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Original research
Regional hyperperfusion in cognitively normal APOE ε4 allele carriers in mid-life: analysis of ASL pilot data from the PREVENT-Dementia cohort
  1. Elizabeth Frances McKiernan1,
  2. Elijah Mak1,
  3. Maria-Eleni Dounavi1,
  4. Katie Wells2,
  5. Craig Ritchie3,
  6. Guy Williams4,
  7. Li Su1,
  8. John O'Brien1
  1. 1 Psychiatry, University of Cambridge, Cambridge, UK
  2. 2 The Centre for Mental Health, Imperial College, London, UK
  3. 3 Centre for Dementia Prevention, University of Edinburgh Centre for Clinical Brain Sciences, Edinburgh, Edinburgh, UK
  4. 4 Wolfson Brain Imaging Centre, Cambridge University, Cambridge, UK
  1. Correspondence to Dr Elizabeth Frances McKiernan, Psychiatry, University of Cambridge, Cambridge CB2 0QQ, UK; em654{at}


Background Regional cerebral hypoperfusion is characteristic of Alzheimer’s disease (AD). Previous studies report conflicting findings in cognitively normal individuals at high risk of AD. Understanding early preclinical perfusion alterations may improve understanding of AD pathogenesis and lead to new biomarkers and treatment targets.

Methods 3T arterial spin labelling MRI scans from 162 participants in the PREVENT-Dementia cohort were analysed (cognitively normal participants aged 40–59, stratified by future dementia risk). Cerebral perfusion was compared vertex-wise according to APOE ε4 status and family history (FH). Correlations between individual perfusion, age and cognitive scores (COGNITO battery) were explored.

Results Regional hyperperfusion was found in APOE ε4+group (left cingulate and lateral frontal and parietal regions p<0.01, threshold-free cluster enhancement, TFCE) and in FH +group (left temporal and parietal regions p<0.01, TFCE). Perfusion did not correlate with cognitive test scores.

Conclusions Regional cerebral hyperperfusion in individuals at increased risk of AD in mid-life may be a very early marker of functional brain change related to AD. Increased perfusion may reflect a functional ‘compensation’ mechanism, offsetting the effects of early neural damage or may itself be risk factor for accelerating spread of degenerative pathology.

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  • Contributors EFM wrote the manuscript with input from the other authors. EFM, EM and M-ED processed and analysed the imaging data. EFM completed the statistical analysis with guidance from LS. KW and GW were key in setting-up and collecting data for the PREVENT-Dementia study. CR led the PREVENT-Dementia study. LS and JO are the joint senior authors, they provided direction and guidance on data processing, analysis and write-up.

  • 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-17–5 19 007) and philanthropic donations. EFM is funded by the UK Alzheimer’s Society (AS-CTF-17b-003). JO and LS are supported by the Cambridge NIHR Biomedical Research Centre. LS is also supported by Alzheimer’s Research UK (ARUK-SRF2017B-1).

  • Competing interests 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 and public involvement statement 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.

  • 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. Applications to analyse data from the PREVENT-Dementia cohort can be submitted to the study team via a form which can be downloaded from the study’s official website