Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.
Alzheimers Res Ther. 2024 Aug 29;16(1):194. doi: 10.1186/s13195-024-01563-z.
Increasing evidence supports the association between body mass index (BMI), Alzheimer's disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer's and vascular markers in relation to metabolic health status.
We recruited 1,736 Asians without dementia (71.6 ± 8.0 years). Participants were categorized into underweight, normal weight, or obese groups based on their BMI. Each group was further divided into metabolically healthy (MH) and unhealthy (MU) groups based on the International Diabetes Foundation definition of metabolic syndrome. The main outcome was Aβ positivity, defined as a Centiloid value of 20.0 or above and the presence of vascular markers, defined as severe white matter hyperintensities (WMH). Logistic regression analyses were performed for Aβ positivity and severe WMH with BMI status or interaction terms between BMI and metabolic health status as predictors. Mediation analyses were performed with hippocampal volume (HV) and baseline Mini-Mental State Examination (MMSE) scores as the outcomes, and linear mixed models were performed for longitudinal change in MMSE scores.
Being underweight increased the risk of Aβ positivity (odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.13-4.98), whereas obesity decreased Aβ positivity risk (OR = 0.63, 95% CI 0.50-0.80). Especially, obesity decreased the risk of Aβ positivity (OR = 0.38, 95% CI 0.26-0.56) in the MH group, but not in the MU group. Obesity increased the risk of severe WMH (OR = 1.69, 1.16-2.47). Decreased Aβ positivity mediate the relationship between obesity and higher HV and MMSE scores, particularly in the MH group. Obesity demonstrated a slower decline in MMSE (β = 1.423, p = 0.037) compared to being normal weight, especially in the MH group.
Our findings provide new evidence that metabolic health has a significant effect on the relationship between obesity and Alzheimer's markers, which, in turn, lead to better clinical outcomes.
越来越多的证据支持体重指数（BMI）、阿尔茨海默病和血管标志物之间的关联。最近，代谢不健康的状况已被报道会影响这些标志物的表达。我们旨在研究 BMI 状态对与代谢健康状态相关的阿尔茨海默病和血管标志物的影响。
我们招募了 1736 名没有痴呆症的亚洲人（71.6±8.0 岁）。根据 BMI，参与者被分为体重不足、正常体重或肥胖组。根据国际糖尿病基金会代谢综合征的定义，每个组进一步分为代谢健康（MH）和代谢不健康（MU）组。主要结局是 Aβ 阳性，定义为 Centiloid 值为 20.0 或更高，以及血管标志物，定义为严重的脑白质高信号（WMH）。使用 BMI 状态或 BMI 和代谢健康状态之间的交互项作为预测因子，进行逻辑回归分析以评估 Aβ 阳性和严重 WMH。使用海马体积（HV）和基线简易精神状态检查（MMSE）评分作为结果进行中介分析，并使用线性混合模型进行 MMSE 评分的纵向变化。
体重不足会增加 Aβ 阳性的风险（比值比[OR] = 2.37，95%置信区间[CI] 1.13-4.98），而肥胖则降低 Aβ 阳性的风险（OR = 0.63，95% CI 0.50-0.80）。特别是，肥胖降低了 MH 组 Aβ 阳性的风险（OR = 0.38，95% CI 0.26-0.56），但在 MU 组没有降低。肥胖增加了严重 WMH 的风险（OR = 1.69，1.16-2.47）。降低的 Aβ 阳性介导了肥胖与更高的 HV 和 MMSE 评分之间的关系，特别是在 MH 组。与正常体重相比，肥胖组 MMSE 的下降速度较慢（β = 1.423，p = 0.037），特别是在 MH 组。
我们的研究结果提供了新的证据，表明代谢健康对肥胖与阿尔茨海默病标志物之间的关系有重要影响，进而导致更好的临床结局。
