Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study.
Association of lifelong exposure to cognitive reserve-enhancing factors with dementia risk: A community-based cohort study.
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DOI：
10.1371/journal.pmed.1002251
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发表时间：
2017-03
期刊：
影响因子：
15.8
通讯作者：
Fratiglioni L
中科院分区：
文献类型：
--
作者：
Wang HX;MacDonald SW;Dekhtyar S;Fratiglioni L
痴呆症临床表现的变化与认知储备的差异有关，尽管对认知储备因素在生命过程中的累积效应知之甚少。我们在一个以社区为基础的老年人队列中研究了认知储备相关因素与痴呆风险之间的关系。1987-1989年，在瑞典斯德哥尔摩的Kungsholmen区，收集了一组75岁以上的无痴呆症社区居民的早期教育、社会经济地位、20岁时工作复杂性、中年职业成就和晚年休闲活动的信息。该队列随访至9年（直到1996年），以检测痴呆事件。为了排除疾病的临床前阶段，在基线后3年首次随访检查时发生痴呆的参与者被排除在外（排除后n = 602）。使用结构方程模型从生命过程中的三个阶段产生认知储备的潜在因素：早期（20岁之前），成年期（30-55岁左右）和晚期（75岁及以上）。早期和成年期的潜在因素之间的相关性很强（γ = 0.9），而早期-晚期（γ = 0.27）和成年-晚期（γ = 0.16）的潜在因素之间的相关性很弱。148名参与者在随访期间患上了痴呆症，454名没有患上痴呆症。使用考克斯模型估计痴呆的相对危险度（RR），分别和同时对生命过程认知储备增强因素进行建模，以评估直接和间接影响。在载脂蛋白E（APOE）ε4等位基因携带者和非携带者中重复分析。在单独的多变量考克斯模型中，痴呆风险降低与早期（RR 0.57; 95% CI 0.36-0.90）、成人（RR 0.60; 95% CI 0.42-0.87）和晚年（RR 0.52; 95% CI 0.37-0.73）储备增强潜在因素相关。在一个相互调整的模型中，由于早期和成年因素之间的强相关性，该模型可能被不精确地估计，但晚年因素保留了其相关性（RR 0.65; 95% CI 0.45-0.94），而中年的影响（RR 0.73; 95% CI 0.50-1.06）和早期生活因素（RR 0.76; 95% CI 0.47-1.23）对痴呆风险的影响减弱。随着对增强储备的潜在因素的累积暴露，风险逐渐下降，并且在生命历程的所有三个阶段中，认知储备增强复合因素得分高与痴呆风险最低相关（RR 0.40; 95%CI 0.20-0.81）。在APOE ε4等位基因携带者和非携带者中检测到类似的关联。局限性包括测量误差和无应答，这两种偏倚都可能有利于零。早期和成年的潜在因素之间的强相关性可能导致损失的精度时，估计相互调整的影响，所有时期。在这项研究中，在一生中累积暴露于储备增强因子与老年痴呆症风险降低有关，即使是在具有遗传倾向的个体中。在一项以社区为基础的队列研究中，Serhiy Dekhtyar及其同事研究了在早期，中期和晚期参与各种认知储备增强因素与75岁后痴呆并发症风险之间的关联。从以前的文献中可以看出，生活方式因素，如体育锻炼，智力刺激或休闲活动与老年痴呆症发生风险降低有关。一种可能性是，这些活动以储备的形式提供保护，在面对累积的脑损伤时促进认知功能的维持。然而，在很大程度上仍然不清楚痴呆症的风险是如何通过在整个生命过程中同时发生的各种储备刺激生活方式因素形成的。我们的研究旨在检查75岁以后痴呆症发生的风险与整个生命过程中参与各种储备增强活动之间的关联。我们估计了一组75岁及以上的老年人患痴呆症的风险，条件是他们参与了10项活动，这些活动预计将在生命过程的三个阶段促进储备。我们发现，就其本身而言，参与早期，成年和晚年的储备增强活动与痴呆症的风险降低有关。然而，当同时评估所有三个因素与痴呆症的相关性时，早期生活和成年因素的影响减弱了。这可能是由于早期生活和成年因素之间的强相关性，而晚年的因素只是适度相关的早期生活或成年标志物的储备。一个重要的发现是，在生命过程中参与刺激活动的频率增加与痴呆症风险的逐步降低有关，这表明生命过程储备和痴呆症风险之间存在剂量反应效应。这种效应似乎与痴呆症的遗传易感性无关。这些发现强烈表明，痴呆症的发展是一个终身的过程，在疾病发作前几十年就开始了。与此同时，启动旨在改变风险的干预措施永远不会太晚，因为晚年参与刺激活动与痴呆症风险降低有关。然而，由于储备增强活动在整个生命过程中是相互关联的，而且由于刺激性活动频率增加的个人所享有的风险最低，因此最有效的策略可能是那些强调在整个生命过程中减少风险的策略。
Variation in the clinical manifestation of dementia has been associated with differences in cognitive reserve, although less is known about the cumulative effects of exposure to cognitive reserve factors over the life course. We examined the association of cognitive reserve-related factors over the lifespan with the risk of dementia in a community-based cohort of older adults. Information on early-life education, socioeconomic status, work complexity at age 20, midlife occupation attainment, and late-life leisure activities was collected in a cohort of dementia-free community dwellers aged 75+ y residing in the Kungsholmen district of Stockholm, Sweden, in 1987–1989. The cohort was followed up to 9 y (until 1996) to detect incident dementia cases. To exclude preclinical phases of disease, participants who developed dementia at the first follow-up examination 3 y after the baseline were excluded (n = 602 after exclusions). Structural equation modelling was used to generate latent factors of cognitive reserve from three periods over the life course: early (before 20 y), adulthood (around 30–55 y), and late life (75 y and older). The correlation between early- and adult-life latent factors was strong (γ = 0.9), whereas early–late (γ = 0.27) and adult–late (γ = 0.16) latent factor correlations were weak. One hundred forty-eight participants developed dementia during follow-up, and 454 remained dementia-free. The relative risk (RR) of dementia was estimated using Cox models with life-course cognitive reserve-enhancing factors modelled separately and simultaneously to assess direct and indirect effects. The analysis was repeated among carriers and noncarriers of the apolipoprotein E (APOE) ε4 allele. A reduced risk of dementia was associated with early- (RR 0.57; 95% CI 0.36–0.90), adult- (RR 