Evaluation of skeletal muscle oxidative metabolism in Alzheimer's disease

Alzheimer disease (AD) is the most common form of dementia affecting the aging population and its hallmark is a progressive cognitive impairment. Beta-amyloid (βAb) peptide deposits in the cerebral tissue are a histopathological feature of AD and cause impairment of central neurotransmission and synaptic plasticity primarily due to mitochondrial dysfunction. Recent studies have also described βAb deposits in peripheral tissues of AD patients, including skeletal muscle cells. PURPOSE: Aim of this study was to evaluate whether in AD patients skeletal muscle oxidative metabolism is impaired. METHODS: Thirteen AD patients (73.0±4 years, mean±SD) and twenty-nine healthy sex-matched control subjects (CTRL) (71.5±5 years) were investigated. During incremental cycle ergometer (CE) and one-leg knee extension (KE) exercise were determined: breath-by-breath pulmonary O2 uptake (VO2); cardiac output (CO); vastus lateralis muscle fractional O2 extraction by near-infrared spectroscopy (Δ[deoxy(Hb±Mb)]). Blood lactate concentration ([La-]) was assessed at rest and after exercise. Maximal isometric knee extension test was performed in order to assess the maximal voluntary contraction (MVC) of the quadriceps muscle. Total daily energy expenditure (TEE) was also measured during three consecutive days. RESULTS: During CE, peak work-rate (94.1±7.1 vs. 128.3±8.5 watt) and VO2peak (22.0±0.8 vs. 26.4±1.1 mL*kg-1*min-1) were significantly lower in AD vs. CTRL. CO was reduced in AD (13.0±0.6 L*min-1) vs. CTRL (16.6±1.0 L*min-1) and Δ[deoxy(Hb±Mb)] was significantly lower in AD (51.1±5.8 %) vs. CTRL (71.4±2.9 %). During KE, VO2peak (10.7±0.7 vs. 13.5±0.6 mL*kg-1*min-1) and Δ[deoxy(Hb±Mb)] (40.0±5.8 vs. 61.0±4.7 %) were significantly lower in AD vs. CTRL. CO and [La-] were not significantly different between AD and CTRL. As for MVC, no significant difference was found between CTRL and AD (440.5±39.5 N vs. 438.3±86.7 N, respectively). TEE was similar in the two groups. CONCLUSIONS: Our findings show that AD patients have a reduced exercise capacity compared to CTRL likely due to a reduced muscle fractional O2 extraction capacity. Indeed, the impairment of muscle oxidative function was confirmed even reducing (by KE) constraints to oxidative function deriving from cardiovascular O2 delivery.