Lazzaris Coelho Paulo Henrique, Gomes Goncalves Natalia, Santos Itamar Souza, Goulart Alessandra C, Barreto Sandhi Maria, Giatti Luana, Caramelli Paulo, Lotufo Paulo A, Bensenor Isabela, Suemoto Claudia Kimie
Division of Geriatrics, University of São Paulo Medical School, Brazil.
Center for Clinical and Epidemiological Research, Hospital Universitário, University of São Paulo, Brazil.
Neurology. 2025 May 13;104(9):e213581. doi: 10.1212/WNL.0000000000213581. Epub 2025 Apr 11.
While midlife obesity is consistently associated with cognitive decline in later life, there is limited understanding of how weight variations from early life to midlife affect cognitive decline. We investigated the association between early- to midlife weight trajectories and mid- to late-life cognitive decline.
This is a longitudinal cohort study that used data from 3 waves (2008-2019) of the Brazilian Longitudinal Study of Adult Health, a multicenter cohort study that enrolled active and retired public servants aged 35+ years from public universities in Brazil. Participants with a history of stroke, missing cognitive data at baseline, and with incomplete body shape data were excluded from the analyses. Self-reported body shapes from ages 5 to 40 using the Stunkard Figure Rating Scale were categorized as underweight, normal, overweight, and obese. Sequence analysis and hierarchical clustering identified weight trajectories. Global cognition Z-scores were derived from memory (immediate recall, delayed recall, and recognition of a word list), phonemic and semantic verbal fluency, and Trail Making Test part B (TMT-B). Linear mixed models adjusted for sociodemographic, clinical, and lifestyle covariates investigated associations between clusters of weight trajectories and global cognition Z-scores. Inverse probability of attrition weighting was used to account for attrition bias.
Among 11,361 participants (mean age: 51.5 ± 8.6, 55% women, 42.4% Black/mixed race), "normal to overweight," "underweight to normal," and "stable overweight" trajectories exhibited faster global cognitive decline than "stable normal" trajectory (β = -0.024; 95% CI -0.043 to -0.005; = 0.015; β = -0.026; 95% CI -0.040 to -0.012; < 0.001; β = -0.034; 95% CI -0.066 to -0.001; = 0.043, respectively), representing 4.6-6.5 excess years of cognitive aging over a median follow-up of 8 years. Cognitive decline associated with weight trajectories was driven mainly by declines in memory and TMT-B performance. Associations were observed only in Black/mixed races and women when stratified.
Weight gain and stable overweight trajectories from early life to midlife were associated with faster cognitive decline than stable normal weight trajectories. Weight management during early life may mitigate cognitive decline. Study limitations include reliance on self-reported body shape data, potential recall bias, and residual confounding from unmeasured early-life factors.
虽然中年肥胖一直与晚年认知能力下降有关，但对于从早年到中年的体重变化如何影响认知能力下降的了解有限。我们研究了早年到中年的体重轨迹与中年到晚年认知能力下降之间的关联。
这是一项纵向队列研究，使用了巴西成人健康纵向研究3个波次（2008 - 2019年）的数据，该研究是一项多中心队列研究，纳入了巴西公立大学35岁及以上在职和退休的公务员。有中风病史、基线时认知数据缺失以及身体形态数据不完整的参与者被排除在分析之外。使用斯图卡德体型评定量表自我报告的5岁至40岁的体型被分为体重过轻、正常、超重和肥胖。序列分析和层次聚类确定了体重轨迹。全球认知Z分数来自记忆（即时回忆、延迟回忆和单词列表识别）、音素和语义语言流畅性以及连线测验B部分（TMT - B）。针对社会人口学、临床和生活方式协变量进行调整的线性混合模型研究了体重轨迹簇与全球认知Z分数之间的关联。使用失访加权的逆概率来解释失访偏差。
在11361名参与者中（平均年龄：51.5±8.6岁，55%为女性，42.4%为黑人/混血种族），“正常到超重”“体重过轻到正常”和“稳定超重”轨迹的全球认知下降速度比“稳定正常”轨迹更快（β = -0.024；95%置信区间 -0.043至 -0.005；P = 0.015；β = -0.026；95%置信区间 -0.040至 -0.012；P < 0.001；β = -0.034；95%置信区间 -0.066至 -0.001；P = 0.043），在8年的中位随访期内，认知衰老额外增加了4.6 - 6.5年。与体重轨迹相关的认知下降主要由记忆和TMT - B表现的下降驱动。分层时仅在黑人/混血种族和女性中观察到关联。
从早年到中年体重增加和稳定超重轨迹与稳定正常体重轨迹相比，与更快的认知下降相关。早年进行体重管理可能会减轻认知下降。研究局限性包括依赖自我报告的身体形态数据、潜在的回忆偏差以及未测量的早年因素导致的残余混杂。
