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Original Investigation
June 2017

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

Author Affiliations
  • 1Department of Radiology, Mayo Clinic–Rochester, Rochester, Minnesota
  • 2Department of Neurology, Mayo Clinic–Rochester, Rochester, Minnesota
  • 3Department of Health Sciences Research, Mayo Clinic–Rochester, Rochester, Minnesota
  • 4Department of Neuroscience, Mayo Clinic–Jacksonville, Jacksonville, Florida
  • 5Department of Psychology, Mayo Clinic–Rochester, Rochester, Minnesota
JAMA Neurol. 2017;74(6):718-726. doi:10.1001/jamaneurol.2017.0244
Key Points

Question  Do factors that influence amyloid- and Alzheimer disease–pattern neurodegeneration differ?

Findings  In this cohort study of 942 elderly individuals enrolled in the Mayo Clinic Study of Aging with magnetic resonance imaging and amyloid scans and, protective factors that influence amyloid- and Alzheimer disease-pattern neurodegeneration differed.

Meaning  Investigating independent and combined protective factors for amyloid and neurodegeneration will enable better prevention strategies to delay the onset and progression of Alzheimer disease.

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-≥90 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.

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