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Association between midlife dementia risk factors and longitudinal brain atrophy: the PREVENT-Dementia study.

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O'Brien, John T 
Ritchie, Karen 
Wells, Katie 
Williams, Guy B 


BACKGROUND: Increased rates of brain atrophy on serial MRI are frequently used as a surrogate marker of disease progression in Alzheimer's disease and other dementias. However, the extent to which they are associated with future risk of dementia in asymptomatic subjects is not clear. In this study, we investigated the relationship between the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score and longitudinal atrophy in middle-aged subjects. MATERIALS AND METHODS: A sample of 167 subjects (aged 40-59 at baseline) from the PREVENT-Dementia programme underwent MRI scans on two separate occasions (mean interval 735 days; SD 44 days). We measured longitudinal rates of brain atrophy using the FSL Siena toolbox. RESULTS: Annual percentage rates of brain volume and ventricular volume change were greater in those with a high (>6) vs low CAIDE score-absolute brain volume percentage loss 0.17% (CI 0.07 to 0.27) and absolute ventricular enlargement 1.78% (CI 1.14 to 2.92) higher in the at risk group. Atrophy rates did not differ between subjects with and without a parental history of dementia, but were significantly correlated with age. Using linear regression, with covariates of age, sex and education, CAIDE score >6 was the only significant predictor of whole brain atrophy rates (p=0.025) while age (p=0.009), sex (p=0.002) and CAIDE>6 (p=0.017) all predicted ventricular expansion rate. CONCLUSION: Our results show that progressive brain atrophy is associated with increased risk of future dementia in asymptomatic middle-aged subjects, two decades before dementia onset.



Adult, Age Factors, Atrophy, Brain, Cerebral Ventricles, Dementia, Disease Progression, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Neuropsychological Tests, Predictive Value of Tests, Risk Factors

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J Neurol Neurosurg Psychiatry

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Alzheimer's Society (via Imperial College London) (PG-2012-188 WM/3213221)
Alzheimer's Society (via Imperial College London) (PG-2012-188 WM/3213221)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Alzheimer's Research UK (ARUK-SRF2017B-1)
This work was funded by a grant for the PREVENT-Dementia programme from the UK Alzheimer’s Society (grant numbers 178 and 264), and the PREVENT Dementia study is also supported by the US Alzheimer’s Association (grant number TriBEKa-17–519007), and philanthropic donations. JOB and LS are supported by the Cambridge NIHR Biomedical Research Centre. MJF is supported by the NIHR Newcastle Biomedical Research Centre awarded to the Newcastle Hospitals NHS Foundation Trust and Newcastle University. LS is also supported by Alzheimer’s Research UK (ARUK-SRF2017B-1). Participants were recruited at West London Mental Health National Health Service (NHS) Trust (now known as West London NHS Trust) and scanning was carried out at the Clinical Imaging Facility, Imperial College London. We thank all the PREVENT-Dementia participants for their enthusiastic participation in this study.