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1. Content Validity of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) Instrument in Spinocerebellar Ataxia.

Author

Potashman, Michele, Rudell, Katja, Pavisic, Ivanna, Suminski, Naomi, Doma, Rinchen, Heinrich, Maggie, Abetz-Webb, Linda, Beiner, Melissa, Kuo, Sheng-Han, Rosenthal, Liana, Zesiwicz, Theresa, Fife, Terry, van de Warrenburg, Bart, Ristori, Giovanni, Synofzik, Matthis, Perlman, Susan, Schmahmann, Jeremy, and LItalien, Gilbert

Subjects
Clinical outcome assessment, Cognitive debriefing, Concept elicitation, Spinocerebellar ataxia, f-SARA, Humans, Spinocerebellar Ataxias, Male, Female, Middle Aged, Adult, Severity of Illness Index, Reproducibility of Results, Aged, Gait, Disease Progression
Abstract

The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 (n = 1) and SCA3 (n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1-2 years, 1-2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials.

Published
2024

2. Detecting and tracking populations at-risk of Alzheimer's disease : studying asymptomatic cognitive profiles and symptomatic clinical presentations

Author

Pavisic, Ivanna Micol

Subjects
616.8
Abstract

Familial Alzheimer's disease (FAD) is a penetrant autosomal dominantly inherited condition. Due to its clinical and neurophysiological similarities with sporadic AD features, it represents an important clinical group in its own right but also offers a potential model for AD. This thesis is largely based on the longitudinal FAD study but also includes data from 'Insight 46' in an attempt to broaden the scope of these investigations to other 'at-risk' cohorts. The overarching aim of the thesis is to study the early subtle cognitive changes (with a particular focus on visual short-term memory but also subjective cognitive decline) and the symptomatic presentations (both cognitive and clinical) that accompany disease progression in AD. The key findings were that over time, presymptomatic mutation carriers (PMCs) had a faster rate of decline in visual short-term memory (VSTM) function, specifically in the ability to remember the location and the target identity. This relational binding deficit was strongest in the most challenging task condition: 3-items, 4s delay (high load, longest delay), and is clinically relevant as it shows sensitivity in tracking individuals during preclinical AD stages. Consequent eye movement investigations of VSTM function, revealed a stronger cognitive effort for PMCs compared to controls during encoding, a finding which may increase the diagnostic value of relational binding tasks. Other important findings were: the higher incidence of subjective cognitive decline symptoms in two otherwise different populations "at-risk" of AD: PMCs carriers and amyloid-positive ~70-year-old participants and the ineffective VSTM function and much smaller influence of mutation specificity on survival time variance in comparison to variance in age at onset for symptomatic FAD individuals. Together, this work has implications for the interpretation of cognitive and clinical data, the understanding of heterogeneity in FAD and may help detect and track subtle cognitive decline of potential value to clinical practice.

Published
2021

3. Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy.

Author

Firth, Nicholas C, Primativo, Silvia, Marinescu, Razvan-Valentin, Shakespeare, Timothy J, Suarez-Gonzalez, Aida, Lehmann, Manja, Carton, Amelia, Ocal, Dilek, Pavisic, Ivanna, Paterson, Ross W, Slattery, Catherine F, Foulkes, Alexander JM, Ridha, Basil H, Gil-Néciga, Eulogio, Oxtoby, Neil P, Young, Alexandra L, Modat, Marc, Cardoso, M Jorge, Ourselin, Sebastien, Ryan, Natalie S, Miller, Bruce L, Rabinovici, Gil D, Warrington, Elizabeth K, Rossor, Martin N, Fox, Nick C, Warren, Jason D, Alexander, Daniel C, Schott, Jonathan M, Yong, Keir XX, and Crutch, Sebastian J

Subjects
Cerebral Cortex, Humans, Alzheimer Disease, Disease Progression, Magnetic Resonance Imaging, Case-Control Studies, Longitudinal Studies, Neuropsychological Tests, Models, Neurological, Middle Aged, Female, Male, Cognitive Dysfunction, Alzheimer’s disease, brain atrophy, dementia, memory, structural MRI, Alzheimer's disease, Models, Neurological, Neurology & Neurosurgery, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer's disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer's disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer's disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer's disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer's disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer's disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer's disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer's disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer's disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer's disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy.

