Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Neuroepidemiology. 2022;56(3):183-191. doi: 10.1159/000524731. Epub 2022 May 2.
This study aimed to characterize the association of cognitive decline starting in midlife with brain pathology in late life in the absence of dementia.
Nondemented Atherosclerosis Risk in Communities participants with brain imaging, all cognitive factor scores (CFSs), and nonmissing covariates were included. CFSs were collected at three visits across 21 years (1990-2013) (short-term cognitive change [1990-1996], long-term cognitive change [1990-2013]), and brain magnetic resonance imaging and florbetapir positron emission tomography (PET) imaging were collected in 2011-13 (PET subset n = 327). Outcomes of interest were total and regional brain volumes (cm3), log2 (white matter hyperintensity volume), white matter integrity (fractional anisotropy, mean diffusivity), ≥1 lacunar infarct (3-20 mm), and elevated brain β-amyloid (SUVR >1.2). Multivariable linear/logistic regression related outcomes to CFS slopes after adjusting for demographics and total intracranial volume.
At baseline, the 1,734 participants had a mean (SD) age of 55 (5.2) years, and were 60% female and 26% Black. After adjustment, a 1-SD larger long-term decline in CFS was associated with a smaller relative total brain volume by 1.2% (95% CI: 1.0, 1.5), a smaller relative temporal lobe meta region volume by 1.9% (1.5, 2.3), a 13% (9, 17) larger volume of white matter hyperintensities, a 1.3-fold (1.2, 1.4) higher odds of having ≥1 lacune, and 1.7-fold (1.3, 2.2) higher odds of elevated brain β-amyloid deposition and worse white matter integrity. Some long-term associations were also found for midlife short-term declines in CFS.
This study provides evidence that starting in midlife, short-term and long-term declines in cognition are associated with multiple deleterious late-life differences in nondemented brains.
本研究旨在探讨在无痴呆的情况下，从中年开始认知能力下降与晚年大脑病理之间的关联。
纳入了有脑成像、所有认知因子评分（CFS）和非缺失协变量的无痴呆动脉粥样硬化风险社区参与者。CFS 在 21 年内的 3 次就诊中收集（1990-1996 年短期认知变化，1990-2013 年长期认知变化），并于 2011-13 年收集脑磁共振成像和氟比他滨正电子发射断层扫描（PET）成像（PET 子集中 n=327）。感兴趣的结局包括总脑容量（cm3）、区域脑容量、log2（脑白质高信号体积）、脑白质完整性（各向异性分数、平均弥散度）、≥1 个腔隙性梗死（3-20mm）和脑β-淀粉样蛋白升高（标准化摄取值比 SUVR＞1.2）。多变量线性/逻辑回归在调整人口统计学和总体颅内体积后，将结局与 CFS 斜率相关联。
在基线时，1734 名参与者的平均（SD）年龄为 55（5.2）岁，60%为女性，26%为黑人。调整后，CFS 长期下降 1 个标准差与总脑容量相对减少 1.2%（95%CI：1.0，1.5）、颞叶meta 区体积相对减少 1.9%（1.5，2.3）、脑白质高信号体积增加 13%（9，17）、腔隙性梗死发生风险增加 1.3 倍（1.2，1.4）和脑β-淀粉样蛋白沉积增加 1.7 倍（1.3，2.2）和脑白质完整性恶化相关。CFS 中年短期下降也与一些长期关联有关。
本研究提供的证据表明，从中年开始，认知的短期和长期下降与无痴呆老年大脑的多种有害晚期差异相关。
