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Original research
Association between midlife dementia risk factors and longitudinal brain atrophy: the PREVENT-Dementia study
  1. John T O'Brien1,
  2. Michael J Firbank2,
  3. Karen Ritchie3,4,
  4. Katie Wells5,
  5. Guy B Williams6,
  6. Craig W Ritchie3,
  7. Li Su1
  1. 1 Department of Psychiatry, University of Cambridge, Cambridge, Cambridgeshire, UK
  2. 2 Institute of Neuroscience and Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
  3. 3 Centre for Dementia Prevention, University of Edinburgh Centre for Clinical Brain Sciences, Edinburgh, UK
  4. 4 INSERM, University of Montpellier, Montpellier, France
  5. 5 The Centre for Psychiatry, Imperial College London, London, UK
  6. 6 Wolfson Brain Imaging Center, University of Cambridge, Cambridge, Cambridgeshire, UK
  1. Correspondence to Dr Michael J Firbank, Institute of Neuroscience and Newcastle University Institute for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK; michael.firbank{at}


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.

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  • Contributors JTO’B helped obtain funding, led the design of the imaging protocol and supervised this study. MJF performed the image analysis, statistical analysis and wrote the paper. KR helped obtain funding and was involved with study design. KW was involved with study design and oversaw data collection. GBW assisted with the detailed design and implementation of the imaging protocol. CWR helped obtain funding, was involved with study design and is Chief Investigator of the PREVENT-Dementia programme. LS assisted with the detailed design and implementation of the imaging protocol and supervised all aspects of the MR data design and collection.

  • Funding Research grants from the UK Alzheimer's Society, the US Alzheimer’s Association and philanthropic donations. 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. JTO'B 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.

  • Competing interests JTO’B has no conflicts related to this study. Unrelated to this work, he has received honoraria for work as DSMB chair or member for TauRx, Axon, Eisai, has acted as a consultant for Lilly and has received honorarium for talks from GE Healthcare and research support from Alliance Medical.

  • Patient consent for publication Not required.

  • Ethics approval NHS Research Ethics Committee London Camberwell St-Giles (REC reference: 12/LO/1023).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.