Published
2019

4. Assessing cognitive dysfunction in Parkinson's disease: An online tool to detect visuo‐perceptual deficits

Author

Weil, Rimona S, Schwarzkopf, Dietrich S, Bahrami, Bahador, Fleming, Stephen M, Jackson, Ben M, Goch, Tristam JC, Saygin, Ayse P, Miller, Luke E, Pappa, Katerina, Pavisic, Ivanna, Schade, Rachel N, Noyce, Alastair J, Crutch, Sebastian J, O'Keeffe, Aidan G, Schrag, Anette E, and Morris, Huw R

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Clinical Research, Dementia, Aging, Acquired Cognitive Impairment, Parkinson's Disease, Neurodegenerative, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Adult, Aged, Aged, 80 and over, Cognition Disorders, Female, Humans, Male, Middle Aged, Motion Perception, Neuropsychological Tests, Online Systems, Parkinson Disease, Perceptual Disorders, Psychomotor Performance, Recognition, Psychology, Signal Detection, Psychological, Visual Acuity, Visual Perception, Parkinson's disease, vision, perception, hallucinations, signal detection theory, Human Movement and Sports Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundPeople with Parkinson's disease (PD) who develop visuo-perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuo-perceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo-perceptual deficits in PD.ObjectiveWe developed an online platform to test visuo-perceptual function. We hypothesised that (1) visuo-perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias.MethodsWe assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks.ResultsPeople with PD were worse than controls at object recognition, showing no deficits in other visuo-perceptual tests. Specifically, they were worse at identifying skewed images (P

Published
2018

6. Dissociable effects of APOE ε4 and β-amyloid pathology on visual working memory

Author

Lu, Kirsty, Nicholas, Jennifer M., Pertzov, Yoni, Grogan, John, Husain, Masud, Pavisic, Ivanna M., James, Sarah-Naomi, Parker, Thomas D., Lane, Christopher A., Keshavan, Ashvini, Keuss, Sarah E., Buchanan, Sarah M., Murray-Smith, Heidi, Cash, David M., Malone, Ian B., Sudre, Carole H., Coath, William, Wong, Andrew, Henley, Susie M. D., Fox, Nick C., Richards, Marcus, Schott, Jonathan M., and Crutch, Sebastian J.

Published
2021
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7. Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: a longitudinal cohort study

Author

O’Connor, Antoinette, Karikari, Thomas K., Poole, Teresa, Ashton, Nicholas J., Lantero Rodriguez, Juan, Khatun, Ayesha, Swift, Imogen, Heslegrave, Amanda J., Abel, Emily, Chung, Elisha, Weston, Philip S. J., Pavisic, Ivanna M., Ryan, Natalie S., Barker, Suzie, Rossor, Martin N., Polke, James M., Frost, Chris, Mead, Simon, Blennow, Kaj, Zetterberg, Henrik, and Fox, Nick C.

Published
2021
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8. Atypical presentations of autosomal dominant familial Alzheimer’s disease: insights into genetic, neuropathological and clinical heterogeneity

Author

Ryan, Natalie S, primary, Willumsen, Nanet, additional, Nicholas, Jennifer M, additional, Poole, Teresa, additional, Pavisic, Ivanna M, additional, Walsh, Phoebe, additional, Rice, Helen, additional, Lu, Kirsty, additional, O'Connor, Antoinette, additional, Weston, Philip SJ, additional, Abel, Emily, additional, Barkhof, Frederik, additional, Barnes, Jo, additional, Lashley, Tammaryn, additional, and Fox, Nick C, additional

Published
2023
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13. Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study

