Publications

Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study.

Marialena Dounavi, Audrey Low, Elizabeth McKiernan, Elijah Mak, Graciela Muniz-Terrera, Karen Ritchie, Craig W Ritchie, Li Su and John O’Brien.

Journal of Cerebral Blood Flow & Metabolism. 2021

DOI: https://journals.sagepub.com/doi/pdf/10.1177/0271678X211020863

Summary

Accumulating evidence suggests vascular dysregulation in preclinical Alzheimer’s disease. In this study, cerebral hemodynamics and their coupling with cognition in middle-aged APOE4 carriers were investigated. MRI data from 158 participants (40–59 years old) in the PREVENT-Dementia study were analysed. Cognition was evaluated using the COGNITO battery. Cerebral blood flow (CBF) and cerebrovascular resistance index (CVRi) were quantified for the flow territories of the anterior, middle and posterior cerebral arteries. At baseline, APOE4 carriers showed increased CBF and decreased CVRi compared to non-carriers in the anterior and middle cerebral arteries, suggestive of potential vasodilation. Hemodynamic changes were similar between groups. Interaction analysis revealed positive associations between CBF changes and performance changes in delayed recall (for APOEe4 noncarriers) and verbal fluency (for APOEe4 carriers) cognitive tests. These observations are consistent with neurovascular ysregulation in middle-aged APOE carriers.

Trauma and depressive symptomatology in middle-aged persons at high risk of dementia: the PREVENT Dementia Study

Trauma and depressive symptomatology in middle-aged persons at high risk of dementia: the PREVENT Dementia Study

Karen Ritchie, Isabelle Carrière, Sarah Gregory, Tam Watermeyer, Samuel Danso, Li Su, Craig W Ritchie, John T O’Brien

Journal of Neurology, Neurosurgery and Psychiatry. 2020

DOI: http://dx.doi.org/10.1136/jnnp-2020-323823

Summary

This study explored the links between childhood trauma, depression, adult cognitive functioning and risk of dementia.

Depression has been found to occur in half of individuals given a diagnosis of Alzheimer’s disease (AD). While evidence suggests depression may be a risk factor for AD, there is also suggestion that depression is a symptom of the disease itself. The exact mechanism behind the association between depression and AD is unknown. However, it is thought the common brain changes associated with childhood trauma, including reduced development of the hippocampus and amygdala and abnormal frontotemporal electrical activity, may play a significant role.

The current study used data from 378 PREVENT participants, from West London, Oxford and Cambridge, to investigate whether midlife adults with a history of childhood trauma had greater risk of both depression, loss of hippocampal volume at midlife and in turn, cognitive performance, and risk of dementia.

It was hypothesised that childhood trauma would be associated with greater clinical depression, lower hippocampal volume and poorer cognitive performance and dementia risk at mid-life. However, while childhood trauma was associated with depression and reduced hippocampal volume, it was not related to current cognitive function or dementia risk.

The findings suggest that the aetiology of depression is different to that of dementia, and the relationship of depression to dementia risk in persons experiencing childhood trauma appears to be neither a risk factor nor a prodromal feature of the disease but that of a comorbidity which may add to brain burden. This study demonstrates that theremay be multiple routes to which depression may appear in individuals with high risk of dementia, and future research in this area should take into account the origins of variety of depression symptomatology.

Key terms and abbreviations:

Aetiology = The cause of a disease

AD = Alzheimer’s disease

Comorbidity = The simultaneous presence of two or more diseases or conditions in one individual.

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

DOI: https://doi.org/10.1007/s00415-020-10383-8

Summary
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).

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

DOI: http://dx.doi.org/10.1136/jnnp-2020-322924

Summary

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

DOI: https://doi.org/10.1007/s00415-020-10000-8