Reaping the Rewards of Resveratrol: How This Compound Boosts Cognition in Postmenopausal Women

Reduced cognitive function and problems with blood flow to the brain are emerging as the leading causes of death in older women. Plus, women aged over 55 years have a greater risk of cardiovascular issues than their male counterparts or younger women. Aging and menopause contribute to dysfunction of blood vessels, causing impaired brain blood flow and accelerated cognitive decline.

Recent clinical trial data from Thuang Zaw and colleagues showed that supplementation with low-dose resveratrol for one year improved blood flow to the brain and cognitive functions in postmenopausal women. This may translate into a slowing of the accelerated cognitive decline due to aging and menopause, especially in late-life women. Further studies are warranted to observe whether these cognitive benefits of resveratrol can reduce the risk of more serious cognitive decline.

“To our knowledge, this is the longest resveratrol trial conducted to evaluate its benefits on multiple aspects of healthy aging in community-dwelling postmenopausal women,” said Thuang Zaw and colleagues. “Our findings provide justification for adopting resveratrol as an effective, non-pharmacological intervention to counteract age- and menopause-related cognitive decline in elderly women,” proposed the research team.

Loss of Estrogen Causes Postmenopausal Brains to Go to Pot

The cognitive decline and problems with blood flow to the brain seen in postmenopausal women can be partly attributed to the rapid mid-life decline in circulating estrogen following menopause. Estrogen is important for memory retention, metabolic regulation, and bone health in premenopausal women. Hence, the loss of estrogen may accelerate age-related cognitive impairment and increase the risk of cardiovascular and cerebrovascular diseases.

Estrogen acts on estrogen receptors on the lining of blood vessels to relax them, causing them to widen and increase circulation. So, the loss of circulating estrogen following menopause negatively impacts the microcirculation, resulting in accelerated arterial stiffening, reduced tissue perfusion, and consequently diminished functionality of tissues and organs.

Estrogen deprivation in postmenopausal women has been shown to reduce the responsiveness of blood vessels in the brain compared to premenopausal women and age-matched men. Reduced blood flow — and, thus, reduced delivery of oxygen and nutrients — in brain regions both at rest and during cognitive demands is in turn linked with cognitive impairment. Reduced responsiveness of brain blood vessels has also been shown to be a predictor of poor cognitive performance in healthy postmenopausal women. So, optimal circulatory function, especially in the brain, is crucial for maintaining cognitive functions.

A potential approach to counteract age- and estrogen deficiency-related endothelial dysfunction is to supplement the diet with resveratrol. It is well established that resveratrol can act through multiple pathways via estrogen receptors to increase the production and bioavailability of nitric oxide — the molecule responsible for relaxing blood vessels.

Resveratrol Restores Brain Blood Flow and Cognition in Postmenopausal Women

Previously, Thuang Zaw and colleagues showed that regular supplementation with resveratrol can improve blood vessel relaxation both throughout the body and in the brain. In a 14-week pilot study in postmenopausal women, they found that, compared to placebo, supplementing with 75 mg of resveratrol twice per day resulted in a sustained enhancement of neurovascular coupling — alterations in brain blood flow that occur in response to changes in neuronal activity. This, in turn, was accompanied by an improved cognitive performance.

Now, the research team aimed to confirm this preliminary finding in a larger, longer-term crossover-design trial. The primary study outcome, overall cognitive performance, was significantly improved by resveratrol and this was reflected by small improvements in each cognitive domain that was assessed. Although the effect on overall cognitive performance was also small, it may still be clinically important, as aging studies have shown that certain cognitive abilities, especially information processing and mental flexibility, decline at an annual rate after the third decade of life. Thus, the observed improvement in cognitive performance may sufficiently delay the progression of cognitive impairment, particularly in late-life.

The improvements in cognition with low-dose resveratrol were accompanied by improvements in cerebral blood flow and perfusion of brain regions at rest and in response to increased cognitive demands. The lining of the brain’s blood vessels microvasculature mediates the acute increases in cerebral blood flow in response to various stimuli. Hence, interventions to reverse or delay cerebral endothelial dysfunction could have important implications for cognitive function in older adults.

Women in late-life (≥65 years old) benefitted more than the younger women from long-term resveratrol supplementation in terms of improved verbal memory (verbal learning and short- and long-term recall), which correlated with improvements in overall neurovascular coupling. Verbal memory involves information acquisition, retention, and retrieval, such as learning a new telephone number or remembering the daily schedule.

“We have shown in our subgroup analysis that women ≥65 years old could preserve their overall cognitive performance at least partially through resveratrol-induced improvements in cerebral vasodilator function,” conclude Thuang Zaw and colleagues. “Altogether, counteracting cerebral endothelial dysfunction with long-term resveratrol supplementation could be a potential strategy to delay accelerated cognitive decline in postmenopausal women, particularly at late-life.”

Proving Preventative Strategies for Aging Brains

The researchers propose that these benefits can be attributed, at least in part, to attenuation of the age-related decline of cerebrovascular function by long-term resveratrol supplementation. The low dose of resveratrol used was so well-tolerated that no attributable side effects were observed.

Considering the lack of preventive strategies with demonstrated efficacy to counteract cognitive aging, particularly in late-life women, resveratrol offers a viable option. It is unknown whether older men would also derive the same benefits. Future prospective studies are required to see whether the attenuation of cognitive decline by resveratrol can translate into a reduced risk of more serious cognitive decline in at-risk populations.

References:

Thaung Zaw JJ, Howe PR, Wong RH. Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study. Clin Nutr. 2021;40(3):820-829. doi:10.1016/j.clnu.2020.08.025