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

Abstract

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+.

Disrupted role of the connectivity between the locus coeruleus and the hippocampus in cognition of healthy, middle-aged individuals at risk of dementia: the PREVENT-Dementia study

“…This result was consistent with previous studies from the same cohort that have reported significant negative associations of CAIDE scores with visuospatial functions and navigational abilities (Ritchie et al, 2018;Ritchie et al, 2017). We did not observe a longitudinal effect, similarly to other studies of this cohort (Dounavi et al, 2021;Low et al, 2021), possibly due to the relatively young age range of the sample and the short follow-up window (Ritchie et al, 2018;Ritchie et al, 2017). We caution that the interpretability of the effect of risk on each individual function is limited by their composite assessment in this study and requires individuation in future studies with a longer longitudinal follow-up window.…”

Modifiable lifestyle activities affect cognition in cognitively healthy middle-aged individuals at risk for late-life Alzheimer’s Disease

“…The use of composite cognitive domains that capture slightly different functions in the two assessment points [24] prevents investigation of the impact of lifestyle on cognitive changes over time in this study. Nevertheless, previous studies from this cohort have shown only subtle changes over the two year period [56-57], possibly due to the relatively young age range of the sample and the short follow up window [23, 39]. Therefore, future studies that follow this cohort over a longer period and test hypotheses informed by the previous study waves are needed to determine the longitudinal impact of lifestyle activities in cognitively healthy middle-aged individuals at risk for late life AD.…”

The characteristics of arterial spin labeling cerebral blood flow in patients with subjective cognitive decline: The Chinese imaging, biomarkers, and lifestyle study

“…In addition to Aβ deposition, recent evidence from neuroimaging cohort studies and animal models strongly suggests other underlying pathophysiological processes of AD, particularly neurovascular dysregulation ( Iturria-Medina et al, 2016 ; Dounavi et al, 2021 ). Vascular dysfunction result in reduced clearance of Aβ by periarteriolar and impaired Aβ transporters across the blood-brain barrier, which can increase Aβ deposition.…”