Age, Vascular Health, and Alzheimer's disease Biomarkers in an Elderly Sample

ABSTRACT

OBJECTIVE: To investigate the associations between age, vascular health, and Alzheimer's disease (AD) imaging biomarkers in an elderly sample.

METHODS: We identified 430 individuals along the cognitive continuum aged>60 years with amyloid-PET, Tau-PET, and MRI scans from the population-based Mayo Clinic Study of Aging. A subset of 329 individuals had FDG-PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from healthcare records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac-arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from PiB-PET, entorhinal cortex tau uptake (ERC-tau) from Tau-PET, and neurodegeneration in AD signature regions from MRI and FDG-PET as surrogates for AD pathophysiology. We dichotomized participants into CMC=0 (CMC-) vs. CMC>0 (CMC+) and tested for age-adjusted group differences in AD biomarkers. Using structural equation models (SEM), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and APOE effects.

RESULTS: CMC+ participants had significantly greater neurodegeneration than CMC- participants but did not differ by amyloid or ERC-tau. The SEM models showed that i) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and ii) vascular health specifically the presence of hyperlipidemia had a significant direct impact on ERC-tau.

INTERPRETATION: Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. This article is protected by copyright. All rights reserved.

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