生活方式、遗传风险、血浆pTau217与WRAP研究中的认知功能障碍发生率

Lifestyle, genetic risk, plasma pTau217, and incident cognitive impairment in WRAP.

作者信息

Studer Rachel L, Cody Karly A, Oomens Julie E, Reyes Ramiro Eduardo Rea, Chin Nathaniel A, Mueller Kimberly D, Hermann Bruce P, Wilson Rachael E, Langhough Rebecca E, Jonaitis Erin M, Johnson Sterling C

机构信息

Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, Wisconsin, USA.

Wisconsin Alzheimer's Disease Research Center, Department of Medicine, School of Medicine and Public Health, University of Wisconsin - Madison, Madison, Wisconsin, USA.

出版信息

Alzheimers Dement. 2025 Aug;21(8):e70573. doi: 10.1002/alz.70573.

DOI:10.1002/alz.70573

PMID:40799136

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12344448/

Abstract

INTRODUCTION

Whether lifestyle-based dementia risk in midlife impacts risk of incident cognitive impairment (ICI) in the presence of apolipoprotein E (APOE) ε4 allele or plasma pTau217 remains unknown.

METHODS

In initially cognitively unimpaired participants (N = 1088; baseline age, M(SD) = 57.8(6.5) years) from the Wisconsin Registry for Alzheimer's Prevention (WRAP), we investigated the relationship between lifestyle-based dementia risk (e.g., low, moderate, and high lifestyle-based risk tertiles) and risk of ICI when accounting for APOEε4 or plasma pTau217-ALZpath using Cox regressions (median follow-up years = 8.2(interquartile range [IQR]: 5.5-10.8)).

RESULTS

Less healthy lifestyle tertiles were associated with higher risk of ICI compared to the healthiest tertile across APOEε4 carriers and non-carriers (moderate, hazard ratio [HR] = 1.58, 95% confidence interval; [CI] 1.17-2.15, p = 0.003; high, HR = 2.08, 95% CI 1.56-2.76, p < 0.001) and across all pTau217 levels (moderate, HR = 1.63, 95% CI 1.20-2.21, p = 0.002; high, HR = 2.19, 95% CI 1.64-2.91, p < 0.001).

DISCUSSION

In WRAP, healthier lifestyle in midlife was associated with lower risk of ICI, regardless of APOEε4 carriage or pTau217 level.

HIGHLIGHTS

Healthier lifestyle is associated with reduced risk of incident impairment. Apolipoprotein E (APOE) ε4 allele carriage and pTau217 are associated with higher risk of incident impairment. No significant lifestyle risk by APOEε4 nor pTau217 interactions were observed. Combined lifestyle tertiles and APOEε4 carriage increased risk monotonically. Lifestyle tertiles increased impairment risk monotonically across pTau217 groups.

摘要

引言

在存在载脂蛋白E（APOE）ε4等位基因或血浆pTau217的情况下，中年时期基于生活方式的痴呆风险是否会影响新发认知障碍（ICI）的风险尚不清楚。

方法

在来自威斯康星州阿尔茨海默病预防登记处（WRAP）的最初认知未受损的参与者（N = 1088；基线年龄，M（标准差）= 57.8（6.5）岁）中，我们使用Cox回归（中位随访年限 = 8.2（四分位间距[IQR]：5.5 - 10.8））研究了基于生活方式的痴呆风险（例如，低、中、高生活方式风险三分位数）与考虑APOEε4或血浆pTau217 - ALZpath时的ICI风险之间的关系。

结果

与最健康的三分位数相比，在APOEε4携带者和非携带者中，健康生活方式较差的三分位数与ICI风险较高相关（中等，风险比[HR] = 1.58，95%置信区间[CI] 1.17 - 2.15，p = 0.003；高，HR = 2.08，95% CI 1.56 - 2.76，p < 0.001），并且在所有pTau217水平上也是如此（中等，HR = 1.63，95% CI 1.20 - 2.21，p = 0.002；高，HR = 2.19，95% CI 1.64 - 2.91，p < 0.001）。

讨论

在WRAP中，中年时期更健康的生活方式与较低的ICI风险相关，无论是否携带APOEε4或pTau217水平如何。

要点

更健康的生活方式与新发障碍风险降低相关。载脂蛋白E（APOE）ε4等位基因携带和pTau217与新发障碍风险较高相关。未观察到APOEε4或pTau217与生活方式风险之间的显著相互作用。综合生活方式三分位数和APOEε4携带情况会单调增加风险。生活方式三分位数在所有pTau217组中都会单调增加障碍风险。