Evaluation of amyloid protective factors and alzheimer disease neurodegeneration protective factors in elderly individuals

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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.

Original languageEnglish (US)
Pages (from-to)718-726
Number of pages9
JournalJAMA Neurology
Volume74
Issue number6
DOIs
StatePublished - Jun 1 2017

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Amyloid
Alzheimer Disease
Dyslipidemias
Hypertension
Linear Models
Obesity
Smoking
Demography
Protective Factors
Positron-Emission Tomography
Population
Cohort Studies
Genotype
Magnetic Resonance Imaging
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{235c407462d242819018da2f7f07be8b,
title = "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-≥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.",
author = "Vemuri, {Prashanthi D} and Knopman, {David S} and Lesnick, {Timothy G.} and Przybelski, {Scott A.} and Mielke, {Michelle M} and Jonathan Graff-Radford and Murray, {Melissa E} and Roberts, {Rosebud O} and Maria Vassilaki and Val Lowe and Machulda, {Mary Margaret} and Jones, {David T} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1001/jamaneurol.2017.0244",
language = "English (US)",
volume = "74",
pages = "718--726",
journal = "JAMA Neurology",
issn = "2168-6149",
publisher = "American Medical Association",
number = "6",

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TY - JOUR

T1 - Evaluation of amyloid protective factors and alzheimer disease neurodegeneration protective factors in elderly individuals

AU - Vemuri, Prashanthi D

AU - Knopman, David S

AU - Lesnick, Timothy G.

AU - Przybelski, Scott A.

AU - Mielke, Michelle M

AU - Graff-Radford, Jonathan

AU - Murray, Melissa E

AU - Roberts, Rosebud O

AU - Vassilaki, Maria

AU - Lowe, Val

AU - Machulda, Mary Margaret

AU - Jones, David T

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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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U2 - 10.1001/jamaneurol.2017.0244

DO - 10.1001/jamaneurol.2017.0244

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