Sex Difference in Aerobic Exercise Efficacy to Improve Cognition in Older Adults with Vascular Cognitive Impairment: Secondary Analysis of a Randomized Controlled Trial

Abstract

Aerobic training (AT) is a promising, non-pharmacological intervention to mitigate the deleterious effects of aging and disease on brain health. However, a large amount of variation exists in its efficacy. This is a secondary analysis of a randomized controlled trial of AT in 71 older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Specifically, we investigated: 1) whether sex moderates the relationship between AT and executive functions, and 2) the role of brain derived neurotrophic factor (BDNF) and gains in functional fitness capacity. Older adults were randomly assigned to either 6-month, thrice-weekly AT or to usual care plus education (CON). At baseline, trial completion, and 6-month follow-up, executive functions were assessed with the Trail Making Test (A & B), verbal digits forward and backward test, and the Stroop Test. Functional fitness capacity was assessed with the 6-Minute Walk Test. Compared with CON, AT significantly improved Trail Making Test performance in females but not males, an effect that was retained at follow-up. AT significantly increased BDNF levels in females but decreased levels in males. On the other hand, AT led to significant gains in functional fitness capacity in males only. This study provides evidence that sex differences exist in AT efficacy on brain health as well as in the biological mechanisms subserving AT.

Sex differences in the effects of exercise on cognition post-stroke: Secondary analysis of a randomized controlled trial

“…While BDNF levels are known to decline with age, this decline is associated with cognitive impairment in older females only (61). Recently, it was reported that circulating levels of BDNF increased in older females following 6 months of aerobic training, whereas it decreased in males (62). Oestrogen has also been associated with greater BDNF expression in the hippocampus and cortex of females (63,64).…”

Sex differences in exercise efficacy to improve cognition: A systematic review and meta-analysis of randomized controlled trials in older humans

“…Furthermore, we have recently shown that 6 months of AT can indeed increase circulating levels of BDNF in the periphery in older women with mild subcortical ischemic vascular cognitive impairment, but decreases levels in men [124]. Thus, more studies focused on understanding the role of different exercise modalities on BDNF levels in women compared to men are required.…”

Sex differences in hippocampal cognition and neurogenesis

“…For example, studies indicate that exercise can offset cognitive decline with the type of exercise related to differential efficacy in men versus women [194] and indeed physical activity can increase hippocampal subregions differently in women versus men [195]. It is vital to understand what exercise regimen (or any type of treatment) may be more beneficial to men versus women to combat disease and agingrelated cognitive decline [194]. A number of studies demonstrate sex differences in associations between hippocampal adult neurogenesis and cognition.…”