Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study.
McKiernan, Elizabeth F
Ritchie, Craig W
O'Brien, John T
J Cereb Blood Flow Metab
MetadataShow full item record
Dounavi, M., Low, A., McKiernan, E. F., Mak, E., Muniz-Terrera, G., Ritchie, K., Ritchie, C. W., et al. (2021). Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study.. J Cereb Blood Flow Metab, 41 (11), 2844-2855. https://doi.org/10.1177/0271678X211020863
Accumulating evidence suggests vascular dysregulation in preclinical Alzheimer's disease. In this study, cerebral hemodynamics and their coupling with cognition in middle-aged apolipoprotein ε4 carriers (APOEε4+) were investigated. Longitudinal 3 T T1-weighted and arterial spin labelling MRI data from 158 participants (40-59 years old) in the PREVENT-Dementia study were analysed (125 two-year follow-up). 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. CBF was corrected for underlying atrophy and individual hematocrit. Hemodynamic measures were the dependent variables in linear regression models, with age, sex, years of education and APOEε4 carriership as predictors. Further analyses were conducted with cognitive outcomes as dependent variables, using the same model as before with additional APOEε4 × hemodynamics interactions. At baseline, APOEε4+ 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 APOEε4 non-carriers) and verbal fluency (for APOEε4 carriers) cognitive tests. These observations are consistent with neurovascular dysregulation in middle-aged APOEε4+.
APOE, arterial spin labelling, cerebral blood flow, dementia, perfusion, Adult, Alzheimer Disease, Apolipoprotein E4, Atrophy, Case-Control Studies, Cerebral Arteries, Cerebrovascular Circulation, Cognition, Female, Follow-Up Studies, Hematocrit, Heterozygote, Humans, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Neurovascular Coupling
External DOI: https://doi.org/10.1177/0271678X211020863
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329816
Embargo: ends 2021-06-02
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: firstname.lastname@example.org