Age, vascular health, and Alzheimer 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.

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…There is debate on whether cardiovascular dysfunction can induce AD, because dementia related to cardiovascular conditions can happen without amyloid accumulation, as shown by the following studies: In elderly people (sample size, 942), only midlife dyslipidemia was found to be associated with amyloid deposition, rather than other risk factors including hypertension (Vemuri, Knopman, et al, 2017); and another study from the same group (sample size, 430) found that people with cardiovascular and metabolic conditions had significantly greater neurodegeneration, but their amyloid and tau were at similar levels (Vemuri, Lesnick, et al, 2017). Another follow‐up study (sample size, 322; median follow‐up, 23.5 years) found that late‐life vascular risk factors are not associated with amyloid standardized uptake value ratios (calculated from florbetapir positron emission tomography, in this case, to reflect the brain amyloid deposition).…”

Development of surface-engineered PLGA nanoparticulate-delivery system of Tet-1-conjugated nattokinase enzyme for inhibition of Aβ₄₀ plaques in Alzheimer’s disease

“…At present, 50% of people with AD are in developing countries, which is 1 Although accumulation of Aβ peptide is considered the trigger point for neuronal degeneration, the actual pathology of AD has not been well documented. 4,5 Aggregation of amyloid fibrils can induce cell death by disrupting cellular calcium ion-homeostasis. 6 Another pathology explaining AD is selective deposition of Aβ peptide in the mitochondria of cells, which inhibits uptake of glucose by neurons and key enzyme functions.…”

Vascular Risk and β‐Amyloid Are Synergistically Associated with Cortical Tau

“…[12][13][14] However, the evidence is mixed as to whether a relationship exists between vascular risk factors and Aβ burden measured concurrently in older adults, 10,12,15 with recent data from our group suggesting no relationship. 14,16,17 Additionally, a recent autopsy study identified an association between late life systolic blood pressure and tau pathology burden. 14,16,17 Additionally, a recent autopsy study identified an association between late life systolic blood pressure and tau pathology burden.…”