Author

Wagen, Aaron Z, primary, Coath, William, additional, Keshavan, Ashvini, additional, James, Sarah-Naomi, additional, Parker, Thomas D, additional, Lane, Christopher A, additional, Buchanan, Sarah M, additional, Keuss, Sarah E, additional, Storey, Mathew, additional, Lu, Kirsty, additional, Macdougall, Amy, additional, Murray-Smith, Heidi, additional, Freiberger, Tamar, additional, Cash, David M, additional, Malone, Ian B, additional, Barnes, Josephine, additional, Sudre, Carole H, additional, Wong, Andrew, additional, Pavisic, Ivanna M, additional, Street, Rebecca, additional, Crutch, Sebastian J, additional, Escott-Price, Valentina, additional, Leonenko, Ganna, additional, Zetterberg, Henrik, additional, Wellington, Henrietta, additional, Heslegrave, Amanda, additional, Barkhof, Frederik, additional, Richards, Marcus, additional, Fox, Nick C, additional, Cole, James H, additional, and Schott, Jonathan M, additional

Published
2022
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14. Longitudinal trajectories of self‐reported subjective cognitive decline in relation to objective cognitive performance in a population‐based cohort.

Author

Street, Rebecca E, Lu, Kirsty, Nicholas, Jennifer M, Keuss, Sarah E, Pavisic, Ivanna M, James, Sarah‐Naomi, Baker, John, Buchanan, Sarah M, Wagen, Aaron Z, Storey, Mathew, Harris, Matthew J, Parker, Thomas D, Lane, Christopher A, Keshavan, Ashvini, Freiberger, Tamar, Murray‐Smith, Heidi, Cash, David M, Coath, William, Wong, Andrew, and Richards, Marcus

Abstract

Background: Subjective Cognitive Decline (SCD) may represent the onset of cognitive decline before impairment on standard cognitive tests occurs (Jessen et al., 2014). Previous cross‐sectional studies were shown to have limited ability to capture objective differences in cognitive performance between groups with and without SCD (Cacciamani et al., 2017). Understanding the interplay between changes in subjective memory ratings and objective cognitive function over time may have utility in identifying people at risk of dementia. Method: 370 cognitively normal (CN) individuals with complete cognitive data (Table 1 for characteristics) from Insight 46, a longitudinal neuroscience sub‐study of the MRC National Survey for Health and Development (the British 1946 Birth Cohort), underwent cognitive, clinical, and physical assessments, and neuroimaging (combined MRI/18F‐Florbetapir‐PET). SCD was measured using MyCog (Rami et al., 2014) a validated tool, from the SCD‐Questionnaire, where higher scores indicate greater subjective complaints. Linear regression models were used to test whether longitudinal cognitive change as measured using the Preclinical Alzheimer Cognitive Composite (PACC) and a visual short‐term memory binding task were influenced by baseline MyCog and whether there are parallel associations between rates of change in MyCog and longitudinal cognitive change. Covariates were sex, age at baseline visit, childhood cognitive ability, educational attainment, and adult socioeconomic position. Result: Baseline MyCog scores did not predict rates of change in PACC or visual short‐term memory binding outcome measures (Table 2). Rates of MyCog change alone did not predict rate of change in PACC, localisation error, total correct number of trials or proportion of misbinding errors (Table 3). However, we observed an interaction effect with baseline amyloid‐b status, whereby greater rates of subjective memory concerns predicted faster rates of decline in the proportion of misbinding errors in amyloid‐b positive participants only (Table 3; Figure 1). Conclusion: These findings suggest that higher amyloid‐b burden in CN individuals with subjective memory complaints is associated with faster rates of decline in visual working memory. Corroborating previous reports that feature binding tasks can objectify subtle cognitive deficits found in SCD (Koppara et al., 2015) and serve as a promising tool for identifying people at risk of dementia. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Fixel‐based analysis of the effect of amyloid beta on white matter tracts in neurologically normal 70 year olds

Author

Wagen, Aaron Z., primary, Zarkali, Angeliki, additional, Coath, William, additional, Buchanan, Sarah M., additional, Keuss, Sarah E., additional, Keshavan, Ashvini, additional, Lu, Kirsty, additional, James, Sarah‐Naomi, additional, Pavisic, Ivanna M., additional, Street, Rebecca E., additional, Parker, Thomas D., additional, Lane, Christopher A., additional, Murray‐Smith, Heidi, additional, Cash, David M., additional, Malone, Ian B., additional, Wong, Andrew, additional, Richards, Marcus, additional, Fox, Nick C., additional, Altmann, Andre, additional, Cole, James H., additional, Weil, Rimona S., additional, and Schott, Jonathan M., additional

