Weili Xu, MD, PhD, Dept. of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Qixiangtai Road 22, Heping District, 300070, Tianjin, P.R. China; Aging Research Center, Karolinska Institutet, Tomtebodavägen 18A Floor 10, SE-171 65 Solna, Stockholm, Sweden. Phone: +46 8 524 858 26; Email:
J Prev Alzheimers Dis. 2024;11(3):739-748. doi: 10.14283/jpad.2024.54.
Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to dementia risk in late life. However, the association between CR and cognitive changes and brain imaging measures, especially in midlife, is unclear.
We aimed to explore the association of CR with cognitive decline and structural brain differences in middle and older age.
This longitudinal study was from the UK Biobank project where participants completed baseline surveys between 2006 to 2010 and were followed (mean follow-up: 9 years).
A population-based study.
A total of 42,301 dementia-free participants aged 40-70 were followed-up to detect cognitive changes. A subsample (n=34,041) underwent brain magnetic resonance imaging scans.
We used latent class analysis to generate a CR indicator (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities. Cognitive tests for global and domain-specific cognition were administrated at baseline and follow-up. Total brain, white matter, grey matter, hippocampal, and white matter hyperintensity volumes (TBV, WMV, GMV, HV, and WMHV) were assessed at the follow-up examination. Data were analyzed using mixed-effects models and analysis of covariance.
At baseline, 16,032 (37.9%), 10,709 (25.3%), and 15,560 (36.8%) participants had low, moderate, and high levels of CR, respectively. Compared with low CR, high CR was associated with slower declines in global cognition (β [95% confidence interval]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). Participants with high CR had lower TBV, WMV, GMV, and WMHV, but higher HV when controlling for global cognition (corrected P <0.01 for all). The significant relationships between CR and cognition and TBV were present among both middle-aged (<60 years) and older (≥60 years) participants. The CR-cognition association remained significant despite reductions in brain structural properties.
Higher CR is associated with slower cognitive decline, higher HV, and lower microvascular burden, especially in middle age. Individuals with high CR could tolerate smaller brain volumes while maintaining cognition. The benefit of CR for cognition is independent of structural brain differences. Our findings highlight the contribution of enhancing CR to helping compensate for neuroimaging alterations and ultimately prevent cognitive decline.
认知储备（CR）有助于在大脑老化和损伤时保持认知。CR 与晚年痴呆风险有关。然而，CR 与认知变化和结构脑成像测量之间的关联尚不清楚，尤其是在中年。
我们旨在探讨 CR 与中年和老年认知下降和结构脑差异的关系。
这是一项来自英国生物银行项目的纵向研究，参与者在 2006 年至 2010 年间完成了基线调查，并进行了随访（平均随访时间：9 年）。
基于人群的研究。
共有 42301 名无痴呆症的参与者年龄在 40-70 岁之间，随访以检测认知变化。一个亚组（n=34041）接受了脑部磁共振成像扫描。
我们使用潜在类别分析根据教育、职业和多种认知刺激活动生成 CR 指标（分为高、中、低）。在基线和随访时进行全球和特定领域认知的认知测试。在随访检查时评估总脑、白质、灰质、海马和白质高信号体积（TBV、WMV、GMV、HV 和 WMHV）。使用混合效应模型和协方差分析进行数据分析。
在基线时，分别有 16032 名（37.9%）、10709 名（25.3%）和 15560 名（36.8%）参与者的 CR 水平较低、中、高。与 CR 水平较低相比，CR 水平较高与全球认知（β[95%置信区间]：0.10[0.08, 0.11]）、前瞻性记忆（0.10[0.06, 0.15]）、流体智力（0.07[0.04, 0.10]）和反应时间（0.04[0.02, 0.06]）的下降速度较慢有关。CR 水平较高的参与者 TBV、WMV、GMV 和 WMHV 较低，但全球认知校正后的 HV 较高（所有校正 P<0.01）。在中年（<60 岁）和老年（≥60 岁）参与者中，CR 与认知和 TBV 的关系均具有显著性。尽管大脑结构特性下降，但 CR 与认知的关联仍然显著。
较高的 CR 与认知下降较慢、HV 较高和微血管负担较低有关，尤其是在中年。CR 较高的个体在保持认知的同时，可能能够耐受较小的脑容量。CR 对认知的益处独立于结构脑差异。我们的研究结果强调了增强 CR 以帮助补偿神经影像学改变并最终预防认知下降的重要性。
