Association between self-reported multimorbidity and longitudinal brain Aβ deposition in Alzheimer's disease

Abstract

Multimorbidity is common in older adults. However, whether multimorbidity accelerates brain beta-amyloid (Aβ) deposition, the molecular driver of Alzheimer's disease (AD), in humans remains largely unknown. In this study, we selected 435 brain Aβ-positive participants with available longitudinal Aβ-PET data (mean duration 3.9 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Twenty-two self-reported chronic disorders were considered as a measure of the severity of multimorbidity. After adjustment for age, sex, education level, APOE-ε4 status and baseline cognitive state, individuals with a high or medium multimorbidity burden had faster rates of brain Aβ accumulation than individuals with a low multimorbidity burden. Moreover, both the central nervous system and peripheral system multimorbidity burdens were associated with longitudinal brain Aβ deposition. These results indicate that peripheral organ and tissue dysfunctions may contribute to AD pathogenesis, which may help researchers better understand AD pathogenesis and tailor interventions for AD from a systemic view.

Fig. 1. Flow diagram of the study.

A Flowchart depicting each step of the selection process for ADNI participant inclusion in the data analyses. B Overview of the study design workflow. ADNI Alzheimer’s Disease Neuroimaging Initiative, AD Alzheimer’s disease, Aβ beta-amyloid, APOE apolipoprotein, CU cognitively unimpaired, FBP ¹⁸F-florbetapir, MCI mild cognitive impairment. Created by Figdraw.com.

Fig. 2. Longitudinal mixed effects model of the multimorbidity-by-time interaction demonstrated a greater rate of longitudinal brain Aβ accumulation in participants with a greater multimorbidity burden.

A Compared with individuals with a low multimorbidity burden of all chronic diseases (0 to 2 chronic disorders), individuals with a medium multimorbidity burden (3 to 5 chronic disorders) and a high multimorbidity burden (6 or more chronic disorders) presented faster rates of Aβ accumulation in the brain during follow-up. B Compared with individuals without chronic disease of central nervous system (0 chronic disorder), individuals with 1 or more chronic disorders presented faster rates of brain Aβ accumulation during follow-up. C Compared with individuals with 0 or 1 chronic disorder of peripheral system, individuals with 2 or more chronic disorders presented faster rates of brain Aβ accumulation during follow-up. The tables show the number of participants available at each time point. Longitudinal brain Aβ SUVR at each follow-up time point were used to generate these figures, which were analyzed via linear mixed effects models adjusted for age, sex, education level, APOE-ε4 status and baseline cognitive state. The lines represent model fits (shaded areas represent the 95% confidence intervals of the regression lines).