Published
2021
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17. Subjective cognitive complaints at age 70: associations with amyloid and mental health

Author

Pavisic, Ivanna M., primary, Lu, Kirsty, additional, Keuss, Sarah E., additional, James, Sarah-Naomi, additional, Lane, Christopher A., additional, Parker, Thomas D., additional, Keshavan, Ashvini, additional, Buchanan, Sarah M., additional, Murray-Smith, Heidi, additional, Cash, David M., additional, Coath, William, additional, Wong, Andrew, additional, Fox, Nick C., additional, Crutch, Sebastian J., additional, Richards, Marcus, additional, and Schott, Jonathan M., additional

Published
2021
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19. Impaired mechanism of visual focal attention in posterior cortical atrophy

Author

Primativo, S, Crutch, S, Pavisic, I, Yong, K, Rossetti, A, Daini, R, Primativo, Silvia, Crutch, Sebastian, Pavisic, Ivanna, Yong, Keir, Rossetti, Alessia, Daini, Roberta, Primativo, S, Crutch, S, Pavisic, I, Yong, K, Rossetti, A, Daini, R, Primativo, Silvia, Crutch, Sebastian, Pavisic, Ivanna, Yong, Keir, Rossetti, Alessia, and Daini, Roberta

Abstract

Objective: Simultanagnosia, a deficit in holistic visual perception, is among the most prominent features of posterior cortical atrophy (PCA). Deficits in visuoperceptual and attentional mechanisms could contribute to simultanagnosia. In the present study, we explored the impaired visual perception of global configuration with two main hypotheses: (a) It is due to a deficit in processing low-spatial frequency stimuli, and (b) it arises from deficits in adjusting attentional focus. Method: The visuoperceptual mechanism was explored by asking participants (5 PCA patients and 20 age- and education-matched healthy controls) to report the local and global elements of incongruent hierarchical letters. Stimuli were unbiased (black letters/white background) and parvocellular biased (red letters/green background). A cued T-detection task, where the stimulus onset asynchrony and the cues' features varied, was used to explore focal attention. Results: PCA patients systematically failed in reporting the global but not the local element. The parvocellular-biased condition partially improved the performance in only 1 patient. In the T-detection task, controls responded faster to targets cued by red dots and small cues as compared to no cues. Conversely, the cue's features did not affect patients' performance. Conclusions: Results only partially support the hypothesis according to which simultanagnosia is driven by an impairment in processing low-spatial frequencies. Data indicate a deficit in the flexibility of focal attention that prevents PCA patients from adapting the attentional window to the stimulus features. Simultanagnosia in PCA can be conceptualized as a complex result of a deficit involving visuoperceptual and exogenous attentional mechanisms.

Published
2020

20. Augmenting cognitive assessment with instruction‐less eye‐tracking tests: A machine learning approach for detecting abnormal oculomotor biomarkers

Author

Mengoudi, Kyriaki, primary, Ravi, Daniele, additional, Yong, Keir XX, additional, Primativo, Silvia, additional, Pavisic, Ivanna M, additional, Brotherhood, Emilie V, additional, Lu, Kirsty, additional, Schott, Jonathan M, additional, Crutch, Sebastian J, additional, and Alexander, Daniel C., additional

Published
2020
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21. Serum neurofilament light and whole brain volume associate with machine‐learning derived brain‐predicted age in the British 1946 birth cohort

