40 results on '"Brayne, Carol"'
Search Results
2. Evaluation of Bedside Tests of Attention and Arousal Assessing Delirium in Parkinson’s Disease, Dementia, and Older Adults
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Lawson, Rachael A., primary, Richardson, Sarah J., additional, Kershaw, Daisy, additional, Davis, Daniel, additional, Stephan, Blossom C.M., additional, Robinson, Louise, additional, Brayne, Carol, additional, Barnes, Linda, additional, Burn, David J., additional, Yarnall, Alison J., additional, Taylor, John-Paul, additional, Parker, Stuart, additional, and Allan, Louise M., additional
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- 2022
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3. TDP-43 Related Neuropathologies and Phosphorylation State: Associations with Age and Clinical Dementia in the Cambridge City over-75s Cohort
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Hunter, Sally, Hokkanen, Suvi RK, Keage, Hannah AD, Fleming, Jane, Minett, Thais, Polvikoski, Tuomo, Allinson, Kieren, Brayne, Carol, Cambridge City Over 75s Cohort Collaboration, Hunter, Sally [0000-0002-8063-6556], Fleming, Jane [0000-0002-8127-2061], Brayne, Carol [0000-0001-5307-663X], and Apollo - University of Cambridge Repository
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Aged, 80 and over ,Inclusion Bodies ,Male ,Neurons ,Aging ,population study ,hippocampus ,phosphorylation ,Age Factors ,nutritional and metabolic diseases ,TAR-DNA binding protein of 43 kDa ,Neurofibrillary Tangles ,nervous system diseases ,nervous system ,TDP-43 Proteinopathies ,mental disorders ,Nerve Degeneration ,Humans ,Dementia ,Female - Abstract
Pathologies associated with the Tar-DNA binding protein 43 KDa (TDP-43) are associated with neurodegenerative diseases and aging. Phosphorylation of cellular proteins is a well-accepted mechanism of biological control and can be associated with disease pathways. Phosphorylation state associated with TDP-43 associated pathology has not been investigated with respect to dementia status in a population representative sample. TDP-43 immunohistochemistry directed toward phosphorylated (TDP-43P) and unphosphorylated (TDP-43U) was assessed in sections of hippocampus and temporal cortex from 222 brains donated to the population representative Cambridge City over-75s Cohort. Relationships between dementia status and age at death for TDP-43 immunoreactive pathologies by phosphorylation state were investigated. TDP-43 pathologies are common in the oldest old in the population and often do not conform to MacKenzie classification. Increasing age is associated with glial (TDP-43P) and neuronal inclusions (TDP-43P and TDP-43U), neurites, and granulovacuolar degeneration (GVD). Dementia status is associated with GVD and glial (TDP-43 P) and neural inclusions (TDP-43 P and U). Dementia severity was associated with glial (TDP-43P) and neuronal inclusions (TDP-43U and TDP-43P), GVD, and neurites. The associations between dementia severity and both glial cytoplasmic inclusions and GVD were independent from other pathologies and TDP-43 neuronal cytoplasmic inclusions. TDP-43 pathology contributes to dementia status and progression in a variety of ways in different phosphorylation states involving both neurons and glia, independently from age and from classic Alzheimer-related pathologies. TDP-43 pathologies as cytoplasmic inclusions in neurons or glia or as GVD contribute independently to dementia.
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- 2020
4. Changes in Cognitive Impairment in the Czech Republic
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Seblova, Dominika, Brayne, Carol, Machů, Vendula, Kuklová, Marie, Kopecek, Miloslav, Cermakova, Pavla, Brayne, Carol [0000-0001-5307-663X], and Apollo - University of Cambridge Repository
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trends ,Aged, 80 and over ,Male ,Aging ,prevalence ,Health Surveys ,Humans ,epidemiology ,Cognitive Dysfunction ,Female ,Independent Living ,Longitudinal Studies ,Prospective Studies ,Alzheimer’s disease ,Czech Republic ,cognitive impairment ,Aged - Abstract
BACKGROUND: Studies from North America and Western Europe suggest stable or declining trends in impaired cognition across birth cohorts. OBJECTIVE: We aimed to examine changes in the age-specific prevalence of cognitive impairment in the Czech Republic. METHODS: The study used two samples from the population-based Czech Survey on Health, Ageing and Retirement in Europe. Age-specific prevalence of cognitive impairment (defined based on scores in verbal fluency, immediate recall, delayed recall, and temporal orientation) was compared between participants in wave 2 (2006/2007; n = 1,107) and wave 6 (2015; n = 3,104). Logistic regression was used to estimate the association between the wave and cognitive impairment, step-wise adjusting for sociodemographic and clinical characteristics. Multiple sensitivity analyses, focusing on alternative operationalizations of relative cognitive impairment, impact of missing cognitive data, and survival bias, were carried out. RESULTS: The most conservative estimate suggested that the age-specific prevalence of cognitive impairment declined by one fifth, from 11% in 2006/2007 to 9% in 2015. Decline was observed in all sensitivity analyses. The change was associated with differences in physical inactivity, management of high blood cholesterol, and increases in length education. CONCLUSION: Older adults in the Czech Republic, a country situated in the Central and Eastern European region, have achieved positive developments in cognitive aging. Longer education, better management of cardiovascular factors, and reduced physical inactivity seem to be of key importance.
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- 2019
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5. The Relationship Between Cognitive Performance Using Tests Assessing a Range of Cognitive Domains and Future Dementia Diagnosis in a British Cohort: A Ten-Year Prospective Study
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Hayat, Shabina A., primary, Luben, Robert, additional, Khaw, Kay-Tee, additional, and Brayne, Carol, additional
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- 2021
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6. Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge city over-75s cohort (CC75C) study
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Brayne, Carol, Richardson, Kathryn, Matthews, Fiona E, Fleming, Jane, Hunter, Sally, Xuereb, John H, Paykel, Eugene, Mukaetova-Ladinska, Elizabeta B, Huppert, Felicia A, O'Sullivan, Angela, Dening, Tom, Cambridge City Over-75s Cohort Cc75c Study Neuropathology Collaboration, Brayne, Carol [0000-0001-5307-663X], Matthews, Fiona [0000-0002-1728-2388], Fleming, Jane [0000-0002-8127-2061], Hunter, Sally [0000-0002-8063-6556], Huppert, Felicia [0000-0003-2696-2286], and Apollo - University of Cambridge Repository
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Aged, 80 and over ,Male ,Brain ,Tissue Donors ,United Kingdom ,Cohort Studies ,Catchment Area, Health ,Alzheimer Disease ,Population Surveillance ,mental disorders ,Humans ,Dementia ,Female ,Aged - Abstract
Key neuropathological changes associated with late-onset dementia are not fully understood. Population-based longitudinal studies offer an opportunity to step back and examine which pathological indices best link to clinical state. CC75C is a longitudinal study of the population aged 75 and over at baseline in Cambridge, UK. We report on the first 213 participants coming to autopsy with sufficient information for an end of life dementia diagnosis. Clinical diagnosis was ascertained by examining retrospective informant interviews, survey responses, and death certificates according to DSM-IV criteria. The neuropathological protocol was based on the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Clinical dementia was present in 113 participants (53%): 67% with Alzheimer's disease, 4% vascular dementia, 22% mixed dementia, and 1% dementia with Lewy bodies. As Alzheimer-type pathology was common, the mutually blinded clinical and neuropathological diagnoses were not strongly related. Multivariable analysis identified associations between dementia during life and entorhinal cortex neuritic plaques, hippocampal diffuse plaques, neocortical neurofibrillary tangles, white matter pallor, Lewy bodies, and hippocampal atrophy. These results were consistent in those with clinical Alzheimer's disease. Vascular pathologies, especially microinfarcts, were more common in those with clinical diagnoses including vascular dementia. Alzheimer-type and cerebrovascular pathology are both common in the very old. A greater burden of these pathologies, Lewy bodies, and hippocampal atrophy, are associated with a higher risk of, but do not define, clinical dementia in old age.
