35年人体测量指标与晚年血浆p-tau217及痴呆的关联：HUNT研究
基于挪威HUNT4队列8,797名≥70岁参与者，分析中年与晚年腰高比（WtHR）和体重指数（BMI）与血浆p-tau217及生物标志物确诊的阿尔茨海默病痴呆的关系。中年中心性与全身性肥胖与较高的晚年p-tau217浓度及生物标志物确诊AD痴呆风险升高相关，而晚年肥胖则呈相反关联。结果表明中年肥胖是可干预的AD病理与痴呆危险因素。
要点
- 中年WtHR≥0.60与晚年p-tau217浓度升高12.8%及生物标志物确诊AD痴呆风险升高相关。
- 晚年WtHR≥0.60与较低的p-tau217浓度及较低的生物标志物确诊AD痴呆风险相关。
- 中年中心性肥胖可能是可干预的AD病理与痴呆危险因素，WtHR有助于早期风险分层。
核心结论
- 中年中心性与全身性肥胖是AD病理和AD痴呆的可干预危险因素，WtHR或有助于早期风险分层并指导减脂干预。
研究设计与样本
- 挪威特伦德拉格健康研究（HUNT4，2017-19）队列研究，纳入8,797名≥70岁普通人群参与者，53.5%为女性，HUNT4时平均年龄77.8岁（SD 6.2）。
- WtHR测量3次（HUNT2-4，1995-2019），BMI测量4次（HUNT1-4，1984-2019），采用线性、逻辑回归及线性混合效应回归并调整人口学、APOE ε4、生活方式与心理健康因素。
主要发现
- 2,649人（30.1%）p-tau217阳性，659人（7%）为生物标志物确诊AD痴呆。
- 中年WtHR≥0.60者晚年p-tau217浓度高12.8%（95%CI 7.3-19.7），p-tau217阳性RRR 1.55（1.21-1.99），生物标志物确诊AD痴呆RRR 1.84（1.27-2.65），参照为WtHR<0.50。
- 晚年WtHR≥0.60者p-tau217浓度低15.6%（95%CI -19.0至-12.2），p-tau217阳性RRR 0.49（0.41-0.59），生物标志物确诊AD痴呆RRR 0.63（0.46-0.86）。
- BMI呈相似模式：中年肥胖与较高p-tau217浓度及生物标志物确诊AD痴呆风险升高相关，晚年超重/肥胖与较低p-tau217及较低风险相关。
- 在p-tau217阳性或生物标志物确诊AD痴呆者中，混合效应回归显示中年肥胖程度较高，至晚年发生逆转。
关键数值与推荐
- 血浆p-tau217浓度≥0.63 pg/mL定义为p-tau217阳性；p-tau217阳性结合临床痴呆诊断定义为生物标志物确诊AD痴呆。
- 中年WtHR≥0.60相较WtHR<0.50：晚年p-tau217浓度高12.8%（95%CI 7.3-19.7），p-tau217阳性RRR 1.55（1.21-1.99），生物标志物确诊AD痴呆RRR 1.84（1.27-2.65）。
- 晚年WtHR≥0.60：p-tau217浓度低15.6%（95%CI -19.0至-12.2），p-tau217阳性RRR 0.49（0.41-0.59），生物标志物确诊AD痴呆RRR 0.63（0.46-0.86）。
临床怎么用
- 可将中年WtHR作为AD早期风险分层的参考指标，识别中心性肥胖人群进行干预。
- 针对中年中心性脂肪堆积的减重干预可能有助于降低AD病理与痴呆风险。
- 晚年体重与脂肪指标与AD生物标志物的反向关联提示解读晚年肥胖指标时需考虑年龄与病程因素。
局限性
- 原文未报告局限性相关内容。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
BACKGROUND AND OBJECTIVES: Central and general adiposity have been linked to dementia risk, but their relation to blood-based Alzheimer disease (AD) biomarkers is unclear. We examined life course adiposity, measured by waist-to-height ratio (WtHR) and body mass index (BMI), in relation to plasma p-tau217 and to AD dementia verified by biomarker status. METHODS: In this cohort study, we included data on participants from the general population aged 70 years or older from the fourth wave of the Norwegian Trøndelag Health Study (HUNT4; 2017-19). Plasma p-tau217 was collected and standardized clinical cognitive assessments were performed at HUNT4. Plasma p-tau217 concentration at ≥0.63 pg/mL defined positive p-tau217. Positive p-tau217 coupled with a clinical dementia diagnosis defined biomarker-verified AD dementia. WtHR was measured 3 times (HUNT2-4; 1995-2019), and BMI was measured 4 times (HUNT1-4; 1984-2019). We performed linear, logistic, and linear mixed-effects regression adjusting for demographics, APOE ε4, lifestyle, and mental health. RESULTS: The final study sample comprised 8,797 participants (53.5% women, mean age at HUNT4 77.8 [SD 6.2]). Of these, 2,649 (30.1%) were p-tau217-positive and 659 (7%) had biomarker-verified AD dementia. Midlife WtHR ≥0.60 was associated with 12.8% (95% CI 7.3-19.7) higher late-life p-tau217 concentration and higher risk of positive p-tau217 (relative risk ratios [RRRs] 1.55, 1.21-1.99) and biomarker-verified AD dementia (RRR 1.84, 1.27-2.65) compared with WtHR <0.50. In late life, WtHR ≥0.60 was associated with 15.6% (-19.0 to -12.2) lower p-tau217 concentration and lower risk of positive p-tau217 (RRR 0.49, 0.41-0.59) and biomarker-verified AD dementia (RRR 0.63, 0.46-0.86). BMI showed similar patterns: Midlife obesity was associated with higher p-tau217 concentration and elevated risk of biomarker-verified AD dementia, whereas late-life overweight/obesity was associated with lower p-tau217 and decreased risk of biomarker-verified AD dementia. Among those with positive p-tau217 or biomarker-verified AD dementia, mixed-effects regression showed higher midlife adiposity, reversing by late life. DISCUSSION: Our results identify midlife central and general adiposity as modifiable risk factors for AD pathology and AD dementia. WtHR may aid early risk stratification and inform interventions targeting central fat reduction.
引用
- Zotcheva E, Strand BH, Sunde A, et al. Associations of Anthropometry Measures Across 35 Years With Late-Life Plasma P-tau217 and Dementia: The HUNT Study. Neurology. 2026. PMID: 42228892. doi:10.1212/WNL.0000000000218093
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。