Basic Science and Pathogenesis

Despite high prevalence of multimorbidity in aging, associations with brain structures and covert vascular brain injury (VBI) remain unexplored.

This population-based study included 1,264 dementia-free participants (age≥60 years) in the MIND-China MRI Substudy (2018-2020). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We measured global structural brain markers (gray matter volume [GMV], white matter volume [WMV], cerebrospinal fluid [CSF] volume), regional AD-related brain structural measures, and covert VBI markers (lacunes, cerebral microbleeds [CMBs], basal ganglia enlarged perivascular spaces [BG-EPVS] and centrum semiovale enlarged perivascular spaces [CSO-EPVS], and deep white matter hyperintensity [DWMH] and periventricular white matter hyperintensity [PWMH]). Data were analyzed using multiple linear regression models, ordinal logistic regression models, and partial correlation analyses.

Having multimorbidity was associated with β-coefficient of -4.40 (95% CI, -8.02 to -0.79) for GMV, -4.54 (-8.68 to -0.40) for WMV, 8.61 (2.01 to 15.20) for CSF volume, -0.20 (-0.39 to -0.02) for precuneus volume, and -0.20 (-0.39 to -0.02) for fusiform gyrus, 0.07 (0.04 to 0.11) for number of lacunes, and 0.03; 0.003 to 0.06) for number of CMBs, and increased likelihoods of BG-EPVS (odds ratio=1.32; 1.06 to 1.64), PWMH Fazekas score (1.34; 1.08 to 1.66), DWMH Fazekas score (1.33; 1.07 to 1.66), and total cerebral small vascular disease (CSVD) burden (1.61; 1.30 to 1.98). The number of chronic diseases was associated with GMV (β=-2.45; 95% CI, -3.90 to -0.99), WMV (-2,73; -4.40 to -1.06), CSF volume (4.91; 2.25 to 7.57), precuneus volume (-0.10; -0.17 to -0.02), fusiform gyrus (-0.10; -0.15 to -0.05), middle temporal gyrus (-0.12; -0.21 to -0.03), angular gyrus (-0.07; -0.14 to 0.01), lacunes (0.03; 0.02 to 0.05), CMBs (0.02; 0.01 to 0.03), BG-EPVS (odds ratio=1.13; 1.04 to 1.23), PWMH Fazekas score (1.21; 1.11 to 1.32), DWMH Fazekas score (1.12; 1.02 to 1.22) and total CSVD burden (1.25; 1.15 to 1.36). In addition, metabolic cluster, and cardiac-musculoskeletal cluster were also significantly related to brain atrophy and VBI markers.

Structural brain alterations of multimorbidity in older adults are characterized by global brain atrophy, atrophy in AD-related brain regions, and covert VBI.