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- 2019
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7. Future Directions for Dementia Risk Reduction and Prevention Research: An International Research Network on Dementia Prevention Consensus
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Anstey, Kaarin J., primary, Peters, Ruth, additional, Zheng, Lidan, additional, Barnes, Deborah E., additional, Brayne, Carol, additional, Brodaty, Henry, additional, Chalmers, John, additional, Clare, Linda, additional, Dixon, Roger A., additional, Dodge, Hiroko, additional, Lautenschlager, Nicola T., additional, Middleton, Laura E., additional, Qiu, Chengxuan, additional, Rees, Glenn, additional, Shahar, Suzana, additional, and Yaffe, Kristine, additional
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- 2020
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8. Association of Prior Atherosclerotic Cardiovascular Disease with Dementia After Stroke: A Retrospective Cohort Study
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Yang, Zhirong, primary, Edwards, Duncan, additional, Burgess, Stephen, additional, Brayne, Carol, additional, and Mant, Jonathan, additional
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- 2020
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9. Common Bacterial Infections and Risk of Dementia or Cognitive Decline: A Systematic Review
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Muzambi, Rutendo, primary, Bhaskaran, Krishnan, additional, Brayne, Carol, additional, Davidson, Jennifer A., additional, Smeeth, Liam, additional, and Warren-Gash, Charlotte, additional
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- 2020
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10. Neuropathological Correlates of Cumulative Benzodiazepine and Anticholinergic Drug Use
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Richardson, Kathryn, primary, Wharton, Stephen B., additional, Grossi, Carlota M., additional, Matthews, Fiona E., additional, Fox, Chris, additional, Maidment, Ian, additional, Loke, Yoon K., additional, Steel, Nicholas, additional, Arthur, Antony, additional, Myint, Phyo Kyaw, additional, Boustani, Malaz, additional, Campbell, Noll, additional, Robinson, Louise, additional, Brayne, Carol, additional, and Savva, George M., additional
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- 2020
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11. Changes in Cognitive Impairment in the Czech Republic
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Seblova, Dominika, primary, Brayne, Carol, additional, Machů, Vendula, additional, Kuklová, Marie, additional, Kopecek, Miloslav, additional, and Cermakova, Pavla, additional
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- 2019
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12. Social Isolation and Cognitive Function in Later Life: A Systematic Review and Meta-Analysis
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Evans, Isobel E.M., primary, Martyr, Anthony, additional, Collins, Rachel, additional, Brayne, Carol, additional, and Clare, Linda, additional
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- 2019
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13. Prevention of Cognitive Decline: A Goal in Sight?
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Brayne, Carol, primary and Richard, Edo, additional
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- 2019
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14. 18F-FDG PET for Prediction of Conversion to Alzheimer’s Disease Dementia in People with Mild Cognitive Impairment: An Updated Systematic Review of Test Accuracy
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Smailagic, Nadja, primary, Lafortune, Louise, additional, Kelly, Sarah, additional, Hyde, Chris, additional, and Brayne, Carol, additional
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- 2018
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15. Dementia Research: Populations, Progress, Problems, and Predictions
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Hunter, Sally, primary, Smailagic, Nadja, additional, and Brayne, Carol, additional
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- 2018
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16. Perspectives on Communicating Biomarker-Based Assessments of Alzheimer’s Disease to Cognitively Healthy Individuals
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Milne, Richard, primary, Bunnik, Eline, additional, Diaz, Ana, additional, Richard, Edo, additional, Badger, Shirlene, additional, Gove, Dianne, additional, Georges, Jean, additional, Fauria, Karine, additional, Molinuevo, Jose-Luis, additional, Wells, Katie, additional, Ritchie, Craig, additional, and Brayne, Carol, additional
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- 2018
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17. Kidney Function and the Risk of Stroke and Dementia: The Rotterdam Study.
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Koop-Nieuwelink, Carolien, Sedaghat, Sanaz, Mutlu, Unal, Licher, Silvan, Franco, Oscar H., Ikram, M. Arfan, Geerlings, Mirjam I., Ikram, M. Kamran, Bos, Daniel, and Brayne, Carol
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DEMENTIA ,STROKE ,GLOMERULAR filtration rate ,KIDNEYS ,DEMENTIA risk factors ,DISEASE risk factors ,KIDNEY diseases ,COMPARATIVE studies ,CREATININE ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,PROTEINS ,RESEARCH ,EVALUATION research ,DISEASE complications - Abstract
Longitudinal population-based data on effects of kidney dysfunction in the development of stroke and dementia remains inconclusive. We investigated associations of kidney function with risk of stroke and dementia in 5,993 community-dwelling individuals (mean age: 69.0 years, 57.2% women). We calculated estimated glomerular filtration rates based on creatinine, cystatin-C, and a combination of these two. During a mean follow-up of 11.6 years (69,790 person-years), 1,360 individuals suffered a stroke (n = 601) or developed dementia (n = 759). We found that an impaired kidney function was related to a higher risk of stroke, but not to dementia. [ABSTRACT FROM AUTHOR]
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- 2019
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18. Designing an Internet-Based Multidomain Intervention for the Prevention of Cardiovascular Disease and Cognitive Impairment in Older Adults: The HATICE Trial.
