of many neurodegenerative diseases; it occurs early and is strongly related to functional deficits. Objective: In this longitudinal observational study, we determine the rate at which synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), and we test the relationship with disease progression. Methods: Our cross‐sectional cohort included 32 participants with probable PSP and 16 with probable CBD (all amyloid‐negative corticobasal syndrome), recruited from tertiary care centers in the United Kingdom, and 33 sex‐ and age‐matched healthy control subjects. Synaptic density was estimated by positron emission tomography imaging with the radioligand [11C]UCB‐J that binds synaptic vesicle 2A. Clinical severity and cognition were assessed by the PSP Rating Scale and the Addenbrooke's cognitive examination. Regional [11C]UCB‐J nondisplaceable binding potential was estimated in Hammersmith Atlas regions of interest. Twenty‐two participants with PSP/CBD had a follow‐up [11C]UCB‐J positron emission tomography scan after 1 year. We calculated the annualized change in [11C]UCB‐J nondisplaceable binding potential and correlated this with the change in clinical severity. Results: We found significant annual synaptic loss within the frontal lobe (−3.5%, P = 0.03) and the right caudate (−3.9%, P = 0.046). The degree of longitudinal synaptic loss within the frontal lobe correlated with the rate of change in the PSP Rating Scale (R = 0.47, P = 0.03) and cognition (Addenbrooke's Cognitive Examination–Revised, R = −0.62, P = 0.003). Conclusions: We provide in vivo evidence for rapid progressive synaptic loss, correlating with clinical progression in primary tauopathies. Synaptic loss may be an important therapeutic target and outcome variable for early‐phase clinical trials of disease‐modifying treatments. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. In vivo 18F-flortaucipir PET does not accurately support the staging of progressive supranuclear palsy
- Author
-
Malpetti, Maura, Kaalund, Sanne, Tsvetanov, Kamen, Rittman, Timothy, Briggs, Mayen, Allinson, Kieren SJ, Passamonti, Luca, Holland, Negin, Jones, P Simon, Fryer, Tim, Hong, Young, Kouli, Antonina, Bevan-Jones, W Richard, Mak, Elijah, Savulich, George, Spillantini, Maria Grazia, Aigbirhio, Franklin I, Williams-Gray, Caroline, O'Brien, John T, Rowe, James B, Malpetti, Maura [0000-0001-8923-9656], Tsvetanov, Kamen A. [0000-0002-3178-6363], Rittman, Timothy [0000-0003-1063-6937], Holland, Negin [0000-0003-3813-0882], Kouli, Antonina [0000-0001-6553-6154], Spillantini, Maria [0000-0002-8544-7332], Aigbirhio, Franklin [0000-0001-9453-5257], Williams-Gray, Caroline [0000-0002-2648-9743], O'Brien, John [0000-0002-0837-5080], Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository
- Subjects
tau pathology ,Positron-Emission Tomography ,18F-flortaucipir ,Humans ,tau Proteins ,progressive supranuclear palsy ,staging ,Supranuclear Palsy, Progressive ,PET-to-autopsy studies ,Carbolines - Abstract
Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by neuro-glial tau pathology. A new staging system for PSP pathology at post-mortem has been described and validated. We used a data-driven approach to test whether post-mortem pathological staging in PSP can be reproduced in vivo with 18F-flortaucipir PET. Methods: N=42 patients with probable PSP and N=39 controls underwent 18F-flortaucipir PET. Conditional inference tree analyses on regional binding potential values identified absent/present pathology thresholds to define in vivo staging. Following the staging system for PSP pathology, the combination of absent/present values across all regions was evaluated to assign each participant to in vivo stages. Analysis of variance was applied to analyse differences among means of disease severity between stages. In vivo staging was compared with post-mortem staging in N=9 patients who also had post-mortem confirmation of the diagnosis and stage. Results: Stage assignment was estimable in 41 patients: N=10 patients were classified in stage I/II, N=26 in stage III/IV, N=5 in stage V/VI, while N=1 was not classifiable. An explorative sub-staging identified N=2 patients in stage I, N=8 in stage II, N=9 in stage III, N=17 in stage IV and N=5 in stage V. However, the nominal 18F-flortaucipir derived stage was not associated with clinical severity and was not indicative of pathology staging at post-mortem. Conclusion: 18F-flortaucipir PET in vivo does not correspond to neuropathological staging in PSP. This analytic approach, seeking to mirror in vivo the neuropathology staging with PET-to-autopsy correlational analyses might enable in vivo staging with next-generation PET tracers for tau, but further evidence and comparison with post-mortem data are needed.