Author

Wagen, Aaron, primary, Coath, William, additional, Keuss, Sarah E, additional, Buchanan, Sarah M, additional, Storey, Mathew, additional, Lu, Kirsty, additional, Pavisic, Ivanna M, additional, James, Sarah‐Naomi, additional, Street, Rebecca E, additional, Parker, Thomas D, additional, Lane, Christopher A, additional, Keshavan, Ashvini, additional, Murray‐Smith, Heidi, additional, Cash, David M, additional, Malone, Ian B, additional, Wong, Andrew, additional, Henley, Susie, additional, Crutch, Sebastian J, additional, Wellington, Henrietta, additional, Heslegrave, Amanda J, additional, Zetterberg, Henrik, additional, Fox, Nick C, additional, Richards, Marcus, additional, Cole, James, additional, and Schott, Jonathan M, additional

Published
2020
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23. Plasma phospho‐tau in familial Alzheimer’s disease

Author

O'Connor, Antoinette, primary, Karikari, Thomas K., additional, Poole, Teresa, additional, Khatun, Ayesha, additional, Swift, Imogen, additional, Heslegrave, Amanda J., additional, Abel, Emily, additional, Chung, Elisha, additional, Weston, Philip S.J., additional, Polke, James, additional, Pavisic, Ivanna M., additional, Rossor, Martin N., additional, Ryan, Natalie S., additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, and Fox, Nick C., additional

Published
2020
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24. Accelerated forgetting is sensitive to β‐amyloid pathology and cerebral atrophy in cognitively normal 72‐year‐olds

Author

Lu, Kirsty, primary, Pavisic, Ivanna M., additional, James, Sarah‐Naomi, additional, Street, Rebecca E., additional, Keuss, Sarah E., additional, Buchanan, Sarah M., additional, Wagen, Aaron, additional, Storey, Mathew, additional, Parker, Thomas D., additional, Lane, Christopher A., additional, Keshavan, Ashvini, additional, Murray‐Smith, Heidi, additional, Cash, David M., additional, Malone, Ian B., additional, Coath, William, additional, Wong, Andrew, additional, Henley, Susie M.D., additional, Crutch, Sebastian J., additional, Fox, Nick C., additional, Richards, Marcus, additional, and Schott, Jonathan M., additional

Published
2020
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25. APOE‐ε4 carriers have superior recall on the ‘What was where?’ visual short‐term memory binding test at age 70, despite a detrimental effect of β‐amyloid

Author

Lu, Kirsty, primary, Nicholas, Jennifer M., additional, Pertzov, Yoni, additional, Grogan, John, additional, Husain, Masud, additional, Pavisic, Ivanna M., additional, James, Sarah‐Naomi, additional, Parker, Thomas D., additional, Lane, Christopher A, additional, Keshavan, Ashvini, additional, Keuss, Sarah E., additional, Buchanan, Sarah M., additional, Murray‐Smith, Heidi, additional, Cash, David M., additional, Malone, Ian B., additional, Coath, William, additional, Wong, Andrew, additional, Henley, Susie M.D., additional, Crutch, Sebastian J., additional, Fox, Nick C., additional, Richards, Marcus, additional, and Schott, Jonathan M., additional

Published
2020
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26. Performance on the graded naming test in a population‐based sample of 72‐year‐olds: Associations with life‐course predictors and β‐amyloid pathology

Author

Street, Rebecca E., primary, Lu, Kirsty, additional, Huckvale, Mark, additional, Brotherhood, Emilie V., additional, Pavisic, Ivanna M., additional, James, Sarah‐Naomi, additional, Keuss, Sarah E., additional, Buchanan, Sarah M., additional, Parker, Thomas D., additional, Lane, Christopher A., additional, Keshavan, Ashvini, additional, Murray‐Smith, Heidi, additional, Cash, David M., additional, Coath, William, additional, Wong, Andrew, additional, Fox, Nick C., additional, Richards, Marcus, additional, Schott, Jonathan M., additional, and Crutch, Sebastian J., additional

Published
2020
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27. Visual short-term memory impairments in presymptomatic familial Alzheimer’s disease: A longitudinal observational study

Author

Pavisic, Ivanna M., primary, Nicholas, Jennifer M., additional, Pertzov, Yoni, additional, O'Connor, Antoinette, additional, Liang, Yuying, additional, Collins, Jessica D., additional, Lu, Kirsty, additional, Weston, Philip S.J., additional, Ryan, Natalie S., additional, Husain, Masud, additional, Fox, Nick C., additional, and Crutch, Sebastian J., additional