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Barbera, Mariagnese, Mangialasche, Francesca, Jongstra, Susan, Guillemont, Juliette, Ngandu, Tiia, Beishuizen, Cathrien, Coley, Nicola, Brayne, Carol, Andrieu, Sandrine, Richard, Edo, Soininen, Hilkka, Kivipelto, Miia, and HATICE study group
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DISEASES in older people ,CARDIOVASCULAR disease prevention ,INTERNET counseling ,MILD cognitive impairment ,DEMENTIA prevention ,RANDOMIZED controlled trials ,COMPARATIVE studies ,COUNSELING ,EXERCISE ,INTERNET ,RESEARCH methodology ,MEDICAL cooperation ,MEDICAL protocols ,RESEARCH ,STATISTICAL sampling ,TELEMEDICINE ,EVALUATION research ,LIFESTYLES - Abstract
Background: Many dementia and cardiovascular disease (CVD) cases in older adults are attributable to modifiable vascular and lifestyle-related risk factors, providing opportunities for prevention. In the Healthy Aging Through Internet Counselling in the Elderly (HATICE) randomized controlled trial, an internet-based multidomain intervention is being tested to improve the cardiovascular risk (CVR) profile of older adults.Objective: To design a multidomain intervention to improve CVR, based on the guidelines for CVR management, and administered through a coach-supported, interactive, platform to over 2500 community-dwellers aged 65+ in three European countries.Methods: A comparative analysis of national and European guidelines for primary and secondary CVD prevention was performed. Results were used to define the content of the intervention.Results: The intervention design focused on promoting awareness and self-management of hypertension, dyslipidemia, diabetes mellitus, and overweight, and supporting smoking cessation, physical activity, and healthy diet. Overall, available guidelines lacked specific recommendations for CVR management in older adults. The comparative analysis of the guidelines showed general consistency for lifestyle-related recommendations. Key differences, identified mostly in methods used to assess the overall CVR, did not hamper the intervention design. Minor country-specific adaptations were implemented to maximize the intervention feasibility in each country.Conclusion: Despite differences in CVR management within the countries considered, it was possible to design and implement the HATICE multidomain intervention. The study can help define preventative strategies for dementia and CVD that are applicable internationally. [ABSTRACT FROM AUTHOR]- Published
- 2018
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19. Nutrition and the Prevalence of Dementia in Mainland China, Hong Kong, and Taiwan: An Ecological Study
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Wu, Yu-Tzu, primary, Grant, William B., additional, Prina, A. Matthew, additional, Lee, Hsin-yi, additional, and Brayne, Carol, additional
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- 2015
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20. Risk Factors and Screening Methods for Detecting Dementia: A Narrative Review
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Stephan, Blossom C.M., primary and Brayne, Carol, additional
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- 2014
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21. Adapting to Dementia in Society: A Challenge for Our Lifetimes and a Charge for Public Health
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D'Alton, Simon, primary, Hunter, Sally, additional, Whitehouse, Peter, additional, Brayne, Carol, additional, and George, Daniel, additional
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- 2014
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22. From Molecule to Clinic and Community for Neurodegeneration: Research to Bridge Translational Gaps
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Brayne, Carol, primary, Barker, Roger A., additional, Harold, Denise, additional, Ince, Paul G., additional, Savva, George M., additional, Williams, Julie, additional, Williams-Gray, Caroline H., additional, and Wharton, Stephen B., additional
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- 2012
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23. The Role of Variation at AβPP, PSEN1, PSEN2, and MAPT in Late Onset Alzheimer's Disease
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Gerrish, Amy, primary, Russo, Giancarlo, additional, Richards, Alexander, additional, Moskvina, Valentina, additional, Ivanov, Dobril, additional, Harold, Denise, additional, Sims, Rebecca, additional, Abraham, Richard, additional, Hollingworth, Paul, additional, Chapman, Jade, additional, Hamshere, Marian, additional, Pahwa, Jaspreet Singh, additional, Dowzell, Kimberley, additional, Williams, Amy, additional, Jones, Nicola, additional, Thomas, Charlene, additional, Stretton, Alexandra, additional, Morgan, Angharad R., additional, Lovestone, Simon, additional, Powell, John, additional, Proitsi, Petroula, additional, Lupton, Michelle K., additional, Brayne, Carol, additional, Rubinsztein, David C., additional, Gill, Michael, additional, Lawlor, Brian, additional, Lynch, Aoibhinn, additional, Morgan, Kevin, additional, Brown, Kristelle S., additional, Passmore, Peter A., additional, Craig, David, additional, McGuinness, Bernadette, additional, Todd, Stephen, additional, Johnston, Janet A., additional, Holmes, Clive, additional, Mann, David, additional, Smith, A. David, additional, Love, Seth, additional, Kehoe, Patrick G., additional, Hardy, John, additional, Mead, Simon, additional, Fox, Nick, additional, Rossor, Martin, additional, Collinge, John, additional, Maier, Wolfgang, additional, Jessen, Frank, additional, Kölsch, Heike, additional, Heun, Reinhard, additional, Schürmann, Britta, additional, Bussche, Hendrik van den, additional, Heuser, Isabella, additional, Kornhuber, Johannes, additional, Wiltfang, Jens, additional, Dichgans, Martin, additional, Frölich, Lutz, additional, Hampel, Harald, additional, Hüll, Michael, additional, Rujescu, Dan, additional, Goate, Alison M., additional, Kauwe, John S. K, additional, Cruchaga, Carlos, additional, Nowotny, Petra, additional, Morris, John C., additional, Mayo, Kevin, additional, Livingston, Gill, additional, Bass, Nicholas J., additional, Gurling, Hugh, additional, McQuillin, Andrew, additional, Gwilliam, Rhian, additional, Deloukas, Panagiotis, additional, Davies, Gail, additional, Harris, Sarah E., additional, Starr, John M., additional, Deary, Ian J., additional, Al-Chalabi, Ammar, additional, Shaw, Christopher E., additional, Tsolaki, Magda, additional, Singleton, Andrew B., additional, Guerreiro, Rita, additional, Mühleisen, Thomas W., additional, Nöthen, Markus M., additional, Moebus, Susanne, additional, Jöckel, Karl-Heinz, additional, Klopp, Norman, additional, Wichmann, H-Erich, additional, Carrasquillo, Minerva M, additional, Pankratz, V Shane, additional, Younkin, Steven G., additional, Jones, Lesley, additional, Holmans, Peter A, additional, O'Donovan, Michael C., additional, Owen, Michael J., additional, and Williams, Julie, additional
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- 2012
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24. TDP-43 Pathology in the Population: Prevalence and Associations with Dementia and Age.
