The Association of Multimorbidity With Preclinical AD Stages and SNAP in Cognitively Unimpaired Persons

Maria Vassilaki, Jeremiah A. Aakre, Walter K Kremers, Michelle M Mielke, Yonas Endale Geda, Rabe E. Alhurani, Taru Dutt, Mary Margaret Machulda, David S Knopman, Prashanthi D Vemuri, Preciosa M. Coloma, Barbara Schauble, Val Lowe, Clifford R Jr. Jack, Ronald Carl Petersen, Rosebud O Roberts

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Abstract

BACKGROUND: Multimorbidity (defined as ≥2 chronic conditions) has been associated with increased risk of mild cognitive impairment and cross-sectionally with imaging biomarkers of neurodegeneration in cognitively unimpaired persons aged ≥70 years. Its association with preclinical Alzheimer's disease stages has not been studied in detail yet. The objective of the study was to assess the cross-sectional association of multimorbidity with preclinical Alzheimer's disease stages and suspected non-amyloid pathophysiology in cognitively unimpaired participants of the Mayo Clinic Study of Aging (≥50 years of age). METHODS: The study included 1,535 cognitively unimpaired participants with multimorbidity, 11C-PiB positron emission topography and magnetic resonance imaging data available. Abnormal (elevated) 11C-PiB-positron emission topography retention ratio (A+; standardized uptake value ratio >1.42) and abnormal (reduced) Alzheimer's disease signature cortical thickness (N+; <2.67 mm) were used to define biomarker combinations (A-N-, A+N-, A-N+, A+N+). Chronic medical conditions were ascertained by using the Rochester Epidemiology Project medical records linkage system and International Classification of Diseases criteria. Cross-sectional associations were examined using multinomial logistic regression models adjusting for age, sex, education, and apolipoprotein E ɛ4 allele status. RESULTS: Frequency of A+, N+, A+N+, and A-N+ biomarker groups increased significantly with increasing number of chronic conditions. Multimorbidity was significantly associated with A+N+ (vs A-N-; odds ratio, 1.76, 95% confidence interval 1.02, 2.90) and A-N+ (vs A-N-; odds ratio, 2.16, 95% confidence interval 1.47, 3.18). There was a dose-response relationship between increasing number of chronic conditions (eg, 0-1, 2-3, and 4+) and the odds of A+N+ and A-N+ (vs A-N-). CONCLUSIONS: Multimorbidity was associated with biomarker combinations that included neurodegeneration with or without elevated amyloid deposition (ie, A-N+, A+N+). The associations should be validated in longitudinal studies.

Original languageEnglish (US)
Pages (from-to)877-883
Number of pages7
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume74
Issue number6
DOIs
StatePublished - May 16 2019

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Comorbidity
Biomarkers
Alzheimer Disease
Medical Record Linkage
Logistic Models
Odds Ratio
Electrons
Confidence Intervals
Apolipoprotein E4
Sex Education
International Classification of Diseases
Amyloid
Longitudinal Studies
Epidemiology
Alleles
Magnetic Resonance Imaging

Keywords

  • Amyloid
  • Multimorbidity
  • Neurodegeneration
  • Preclinical AD
  • SNAP

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

@article{61191d7b695746b4a27024c0bd2946c6,
title = "The Association of Multimorbidity With Preclinical AD Stages and SNAP in Cognitively Unimpaired Persons",
abstract = "BACKGROUND: Multimorbidity (defined as ≥2 chronic conditions) has been associated with increased risk of mild cognitive impairment and cross-sectionally with imaging biomarkers of neurodegeneration in cognitively unimpaired persons aged ≥70 years. Its association with preclinical Alzheimer's disease stages has not been studied in detail yet. The objective of the study was to assess the cross-sectional association of multimorbidity with preclinical Alzheimer's disease stages and suspected non-amyloid pathophysiology in cognitively unimpaired participants of the Mayo Clinic Study of Aging (≥50 years of age). METHODS: The study included 1,535 cognitively unimpaired participants with multimorbidity, 11C-PiB positron emission topography and magnetic resonance imaging data available. Abnormal (elevated) 11C-PiB-positron emission topography retention ratio (A+; standardized uptake value ratio >1.42) and abnormal (reduced) Alzheimer's disease signature cortical thickness (N+; <2.67 mm) were used to define biomarker combinations (A-N-, A+N-, A-N+, A+N+). Chronic medical conditions were ascertained by using the Rochester Epidemiology Project medical records linkage system and International Classification of Diseases criteria. Cross-sectional associations were examined using multinomial logistic regression models adjusting for age, sex, education, and apolipoprotein E ɛ4 allele status. RESULTS: Frequency of A+, N+, A+N+, and A-N+ biomarker groups increased significantly with increasing number of chronic conditions. Multimorbidity was significantly associated with A+N+ (vs A-N-; odds ratio, 1.76, 95{\%} confidence interval 1.02, 2.90) and A-N+ (vs A-N-; odds ratio, 2.16, 95{\%} confidence interval 1.47, 3.18). There was a dose-response relationship between increasing number of chronic conditions (eg, 0-1, 2-3, and 4+) and the odds of A+N+ and A-N+ (vs A-N-). CONCLUSIONS: Multimorbidity was associated with biomarker combinations that included neurodegeneration with or without elevated amyloid deposition (ie, A-N+, A+N+). The associations should be validated in longitudinal studies.",
keywords = "Amyloid, Multimorbidity, Neurodegeneration, Preclinical AD, SNAP",
author = "Maria Vassilaki and Aakre, {Jeremiah A.} and Kremers, {Walter K} and Mielke, {Michelle M} and Geda, {Yonas Endale} and Alhurani, {Rabe E.} and Taru Dutt and Machulda, {Mary Margaret} and Knopman, {David S} and Vemuri, {Prashanthi D} and Coloma, {Preciosa M.} and Barbara Schauble and Val Lowe and Jack, {Clifford R Jr.} and Petersen, {Ronald Carl} and Roberts, {Rosebud O}",
year = "2019",
month = "5",
day = "16",
doi = "10.1093/gerona/gly149",
language = "English (US)",
volume = "74",
pages = "877--883",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - The Association of Multimorbidity With Preclinical AD Stages and SNAP in Cognitively Unimpaired Persons

AU - Vassilaki, Maria

AU - Aakre, Jeremiah A.

