Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
JAMA Psychiatry. 2022 Dec 1;79(12):1180-1187. doi: 10.1001/jamapsychiatry.2022.3446.
IMPORTANCE: Body mass index (BMI) trajectories before the onset of mild cognitive impairment (MCI) and during the progression from MCI to dementia remain unclear. OBJECTIVE: To assess the long-term BMI trajectories preceding incident MCI and dementia and explore whether they are associated with brain pathologies. DESIGN, SETTING, AND PARTICIPANTS: The Rush Memory and Aging Project (MAP) was an ongoing community-based cohort study. This study included cognitively intact participants aged 60 to 90 years at baseline with annual follow-up from October 1997 to December 2020 (maximum follow-up of 22 years). During the follow-up, participants underwent brain autopsies. Data were analyzed from August 2021 to February 2022 using mixed-effect models. EXPOSURES: BMI was calculated using height and weight measured at baseline and follow-ups. MAIN OUTCOMES AND MEASURES: Incident MCI and dementia were diagnosed following standard criteria. Neuropathological assessments (including global Alzheimer disease and vascular pathology) were performed for autopsies. RESULTS: A total of 1390 participants (mean [SD] age, 78.4 [6.5] years; 1063 female [76.5%]) were included in the study. In the analysis of BMI trajectories before MCI (n = 939), during the follow-up (median [IQR] duration, 6 [3-9] years), 371 participants (39.5%) developed MCI, of whom 88 (23.7%) progressed to dementia. Those who developed MCI were older (mean [SD] age, 79.6 [5.9] years vs 76.9 [6.6] years), consumed less alcohol (median [IQR] consumption, 0 [0-5.8] g/day vs 1.1 [0-6.9] g/day), had a lower BMI (mean [SD], 27.2 [4.9] vs 28.2 [5.9]), and were more likely to be apolipoprotein E (APOE) ε4 carriers (89 of 371 [24.0%] vs 98 of 568 [17.3%]) compared with those who remained cognitively intact over follow-up. Those who developed dementia were older (mean [SD] age, 81.0 [5.2] years vs 79.1 [6.0] years), had a lower level of physical activity (median [IQR] activity, 1.0 [0-2.5] h/week vs 1.8 [0.2-3.8] h/week), and were more likely to be APOE ε4 carriers than those who were dementia-free (33 of 88 [37.5%] vs 56 of 283 [19.8%]). Compared with participants who remained cognitively intact, in those with incident MCI, BMI tended to decline earlier and faster. From 7 years before diagnosis, people with incident MCI had an associated significantly lower BMI (mean difference, -0.96; 95% CI, -1.85 to -0.07) than those who were cognitively intact. Among people with incident MCI, the slopes of BMI decline did not differ significantly between those who did and did not develop dementia (β, -0.03; 95% CI, -0.21 to 0.15). In the analysis of BMI trajectories before autopsy (n = 358), BMI was associated with a faster declination among participants with a high burden of global Alzheimer disease pathology (β for pathology × time highest vs lowest tertile, -0.14; 95% CI, -0.26 to -0.02) or vascular pathology (β for pathology × time2 highest vs lowest tertile, 0.02; 95% CI, 0-0.05). CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that among cognitively intact people, significantly lower BMI occurs beginning approximately 7 years before MCI diagnosis. After MCI diagnosis, BMI declines at the same pace in people who develop dementia and those who do not. High brain pathologies may underly the BMI decline preceding dementing disorders.
重要性:轻度认知障碍 (MCI) 发病前和从 MCI 进展为痴呆期间的体重指数 (BMI) 轨迹仍不清楚。 目的:评估发病前 MCI 和痴呆的 BMI 轨迹,并探讨它们是否与脑病理有关。 设计、地点和参与者:Rush 记忆与衰老项目 (MAP) 是一项正在进行的基于社区的队列研究。本研究包括基线时年龄在 60 至 90 岁、认知正常的参与者,随访时间从 1997 年 10 月至 2020 年 12 月(最长随访时间 22 年)。在随访期间,参与者接受了脑部尸检。使用混合效应模型对 2021 年 8 月至 2022 年 2 月的数据进行了分析。 暴露情况:使用基线和随访时测量的身高和体重计算 BMI。 主要结果和测量:根据标准标准诊断出 MCI 和痴呆的发病情况。对尸检进行了神经病理学评估(包括全球阿尔茨海默病和血管病理学)。 结果:共纳入 1390 名参与者(平均年龄 [标准差],78.4 [6.5] 岁;1063 名女性 [76.5%])。在 MCI 前 BMI 轨迹分析中(n = 939),在随访期间(中位数 [IQR] 持续时间,6 [3-9] 年),371 名参与者(39.5%)发展为 MCI,其中 88 名(23.7%)进展为痴呆。发展为 MCI 的参与者年龄更大(平均年龄 [标准差],79.6 [5.9] 岁 vs 76.9 [6.6] 岁),饮酒量较少(中位数 [IQR] 饮酒量,0 [0-5.8] g/天 vs 1.1 [0-6.9] g/天),BMI 较低(平均 [标准差],27.2 [4.9] vs 28.2 [5.9]),载脂蛋白 E (APOE) ε4 携带者的比例更高(371 名中的 89 名 [24.0%] vs 568 名中的 98 名 [17.3%]),与在随访期间保持认知正常的参与者相比。发展为痴呆的参与者年龄更大(平均年龄 [标准差],81.0 [5.2] 岁 vs 79.1 [6.0] 岁),身体活动水平较低(中位数 [IQR] 活动量,1.0 [0-2.5] 小时/周 vs 1.8 [0.2-3.8] 小时/周),载脂蛋白 E (APOE) ε4 携带者的比例高于无痴呆的参与者(88 名中的 33 名 [37.5%] vs 283 名中的 56 名 [19.8%])。与认知正常的参与者相比,在患有 MCI 的参与者中,BMI 更早且更快地下降。从发病前 7 年开始,患有 MCI 的人就与明显较低的 BMI 相关(平均差异,-0.96;95%CI,-1.85 至 -0.07),与认知正常的人相比。在患有 MCI 的人群中,发展为痴呆和不发展为痴呆的参与者之间,BMI 下降的斜率没有显著差异(β,-0.03;95%CI,-0.21 至 0.15)。在尸检前 BMI 轨迹分析中(n = 358),BMI 与高全球阿尔茨海默病病理负担的参与者(β 为病理量 × 时间最高与最低三分位数,-0.14;95%CI,-0.26 至 -0.02)或血管病理(β 为病理量 × 时间最高与最低三分位数,0.02;95%CI,0-0.05)的更快下降相关。 结论和相关性:这项队列研究的结果表明,在认知正常的人群中,在 MCI 诊断前约 7 年,BMI 明显下降。在 MCI 诊断后,发展为痴呆和不发展为痴呆的患者的 BMI 下降速度相同。大脑病理的增加可能是痴呆前疾病中 BMI 下降的基础。
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