Alzheimer's disease (AD) has become one of the most worrying problems for the elderly.
In the absence of relevant treatments, prevention is crucial. Substantial evidence suggests that lifestyle (eg, physical activity and cognitive stimulation) may attenuate age-related cognitive decline, delay the onset of AD, and enhance cognitive reserve (eg, thinking speed and memory) [1-6].
However, the benefits are actually "different from person to person".
Recently, Dr. Judy Pa from the University of California, San Diego, and her research team researchers published a study in Neurology [7] , showing that the more physical activities they participate in, the faster the thinking speed reserve of women , but not men. This association was observed . However, engaging in more mental activity was associated with increased mental speed reserve in both men and women .
At the same time, the AD risk gene APOE 4 can attenuate the benefits of physical activity and mental activity in women.
Although some meta-analyses of retrospective studies have shown that the relationship between exercise and cognition is stronger in women than in men [8,9], more recent prospective studies, including a randomized controlled trial of exercise, have shown Men experience a greater cognitive boost after exercise than women [10]. So who benefits more from exercise than men and women ?
It is well known that APOE 4 is a risk gene for AD. How, then, are the associations between lifestyle factors and cognitive reserve influenced by gender and APOE 4 ? To find out, the researchers designed the study using the Washington Heights-Inwood Columbia Project on Aging (WHICAP).
The study included 758 participants with an average age of 76 years and 62% were women. Of these, some had no thinking or memory problems (CN), some had mild cognitive impairment (MCI), and still others had dementia. Participants underwent brain scans, tests of thinking speed and memory, and APOE genotypes were determined using restricted isotyping [11].
To quantify lifestyle factors, the researchers used two measures of metabolic equivalents (METS) and cognitive activity (COGACT) . The METS was transformed from physical activity assessed using the Godin Recreational Exercise Questionnaire [12] and constructed as minutes × times × coefficient (9 for vigorous activity, 5 for moderate activity, and 3 for light activity).
COGACT is defined as the total score of participating in the following activities in the past 13 months: reading magazines, newspapers, or books; attending classes; playing cards or bingo [13]. Cognitive reserve is the buffer that people can have when they have strong thinking skills , and the study focused on memory and thinking speed reserves, tested by selective reminder tests (full recall, immediate recall, and delayed recall) and color tracking tests A and B respectively quantization [14].
研究者们首先分析了性别是如何改变生活方式因素与认知储备之间的关联的。在不考虑性别时，所有参与者的METS与思维速度储备呈正相关（β=0.05，95% CI: 0.01-0.08）。但性别分层分析显示，此关联仅在女性中存在（β=0.04，95% CI: 0-0.08），而男性中则未观察到。此外，无论男性还是女性，METS都与记忆储备无关（β=0.004，95% CI: -0.04-0.05）。
对于COGACT而言，所有参与者的COGACT与思维速度储备存在正相关（β=0.13，95% CI: 0.05-0.21），不因性别而异。但具体来看，性别差异还是有点明显，平均每多参加一次认知活动，思维处理速度的老化就会减少13年，如果根据性别区分，女性减少10年，男性减少17年。与此相反，虽然COGACT与记忆储备无关联（β=0.04，95% CI: -0.03-0.11），但性别分层分析显示，在女性中有正相关的趋势（β=0.06，95% CI: -0.02-0.14），而男性则不然。
紧接着，研究人员将关注点转移到APOE 4携带状态上，发现APOE 4等位基因的存在调节了女性METS与思维速度储备之间的关系（β=0.08，95% CI: 0-0.15）。即与APOE 4携带者相比，非携带者女性在METS和思维速度储备之间具有更强的关联（β=0.06，95% CI: 0.02-0.11），而男性则不受APOE 4等位基因调节。同时，APOE 4等位基因也不影响METS与记忆储备之间的关系。
与METS类似，APOE 4等位基因也调节了女性COGACT与思维速度储备之间的关系（β=0.24，95% CI: 0.03-0.44），即女性携带APOE 4会减弱COGACT与思维速度储备的有益关系（β=-0.11，95% CI: -0.31-0.09）。男性中并没有观察到显著的APOE 4调节。此外，在COGACT与记忆储备的关联中，也发现了女性中APOE 4的调节，不携带APOE 4会使COGACT与记忆储备的正相关变得显著（β=0.15，95% CI: 0.05-0.25）。
总的来说，该研究提出在生活方式因素对认知储备的有益关联中，性别和APOE 4携带状态是需要考虑的重要因素。
然而，本研究值得注意的一点是，活动分数来自参与者自我报告的问卷答案，而这可能因性别或认知障碍个体存在记忆偏差而导致结果不是那么准确。
未来的研究应利用客观活动水平（如加速度计）来测量体力活动，这将有助于确定该研究结果的有效性。此外，未来的研究需要检验生活方式活动与认知储备之间的因果关系，以及性别和APOE 4如何改变因果关系，这将有利于根据性别和APOE 4状态制定更精确的生活方式建议。
参考文献
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