- Published
- 2022
45. Structural and Functional Thalamic Changes in Progressive Supranuclear Palsy
- Author
-
Tan, Sean YW, primary, Jones, P Simon, additional, Whiteside, David J, additional, Rowe, James, additional, and Rittman, Timothy, additional
- Published
- 2022
- Full Text
- View/download PDF
46. Locus Coeruleus Integrity from 7 T MRI Relates to Apathy and Cognition in Parkinsonian Disorders
- Author
-
Ye, Rong, primary, O'Callaghan, Claire, additional, Rua, Catarina, additional, Hezemans, Frank H., additional, Holland, Negin, additional, Malpetti, Maura, additional, Jones, P. Simon, additional, Barker, Roger A., additional, Williams‐Gray, Caroline H., additional, Robbins, Trevor W., additional, Passamonti, Luca, additional, and Rowe, James, additional
- Published
- 2022
- Full Text
- View/download PDF
47. Noradrenergic deficits contribute to apathy in Parkinson’s disease through the precision of expected outcomes
- Author
-
Hezemans, Frank H., primary, Wolpe, Noham, additional, O’Callaghan, Claire, additional, Ye, Rong, additional, Rua, Catarina, additional, Jones, P. Simon, additional, Murley, Alexander G., additional, Holland, Negin, additional, Regenthal, Ralf, additional, Tsvetanov, Kamen A., additional, Barker, Roger A., additional, Williams-Gray, Caroline H., additional, Robbins, Trevor W., additional, Passamonti, Luca, additional, and Rowe, James B., additional
- Published
- 2022
- Full Text
- View/download PDF
48. The neurophysiological effect of NMDA-R antagonism of frontotemporal lobar degeneration is conditional on individual GABA concentration
- Author
-
Perry, Alistair, primary, Hughes, Laura, additional, Adams, Natalie, additional, Naessens, Michelle, additional, Murley, Alexander, additional, Rouse, Matthew, additional, Street, Duncan, additional, Jones, P Simon, additional, Cope, Thomas, additional, Kocagoncu, Ece, additional, and Rowe, James, additional
- Published
- 2022
- Full Text
- View/download PDF
49. 18F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy
- Author
-
Passamonti, Luca, Vázquez Rodríguez, Patricia, Hong, Young T., Allinson, Kieren S. J., Williamson, David, Borchert, Robin J., Sami, Saber, Cope, Thomas E., Bevan-Jones, W. Richard, Jones, P. Simon, Arnold, Robert, Surendranathan, Ajenthan, Mak, Elijah, Su, Li, Fryer, Tim D., Aigbirhio, Franklin I., O’Brien, John T., and Rowe, James B.
- Published
- 2017
- Full Text
- View/download PDF
50. Biased visualization of hypoperfused tissue by computed tomography due to short imaging duration: improved classification by image down-sampling and vascular models
- Author
-
Mikkelsen, Irene Klærke, Jones, P. Simon, Ribe, Lars Riisgaard, Alawneh, Josef, Puig, Josep, Bekke, Susanne Lise, Tietze, Anna, Gillard, Jonathan H., Warburton, Elisabeth A., Pedraza, Salva, Baron, Jean-Claude, Østergaard, Leif, and Mouridsen, Kim
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.