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Alzheimer's Imaging Consortium.

Xiaqing Jiang1, Sid E O'Bryant2, Robert A Rissman3

  • 1University of California, San Francisco, San Francisco, CA, USA.

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Summary

Multimorbidity, having multiple chronic conditions, is linked to poorer cognition and increased Alzheimer disease (AD) pathology, neurodegeneration, and cerebral small vessel disease (SVD). These conditions may impact cognitive aging through neurodegenerative and AD-related pathways.

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Area of Science:

  • Neurology
  • Gerontology
  • Public Health

Background:

  • Multimorbidity, the presence of multiple chronic conditions, is increasingly recognized as a significant factor in cognitive aging.
  • The precise mechanisms linking multimorbidity to cognitive decline, Alzheimer disease (AD), and related dementias remain incompletely understood.

Purpose of the Study:

  • To investigate the association between multimorbidity burden and cognitive function in older adults.
  • To explore the mediating roles of Alzheimer disease (AD) pathology, neurodegeneration, and cerebral small vessel disease (SVD) in this relationship.

Main Methods:

  • A cross-sectional study of 2,951 dementia-free participants aged 50 years and older from the Health and Aging Brain Study: Health Disparities cohort.
  • Multimorbidity burden was quantified by counting the number of chronic conditions. Cognitive function was assessed using a latent factor score from neuropsychological tests. Biomarkers for AD pathology, neurodegeneration, and SVD were measured using PET, plasma assays, and MRI.
  • Linear regression and structural equation modeling (SEM) were employed to analyze the associations and mediating pathways.

Main Results:

  • A higher multimorbidity burden was significantly associated with worse overall cognition.
  • Increased multimorbidity was also linked to elevated biomarkers of AD pathology, neurodegeneration, and SVD.
  • Structural equation modeling indicated that the association between multimorbidity and cognitive decline was primarily mediated by neurodegeneration (74%) and secondarily by AD pathology (22%).

Conclusions:

  • In individuals without dementia, a greater burden of multimorbidity is associated with adverse biomarkers for AD pathology, neurodegeneration, and SVD.
  • Multimorbidity appears to negatively impact cognition through pathways involving neurodegeneration and AD pathology, highlighting potential targets for intervention.