[p4–276]: Apoe Genotype Influences How Cerebral Blood Flow and Vasoreactivity Predict Neuropsychological Decline Over an 18‐month Follow‐up: the Vanderbilt Memory and Aging Study
Year: 2017
Type: article
Study design: Observational Study
Abstract: Lower cerebral blood flow (CBF) and worse cerebrovascular reactivity (CVR) cross-sectionally relate to poorer neuropsychological performances among older adults, albeit inconsistently. Additional research is needed to elucidate how CBF and CVR may predict cognitive trajectory longitudinally, particularly among individuals at risk for Alzheimer's disease (AD) and dementia. Resting CBF and CVR were measured at baseline among 286 community-dwelling older adults free of clinical stroke or dementia (73±7 years) using pseudo-continuous arterial spin labeling magnetic resonance imaging. Quantified gray matter volume adjustments corrected for partial volume effects. Neuropsychological assessment was conducted at baseline and 18-month follow-up. Interactions of CBF and time point (baseline, 18-months) on cognitive outcomes related baseline CBF to longitudinal cognitive performance across follow-up. Three-way interactions (CBF x time point x APOE-ε4 carrier status) assessed whether genetic risk for AD influenced relations between CBF and cognitive trajectory. All models were repeated for CVR. Models adjusted for age, sex, race/ethnicity, education, modified (age excluded) Framingham Stroke Risk Profile score, APOE-ε4 status (for two-way interactions), cognitive status, and corresponding region-of-interest tissue volume. As expected, lower baseline resting CBF by hemisphere predicted steeper neuropsychological decline (e.g., letter fluency β=0.08, p<0.05 for left, β=0.10, p=0.003 for right; California Verbal Learning Test-II Total Learning β=0.09, p=0.04 for left; Biber Figure Learning Test (BFLT) Total Learning β=0.35, p=0.004 for left, β=0.27, p=0.02 for right; BFLT Long Delay β=0.10, p=0.003 for left, β=0.07, p=0.03 for right). Interestingly, among APOE-ε4 carriers, higher CBF predicted steeper decline for a measure sensitive to AD pathology (category (animal) fluency β=-0.135, p=0.005 for left, β=-0.145, p<0.001 for right). A similar pattern emerged for CVR, with higher CVR predicting steeper decline among APOE-ε4 carriers (e.g., Boston Naming Test β=-0.189, p=0.04 for left; Delis-Kaplan Executive Functions System Color-Word Interference β=2.28, p=0.02 for left, β=2.213, p=0.02 for right). Findings suggest APOE-ε4 interacts with both CBF and CVR on neuropsychological trajectory. Enhanced CBF and CVR among APOE-ε4 carriers may reflect hemodynamic compensatory responses to early neurodegenerative changes, predicting worse cognitive prognosis. Prior cross-sectional cognitive links with CBF and CVR may fail to capture complex, dynamic cerebral perfusion processes occurring prior to AD clinical manifestation.
Source: Alzheimer s & Dementia
Institutions: Vanderbilt University Medical Center, Vanderbilt University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2765148279