Cannon Ethan J, Windham B Gwen, Griswold Michael, Palta Priya, Knopman David S, Sedaghat Sanaz, Lutsey Pamela L
Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis.
Division of Geriatrics, Department of Medicine, University of Mississippi Medical Center, Jackson.
Neurology. 2025 May 13;104(9):e213534. doi: 10.1212/WNL.0000000000213534. Epub 2025 Apr 11.
Midlife obesity is a risk factor of dementia, but late-life obesity has been associated with lower dementia risk. We investigated this paradox by exploring the relationship between late-life body mass index (BMI) category and dementia, with and without considering midlife to late-life BMI change.
This observational cohort study included participants of the community-based Atherosclerosis Risk in Communities (ARIC) study who were dementia-free at visit 5 (2011-2013). Dementia was ascertained by expert-adjudicated, algorithmic classification from an in-person neuropsychological battery, as well as telephone interviews and International Classification of Diseases codes from medical records. We first assessed the association of incident dementia with visit 5 BMI categories (normal weight, overweight, obese). Next, we used a cross-classification of visit 5 BMI categories with visit 4-visit 5 BMI change (decrease [loss of ≥2 kg/m], increase [gain of ≥2 kg/m], or stable [loss or gain of <2 kg/m]) occurring during the 15 years before baseline. Cox regression was used.
A total of 5,129 participants were included in the study (59% female; 22% identified as Black; mean (standard deviation) age at visit 5 of 75 (5) years). Over 8 years of follow-up, 20% of the sample developed dementia (n = 1,026). After covariate adjustment, participants with high late-life BMI had a lower risk of dementia; the hazard ratio (95% CI) was 0.86 (0.73-1.00) for overweight and 0.81 (0.68-0.96) for obesity. In stratified models, elevated dementia risk was observed only for participants of each late-life BMI category whose BMI had decreased from midlife to late life. Compared with normal-weight individuals who had maintained BMI from midlife to late life, the hazard ratio (95% CI) for those with BMI loss was 2.08 (1.62-2.67) for normal-weight individuals, 1.62 (1.25-2.10) for those with overweight, and 1.36 (1.00-1.85) for those with obesity.
Our results provide insight into the dementia obesity paradox at older ages, tempering a causal interpretation of high late-life BMI as protective against dementia. Instead, they highlight the importance of considering weight loss from midlife to late life in conjunction with late-life BMI in dementia risk stratification.
中年肥胖是痴呆症的一个风险因素，但晚年肥胖却与较低的痴呆症风险相关。我们通过探讨晚年体重指数（BMI）类别与痴呆症之间的关系来研究这一矛盾现象，同时考虑和不考虑从中年到晚年的BMI变化情况。
这项观察性队列研究纳入了基于社区的动脉粥样硬化风险社区（ARIC）研究的参与者，这些参与者在第5次随访（2011 - 2013年）时未患痴呆症。通过专家判定、基于面对面神经心理测试组合的算法分类，以及电话访谈和病历中的国际疾病分类编码来确定痴呆症。我们首先评估了新发痴呆症与第5次随访时的BMI类别（正常体重、超重、肥胖）之间的关联。接下来，我们对第5次随访时的BMI类别与基线前15年期间发生的第4次随访至第5次随访的BMI变化（降低[体重减轻≥2 kg/m²]、增加[体重增加≥2 kg/m²]或稳定[体重减轻或增加<2 kg/m²]）进行交叉分类。使用Cox回归分析。
共有5129名参与者纳入研究（59%为女性；22%为黑人；第5次随访时的平均（标准差）年龄为75（5）岁）。在超过8年的随访中，20%的样本患了痴呆症（n = 1026）。经过协变量调整后，晚年BMI高的参与者患痴呆症的风险较低；超重者的风险比（95%CI）为0.86（0.73 - 1.00），肥胖者为0.81（0.68 - 0.96）。在分层模型中，仅在每个晚年BMI类别中BMI从中年到晚年下降的参与者中观察到痴呆症风险升高。与从中年到晚年维持BMI的正常体重个体相比，BMI下降的正常体重个体的风险比（95%CI）为2.08（1.62 - 2.67），超重者为1.62（1.25 - 2.10），肥胖者为1.36（1.00 - 1.85）。
我们的结果为老年痴呆症与肥胖的矛盾现象提供了见解，弱化了将晚年高BMI视为预防痴呆症的因果解释。相反，它们强调了在痴呆症风险分层中，结合晚年BMI考虑从中年到晚年体重减轻的重要性。
