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 E. Geda, Rabe E. Alhurani, Taru Dutt, Mary M. Machulda, David S. Knopman, Prashanthi Vemuri, Preciosa M. Coloma, Barbara Schauble, Val J. Lowe, Clifford R. Jack, Ronald C. Petersen, Rosebud O. Roberts

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number6
StatePublished - May 16 2019
Externally publishedYes


  • Amyloid
  • Multimorbidity
  • Neurodegeneration
  • Preclinical AD
  • SNAP

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology


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