Temporal Muscle Thickness as a New Biomarker: Its Association With Alzheimer Pathology and Cognitive Impairment in...

The association between skeletal muscle mass loss and cognitive decline remains unclear. Temporal muscle thickness (TMT) has been validated as an easily obtainable surrogate marker for muscle mass loss in neurological patients. This study was aimed at exploring whether a decline in TMT correlates with Alzheimer's disease (AD)-related cognitive impairment and its underlying mechanisms.

This study was a cross-sectional substudy of the Chinese preclinical AD study, which included data from 801 participants. TMT was measured using cranial magnetic resonance imaging. Appendicular skeletal muscle index (ASMI) was estimated using an anthropometric equation as a control. Cognitive function was assessed using a battery of standardised neuropsychological tests, and participants were categorised into three groups based on clinical diagnosis: normal cognition (NC), mild cognitive impairment (MCI) and AD. Functional performance was evaluated using the Functional Activities Questionnaire. Of the 801 participants, 733 underwent ¹⁸F-florbetapir PET scans to assess cerebral amyloid-beta (Aβ) deposition. Additionally, 165 Aβ-PET-positive participants were randomly selected for further evaluation of cerebral tau burden using ¹⁸F-MK6240 PET.

Significant differences in TMT measurements were observed by age and sex, with thinner TMT found in females and older adults. TMT was significantly associated with ASMI, handgrip strength and mobility. Regarding cognition, TMT, but not ASMI, was thinner in MCI and AD participants than those with NC. TMT was positively correlated with Montreal Cognitive Assessment-Basic (MoCA-B) scores (r = 0.124, p = 0.001), independent of confounders such as age, sex, education level, nutritional risk, history of hypertension and apolipoprotein E ε4 genotype. Among cognitive domains, TMT was most closely associated with performance on the Auditory Verbal Learning Test recognition (p < 0.05). Stratified analyses revealed that the correlation between TMT and MoCA-B remained significant in MCI participants but not in AD participants. Multivariable logistic regression analysis showed that higher TMT was significantly associated with a lower risk of MCI (OR: 0.494, 95% CI: 0.287-0.849, p < 0.05) and a reduced likelihood of functional dependence (OR: 0.791, 95% CI: 0.670-0.935, p < 0.01). Furthermore, TMT was lower in participants with higher brain tau deposition and was negatively associated with tau PET Braak stages (both p < 0.01).

A decline in TMT was associated with worse cognitive function, increased cerebral tau deposition and impaired functional performance. TMT may serve as a simple, noninvasive and cost-effective marker for MCI due to AD.