The association of multimorbidity with preclinical AD stages and SNAP in cognitively unimpaired persons

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.