Impact of appendicular skeletal muscle mass on Alzheimer’s disease in relation to age and comorbidities: an 8-year longitudinal follow-up study of a nationwide cohort

This study investigated whether low appendicular skeletal muscle mass (ASM) was associated with an increased risk of developing dementia of the Alzheimer type (DAT) and examined the potential moderating effects of age and comorbidities. This study analyzed anonymized health examination data from the Korean National Health Insurance Service, including 1,897,197 individuals aged ≥ 60 years (mean age 66.1 ± 6.5 years; 46.1% men). ASM was estimated using validated prediction equations based on anthropometric measurements and serum creatinine level. Participants were classified into low ASM (sex-specific lowest quartile, Q1) and normal ASM (Q2–Q4) groups. DAT was defined using ICD-10 codes (F00 or G30) in combination with anti-dementia medication prescriptions under national insurance criteria. The association between low ASM and dementia development was assessed using Cox proportional hazards models after adjusting for potential confounders. Compared with individuals with normal ASM, those with low ASM showed higher incidence rates of DAT in both sexes. Participants with low ASM had a significantly elevated risk of DAT compared to those with normal ASM in both sexes (hazard ratio [HR] = 1.34, 95% confidence interval [CI] 1.32–1.36 in men; HR = 1.27, 95% CI 1.25–1.28 in women). A similar association was observed for vascular dementia (VD). The association between low ASM and DAT risk weakened with advancing age in both sexes (p for low ASM × age < 0.001 in both sexes). A stronger association between low ASM and DAT was observed in participants with a lower comorbidity burden (low Charlson Comorbidity Index [CCI] group) in both sexes (p for low ASM × CCI group = 0.018 in men and < 0.001 in women). Low ASM is associated with an increased risk of DAT in both men and women, particularly among relatively younger and healthier older adults. This large-scale nationwide longitudinal cohort study provides novel evidence that the impact of ASM on DAT risk varies according to age and comorbidity burden.