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Keage, Hannah A.D., Hunter, Sally, Matthews, Fiona E., Ince, Paul G., Hodges, John, Hokkanen, Suvi R.K., Highley, J. Robin, Dening, Tom, and Brayne, Carol
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ALZHEIMER'S disease research ,DNA-binding proteins ,DEMENTIA research ,PHYSIOLOGICAL aspects of aging ,NEUROLOGICAL disorders - Abstract
Background: The significance of TDP-43 pathology in relation to aging and dementia in the population is unclear. Objective: We aimed to determine the prevalence of transactive response DNA-binding protein of 43 kDA (TDP-43) neuronal inclusions in a population-based sample, and associations with age group at death (≤90 and >90 years) and clinical dementia status prior to death. Further, we investigate associations between TDP-43 inclusions and other key dementia-related neuropathologies (plaques, tangles, and neuronal loss) within the hippocampus and entorhinal and temporal cortices. Methods: All brain donors within the Cambridge City over-75 s Cohort (CC75C), which is population-based and longitudinally tracked (n = 228), were included. Age at death ranged from 78 to 106 years. TDP-43 neuronal inclusions were assessed in the hippocampus, entorhinal cortex, and temporal cortex. These data were combined with existing clinical and neuropathological data. Results: TDP-43 neuronal inclusions were present in 27% of the sample, 36% of those with clinical dementia and 18% without dementia. Individuals who died later (>90 years) or with clinical dementia were more likely to show TDP-43 inclusions. Hippocampal and entorhinal TDP-43 inclusions were significantly associated with dementia severity and increasing age, taking into account other neuropathologies. TDP-43 neuronal inclusions appeared to be co-localize with severe neuronal loss. Conclusion: Findings indicate that hippocampal and entorhinal TDP-43 inclusions are important substrates of late onset dementia which appear to co-localize with severe neuronal loss, but not with Alzheimer's disease markers of amyloid and tau. This broadens the accepted view of TDP-43 pathology in dementias. [ABSTRACT FROM AUTHOR]
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- 2014
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25. From Molecule to Clinic and Community for Neurodegeneration: Research to Bridge Translational Gaps.
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Brayne, Carol, Barker, Roger A., Harold, Denise, Ince, Paul G., Savva, George M., Williams, Julie, Williams-Gray, Caroline H., and Wharton, Stephen B.
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ALZHEIMER'S disease , *DEMENTIA , *EPIDEMIOLOGY , *GENETICS , *PATHOLOGY - Abstract
Six papers based on studies with particular epidemiological designs are presented here which have been selected on the basis of their visibility in the literature. The designs are intended to provide robust evidence on risk, natural history, and underpinning neurobiology and outcomes relevant to aging populations. There is a large case control study (the Late Onset Alzheimer's Disease study), a case cohort study of Parkinson's Disease (the CamPaIGN study), and the Medical Research Council Cognitive Function and Ageing Study. Each study has included genetic investigation and risk, and the latter two include investigation of the clinical syndromes and their natural histories in relation to underlying pathology. Each aimed to provide results which were as generalizable to usual older populations as possible and each has produced findings which have contributed to current understanding of genetic risk, the heterogeneity of the syndrome of Parkinson's disease, and the underlying neuropathology of dementia in older population. They have influenced thinking about future directions, and the cohorts on which the findings are based will continue to provide an important resource for novel areas of research and future health care planning. [ABSTRACT FROM AUTHOR]
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- 2013
26. Alzheimer and Vascular Neuropathological Changes Associated with Different Cognitive States in a Non-Demented Sample.
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Stephan, Blossom C.M., Matthews, Fiona E., Ma, Brandy, Muniz, Graciela, Hunter, Sally, Davis, Daniel, McKeith, Ian G., Foster, Gill, Ince, Paul G., and Brayne, Carol
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ALZHEIMER'S disease ,AGING ,MILD cognitive impairment ,NEUROLOGICAL disorders ,COGNITIVE ability ,NEURODEGENERATION - Abstract
The state between aging with no cognitive impairment and dementia has become a major focus for intervention. The neuropathological and neurobiological correlates of this intermediate state are therefore of considerable interest, particularly from population representative samples. Here we investigate the neuropathological profile associated with different cognitive ability levels measured using strata defined by Mini Mental State Examination (MMSE) scores. One hundred and fifty one individuals were stratified into three cognitive groups including: non-, mildly, and moderately impaired at death. Alzheimer's disease, atrophy, and vascular pathologies were investigated. Mild impairment was associated with an increased risk of vascular pathologies including small vessel disease and lacunes. In contrast, the moderately impaired group showed a more extensive pattern of pathology, including tangles and neuritic plaques (entorhinal/hippocampus), atrophy (cortical and hippocampal), and vascular disease (small vessel disease, lacunes, and infarcts). In a population-based sample of older people, MMSE score defined strata are associated with multiple pathologies. The profile of AD and vascular changes becomes more complex with increased cognitive impairment and these changes are likely to constitute a major substrate for age associated cognitive impairment. The results highlight the need for rigorous investigation of both neurodegenerative and vascular risks factors in old age. [ABSTRACT FROM AUTHOR]
- Published
- 2012
27. Impact of Less Common and 'Disregarded' Neurodegenerative Pathologies on Dementia Burden in a Population-Based Cohort.
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Keage, Hannah A.D., Ince, Paul G., Matthews, Fiona E., Wharton, Stephen B., McKeith, Ian G., and Brayne, Carol
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NEURODEGENERATION ,DEMENTIA research ,AGING ,BRAIN physiology ,NEURONS - Abstract
Epidemiological studies investigating the pathological bases of late onset dementia focus on classical markers such as plaques and tangles. The significance of pathologies characteristically associated with rare dementia syndromes such as Pick bodies and severe neuronal loss are considered to be well defined. The significance of other pathologies, often accepted as a feature of neurodegenerative syndromes, such as Hirano bodies and gliosis is not clear. This study investigated the significance of these rarer and 'disregarded' pathologies to dementia in the population. A total of 627 individuals aged 71-103 from the Epidemiological CLInicoPathologial Studies in Europe (EClipSE) project with clinical dementia status at death determined were assessed. Pathologies assessed included Pick bodies, severe neuronal loss, gliosis, and granulovacuolar degeneration (GVD) in the cortex and/or hippocampus, along with brainstem plaques, tangles, neuronal loss, gliosis, pigmentary incontinence, and Lewy bodies. All pathologies were associated with dementia when controlling for plaques and tangles except Hirano bodies, GVD, and brainstem plaques. These included hippocampal and entorhinal gliosis; cortical, hippocampal, and entorhinal neuronal loss; along with brainstem neuronal loss, gliosis, pigmentary incontinence, Lewy bodies, and tangles. Pick bodies were present in five individuals, all with clinical dementia. These epidemiological data indicate that dementia in old age is associated with a broad range of pathological and anatomical substrates pointing to potential areas for future research, particularly the brainstem. [ABSTRACT FROM AUTHOR]
- Published
- 2012
28. Active cognitive lifestyle associates with cognitive recovery and a reduced risk of cognitive decline.
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Marioni RE, van den Hout A, Valenzuela MJ, Brayne C, Matthews FE, Marioni, Riccardo E, van den Hout, Ardo, Valenzuela, Michael J, Brayne, Carol, Matthews, Fiona E, and MRC Cognitive Function and Ageing Study
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Education and lifestyle factors linked with complex mental activity are thought to affect the progression of cognitive decline. Collectively, these factors can be combined to create a cognitive reserve or cognitive lifestyle score. This study tested the association between cognitive lifestyle score and cognitive change in a population-based cohort of older persons from five sites across England and Wales. Data came from 13,004 participants of the Medical Research Council Cognitive Function and Ageing Study who were aged 65 years and over. Cognition was assessed at multiple waves over 16 years using the Mini-Mental State Examination. Subjects were grouped into four cognitive states (no impairment, slight impairment, moderate impairment, severe impairment) and cognitive lifestyle score was assessed as a composite measure of education, mid-life occupation, and current social engagement. A multi-state model was used to test the effect of cognitive lifestyle score on cognitive transitions. Hazard ratios for cognitive lifestyle score showed significant differences between those in the upper compared to the lower tertile with a more active cognitive lifestyle associating with: a decreased risk of moving from no to slight impairment (0.58, 95% CI (0.45, 0.74)); recovery from a slightly impaired state back to a non-impaired state (2.93 (1.35, 6.38)); but an increased mortality risk from a severely impaired state (1.28 (1.12, 1.45)). An active cognitive lifestyle is associated with a more favorable cognitive trajectory in older persons. Future studies would ideally incorporate neuroradiological and neuropathological data to determine if there is causal evidence for these associations. [ABSTRACT FROM AUTHOR]
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- 2012
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29. Epidemiological Neuropathology: The MRC Cognitive Function and Aging Study Experience.
