Andrew C Robinson1, Roseanne McNamee2, Yvonne S Davidson1, Michael A Horan1, Julie S Snowden3, Lynn McInnes4, Neil Pendleton1, David M A Mann1. 1. Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Neuroscience and Experimental Psychology, University of Manchester, Salford Royal Hospital, Salford, United Kingdom. 2. Faculty of Biology, Medicine and Health, School of Health Sciences, Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, United Kingdom. 3. Cerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, Salford, United Kingdom. 4. Department of Psychology, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom.
Abstract
BACKGROUND: Community- or population-based longitudinal studies of cognitive ability with a brain donation end point offer an opportunity to examine relationships between pathology and cognitive state prior to death. Discriminating the earliest signs of dementing disorders, such as Alzheimer disease (AD), is necessary to undertake early interventions and treatments. METHODS: The neuropathological profile of brains donated from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, including CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and Braak stage, was assessed by immunohistochemistry. Cognitive test scores collected 20 years prior to death were correlated with the extent of AD pathology present at death. RESULTS: Baseline scores from the Memory Circle test had the ability to distinguish between individuals who developed substantial AD pathology and those with no, or low, AD pathology. Predicted test scores at the age of 65 years also discriminated between these pathology groups. The addition of APOE genotype further improved the discriminatory ability of the model. CONCLUSIONS: The results raise the possibility of identifying individuals at future risk of the neuropathological changes associated with AD over 20 years before death using a simple cognitive test. This work may facilitate early interventions, therapeutics and treatments for AD by identifying at-risk and minimally affected (in pathological terms) individuals.
BACKGROUND: Community- or population-based longitudinal studies of cognitive ability with a brain donation end point offer an opportunity to examine relationships between pathology and cognitive state prior to death. Discriminating the earliest signs of dementing disorders, such as Alzheimer disease (AD), is necessary to undertake early interventions and treatments. METHODS: The neuropathological profile of brains donated from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, including CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and Braak stage, was assessed by immunohistochemistry. Cognitive test scores collected 20 years prior to death were correlated with the extent of AD pathology present at death. RESULTS: Baseline scores from the Memory Circle test had the ability to distinguish between individuals who developed substantial AD pathology and those with no, or low, AD pathology. Predicted test scores at the age of 65 years also discriminated between these pathology groups. The addition of APOE genotype further improved the discriminatory ability of the model. CONCLUSIONS: The results raise the possibility of identifying individuals at future risk of the neuropathological changes associated with AD over 20 years before death using a simple cognitive test. This work may facilitate early interventions, therapeutics and treatments for AD by identifying at-risk and minimally affected (in pathological terms) individuals.
Authors: Kristina M Gicas; William G Honer; Robert S Wilson; Patricia A Boyle; Sue E Leurgans; Julie A Schneider; David A Bennett Journal: Neurology Date: 2020-11-03 Impact factor: 9.910
Authors: Andrew C Robinson; Federico Roncaroli; Yvonne S Davidson; James Minshull; Calvin Heal; Daniela Montaldi; Antony Payton; Michael A Horan; Neil Pendleton; David M A Mann Journal: Int J Geriatr Psychiatry Date: 2020-11-20 Impact factor: 3.485