Multimorbidity and neuroimaging biomarkers among cognitively normal persons

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To assess the cross-sectional association between multimorbidity and imaging biomarkers of brain pathology in the population-based Mayo Clinic Study of Aging (MCSA).


The study consisted of 1,449 MCSA participants who were cognitively normal at the time of MRI. A subset of the participants also had 11C-Pittsburgh compound B (n = 689) and 18fluorodeoxyglucose (n = 688) PET scans available. Information on multimorbidity (defined as ≥2 chronic conditions) in the 5 years prior to the first imaging study was captured from the medical record using ICD-9 codes for chronic conditions and the Rochester Epidemiology Project medical records linkage system. The cross-sectional association of multimorbidity and imaging biomarkers was examined using logistic and linear regression models.


Among 1,449 cognitively normal participants (mean age 79 years; 50.9% men), 85.4% had multimorbidity (≥2 chronic conditions). Multimorbidity and severe multimorbidity (≥4 chronic conditions) were associated with abnormal Alzheimer disease (AD) signature meta–region of interest (meta-ROI) 18F-FDG hypometabolism (odds ratio [OR] 2.03; 95% confidence interval [CI] 1.10–3.77 and OR 2.22; 95% CI 1.18–4.16, respectively), and with abnormal AD signature MRI cortical thickness (OR 1.53; 95% CI 1.09–2.16 and OR 1.76; 95% CI 1.24–2.51, respectively), but was not associated with amyloid accumulation.


Multimorbidity was associated with brain pathology through mechanisms independent of amyloid deposition and such neuronal injury and pathology was present before any symptomatic evidence of cognitive impairment. Longitudinal follow-up will provide insights into potential causal associations of multimorbidity with changes in brain pathology.

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