Evaluation of skeletal muscle oxidative metabolism in Alzheimer disease patients

Introduction Alzheimer disease (AD) is the most common form of dementia affecting the aging population and its hallmark is a progressive deterioration in cognitive function (1). The pathogenesis of AD is characterized by beta-amyloid (βAP) over production and its deposition in the brain (2). Recently, evidence has been provided that βAP deposits can be also present in skeletal muscles of AD patients (3). Abnormalities of mitochondrial morphology and respiratory chain dysfunction in peripheral tissues of AD patients have been also described (4). Aim of this study was to evaluate whether in AD patients skeletal muscle oxidative metabolism is impaired. Methods Thirteen AD patients (71,5±5,2 years, mean±SD) and twenty-nine healthy sex-matched control subjects (CTRL) (73,8±4,7 years) were investigated. Skeletal muscle oxidative metabolism was evaluated during two incremental exercises performed up to voluntary exhaustion: a cycloergometer (CE) and a one-leg knee extension (KE) exercise. The following variables were determined: breath-by-breath pulmonary O2 uptake (VO2); heart rate (HR) and cardiac output (CO); vastus lateralis muscle fractional O2 extraction by near-infrared spectroscopy (Δ[deoxy(Hb±Mb)]); blood lactate concentration ([La-]) at rest and after exercise. Results During CE, peak work-rate (92,9±32,5 vs 128,3±41,8 watt) and VO2 peak (1,44±0,41 vs 1,86±0,5 L*min-1) were significantly lower in AD patients vs CTRL. CO was similar between AD patients (18.1±2.4 L*min-1) and CTRL (17.9±3.1 L*min-1) whereas Δ[deoxy(Hb±Mb)] was significantly lower in AD patients (52,6±3,3 %) vs CTRL (69,0±6,4 %). During KE, VO2 peak (0,78±0,22 vs 0,99±0,25 L*min-1) and Δ[deoxy(Hb±Mb)] (31,2±4,8 vs 58,9±6,6 %) were significantly lower in AD patients vs CTRL. RPE and [La-] were not different in the two groups, both for CE and KE. Conclusions Our findings show that AD patients have a reduced exercise capacity compared to healthy control subjects, likely due to a reduced muscle fractional O2 extraction capacity. Indeed, the impairment of muscle oxidative function was confirmed even reducing constraints (by KE) to oxidative function deriving from cardiovascular O2 delivery. If confirmed on a larger number of patients, these observations lead to some interesting prospects, the most striking of which is that AD may be a systemic disease rather than exclusively a disease of the central nervous system. References. 1) Harrison J. Med Clin North Am. 2013, 97:425-38 2) Shea et al. Curr Top Med Chem. 2012, 12:2596-610 3) Kuo et al. Am J Pathol. 2000, 156: 797-805. 4) Parker Jr et al. Neurology. 1994, 44: 1086-1090