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Wharton, Stephen B., Brayne, Carol, Savva, George M., Matthews, Fiona E., Forster, Gill, Simpson, Julie, Lace, Gemma, and Ince, Paul G.
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NEUROLOGICAL disorders , *PHYSIOLOGICAL aspects of aging , *EPIDEMIOLOGY , *DEMENTIA - Abstract
We here describe the study-design major findings from the neuropathological component of the Medical Research Council Cognitive Function and Aging Study (MRC CFAS). MRC CFAS is a population-representative study of aging and health including more than 18000 participants at baseline. More than 500 brain donations were accrued to date and have been subjected to comprehensive pathological assessment. This resource enables a thorough epidemiological description of the neuropathology associated with dementia in the UK. Results to date reveal a high prevalence of mixed Alzheimer and vascular pathology, a significant population who die with dementia but with a more limited pathological burden than is traditionally associated with dementia, and a group who die with a significant pathological burden yet remained cognitively intact until death. This dissociation between pathology and dementia increases with increasing age. Further studies have described the distribution and etiology of neurodegenerative disease in the population, and determined pathological correlates of cognitive impairment and dementia. Brain donation programs linked to epidemiological studies provide an invaluable resource for describing the pathological correlates of dementia in a way that is representative of the population, thereby identifying targets for and assessing the likely effect of therapeutic and preventive interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2011
30. Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge city over-75s cohort (CC75C) study.
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Brayne, Carol, Richardson, Kathryn, Matthews, Fiona E., Fleming, Jane, Hunter, Sally, Xuereb, John H., Paykel, Eugene, Mukaetova-Ladinska, Elizabeta B., Huppert, Felicia A., O'Sullivan, Angela, Dening, Tom, and Cambridge City Over-75s Cohort Cc75c Study Neuropathology Collaboration
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MEDICAL research , *DEMENTIA , *NEUROLOGICAL disorders , *BRAIN transplantation , *ORGAN donors , *ALZHEIMER'S disease , *BRAIN , *COMPARATIVE studies , *HEALTH service areas , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *PUBLIC health surveillance , *RESEARCH , *RESEARCH funding , *EVALUATION research - Abstract
Key neuropathological changes associated with late-onset dementia are not fully understood. Population-based longitudinal studies offer an opportunity to step back and examine which pathological indices best link to clinical state. CC75C is a longitudinal study of the population aged 75 and over at baseline in Cambridge, UK. We report on the first 213 participants coming to autopsy with sufficient information for an end of life dementia diagnosis. Clinical diagnosis was ascertained by examining retrospective informant interviews, survey responses, and death certificates according to DSM-IV criteria. The neuropathological protocol was based on the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Clinical dementia was present in 113 participants (53%): 67% with Alzheimer's disease, 4% vascular dementia, 22% mixed dementia, and 1% dementia with Lewy bodies. As Alzheimer-type pathology was common, the mutually blinded clinical and neuropathological diagnoses were not strongly related. Multivariable analysis identified associations between dementia during life and entorhinal cortex neuritic plaques, hippocampal diffuse plaques, neocortical neurofibrillary tangles, white matter pallor, Lewy bodies, and hippocampal atrophy. These results were consistent in those with clinical Alzheimer's disease. Vascular pathologies, especially microinfarcts, were more common in those with clinical diagnoses including vascular dementia. Alzheimer-type and cerebrovascular pathology are both common in the very old. A greater burden of these pathologies, Lewy bodies, and hippocampal atrophy, are associated with a higher risk of, but do not define, clinical dementia in old age. [ABSTRACT FROM AUTHOR]
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- 2009
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31. Neuropathological Correlates of Cumulative Benzodiazepine and Anticholinergic Drug Use
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Chris Fox, Antony Arthur, Yoon K. Loke, George M. Savva, Nicholas Steel, Ian Maidment, Malaz Boustani, Noll L. Campbell, Stephen B. Wharton, Kathryn Richardson, Louise Robinson, Carlota M. Grossi, Carol Brayne, Phyo K. Myint, Fiona E. Matthews, Brayne, Carol [0000-0001-5307-663X], and Apollo - University of Cambridge Repository
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Male ,0301 basic medicine ,Drug ,Aging ,medicine.medical_specialty ,medicine.drug_class ,media_common.quotation_subject ,Population ,Neuropathology ,Cholinergic Antagonists ,Benzodiazepines ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Cost of Illness ,Alzheimer Disease ,Internal medicine ,Anticholinergic ,medicine ,Humans ,Dementia ,Cognitive decline ,education ,Aged ,media_common ,Aged, 80 and over ,Cerebral Cortex ,neuropathology ,Benzodiazepine ,education.field_of_study ,basal nucleus of Meynert ,business.industry ,General Neuroscience ,Neurofibrillary Tangles ,General Medicine ,Odds ratio ,neuritic plaques ,medicine.disease ,Substantia Nigra ,Psychiatry and Mental health ,Clinical Psychology ,030104 developmental biology ,Female ,Atrophy ,Geriatrics and Gerontology ,business ,Alzheimer’s disease ,030217 neurology & neurosurgery - Abstract
Background:\ud Benzodiazepines and anticholinergic drugs have been implicated in causing cognitive decline and potentially increasing dementia risk. However, evidence for an association with neuropathology is limited.\ud \ud Objective:\ud To estimate the correlation between neuropathology at death and prior use of benzodiazepines and anticholinergic drugs.\ud \ud Methods:\ud We categorized 298 brain donors from the population-based Medical Research Council Cognitive Function and Ageing Study, according to their history of benzodiazepine (including Z-drugs) or anticholinergic medication (drugs scoring 3 on the Anticholinergic Cognitive Burden scale) use. We used logistic regression to compare dichotomized neuropathological features for those with and without history of benzodiazepine and anticholinergic drug use before dementia, adjusted for confounders.\ud \ud Results:\ud Forty-nine (16%) and 51 (17%) participants reported benzodiazepine and anticholinergic drug use. Alzheimer’s disease neuropathologic change was similar whether or not exposed to either drug, for example 46% and 57% had intermediate/high levels among those with and without anticholinergic drug use. Although not significant after multiple testing adjustments, we estimated an odds ratio (OR) of 0.40 (95% confidence interval [95% CI] 0.18–0.87) for anticholinergic use and cortical atrophy. For benzodiazepine use, we estimated ORs of 4.63 (1.11–19.24) and 3.30 (1.02–10.68) for neuronal loss in the nucleus basalis and substantial nigra. There was evidence of neuronal loss in the nucleus basalis with anticholinergic drug use, but the association reduced when adjusted for confounders.\ud \ud Conclusions:\ud We found no evidence that benzodiazepine or anticholinergic drug use is associated with typical pathological features of Alzheimer’s disease; however, we cannot rule out effects owing to small numbers.