Published
2020
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30. Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer’s disease: a longitudinal cohort study

Author

O’Connor, Antoinette, primary, Karikari, Thomas K., additional, Poole, Teresa, additional, Ashton, Nicholas J., additional, Lantero Rodriguez, Juan, additional, Khatun, Ayesha, additional, Swift, Imogen, additional, Heslegrave, Amanda J., additional, Abel, Emily, additional, Chung, Elisha, additional, Weston, Philip S. J., additional, Pavisic, Ivanna M., additional, Ryan, Natalie S., additional, Barker, Suzie, additional, Rossor, Martin N., additional, Polke, James M., additional, Frost, Chris, additional, Mead, Simon, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, and Fox, Nick C., additional

Published
2020
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32. Longitudinal neuroanatomical and cognitive progression of posterior cortical atrophy

Author

Alzheimer's Research UK, Economic and Social Research Council (UK), Engineering and Physical Sciences Research Council (UK), Alzheimer Society of Canada, Brain Research Trust, Wolfson Foundation, National Institute for Health Research (UK), National Institutes of Health (US), European Commission, Firth, Nicholas C., Primativo, Silvia, Marinescu, Razvan-Valentin, Shakespeare, Timothy J., Suárez-González, Aida, Lehmann, Manja, Carton, Amelia, Ocal, Dilek, Pavisic, Ivanna, Paterson, Ross W., Slattery, Catherine F., Foulkes, Alexander J. M., Ridha, Basil H., Gil-Néciga, Eulogio, Oxtoby, Neil P., Young, Alexandra L., Modat, Marc, Cardoso, M. Jorge, Ourselin, Sebastien, Ryan, Natalie S., Miller, Bruce L., Rabinovici, Gil D., Warrington, Elizabeth K., Rossor, Martin N., Fox, Nick C., Warren, Jason D., Alexander, Daniel C., Schott, Jonathan M., Yong, Keir X. X., Crutch, Sebastian J., Alzheimer's Research UK, Economic and Social Research Council (UK), Engineering and Physical Sciences Research Council (UK), Alzheimer Society of Canada, Brain Research Trust, Wolfson Foundation, National Institute for Health Research (UK), National Institutes of Health (US), European Commission, Firth, Nicholas C., Primativo, Silvia, Marinescu, Razvan-Valentin, Shakespeare, Timothy J., Suárez-González, Aida, Lehmann, Manja, Carton, Amelia, Ocal, Dilek, Pavisic, Ivanna, Paterson, Ross W., Slattery, Catherine F., Foulkes, Alexander J. M., Ridha, Basil H., Gil-Néciga, Eulogio, Oxtoby, Neil P., Young, Alexandra L., Modat, Marc, Cardoso, M. Jorge, Ourselin, Sebastien, Ryan, Natalie S., Miller, Bruce L., Rabinovici, Gil D., Warrington, Elizabeth K., Rossor, Martin N., Fox, Nick C., Warren, Jason D., Alexander, Daniel C., Schott, Jonathan M., Yong, Keir X. X., and Crutch, Sebastian J.

Abstract

Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer’s disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer’s disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer’s disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer’s disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer’s disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer’s disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer’s disease showed early h

Published
2019

34. P1-318: PERCEPTION OF VERTICALITY IN TYPICAL ALZHEIMER'S DISEASE AND POSTERIOR CORTICAL ATROPHY: NEUROANATOMICAL AND NEUROPSYCHOLOGICAL CORRELATES

Author

Ocal, Dilek, primary, Peters, Amy, additional, Cash, David M., additional, Bancroft, Matthew, additional, Kaski, Diego, additional, Veale, Thomas D., additional, Lane, Christopher A., additional, Parker, Thomas D., additional, Gonzalez, Aida Suarez, additional, Pavisic, Ivanna M., additional, Collins, Jessica, additional, Ryan, Natalie S., additional, Schott, Jonathan M., additional, Yong, Keir, additional, Day, Brian, additional, and Crutch, Sebastian, additional

