老年人运动能力和认知能力下降的时间过程及其与脑部病变的关系:一项多队列研究

IF 13.4 Q1 GERIATRICS & GERONTOLOGY Lancet Healthy Longevity Pub Date : 2024-05-01 DOI:10.1016/S2666-7568(24)00033-3
Shahram Oveisgharan MD , Tianhao Wang PhD , Lisa L Barnes PhD , Julie A Schneider MD , David A Bennett MD , Aron S Buchman MD
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引用次数: 0

摘要

背景许多研究报告称,老年人的步态受损先于认知功能受损。我们的目的是描述老年人认知和运动能力下降的时间过程,以及这些下降与阿尔茨海默病和相关痴呆症的病理变化之间的联系。方法这项多队列研究使用了三项基于社区的队列研究(均在美国进行的宗教命令研究、拉什记忆与老龄化项目和少数族裔老龄化研究)的数据。这三项队列研究的纳入标准都是在入选时没有临床痴呆症,并同意每年进行临床评估。符合条件的参与者同意捐赠死后大脑,并接受死后病理评估和三次或三次以上的认知和运动功能年度重复测量。临床和尸检数据采用功能混合效应模型进行分析。总体认知能力基于19项神经心理学测试,手部力量评分基于握力和捏力,步态评分基于步行8英尺和360°转身的步数和时间。研究结果从 1994 年到 2022 年,共有 1570 名年龄在 65 岁或以上的符合条件的队列参与者,其中 1303 人进行了认知和运动测量并纳入分析。死亡时的平均年龄为 90-3 岁(SD 6-3),其中 905 人(69%)为女性,398 人(31%)为男性。随访时间中位数为 9 年(IQR 5-11)。平均而言,认知能力在死亡前的 25 到 15 年间保持稳定,之后认知能力开始下降。相比之下,步态功能和手部力量在整个研究期间都在下降。与认知能力和运动能力下降相关的阿尔茨海默病和相关痴呆症病理组合及其关联的起始时间各不相同;只有陶粒缠结、帕金森病病理和大梗死与所有三种表型的下降相关。Tau 蛋白结节与认知能力下降、步态功能下降和手部功能下降有明显的相关性(p<0-0001);然而,与认知能力下降的相关性在死亡前持续了11年以上,但与手部力量的相关性在死亡前3-57年才开始,与步态的相关性在死亡前3-49年才开始。相比之下,大面积脑梗塞与步态功能下降的关系始于死前9-25年(p<0-0001),而认知功能下降与步态功能下降的关系始于死前6-65年(p=0-0005),手部力量下降与步态功能下降的关系始于死前2-66年(p=0-024)。大梗死与认知功能衰退之前的步态功能衰退有关,但与 tau 蛋白缠结无关。这表明有必要进行进一步的研究,以检验步态障碍是否是临床前血管性认知障碍的临床代表。
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The time course of motor and cognitive decline in older adults and their associations with brain pathologies: a multicohort study

Background

Many studies have reported that impaired gait precedes cognitive impairment in older people. We aimed to characterise the time course of cognitive and motor decline in older individuals and the association of these declines with the pathologies of Alzheimer's disease and related dementias.

Methods

This multicohort study used data from three community-based cohort studies (Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study, all in the USA). The inclusion criteria for all three cohorts were no clinical dementia at the time of enrolment and consent to annual clinical assessments. Eligible participants consented to post-mortem brain donation and had post-mortem pathological assessments and three or more repeated annual measures of cognition and motor functions. Clinical and post-mortem data were analysed using functional mixed-effects models. Global cognition was based on 19 neuropsychological tests, a hand strength score was based on grip and pinch strength, and a gait score was based on the number of steps and time to walk 8 feet and turn 360°. Brain pathologies of Alzheimer's disease and related dementias were assessed at autopsy.

Findings

From 1994 to 2022, there were 1570 eligible cohort participants aged 65 years or older, 1303 of whom had cognitive and motor measurements and were included in the analysis. Mean age at death was 90·3 years (SD 6·3), 905 (69%) participants were female, and 398 (31%) were male. Median follow-up time was 9 years (IQR 5–11). On average, cognition was stable from 25 to 15 years before death, when cognition began to decline. By contrast, gait function and hand strength declined during the entire study. The combinations of pathologies of Alzheimer's disease and related dementias associated with cognitive and motor decline and their onsets of associations varied; only tau tangles, Parkinson's disease pathology, and macroinfarcts were associated with decline of all three phenotypes. Tau tangles were significantly associated with cognitive decline, gait function decline, and hand function decline (p<0·0001 for each); however, the association with cognitive decline persisted for more than 11 years before death, but the association with hand strength only began 3·57 years before death and the association with gait began 3·49 years before death. By contrast, the association of macroinfarcts with declining gait function began 9·25 years before death (p<0·0001) compared with 6·65 years before death (p=0·0005) for cognitive decline and 2·66 years before death (p=0·024) for decline in hand strength.

Interpretation

Our findings suggest that average motor decline in older adults precedes cognitive decline. Macroinfarcts but not tau tangles are associated with declining gait function that precedes cognitive decline. This suggests the need for further studies to test if gait impairment is a clinical proxy for preclinical vascular cognitive impairment.

Funding

National Institutes of Health.

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来源期刊
Lancet Healthy Longevity
Lancet Healthy Longevity GERIATRICS & GERONTOLOGY-
CiteScore
16.30
自引率
2.30%
发文量
192
审稿时长
12 weeks
期刊介绍: The Lancet Healthy Longevity, a gold open-access journal, focuses on clinically-relevant longevity and healthy aging research. It covers early-stage clinical research on aging mechanisms, epidemiological studies, and societal research on changing populations. The journal includes clinical trials across disciplines, particularly in gerontology and age-specific clinical guidelines. In line with the Lancet family tradition, it advocates for the rights of all to healthy lives, emphasizing original research likely to impact clinical practice or thinking. Clinical and policy reviews also contribute to shaping the discourse in this rapidly growing discipline.
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