脑白质病变可能是与年龄相关的认知能力下降的早期标志物。

White matter lesions may be an early marker for age-related cognitive decline.

机构信息

McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, H3A 2B4 Montreal, Quebec, Canada.

Department of Psychiatry, McGill University, H3A 1A1 Montreal, Quebec, Canada; Douglas Mental Health University Institute, Studies on Prevention of Alzheimer's Disease (StoP-AD) Centre, H4H 1R3 Montreal, Quebec, Canada.

出版信息

Neuroimage Clin. 2022;35:103096. doi: 10.1016/j.nicl.2022.103096. Epub 2022 Jun 22.

DOI:10.1016/j.nicl.2022.103096

PMID:35764028

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9241138/

Abstract

BACKGROUND

Research suggests that cerebral small vessel disease (CSVD), amyloid, and pTau contribute to age-related cognitive decline. It remains unknown how these factors relate to one another and how they jointly contribute to cognitive decline in normal aging. This project examines the association between these factors and their relationship to cognitive decline in cognitively unimpaired older adults without subjective cognitive decline.

METHODS

A total of 230 subjects with cerebrospinal fluid (CSF) Aß42, CSF pTau181, white matter lesions (WMLs) used as a proxy of CSVD, and cognitive scores from the Alzheimer's Disease Neuroimaging Initiative were included. Associations between each factor and cognitive score were investigated using regression models. Furthermore, relationships between the three pathologies were also examined using regression models.

RESULTS

At baseline, there was an inverse association between WML load and Aß42 (t = -4.20, p <.001). There was no association between WML load and pTau (t = 0.32, p = 0.75), nor with Aß42 and pTau (t = 0.51, p =.61). Correcting for age, sex and education, baseline WML load was associated with baseline ADAS-13 scores (t = 2.59, p =.01) and lower follow-up executive functioning (t = -2.84, p =.005). Baseline Aß42 was associated with executive function at baseline (t = 3.58, p<.004) but not at follow-up (t = 1.05, p = 0.30), nor with ADAS-13 at baseline (t = -0.24, p = 0.81) or follow-up (t = 0.09, p = 0.93). Finally, baseline pTau was not associated with any cognitive measure at baseline or follow-up.

CONCLUSION

Both baseline Aß42 and WML load are associated with some baseline cognition scores, but only baseline WML load is associated with follow-up executive functioning. This finding suggests that WMLs may be one of the earliest clinical manifestations that contributes to future cognitive decline in cognitively healthy older adults. Given that healthy older adults with WMLs exhibit declines in cognitive functioning, they may be less resilient to future pathology increasing their risk for cognitive impairment due to dementia than those without WMLs.

摘要

背景

研究表明，脑小血管疾病（CSVD）、淀粉样蛋白和 pTau 与年龄相关的认知能力下降有关。目前尚不清楚这些因素之间的关系以及它们如何共同导致正常衰老中的认知能力下降。本项目研究了这些因素之间的关联及其与无主观认知下降的认知正常老年人认知能力下降的关系。

方法

共纳入 230 名阿尔茨海默病神经影像学倡议的脑脊液（CSF）Aβ42、CSF pTau181、白质病变（WML）作为 CSVD 的替代标志物和认知评分的受试者。使用回归模型研究每个因素与认知评分之间的关联。此外，还使用回归模型检查了三种病理之间的关系。

结果

在基线时，WML 负荷与 Aβ42 呈负相关（t=-4.20，p<.001）。WML 负荷与 pTau 之间没有关联（t=0.32，p=0.75），也没有与 Aβ42 和 pTau 之间的关联（t=0.51，p=0.61）。在校正年龄、性别和教育程度后，基线 WML 负荷与基线 ADAS-13 评分相关（t=2.59，p=.01），与随访时的执行功能下降相关（t=-2.84，p=.005）。基线 Aβ42 与基线时的执行功能相关（t=3.58，p<.004），但与随访时的执行功能无关（t=1.05，p=0.30），与基线或随访时的 ADAS-13 也无关（t=-0.24，p=0.81）或（t=0.09，p=0.93）。最后，基线 pTau 与基线或随访时的任何认知测量均无关。

结论

基线 Aβ42 和 WML 负荷均与某些基线认知评分相关，但只有基线 WML 负荷与随访时的执行功能相关。这一发现表明，WML 可能是导致认知正常的老年人大脑健康认知能力下降的最早临床表现之一。鉴于有 WML 的健康老年人大脑认知功能下降，他们可能不如没有 WML 的人更有弹性，更容易因痴呆而导致认知障碍的潜在病理增加，从而增加认知障碍的风险。