Sarcopenia is a predictor for Alzheimer's continuum and related clinical outcomes

Abstract

Low body mass index is closely related to a high risk of Alzheimer's disease (AD) and related biomarkers including amyloid-β (Aβ) deposition. However, the association between sarcopenia and Aβ-confirmed AD remains controversial. Therefore, we investigated the relationship between sarcopenia and the AD continuum. We explored sarcopenia's association with clinical implications of participants on the AD continuum. We prospectively enrolled 142 participants on the AD continuum (19 with preclinical AD, 96 with mild cognitive impairment due to AD, and 28 with AD dementia) and 58 Aβ-negative cognitively unimpaired participants. Sarcopenia, assessed using dual-energy X-ray absorptiometry and hand grip measurements, was considered a predictor. AD continuum, defined by Aβ deposition on positron emission tomography served as an outcome. Clinical severity in participants on the AD continuum assessed using hippocampal volume, Mini-Mental State Examination (MMSE), Seoul Verbal Learning Test (SVLT), and Clinical Dementia Rating Scale Sum of Boxes Scores (CDR-SOB) were also considered an outcome. Sarcopenia (odds ratio = 4.99, p = 0.004) was associated independently with the AD continuum after controlling for potential confounders. Moreover, sarcopenia was associated with poor downstream imaging markers (decreased hippocampal volume, β = - 0.206, p = 0.020) and clinical outcomes (low MMSE, β = - 1.364, p = 0.025; low SVLT, β = - 1.077, p = 0.025; and high CDR-SOB scores, β = 0.783, p = 0.022) in participants on the AD continuum. Sarcopenia was associated with the AD continuum and poor clinical outcome in individuals with AD continuum. Therefore, our results provide evidence for future studies to confirm whether proper management of sarcopenia can effective strategies are required for sarcopenia management to prevent the AD continuum and its clinical implications.

Keywords: AD continuum; Alzheimer’s disease (AD); Amyloid-β (Aβ); Clinical; Sarcopenia.

Figure 1

The proportion of sarcopenia across participants with Aβ-CU, preclinical AD, MCI due to AD, AD dementia. Values depicted in the bar plot represent the proportion of sarcopenia. Aβ− amyloid-β-negative; AD Alzheimer’s disease; CU cognitively unimpaired; MCI mild cognitive impairment.

Figure 2

Schematic diagram of the mediation analyses among sarcopenia, hippocampal volume, and cognitive function. Mediation analyses were performed using sarcopenia as a predictor, hippocampal as a mediator, and each cognitive function (MMSE, SVLT, or CDR-SOB) as an outcome after controlling for age, sex, years of education, hypertension, diabetes, and intracranial volume in participants on the AD continuum. AD Alzheimer’s disease; CDR-SOB clinical dementia rating scale sum of boxes scores; MMSE mini-mental state examination; SVLT delayed recall task of the Seoul verbal learning test.