Published
2019
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36. O2-09-05: LONGITUDINAL F-AV-1451 TAU PET IN FAMILIAL ALZHEIMER'S DISEASE

Author

O'Connor, Antoinette, primary, Markiewicz, Pawel J., additional, Cash, David M., additional, Schöll, Michael, additional, Weston, Philip SJ., additional, Ryan, Natalie S., additional, Pavisic, Ivanna M., additional, Lu, Kirsty, additional, Fraser, Maggie R., additional, Malone, Ian B., additional, and Fox, Nick C., additional

Published
2019
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37. P3-480: PERCEPTION OF VERTICALITY IN TYPICAL ALZHEIMER'S DISEASE AND POSTERIOR CORTICAL ATROPHY: NEUROANATOMICAL AND NEUROPSYCHOLOGICAL CORRELATES

Author

Ocal, Dilek, primary, Peters, Amy, additional, Cash, David M., additional, Bancroft, Matthew, additional, Kaski, Diego, additional, Veale, Thomas D., additional, Lane, Christopher A., additional, Parker, Thomas D., additional, Gonzalez, Aida Suarez, additional, Collins, Jessica, additional, Pavisic, Ivanna M., additional, Ryan, Natalie S., additional, Schott, Jonathan M., additional, Yong, Keir, additional, Day, Brian, additional, and Crutch, Sebastian, additional

Published
2019
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39. Eyetracking Metrics in Young Onset Alzheimer’s Disease: A Window into Cognitive Visual Functions

Author

Pavisic, Ivanna M., Firth, Nicholas C., Parsons, Samuel, Rego, David Martinez, Shakespeare, Timothy J., Yong, Keir X. X., Slattery, Catherine F., Paterson, Ross W., Foulkes, Alexander J. M., Macpherson, Kirsty, Carton, Amelia M., Alexander, Daniel C., Shawe-Taylor, John, Fox, Nick C., Schott, Jonathan M., Crutch, Sebastian J., and Primativo, Silvia

Subjects
eye movements, machine learning, eyetracking metrics, classification model, young onset Alzheimer’s disease, cognitive visual functions, lcsh:Neurology. Diseases of the nervous system, lcsh:RC346-429, Original Research, Neuroscience
Abstract

Young onset Alzheimer’s disease (YOAD) is defined as symptom onset before the age of 65 years and is particularly associated with phenotypic heterogeneity. Atypical presentations, such as the clinic-radiological visual syndrome posterior cortical atrophy (PCA), often lead to delays in accurate diagnosis. Eyetracking has been used to demonstrate basic oculomotor impairments in individuals with dementia. In the present study, we aim to explore the relationship between eyetracking metrics and standard tests of visual cognition in individuals with YOAD. Fifty-seven participants were included: 36 individuals with YOAD (n = 26 typical AD; n = 10 PCA) and 21 age-matched healthy controls. Participants completed three eyetracking experiments: fixation, pro-saccade, and smooth pursuit tasks. Summary metrics were used as outcome measures and their predictive value explored looking at correlations with visuoperceptual and visuospatial metrics. Significant correlations between eyetracking metrics and standard visual cognitive estimates are reported. A machine-learning approach using a classification method based on the smooth pursuit raw eyetracking data discriminates with approximately 95% accuracy patients and controls in cross-validation tests. Results suggest that the eyetracking paradigms of a relatively simple and specific nature provide measures not only reflecting basic oculomotor characteristics but also predicting higher order visuospatial and visuoperceptual impairments. Eyetracking measures can represent extremely useful markers during the diagnostic phase and may be exploited as potential outcome measures for clinical trials.

