L-Arginine Improves Cognitive Impairment in Hypertensive Frail Older Adults

Abstract

Cognitive impairment is a prevailing event in hypertensive patients and in frail older adults. Endothelial dysfunction has been shown to underlie both hypertension and cognitive dysfunction. Our hypothesis is that L-Arginine, which is known to ameliorate endothelial dysfunction, could counteract cognitive impairment in a high-risk population of hypertensive frail older adults. We designed a clinical trial to verify the effects of 4-weeks oral supplementation of L-Arginine on global cognitive function of hypertensive frail older patients. The study was successfully completed by 35 frail hypertensive elderly patients assigned to L-Arginine and 37 assigned to placebo. At follow-up, we found a significant difference in the Montreal Cognitive Assessment (MoCA) test score between the L-Arginine treated group and placebo (p: 0.0178). Moreover, we demonstrated that L-Arginine significantly attenuates Angiotensin II-induced mitochondrial oxidative stress in human endothelial cells. In conclusion, our findings indicate for the first time that oral L-Arginine supplementation significantly improves cognitive impairment in frail hypertensive older adults.

Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT04962841.

Keywords: L-Arg; L-Arginine; cardiac rehabilitation; cognitive impairment; endothelial (dys)function; frail adults; frailty.

Figure 1

Flow chart of the study.

Figure 2

MoCA (Montreal Cognitive Assessment) score evaluated at baseline and at follow-up in the placebo and in the L-Arginine arms. Data are means ± SE; *: p < 0.05.

Figure 3

Mitochondrial production of reactive oxygen species (ROS) evaluated in human endothelial cells treated with Angiotensin II (Ang II) (1 μM) + vehicle or Ang II + L-Arginine (500 μM) for 24 hours; A.U., arbitrary units. Data are means ± SE; *: p < 0.01.