Homocysteine Is Associated With Cognitive Impairment and Sarcopenia in Alzheimer's Disease

OBJECTIVE: To investigate differences in neuropsychological characteristics between patients with Alzheimer's disease (AD) with and without sarcopenia, and to examine their associations with serum homocysteine (HCY) levels. METHODS: A total of 41 patients with AD diagnosed at a memory clinic with Aβ-PET confirmation were enrolled, including 21 patients with sarcopenia (ADSa) and 20 without sarcopenia (ADNSa). In addition, 35 cognitively normal individuals were recruited as normal controls (NCs) from a health examination center. Demographic characteristics, sarcopenia-related parameters, neuropsychological assessments, and serum HCY levels were collected. Group differences in neuropsychological performance and HCY levels were compared, and partial correlation analyses were performed after adjustment for potential confounders. RESULTS: HCY levels were significantly higher in the AD group than in the NC group. The AD group had a higher prevalence of sarcopenia, and its muscle strength, mass, and physical function were significantly worse than those of the NC group (all p < 0.05). The AD-NSa group performed worse on neuropsychological tests such as MoCA, DST, BNT, and AFT. After adjusting for confounding factors, HCY was positively correlated with CDR and five-times sit-to-stand test scores and negatively correlated with MMSE, DSST, and ASMI scores (all p < 0.01). Using a logistic regression model to calculate the odds ratio (OR), the significant correlation between HCY levels and AD status remained after adjusting for potential confounding factors (all p < 0.01). CONCLUSION: Elevated serum HCY levels are significantly associated with sarcopenia and multidimensional cognitive impairment in patients with AD. In an AD cohort with amyloid pathology confirmed by Aβ-PET, this study provides the first integrative analysis of the associations among HCY, sarcopenia, and cognitive function. These findings suggest that HCY may represent a potential biomarker linking the comorbidity of AD and sarcopenia and may offer a theoretical basis for dual-target interventions addressing both HCY metabolism and muscle function in this vulnerable population.