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- 2020
32. The Relationship Between Cognitive Performance Using Tests Assessing a Range of Cognitive Domains and Future Dementia Diagnosis in a British Cohort: A Ten-Year Prospective Study
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Carol Brayne, Shabina Hayat, Kay-Tee Khaw, Robert Luben, Hayat, Shabina [0000-0001-9068-8723], Luben, Robert [0000-0002-5088-6343], Brayne, Carol [0000-0001-5307-663X], and Apollo - University of Cambridge Repository
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Gerontology ,Male ,medicine.medical_specialty ,Population ,Neuropsychological Tests ,03 medical and health sciences ,0302 clinical medicine ,Cognition ,Epidemiology ,medicine ,Dementia ,Humans ,Cognitive Dysfunction ,030212 general & internal medicine ,Prospective Studies ,education ,Prospective cohort study ,risk ,Aged ,Aged, 80 and over ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,General Neuroscience ,General Medicine ,Neuropsychological test ,Middle Aged ,medicine.disease ,Cognitive test ,Psychiatry and Mental health ,Clinical Psychology ,Cohort ,epidemiology ,Female ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery ,Research Article - Abstract
Background: Exploring the domains of cognitive function which are most strongly associated with future dementia may help with understanding risk factors for, and the natural history of dementia. Objective: To examine the association of performance on a range of cognitive tests (both global and domain specific) with subsequent diagnosis of dementia through health services in a population of relatively healthy men and women and risk of future dementia. Methods: We examined the association between performance on different cognitive tests as well as a global score and future dementia risk ascertained through health record linkage in a cohort of 8,581 individuals (aged 48–92 years) between 2004–2019 with almost 15 years follow-up (average of 10 years) before and after adjustment for socio-demographic, lifestyle, and health characteristics. Results: Those with poor performance for global cognition (bottom 10%) were almost four times as likely to receive a dementia diagnosis from health services over the next 15 years than those who performed well HR = 3.51 (95% CI 2.61, 4.71 p
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- 2021
33. Association of Prior Atherosclerotic Cardiovascular Disease with Dementia After Stroke: A Retrospective Cohort Study
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Zhirong Yang, Carol Brayne, Duncan Edwards, Jonathan Mant, Stephen Burgess, Edwards, Duncan [0000-0003-1500-2108], Burgess, Stephen [0000-0001-5365-8760], Brayne, Carol [0000-0001-5307-663X], Mant, Jonathan [0000-0002-9531-0268], and Apollo - University of Cambridge Repository
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Adult ,Male ,medicine.medical_specialty ,Coronary artery disease ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,peripheral arterial disease ,Risk Factors ,Internal medicine ,cohort study ,Medicine ,Dementia ,Humans ,030212 general & internal medicine ,Risk factor ,Stroke ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Proportional hazards model ,General Neuroscience ,Hazard ratio ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Atherosclerosis ,stroke ,Psychiatry and Mental health ,Clinical Psychology ,Cardiovascular Diseases ,Atherosclerotic cardiovascular disease ,Female ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery ,coronary artery disease ,Research Article ,Cohort study ,Follow-Up Studies - Abstract
Background: Prior atherosclerotic cardiovascular disease (ASCVD), including coronary heart disease (CHD) and peripheral artery disease (PAD), are common among patients with stroke, a known risk factor for dementia. However, whether these conditions further increase the risk of post-stroke dementia remains uncertain. Objective: To examine whether prior ASCVD is associated with increased risk of dementia among stroke patients. Methods: A retrospective cohort study was conducted using the Clinical Practice Research Datalink with linkage to hospital data. Patients with first-ever stroke between 2006 and 2017 were followed up to 10 years. We used multi-variable Cox regression models to examine the associations of prior ASCVD with dementia and the impact of prior ASCVD onset and duration. Results: Among 63,959 patients, 7,265 cases (11.4%) developed post-stroke dementia during a median of 3.6-year follow-up. The hazard ratio (HR) of dementia adjusted for demographics and lifestyle was 1.18 (95% CI: 1.12–1.25) for ASCVD, 1.16 (1.10–1.23) for CHD, and 1.25 (1.13–1.37) for PAD. The HRs additionally adjusted for multimorbidity and medications were 1.07 (1.00–1.13), 1.04 (0.98–1.11), and 1.11 (1.00–1.22), respectively. Based on the fully adjusted estimates, there was no linear relationship between the age of ASCVD onset and post-stroke dementia (all p-trend >0.05). The adjusted risk of dementia was not increased with the duration of pre-stroke ASCVD (all p-trend >0.05). Conclusion: Stroke patients with prior ASCVD are more likely to develop subsequent dementia. After full adjustment for confounding, however, the risk of post-stroke dementia is attenuated, with only a slight increase with prior ASCVD.
