Regional hyperperfusion in cognitively normal APOE ε4 allele carriers in mid-life: analysis of ASL pilot data from the PREVENT-Dementia cohort

Elizabeth McKiernan, Elijah Mak, Maria Eleni-Dounavi, Katie Wells, Craig Ritchie, Guy Williams, Li Su, John O’Brien

Journal of Neurology, Neurosurgery and Psychiatry. 2020



This study explored the relationship between dementia and cerebral blood flow (CBF) as cerebral hypoperfusion (reduced blood flow in the brain) is characteristic of cognitive impairment and Alzheimer’s disease.

The current study used data from participants’ ASL MRI scans to investigate whether changes in CBF would be seen in our healthy mid life participants, and whether these would be associated with dementia risk, as defined by ones APOEe4 status, Family history and cognitive performance on the COGNITO assessment.

As expected, perfusion (blood flow) was correlated with the APOEe4 allele and participants family history, however not cognitive performance. Differences in the location of the CBF were found in participants carrying the APOEe4 allele compared to participants with a family history of dementia. However, intriguingly, the direction of change was opposite to what was expected. Rather than finding regional hypoperfusion, our at-risk participants showed regional hyperperfusion (increased blood flow) across these areas.

The impact of these findings is not yet clear, however further examination of longitudinal data, including that of full PREVENT-Dementia cohort will help to determine at what point CBF changes occur and what mechanisms are at play.

Key terms and abbreviations:

  • ASL MRI= Arterial spin labelling Magnetic Resonance Imaging: a non-invasive perfusion imaging technique for the measurement of cerebral blood flow
  • APOEe4 allele= One of the possible genetic risk factors for dementia


Midlife alcohol consumption and longitudinal brain atrophy: the PREVENT-Dementia study

Michael Firbank, John O’Brien, Karen Ritchie, Katie Wells, Guy Williams, Li Su, Craig Ritchie

Journal of Neurology. 2020



Hippocampal Subfield Volumes in Middle-Aged Adults at Risk of Dementia

Anna McKeever, Alvar Paris, James Cullen, Lawrence Hayes, Craig Ritchie, Karen Ritchie, Adam Waldman, Katie Wells, Albert Busza, Isabelle Carriere, John O’Brien

Journal of Alzheimer’s Disease. 2020



One abnormality commonly found in the brains of those living with Alzheimer’s disease is the reduced volume of a subfield of the hippocampus called the CA1. The current study sought to investigate whether this change is apparent at midlife.

In line with previous research, lower CA1 volume was found to be associated with both a family history of dementia and greater cardiovascular risk factors, and this change was evident at a mean age of 53. This is important, as it demonstrates that the change can be seen in midlife before symptoms of Alzheimer’s disease have begun. This study also revealed a second, unexpected finding: Individuals with a family history of dementia showed an increase in three other hippocampal regions combined (CA3, CA4, DG), perhaps indicating an early inflammatory or neurogenesis response to early Alzheimer’s disease.

Volumetric alterations in the hippocampal subfields of subjects at increased risk of dementia

Maria-Eleni Dounavi, Elijah Mak, Katie Wells, Karen Ritchie, Craig W. Ritchie,  Li Su, John T.O’ Brien 

Neurobiology of Ageing. 2020



In this study, we found that participants with an APOEe4 genotype (a known genetic risk factor for dementia) were more likely to have a smaller hippocampal molecular layer, and this change was apparent at both the baseline and 2-year follow up.

Together with previous findings, it appears that the molecular layer may be one of the first areas to show vulnerability to the pathological hallmarks of Alzheimer’s. However, it was noted that differences in the molecular layer were not significantly related to dementia risk defined by family history or cardiovascular factors.

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

John T O’Brien, Michael J Firbank, Karen Ritchie,, Katie Wells, Guy B Williams, Craig W Ritchie, Li Su

Journal of Neurology, Neurosurgery & Psychiatry. 2019

DOI: 10.1136/jnnp-2019-321652 

Individuals with a higher likelihood of developing Alzheimer’s disease dementia in the future, as predicted by their mid-life CAIDE score, show more shrinkage of brain volume, measured over the course of two years.

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Lifestyle and neurodegeneration in midlife as expressed on functional magnetic resonance imaging: A systematic review

Hinesh Topiwala, Graciela Muniz Terrera, Lucy Stirland, Kathryn Saunderson, Tom C. Russ, Marshall F. Dozier and Craig W. Ritchie

Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 2018

DOI: 10.1016/j.trci.2018.04.001