Higher midlife CAIDE score is associated with increased brain atrophy in a cohort of cognitively healthy middle-aged individuals

Xulin Liu, Maria-Eleni Dounavi, Karen Ritchie, Katie Wells, Craig W. Ritchie, Li Su, Graciela Muniz-Terrera & John T. O’Brien

Journal of Neurology. 2021


Cardiovascular factors have a strong association with Alzheimer’s disease (AD) and brain atrophy. However, until recently, there has been limited longitudinal research in cognitive healthy middle-aged adults investigating these links. A recent PREVENT Dementia study used data from 167 participants in the PREVENT London cohort, to investigate associations between the CAIDE (Cardiovascular Risk Factors, Aging, and Dementia) score and structural MRI scans at both baseline and 2-year follow up. Participants in the high-risk group (i.e., those with a CAIDE score above 6) were on average, found to have a greater rate of brain atrophy. However, to identify the specific regions and structures driving this atrophy pattern, additional analysis was conducted using voxel based morphometry (VBM).

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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.

Associations between midlife chronic conditions and medication use with anxiety and depression: A cross-sectional analysis of the PREVENT Dementia study

Lucy E Stirland , Sarah Gregory, Tom C Russ, Craig W Ritchie, Graciela Muniz-Terrera
Journal of Comorbidity. 2020


There is evidence to suggest that brain health is associated with multimorbidity, polypharmacy, depression and anxiety. This study aimed to investigate the interactions between these four-potential dementia-risk factors (depression, anxiety, multimorbidity and polypharmacy) at mid-life.

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