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- 2020
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34. 18F-FDG PET for Prediction of Conversion to Alzheimer’s Disease Dementia in People with Mild Cognitive Impairment: An Updated Systematic Review of Test Accuracy
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Louise Lafortune, Carol Brayne, Chris Hyde, Sarah Kelly, Nadja Smailagic, Lafortune, Louise [0000-0002-9018-1217], Kelly, Sarah [0000-0002-1114-2456], Brayne, Carol [0000-0001-5307-663X], and Apollo - University of Cambridge Repository
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medicine.medical_specialty ,Disease ,Neuropsychological Tests ,Statistical parametric mapping ,Alzheimer’s disease dementia ,030218 nuclear medicine & medical imaging ,18f fdg pet ,03 medical and health sciences ,mild cognitive impairment ,0302 clinical medicine ,Physical medicine and rehabilitation ,Alzheimer Disease ,Fluorodeoxyglucose F18 ,medicine ,Humans ,Dementia ,Cognitive Dysfunction ,conversion ,Cognitive impairment ,Accuracy ,business.industry ,General Neuroscience ,test predictive value ,Brain ,General Medicine ,medicine.disease ,Test (assessment) ,Psychiatry and Mental health ,Clinical Psychology ,Positron-Emission Tomography ,Disease Progression ,Metric (unit) ,Geriatrics and Gerontology ,Alzheimer's disease ,business ,030217 neurology & neurosurgery ,Research Article ,18F-FDG PET - Abstract
Background A previous Cochrane systematic review concluded there is insufficient evidence to support the routine use of 18F-FDG PET in clinical practice in people with mild cognitive impairment (MCI). Objectives To update the evidence and reassess the accuracy of 18F-FDG-PET for detecting people with MCI at baseline who would clinically convert to Alzheimer's disease (AD) dementia at follow-up. Methods A systematic review including comprehensive search of electronic databases from January 2013 to July 2017, to update original searches (1999 to 2013). All key review steps, including quality assessment using QUADAS 2, were performed independently and blindly by two review authors. Meta-analysis could not be conducted due to heterogeneity across studies. Results When all included studies were examined across all semi-quantitative and quantitative metrics, exploratory analysis for conversion of MCI to AD dementia (n = 24) showed highly variable accuracy; half the studies failed to meet four or more of the seven sets of QUADAS 2 criteria. Variable accuracy for all metrics was also found across eleven newly included studies published in the last 5 years (range: sensitivity 56-100%, specificity 24-100%). The most consistently high sensitivity and specificity values (approximately ≥80%) were reported for the sc-SPM (single case statistical parametric mapping) metric in 6 out of 8 studies. Conclusion Systematic and comprehensive assessment of studies of 18FDG-PET for prediction of conversion from MCI to AD dementia reveals many studies have methodological limitations according to Cochrane diagnostic test accuracy gold standards, and shows accuracy remains highly variable, including in the most recent studies. There is some evidence, however, of higher and more consistent accuracy in studies using computer aided metrics, such as sc-SPM, in specialized clinical settings. Robust, methodologically sound prospective longitudinal cohort studies with long (≥5 years) follow-up, larger consecutive samples, and defined baseline threshold(s) are needed to test these promising results. Further evidence of the clinical validity and utility of 18F-FDG PET in people with MCI is needed.
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- 2018
35. Social Isolation and Cognitive Function in Later Life: A Systematic Review and Meta-Analysis
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Anthony Martyr, Carol Brayne, Linda Clare, Isobel E.M. Evans, Rachel Collins, Brayne, Carol [0000-0001-5307-663X], and Apollo - University of Cambridge Repository
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0301 basic medicine ,cognition ,Aging ,social isolation ,media_common.quotation_subject ,CINAHL ,PsycINFO ,03 medical and health sciences ,0302 clinical medicine ,Memory ,Activities of Daily Living ,medicine ,Humans ,Social isolation ,Association (psychology) ,Function (engineering) ,Aged ,media_common ,Cognitive reserve ,Aged, 80 and over ,General Neuroscience ,Cognition ,General Medicine ,cognitive reserve ,Psychiatry and Mental health ,Clinical Psychology ,030104 developmental biology ,Meta-analysis ,Quality of Life ,Geriatrics and Gerontology ,medicine.symptom ,Psychology ,030217 neurology & neurosurgery ,Research Article ,Clinical psychology - Abstract
Background There is some evidence to suggest that social isolation may be associated with poor cognitive function in later life. However, findings are inconsistent and there is wide variation in the measures used to assess social isolation. Objective We conducted a systematic review and meta-analysis to investigate the association between social isolation and cognitive function in later life. Methods A search for longitudinal studies assessing the relationship between aspects of social isolation (including social activity and social networks) and cognitive function (including global measures of cognition, memory, and executive function) was conducted in PsycInfo, CINAHL, PubMed, and AgeLine. A random effects meta-analysis was conducted to assess the overall association between measures of social isolation and cognitive function. Sub-analyses investigated the association between different aspects of social isolation and each of the measures of cognitive function. Results Sixty-five articles were identified by the systematic review and 51 articles were included in the meta-analysis. Low levels of social isolation characterized by high engagement in social activity and large social networks were associated with better late-life cognitive function (r = 0.054, 95% CI: 0.043, 0.065). Sub-analyses suggested that the association between social isolation and measures of global cognitive function, memory, and executive function were similar and there was no difference according to gender or number of years follow-up. Conclusions Aspects of social isolation are associated with cognitive function in later life. There is wide variation in approaches to measuring social activity and social networks across studies which may contribute to inconsistencies in reported findings.
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- 2019
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36. Perspectives on Communicating Biomarker-Based Assessments of Alzheimer’s Disease to Cognitively Healthy Individuals
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Carol Brayne, Jean-Jacques Georges, Karine Fauria, Richard Milne, Shirlene Badger, Katie Wells, Dianne Gove, Eline M. Bunnik, Ana Diaz, José Luis Molinuevo, Edo Richard, Craig W. Ritchie, Grill, Joshua, Rosen, Allyson, Milne, Richard [0000-0002-8770-2384], Brayne, Carol [0000-0001-5307-663X], Apollo - University of Cambridge Repository, and Public Health
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Gerontology ,Adult ,Male ,Ethics Review ,Disease ,Social group ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Alzheimer Disease ,medicine ,Dementia ,Humans ,030212 general & internal medicine ,Aged ,General Neuroscience ,General Medicine ,Middle Aged ,medicine.disease ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Focus group ,ethics ,United Kingdom ,Clinical trial ,Psychiatry and Mental health ,Clinical Psychology ,Caregivers ,Spain ,Biomarker (medicine) ,focus groups ,Female ,Geriatrics and Gerontology ,Alzheimer's disease ,Psychology ,disclosure ,030217 neurology & neurosurgery ,Biomarkers ,qualitative research ,Qualitative research - Abstract
Contains fulltext : 191185.pdf (Publisher’s version ) (Open Access) In clinical trials which target pathophysiological mechanisms associated with Alzheimer's disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer's dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants' experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer's disease biomarkers.
