Aging, Mobility, and Cognitive Neuroscience Lab, Department of Physical Therapy, University of British Columbia, Vancouver, Canada.
Djavad Mowafaghian Centre for Brain Health C/O Liu-Ambrose Lab, 2215 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Biol Sex Differ. 2023 Apr 3;14(1):16. doi: 10.1186/s13293-023-00499-7.
Aerobic exercise promotes cognitive function in older adults; however, variability exists in the degree of benefit. The brain-derived neurotropic factor (BDNF) Val66Met polymorphism and biological sex are biological factors that have been proposed as important modifiers of exercise efficacy. Therefore, we assessed whether the effect of aerobic exercise on executive functions was dependent on the BDNFval66met genotype and biological sex.
We used data from a single-blind randomized controlled trial in older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Fifty-eight older adults were randomly assigned to either the 6 months, three times per week progressive aerobic training (AT) group or the usual care plus education control (CON) group. The secondary aim of the parent study included executive functions which were assessed with the Trail Making Test (B-A) and the Digit Symbol Substitution Test at baseline and trial completion at 6 months.
Analysis of covariance, controlling for baseline global cognition and baseline executive functions performance (Trail Making Test or Digit Symbol Substitution Test), tested the three-way interaction between experimental group (AT, CON), BDNFval66met genotype (Val/Val carrier, Met carrier), and biological sex (female, male). Significant three-way interactions were found for the Trail Making Test (F(1,48) = 4.412, p < 0.04) and Digit Symbol Substitution Test (F(1,47) = 10.833, p < 0.002). Posthoc analyses showed female Val/Val carriers benefited the most from 6 months of AT compared with CON for Trail Making Test and Digit Symbol Substitution Test performance. Compared with CON, AT did not improve Trail Making Test performance in male Val/Val carriers or Digit Symbol Substitution Test performance in female Met carriers.
These results suggest that future randomized controlled trials should take into consideration BDNF genotype and biological sex to better understand the beneficial effects of AT on cognitive function in vascular cognitive impairment to maximize the beneficial effects of exercise and help establish exercise as medicine for cognitive health.
有氧运动可促进老年人的认知功能；然而，其益处存在差异。脑源性神经营养因子（BDNF）Val66Met 多态性和生物性别是被认为是运动效果的重要调节因素的生物学因素。因此，我们评估了有氧运动对执行功能的影响是否取决于 BDNFval66met 基因型和生物性别。
我们使用了一项针对皮质下缺血性血管性认知障碍老年人的单盲随机对照试验（NCT01027858）的数据。58 名老年人被随机分配到为期 6 个月、每周 3 次的渐进性有氧运动（AT）组或常规护理加教育对照组（CON）。该研究的次要目的包括执行功能，在基线和 6 个月时使用连线测试（B-A）和数字符号替代测试进行评估。
协方差分析，控制基线整体认知和基线执行功能表现（连线测试或数字符号替代测试），测试了实验组（AT、CON）、BDNFval66met 基因型（Val/Val 携带者、Met 携带者）和生物性别（女性、男性）之间的三向相互作用。在连线测试（F(1,48) = 4.412，p < 0.04）和数字符号替代测试（F(1,47) = 10.833，p < 0.002）中发现了显著的三向相互作用。事后分析显示，与 CON 相比，6 个月的 AT 使女性 Val/Val 携带者在连线测试和数字符号替代测试中的表现获益最多。与 CON 相比，AT 并未改善男性 Val/Val 携带者的连线测试表现或女性 Met 携带者的数字符号替代测试表现。
这些结果表明，未来的随机对照试验应考虑 BDNF 基因型和生物性别，以更好地了解 AT 对血管性认知障碍认知功能的有益影响，从而最大限度地发挥运动的有益作用，并帮助确立运动作为认知健康的医学。
