Key Points:
- NR treatment was associated with increased blood flow to a brain region crucial for memory and mental skills related to organizing daily tasks after performing a cognition stimulation task.
- Taking NR was also associated with trends toward a modestly improved capacity to reason, recognize patterns, and devise solutions in unfamiliar circumstances.
Peripheral artery disease (PAD) is an age-related condition where arteries that carry blood to the limbs, especially the legs and feet, become narrowed or blocked by plaque buildup. This reduced blood flow can cause pain, numbness, and is even associated with impaired cognitive function.
As published in the Journal of Pharmacology and Experimental Therapeutics, Yabluchanskiy and colleagues from the University of Oklahoma unveil data suggesting that a nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide riboside (NR), improves blood flow to a certain brain region involved in memory and organization of daily tasks. This finding was obtained after participants completed a cognition-stimulating task. Furthermore, taking NR was also associated with statistical trends toward improved cognition as measured by a test of fluid cognition—the ability to think logically, solve problems, and adapt to new situations without any prior knowledge or experience. These findings suggest that, in patients with PAD, which can serve to exemplify accelerated vascular aging, taking NR may improve blood flow to the brain and modestly improve cognition.
The deteriorating cognitive function associated with PAD stems from reduced blood flow to the brain that hinders the brain’s intake of sufficient oxygen and nutrients. The condition, according to Yabluchanskiy and colleagues, can serve to exemplify accelerated vascular aging because it is caused by the age-related condition atherosclerosis in the limbs, which drives vascular plaque buildup. Furthermore, another age-related feature of PAD, vessel cell dysfunction, arises from a lack of nitric oxide (a blood vessel dilating molecule) in blood vessel walls. As such, nitric oxide reductions in blood vessels have been associated with aging in humans.
Along these lines, only one other human trial using NR in this condition with accelerated vascular aging—patients with PAD—had been performed. That study suggested that taking the NR improved physical function as measured by walking performance. Because the data from that study suggested the NAD+ precursor improves physical function, which declines in PAD patients, the Oklahoma-based researchers sought to test whether NR can improve another symptom of PAD—deteriorating cognition. To test NR’s possible effects on cognition, participants took 1,000 mg of NR daily for four weeks.
NR Enhances Blood Flow to a Particular Brain Region and Trends Toward Improving Cognition
Because research has suggested that reduced blood flow to the brain in patients with PAD facilitates the cognitive decline associated with this condition, Yabluchanskiy and colleagues tested whether taking NR improves blood flow to the brain. More specifically, the researchers measured brain blood perfusion after the performance of three separate tasks that stimulated cognition, which differed in their degree of difficulty. For example, the low-difficulty task, called the 0-back task, involved clicking a mouse whenever the letter W appeared on a screen throughout a presentation of various letters. The moderate-difficulty cognition-stimulating task, called the 1-back task, required clicking a mouse after a letter appeared twice in a row during a presentation of letter sequences (e.g., S-G-C-C). The higher-difficulty task, referred to as the 2-back task, involved clicking a mouse when a letter was repeated with one intervening letter (e.g., T-A-E-A).
Following a brief, 72-second round of each of these cognitive stimulation tasks, the researchers used a brain imaging technique to measure blood flow throughout the brain. Notably, they found a higher level of blood perfusion to a brain region called the left dorsolateral prefrontal cortex, a region crucial to memory and executive function (mental skills that help plan, organize, and manage daily tasks). Significantly higher levels of blood perfusion in the left dorsolateral prefrontal cortex were measured when comparing brain blood perfusion in the higher-difficulty 2-back task compared to either the 1-back task or the 0-back task. This effect on the dorsolateral prefrontal cortex was more robust after four weeks of taking NR compared to before treatment. These findings suggest that NR supplementation improves blood flow to the brain following tasks requiring increased cognitive function.
Since the left dorsolateral prefrontal cortex plays such a critical role in key aspects of cognition and because NR increased blood perfusion to this region, the researchers tested whether NR also improved facets of cognition. Along those lines, increased blood flow to any brain region has been associated with enhanced metabolism in that region, which may facilitate enhanced cognition. Interestingly, Yabluchanskiy and colleagues found a statistical trend where four weeks of NR treatment modestly enhanced fluid cognition compared to an assessment before taking NR. According to the researchers, this finding suggests that NR may modestly enhance the ability to think logically, solve problems, and adapt to new situations without relying on prior knowledge or experience.
Further Research Required with More Participants Over Longer Durations to Prove NR’s Possible Cognition-Enhancing Effects
The study from Yabluchanskiy and colleagues has some limitations. Notably, the study only had eight participants, making the likelihood of detecting a statistically significant effect that is real (the statistical power) lower. Moreover, the study only lasted four weeks, so perhaps a more significant effect on cognition could have arisen from taking NR over a longer time course, or perhaps administering NR for a longer period would show its effects on cognition are short-lived. Finally, this human study did not include a group of participants who did not take NR (a control group), making it more difficult to assert that NR has a causative effect on cognition.
Altogether, this study’s data gives some glimmer of hope that supplementing with NR may improve certain aspects of cognition during aging, when vascular function declines. Further research is needed to test NR on more participants with PAD over longer durations to add statistical power to any future study and to figure out whether NR’s possible cognition-enhancing effects are sustained. Furthermore, future studies assessing NR’s effects on patients with PAD should include a control group that does not receive NR to provide some clarity on whether NR causally improves cognition.
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