0.60; 95% CI 0.42–0.87), and late-life (RR 0.52; 95% CI 0.37–0.73) reserve-enhancing latent factors in separate multivariable Cox models. In a mutually adjusted model, which may have been imprecisely estimated because of strong correlation between early- and adult-life factors, the late-life factor preserved its association (RR 0.65; 95% CI 0.45–0.94), whereas the effect of midlife (RR 0.73; 95% CI 0.50–1.06) and early-life factors (RR 0.76; 95% CI 0.47–1.23) on the risk of dementia was attenuated. The risk declined progressively with cumulative exposure to reserve-enhancing latent factors, and having high scores on cognitive reserve-enhancing composite factors in all three periods over the life course was associated with the lowest risk of dementia (RR 0.40; 95% CI 0.20–0.81). Similar associations were detected among APOE ε4 allele carriers and noncarriers. Limitations include measurement error and nonresponse, with both biases likely favouring the null. Strong correlation between early- and adult-life latent factors may have led to a loss in precision when estimating mutually adjusted effects of all periods. In this study, cumulative exposure to reserve-enhancing factors over the lifespan was associated with reduced risk of dementia in late life, even among individuals with genetic predisposition. In a community-based cohort study, Serhiy Dekhtyar and colleagues examine the association between engagement in various cognitive reserve-enhancing factors at early, mid, and late life and risk of dementia concurrence after 75. It has emerged from previous literature that lifestyle factors such as physical exercise, intellectual stimulation, or leisure activities are associated with a reduced risk of dementia occurrence in late life. One possibility is that these activities provide protection in the form of reserve, facilitating the maintenance of cognitive function in the face of cumulative brain damage. It is, however, still largely unknown how the risk of dementia is shaped by various reserve-stimulating lifestyle factors simultaneously taking place throughout the entire life course. Our study was designed to examine the association between the risk of dementia occurrence after age 75 and engagement in a variety of reserve-enhancing activities over the entire life course. We estimated the risk of dementia occurrence in a cohort of individuals aged 75 y and older conditional on their engagement in ten activities that were expected to promote reserve in three stages over the life course. We found that, on its own, engagement in early-, adulthood-, and late-life reserve-enhancing activities was associated with a reduced risk of dementia. However, when all three factors were simultaneously evaluated for their association with dementia, the effects of early-life and adulthood factors were attenuated. This could be due to the strong correlation between early-life and adulthood factors, whereas the late-life factor was only moderately related to either early-life or adulthood markers of reserve. An important finding was that increased frequency of engagement in stimulating activities over the life course was associated with a progressively reduced risk of dementia, suggesting a dose-response effect between life-course reserve and dementia risk. This effect appeared to operate irrespective of genetic predisposition to dementia. These findings strongly suggest that development of dementia is a lifelong process that begins decades before the onset of the disease. At the same time, it is never too late to initiate interventions aimed at risk modifying, since late-life engagement in stimulating activities was associated with a lower risk of dementia. However, because reserve-enhancing activities are correlated over the life course, and because the lowest risk is enjoyed by individuals with increased frequency of stimulating engagements, the most effective strategies are likely to be those emphasizing risk reduction throughout the entire life course.