Sarcopenia Is Associated With Incident Alzheimer's Dementia, Mild Cognitive Impairment, and Cognitive Decline

Michal S. Beeri PhD; Sue E. Leugrans PhD; Osvaldo Delbono MD, PhD; David A. Bennett MD; Aron S. Buchman MD


J Am Geriatr Soc. 2021;69(7):1826-1835. 

In This Article

Abstract and Introduction


Objective: We examined whether sarcopenia is associated with the occurrence of late-life cognitive impairment.

Methods: Nondemented older adults (N = 1175) underwent annual testing with 17 cognitive tests summarized as a global cognitive score. A composite sarcopenia score was constructed based on muscle mass measured with bioelectrical impedance and muscle function based on grip strength. Cox proportional hazard models were employed to examine associations of sarcopenia with incident Alzheimer's dementia (AD) and incident mild cognitive impairment (MCI). Linear mixed-effect models determined the association of sarcopenia with cognitive decline. All models controlled for age, sex, education, race, and height squared.

Results: Average follow-up was 5.6 years. More severe sarcopenia at baseline was associated with a higher risk of incident AD (hazard ratio [HR], 1.50 [95% confidence interval 1.20–1.86]; p < 0.001) and of MCI (1.21 [1.01–1.45]; 0.04) and a faster rate of cognitive decline (estimate = −0.013; p = 0.01). Analyses of the individual components of sarcopenia showed that muscle function was associated with incident AD, incident MCI, and cognitive decline with and without a term for lean muscle mass in the model. In contrast, lean muscle mass was not associated with incident cognitive impairment or cognitive decline when a term for muscle function was included in the model.

Conclusions: Poor muscle function, but not reduced lean muscle mass, drives the association of sarcopenia with late-life cognitive impairment. Further work is needed to identify features of muscle structure, which may increase the specificity of sarcopenia for identifying older adults at risk for late-life cognitive impairment.


Sarcopenia is a common aging phenotype defined as loss of muscle structure and its function.[1–3] While cross-sectional studies suggest an association of sarcopenia with cognition, there is little data on the association of sarcopenia with incident cognitive impairments and cognitive decline. Motor function is a complex volitional behavior and its impairment precedes and predicts cognitive decline, incident mild cognitive impairment (MCI), and Alzheimer's dementia (AD) in many older adults.[4–6] Considerable data suggest that shared neural substrate underlies motor and cognitive resources underlying volitional motor control, suggesting a common etiopathogenesis. For example, both motor and cognitive decline are related to many of the same AD and other related brain pathologies[7] as well as cortical proteins,[8] which drive late-life decline. Higher body mass index (BMI), which encompasses muscle mass, is related to faster cognitive decline and incident AD.[9,10] Changes in BMI in older adults is also related to the same ADRD brain pathologies underlying cognitive decline[11] and recent reports suggest that muscle proteins may reach the central nervous system (CNS) via systemic circulation to affect cognition.[12] These studies support the biological plausibility for prior observational studies linking both elements of sarcopenia, that is, muscle structure and function with late-life cognitive impairment.

Recently, emerging technologies, such as bioimpedance, have made it easier to obtain measures of muscle mass outside of the laboratory setting permitting a reassessment of the independent role of lean muscle mass metrics as part of the construct of sarcopenia in predicting adverse health outcomes such as mortality and disability.[1,3] We are unaware of prior studies which have examined whether lean muscle mass is independently associated with incident AD, incident MCI, and cognitive decline when controlling for muscle function.

In this study we combine measures of grip strength with measures of lean muscle mass to assess the association of sarcopenia with incident AD, MCI, and cognitive decline in a sample of approximately 1200 community-dwelling older adults participating in the Rush Memory and Aging Project (MAP).[13] In further analyses, we examined each of the components used to assess sarcopenia to test the hypothesis that lean muscle mass is independently associated with incident MCI and AD as well as the rate of cognitive decline when controlling for muscle function.