ACE Inhibitors Improve Skeletal Muscle by Preserving Neuromuscular Junctions in Patients with Alzheimer's Disease

Background: Hypertension and skeletal muscle decline are common findings in patients with Alzheimer's disease (AD). Angiotensin-converting enzyme (ACE) inhibitors preserve skeletal muscle and physical capacity; however, the driving mechanisms are poorly understood. Objective: We investigated the effects of ACE inhibitors on the neuromuscular junction (NMJ) with relevance to skeletal muscle and physical capacity in AD patients and age-matched controls. Methods: We evaluated controls (n = 59) and three groups of AD patients, including normotensive (n = 51) and patients with hypertension taking ACE inhibitors (n = 53) or other anti-hypertensive medications (n = 49) at baseline and one year later. We measure plasma c-terminal agrin fragment-22 (CAF22) as a marker of NMJ degradation, handgrip strength (HGS), and Short Physical Performance Battery (SPPB) as markers of physical capacity. Results: At baseline AD patients demonstrated lower HGS and SPPB scores and higher CAF22 levels than controls, irrespective of the hypertension status (all p < 0.05). The use of ACE inhibitors was associated with higher HGS and relative maintenance of SPPB scores, gait speed, and plasma CAF22 levels. Conversely, other anti-hypertensive medications were associated with an unaltered HGS, reduced SPPB scores and elevated plasma CAF22 levels (both p < 0.05). We also found dynamic associations of CAF22 with HGS, gait speed, and SPPB in AD patients taking ACE inhibitors (all p < 0.05). These changes were associated with reduced oxidative stress in AD patients taking ACE inhibitors (p < 0.05). Conclusion: Altogether, ACE inhibitors are associated with higher HGS, preserved physical capacity, and the prevention of NMJ degradation in hypertensive AD patients.

Automated summary

ACE inhibitors are beneficial for hypertensive Alzheimer's disease (AD) patients, as they can preserve neuromuscular junction (NMJ) function, improve muscle strength and physical capacity. ACE inhibitors show superior effects compared to other antihypertensive medications on muscle strength, physical capacity, and prevention of NMJ degradation. These changes are associated with reduced oxidative stress.