AU - Kremers, Walter K

AU - Mielke, Michelle M

AU - Geda, Yonas Endale

AU - Alhurani, Rabe E.

AU - Dutt, Taru

AU - Machulda, Mary Margaret

AU - Knopman, David S

AU - Vemuri, Prashanthi D

AU - Coloma, Preciosa M.

AU - Schauble, Barbara

AU - Lowe, Val

AU - Jack, Clifford R Jr.

AU - Petersen, Ronald Carl

AU - Roberts, Rosebud O

PY - 2019/5/16

Y1 - 2019/5/16

N2 - BACKGROUND: Multimorbidity (defined as ≥2 chronic conditions) has been associated with increased risk of mild cognitive impairment and cross-sectionally with imaging biomarkers of neurodegeneration in cognitively unimpaired persons aged ≥70 years. Its association with preclinical Alzheimer's disease stages has not been studied in detail yet. The objective of the study was to assess the cross-sectional association of multimorbidity with preclinical Alzheimer's disease stages and suspected non-amyloid pathophysiology in cognitively unimpaired participants of the Mayo Clinic Study of Aging (≥50 years of age). METHODS: The study included 1,535 cognitively unimpaired participants with multimorbidity, 11C-PiB positron emission topography and magnetic resonance imaging data available. Abnormal (elevated) 11C-PiB-positron emission topography retention ratio (A+; standardized uptake value ratio >1.42) and abnormal (reduced) Alzheimer's disease signature cortical thickness (N+; <2.67 mm) were used to define biomarker combinations (A-N-, A+N-, A-N+, A+N+). Chronic medical conditions were ascertained by using the Rochester Epidemiology Project medical records linkage system and International Classification of Diseases criteria. Cross-sectional associations were examined using multinomial logistic regression models adjusting for age, sex, education, and apolipoprotein E ɛ4 allele status. RESULTS: Frequency of A+, N+, A+N+, and A-N+ biomarker groups increased significantly with increasing number of chronic conditions. Multimorbidity was significantly associated with A+N+ (vs A-N-; odds ratio, 1.76, 95% confidence interval 1.02, 2.90) and A-N+ (vs A-N-; odds ratio, 2.16, 95% confidence interval 1.47, 3.18). There was a dose-response relationship between increasing number of chronic conditions (eg, 0-1, 2-3, and 4+) and the odds of A+N+ and A-N+ (vs A-N-). CONCLUSIONS: Multimorbidity was associated with biomarker combinations that included neurodegeneration with or without elevated amyloid deposition (ie, A-N+, A+N+). The associations should be validated in longitudinal studies.

AB - BACKGROUND: Multimorbidity (defined as ≥2 chronic conditions) has been associated with increased risk of mild cognitive impairment and cross-sectionally with imaging biomarkers of neurodegeneration in cognitively unimpaired persons aged ≥70 years. Its association with preclinical Alzheimer's disease stages has not been studied in detail yet. The objective of the study was to assess the cross-sectional association of multimorbidity with preclinical Alzheimer's disease stages and suspected non-amyloid pathophysiology in cognitively unimpaired participants of the Mayo Clinic Study of Aging (≥50 years of age). METHODS: The study included 1,535 cognitively unimpaired participants with multimorbidity, 11C-PiB positron emission topography and magnetic resonance imaging data available. Abnormal (elevated) 11C-PiB-positron emission topography retention ratio (A+; standardized uptake value ratio >1.42) and abnormal (reduced) Alzheimer's disease signature cortical thickness (N+; <2.67 mm) were used to define biomarker combinations (A-N-, A+N-, A-N+, A+N+). Chronic medical conditions were ascertained by using the Rochester Epidemiology Project medical records linkage system and International Classification of Diseases criteria. Cross-sectional associations were examined using multinomial logistic regression models adjusting for age, sex, education, and apolipoprotein E ɛ4 allele status. RESULTS: Frequency of A+, N+, A+N+, and A-N+ biomarker groups increased significantly with increasing number of chronic conditions. Multimorbidity was significantly associated with A+N+ (vs A-N-; odds ratio, 1.76, 95% confidence interval 1.02, 2.90) and A-N+ (vs A-N-; odds ratio, 2.16, 95% confidence interval 1.47, 3.18). There was a dose-response relationship between increasing number of chronic conditions (eg, 0-1, 2-3, and 4+) and the odds of A+N+ and A-N+ (vs A-N-). CONCLUSIONS: Multimorbidity was associated with biomarker combinations that included neurodegeneration with or without elevated amyloid deposition (ie, A-N+, A+N+). The associations should be validated in longitudinal studies.

KW - Amyloid

KW - Multimorbidity

KW - Neurodegeneration

KW - Preclinical AD

KW - SNAP

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U2 - 10.1093/gerona/gly149

DO - 10.1093/gerona/gly149

M3 - Article

VL - 74

SP - 877

EP - 883

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

IS - 6

ER -