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- 2018
37. Impact of Less Common and 'Disregarded' Neurodegenerative Pathologies on Dementia Burden in a Population-Based Cohort
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Fiona E. Matthews, Ian G. McKeith, Had Keage, Stephen B. Wharton, Mrc, Cfas, Cc C, P. G. Ince, Carol Brayne, Keage, Hannah AD, Ince, Paul G, Matthews, Fiona E, Wharton, Stephen, McKeith, Ian G, and Brayne, Carol
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Male ,Gerontology ,Pathology ,medicine.medical_specialty ,brain ,Population ,Hippocampus ,Hippocampal formation ,Community Health Planning ,Cohort Studies ,medicine ,Humans ,Dementia ,education ,Pathological ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,General Neuroscience ,aging ,Age Factors ,Brain ,Neurodegenerative Diseases ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,age ,Gliosis ,pathology ,Female ,Brainstem ,Hirano body ,Geriatrics and Gerontology ,medicine.symptom ,business ,dementia - Abstract
Epidemiological studies investigating the pathological bases of late onset dementia focus on classical markers such as plaques and tangles. The significance of pathologies characteristically associated with rare dementia syndromes such as Pick bodies and severe neuronal loss are considered to be well defined. The significance of other pathologies, often accepted as a feature of neurodegenerative syndromes, such as Hirano bodies and gliosis is not clear. This study investigated the significance of these rarer and 'disregarded' pathologies to dementia in the population. A total of 627 individuals aged 71-103 from the Epidemiological CLInicoPathologial Studies in Europe (EClipSE) project with clinical dementia status at death determined were assessed. Pathologies assessed included Pick bodies, severe neuronal loss, gliosis, and granulovacuolar degeneration (GVD) in the cortex and/or hippocampus, along with brainstem plaques, tangles, neuronal loss, gliosis, pigmentary incontinence, and Lewy bodies. All pathologies were associated with dementia when controlling for plaques and tangles except Hirano bodies, GVD, and brainstem plaques. These included hippocampal and entorhinal gliosis; cortical, hippocampal, and entorhinal neuronal loss; along with brainstem neuronal loss, gliosis, pigmentary incontinence, Lewy bodies, and tangles. Pick bodies were present in five individuals, all with clinical dementia. These epidemiological data indicate that dementia in old age is associated with a broad range of pathological and anatomical substrates pointing to potential areas for future research, particularly the brainstem. Refereed/Peer-reviewed
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- 2012
38. Cohort profile: Epidemiological Clinicopathological Studies in Europe (EClipSE)
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Hannah Keage, Carol Brayne, Fiona Matthews, Brayne, Carol, Ince, Paul, Keage, Hannah, McKeith, ian, Matthews, Fiona, Polvikoski, Tuomo, and Sulkava, R
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Male ,Gerontology ,medicine.medical_specialty ,Pathology ,brain ,Population ,population ,Neuropathology ,Cohort Studies ,Epidemiology ,Prevalence ,medicine ,Humans ,Dementia ,education ,Aged ,Eclipse ,Aged, 80 and over ,education.field_of_study ,business.industry ,General Neuroscience ,aging ,Brain ,health ,Cognition ,General Medicine ,medicine.disease ,Tissue Donors ,Europe ,Psychiatry and Mental health ,Clinical Psychology ,Cohort ,Other Psychology and Cognitive Sciences ,epidemiology ,Female ,Geriatrics and Gerontology ,business ,dementia - Abstract
Epidemiological Clinicopathological Studies in Europe (EClipSE) is the harmonization of neuropathological and longitudinal clinical data from three population-based prospective longitudinal studies of aging. The EClipSE database (Version 1.0) comprises data from the first 970 people who donated their brain at death and this number will increase. EClipSE enables sociodemographic, health, cognitive, and genetic measures collected during life to be related to neuropathology at death, testing hypotheses which require more power than has been previously possible. EClipSE aims to help throw light on relationships between biological, health and psychological factors underlying ageing and the manifestation of clinical dementia.
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- 2009
39. Attitudes and Preferences Towards Screening for Dementia with a Focus on Ethnic Minority and Low Socio-Economic Groups: A Systematic Review of Research Studies Written in the English Language.
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Brar M, Mc Ardle R, Hagan A, Al-Oraibi A, Hanjari M, Stephan B, Brayne C, Lafortune L, Bains M, Qureshi N, and Robinson L
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Background: Increased understanding of dementia risk-reduction and early detection of Alzheimer's disease and related disorders has spurred interest in the identification of risks for dementia, underlying putative biologies, or dementia itself. Implementation of such approaches require acceptability to the public. Research prior to 2012 indicated limited acceptability for population dementia screening. The changing landscape of dementia prevention research may influence recent perceptions. Additionally, perspectives from underserved populations, such as ethnic minorities and low socio-economic groups, are lacking., Objective: In this systematic review, we sought published studies since 2012 on attitudes and preferences of people with dementia, carers and the general public from ethnic minorities and low socio-economic groups regarding dementia screening., Methods: This review was preregistered on PROSPERO (CRD42023384115) and followed PRISMA guidelines. Key search terms were entered into five databases. Articles were included if they focused on population or risk screening for dementia via primary/community care-based assessments, and which included majority ethnic minority or low socio-economic groups or discretely considered these groups in data analysis. Data were synthesized narratively., Results: Seven studies reported perspectives of ethnic minorities regarding dementia screening; one study included people from low socio-economic groups. Results indicated that participants from ethnic minorities were willing to undergo dementia screening. Predictors of willingness included belief in benefits, desire to boost diversity, and to implement lifestyle changes. Unwillingness was associated with anxiety regarding results., Conclusions: Although there seems to be high acceptability for screening in the studied groups, more research is necessary to explore the practical considerations for screening such as cultural and economic barriers, trust, and post-screening actions.
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- 2024
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40. TDP-43 Related Neuropathologies and Phosphorylation State: Associations with Age and Clinical Dementia in the Cambridge City over-75s Cohort.
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Hunter S, Hokkanen SRK, Keage HAD, Fleming J, Minett T, Polvikoski T, Allinson K, and Brayne C
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- Age Factors, Aged, 80 and over, Aging genetics, Aging metabolism, Aging pathology, Dementia genetics, Dementia pathology, Female, Hippocampus pathology, Humans, Inclusion Bodies metabolism, Inclusion Bodies pathology, Male, Nerve Degeneration genetics, Nerve Degeneration pathology, Neurofibrillary Tangles metabolism, Neurofibrillary Tangles pathology, Neurons metabolism, Neurons pathology, Phosphorylation, TDP-43 Proteinopathies genetics, TDP-43 Proteinopathies pathology, Dementia metabolism, Hippocampus metabolism, Nerve Degeneration metabolism, TDP-43 Proteinopathies metabolism
- Abstract
Pathologies associated with the Tar-DNA binding protein 43 KDa (TDP-43) are associated with neurodegenerative diseases and aging. Phosphorylation of cellular proteins is a well-accepted mechanism of biological control and can be associated with disease pathways. Phosphorylation state associated with TDP-43 associated pathology has not been investigated with respect to dementia status in a population representative sample. TDP-43 immunohistochemistry directed toward phosphorylated (TDP-43P) and unphosphorylated (TDP-43U) was assessed in sections of hippocampus and temporal cortex from 222 brains donated to the population representative Cambridge City over-75s Cohort. Relationships between dementia status and age at death for TDP-43 immunoreactive pathologies by phosphorylation state were investigated. TDP-43 pathologies are common in the oldest old in the population and often do not conform to MacKenzie classification. Increasing age is associated with glial (TDP-43P) and neuronal inclusions (TDP-43P and TDP-43U), neurites, and granulovacuolar degeneration (GVD). Dementia status is associated with GVD and glial (TDP-43 P) and neural inclusions (TDP-43 P and U). Dementia severity was associated with glial (TDP-43P) and neuronal inclusions (TDP-43U and TDP-43P), GVD, and neurites. The associations between dementia severity and both glial cytoplasmic inclusions and GVD were independent from other pathologies and TDP-43 neuronal cytoplasmic inclusions. TDP-43 pathology contributes to dementia status and progression in a variety of ways in different phosphorylation states involving both neurons and glia, independently from age and from classic Alzheimer-related pathologies. TDP-43 pathologies as cytoplasmic inclusions in neurons or glia or as GVD contribute independently to dementia.
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- 2020
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