The POINTER Imaging baseline cohort: Associations between multimodal neuroimaging biomarkers, cardiovascular health, and cognition

Alzheimers Dement. 2024 Dec 6. doi: 10.1002/alz.14399. Online ahead of print.

Abstract

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study.

Methods: Participants underwent health and cognitive assessments and neuroimaging with multimodal positron emission tomography (PET) (beta-amyloid [Aβ] and tau) and magnetic resonance imaging (MRI). Framingham risk score (FRS) was used to quantify cardiovascular disease (CVD) risk.

Results: A total of 1052 participants (31% from underrepresented ethnoracial groups) were enrolled. Compared to Aβ-, Aβ+ (29%) participants were older, had higher apolipoprotein E (APOE) ε4 carriage rate and white matter hyperintensity volume, and greater temporal tau. FRS was related to MRI measures, but not AD biomarkers. FRS and tau had independent effects on cognition.

Discussion: In this heterogenous, at-risk cohort, CVD risk was related to more abnormal brain structure and poorer cognition, representing a putative non-AD (Alzheimer's disease) pathway to brain injury and cognitive decline.

Highlights: ·The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) cohort is enriched for cardiovascular disease (CVD) and poor lifestyle ·POINTER Imaging collected multimodal neuroimaging data in this unique, at-risk cohort ·Amyloid burden was related to age, apolipoprotein E (APOE) ε4 carriage, and measures of disease progression ·Associations between amyloid and tau, and tau and cognition, were relatively weak ·CVD risk and tau pathology were independently related to memory.

Keywords: Framingham risk score; MRI; PET; amyloid; cerebrovascular injury; memory; minoritized groups; preclinical Alzheimer's disease; tau.