Published
2017
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40. P1‐524: VISUAL SHORT‐TERM BINDING DEFICIT IN FAMILIAL ALZHEIMER'S DISEASE: A LONGITUDINAL STUDY

Author

Pavisic, Ivanna M., primary, Pertzov, Yoni, additional, O'Connor, Antoinette, additional, Nicholas, Jennifer M., additional, Macpherson, Kirsty, additional, Collins, Jessica, additional, Jane, Douglas, additional, Weston, Philip SJ., additional, Liang, Yuying, additional, Yong, Keir, additional, Ryan, Natalie S., additional, Husain, Masud, additional, Fox, Nick C., additional, and Crutch, Sebastian J., additional

Published
2018
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41. P3‐261: SERUM NEUROFILAMENT LIGHT CONCENTRATION AND PROGRESSION IN FAMILIAL ALZHEIMER'S DISEASE

Author

O'Connor, Antoinette, primary, Poole, Teresa, additional, Weston, Philip S.J., additional, Ryan, Natalie S., additional, Liang, Yuying, additional, Macpherson, Kirsty, additional, Pavisic, Ivanna M., additional, Collins, Jessica, additional, Druyeh, Ronald, additional, Mead, Simon, additional, Blennow, Kaj, additional, Rossor, Martin N., additional, Schott, Jonathan M., additional, Zettenberg, Henrik, additional, and Fox, Nick C., additional

Published
2018
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42. P2‐514: CAN EYETRACKING METRICS PROVIDE INSIGHT INTO THE DIAGNOSIS OF DIFFERENT DEMENTIA TYPES? A SPATIAL ANTICIPATION TASK

Author

Pavisic, Ivanna M., primary, Primativo, Silvia, additional, Yong, Keir, additional, Russell, Lucy L., additional, Hardy, Chris J.D., additional, Bond, Rebecca L., additional, Marshall, Charles R., additional, Brotherhood, Emilie V., additional, Warren, Jason D., additional, Rohrer, Jonathon D., additional, and Crutch, Sebastian J., additional

Published
2018
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43. PO107 Cats & dogs: an online test of early visual deficits in parkinson’s

Author

Rachel N. Schade, Pavisic Ivanna, Katerina Pappa, Rimona S. Weil, Huw R. Morris, Bahador Bahrami, and Dietrich Schwarzkopt

Subjects
medicine.medical_specialty, CATS, Visual acuity, business.industry, Neuropsychology, Repeated measures design, Audiology, medicine.disease, Clinical trial, Visual processing, Psychiatry and Mental health, Cohort, Medicine, Dementia, Surgery, Neurology (clinical), medicine.symptom, business
Abstract

Background Half of patients with Parkinson’s disease (PD) develop dementia. Early detection allows enrichment for clinical trials, but there are no robust clinical markers. Patients with disease in visual processing regions show greatest risk of PD dementia. However current visuo-perception tests are poorly sensitive. We present a sensitive online visuo-perceptual test based on skewed images of cats and dogs. Methods Cat and dog stimuli on the online site were skewed using an affine matrix transformation at 3 levels of skew. Participants indicated whether each image was a cat or dog. Performance at each level of skew was compared using a repeated measures ANOVA. The test was validated in a face-to-face clinical cohort (n=31) using approved scales (MDS-UPDRS, visual acuity, neuropsychology). Results 56 patients with PD and 247 age-matched controls accessed the website. Patients with PD were worse at identifying skewed images than controls, F=3.71, p=0.025. Performance in the Cats and Dogs Test correlated with neuropsychology in a face-to-face cohort without dementia (R2=0.33, p=0.00043). Conclusions Patients with PD were worse at the online Cats and Dogs test than controls. This test may detect the earliest stages of PD dementia. Its online delivery makes it a useful tool for collaboration.

Published
2017
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44. [O2–16–03]: MODELLING EYE‐TRACKING DATA TO DISCRIMINATE BETWEEN ALZHEIMER'S PATIENTS AND HEALTHY CONTROLS

Author

Parsons, Samuel, primary, Rego, David Martinez, additional, Shawe‐Taylor, John, additional, Firth, Nicholas C., additional, Primativo, Silvia, additional, Crutch, Sebastian J., additional, Shakespeare, Timothy J., additional, Slattery, Catherine F., additional, Macpherson, Kirsty, additional, Carton, Amelia M., additional, Schott, Jonathan M., additional, Alexander, Daniel C., additional, Paterson, Ross W., additional, Foulkes, Alexander J.M., additional, Fox, Nick C., additional, and Pavisic, Ivanna M., additional

Published
2017
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