Evaluation of Amyloid Protective Factors and Alzheimer Disease Neurodegeneration Protective Factors in Elderly Individuals

Abstract

IMPORTANCE While amyloid and neurodegeneration are viewed together as Alzheimer disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern neurodegeneration may be considerably different. Protection from these ADP factors may be important for aging without significant ADP. OBJECTIVE To identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration in a population-based sample and to test the hypothesis that "exceptional agers" with advanced ages do not have significant ADP because they have protective factors for amyloid and neurodegeneration. DESIGN, SETTING, AND PARTICIPANTS This cohort study conducted a prospective analysis of 942 elderly individuals (70-Ն90 years) with magnetic resonance imaging and Pittsburgh compound B-positron emission tomography scans enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We operationalized "exceptional aging" without ADP by considering individuals 85 years or older to be without significant evidence of ADP. MAIN OUTCOMES AND MEASURES We evaluated predictors including demographics, APOE, intellectual enrichment, midlife risk factors (physical inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia), and the total number of late-life cardiac and metabolic conditions. We used multivariate linear regression models to identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration. Using a subsample of the cohort 85 years of age or older, we computed Cohen d-based effect size estimations to compare the quantitative strength of each predictor variable in their contribution with exceptional aging without ADP. RESULTS The study participants included 423 (45%) women and the average age of participants was 79.7 (5.9) years. Apart from demographics and the APOE genotype, only midlife dyslipidemia was associated with amyloid deposition. Obesity, smoking, diabetes, hypertension, and cardiac and metabolic conditions, but not intellectual enrichment, were associated with greater AD-pattern neurodegeneration. In the 85 years or older cohort, the Cohen d results showed small to moderate effects (effect sizes > 0.2) of several variables except job score and midlife hypertension in predicting exceptional aging without ADP. CONCLUSIONS AND RELEVANCE The protective factors that influence amyloid and AD-pattern neurodegeneration are different. "Exceptional aging" without ADP may be possible with a greater number of protective factors across the lifespan but warrants further investigation.

Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

“…From the sensitivity SEM analyses in Figure 4, we found that the primary predictor of the association between vascular health and ERC-tau seen in Figure 2 was hyperlipidemia. In our recent study 34 as well as this paper, we found evidence that lipids play an important role in the pathogenesis of processes upstream to AD neurodegeneration. Using Tau-PET and amyloid PET together here, we were able to further discern that tau deposition is specifically influenced by hyperlipidemia.…”

Ideal Cardiovascular Health and Biomarkers of Subclinical Brain Aging: The Northern Manhattan Study

“…Long‐term exposure to vascular risk factors through adulthood, including diabetes mellitus, hypertension, hypercholesterolemia, and obesity, are likely to impair brain health by altering the structure and function of cerebral blood vessels, limiting blood flow, and therefore reducing the availability of oxygen and glucose to the brain. Additionally, the relationship between vascular risk factors and neurodegenerative processes has been suggested in recent epidemiological studies that show an association between vascular risk factors and markers of neurodegeneration 27. All together, these data suggest that modifiable vascular risk factors may impact neurodegenerative processes.…”

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. [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.…”