Stafford J, Dekhtyar S, Russ T C, Singh-Manoux A, Maddock J, Walters K, Orgeta V, Davies N, Kirkbride J B, Richards M, Howard R, Patalay P
Advanced Care Research Centre, University of Edinburgh, Usher Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, UK.
Unit for Lifelong Health and Ageing at UCL, Faculty of Population Health, University College London (UCL), London UK.
medRxiv. 2025 Aug 21:2025.08.19.25333919. doi: 10.1101/2025.08.19.25333919.
Psychological distress has been linked with later cognitive impairment and dementia, although the nature of the association remains unclear. Using a multi-cohort approach, we examined longitudinal associations of psychological distress with subsequent cognition and dementia, testing whether findings varied by age of assessment, severity, and persistence of psychological distress.
We used five longitudinal studies: Caerphilly Prospective Study, English Longitudinal Study of Ageing, National Child Development Study, National Survey of Health and Development, and Whitehall II. We examined associations with changes in cognition using linear and mixed effects models, and dementia using logistic regression. Results were pooled using two-stage individual participant data meta-analysis.
Pooled analyses (total N=24,564) showed that greater psychological distress was associated with lower subsequent cognitive level (β=-0.03 [95% CI: -0.06; -0.01]; I2=69.7%). Associations were present for clinically-significant (β=-0.06 [-0.12; -0.00]; I2=62.2%), persistent (β=-0.12 [-0.23; -0.02]; I2=82.5%) and intermittent distress (β=-0.09 [-0.12; -0.05]; I2=0%). Baseline distress was not associated with rates of subsequent cognitive decline. Psychological distress was associated with subsequent dementia (OR=1.12 [1.04; 1.20]; I2=0%), including for clinically-significant (OR=1.28 [1.07; 1.52; I2=0%]), persistent (OR=1.43 [1.04; 1.98]; I2=44.0%) and intermittent symptoms (OR=1.32 [1.02; 1.71]; I2=40.3%). Dementia was associated with psychological distress assessed in later life (age 65-75 OR: 1.29 [1.18; 1.40]; I2=13.9%), but not mid-life (age 45-54 OR: 1.09 [0.93; 1.28]; I2=34.0%).
In this multi-cohort study, psychological distress was associated with subsequent dementia and lower subsequent cognitive level, including for both persistent and intermittent distress. Associations with dementia were present when distress was assessed at older ages but not at ages 45-54 years, suggesting that associations might partly represent early preclinical markers of dementia neuropathology. Findings highlight the potential relevance of psychological distress in informing dementia prevention and supporting identification of high-risk groups, both of which are major global public health priorities.
心理困扰与后期认知障碍和痴呆症有关，尽管这种关联的性质尚不清楚。我们采用多队列研究方法，研究心理困扰与随后的认知和痴呆症之间的纵向关联，检验研究结果是否因心理困扰的评估年龄、严重程度和持续性而有所不同。
我们使用了五项纵向研究：卡菲利前瞻性研究、英国老龄化纵向研究、全国儿童发展研究、全国健康与发展调查以及白厅II研究。我们使用线性和混合效应模型研究与认知变化的关联，使用逻辑回归研究与痴呆症的关联。结果通过两阶段个体参与者数据荟萃分析进行汇总。
汇总分析（总样本量N = 24,564）表明，心理困扰程度越高，随后的认知水平越低（β=-0.03 [95%置信区间：-0.06；-0.01]；I2 = 69.7%）。在具有临床意义的心理困扰（β=-0.06 [-0.12；-0.00]；I2 = 62.2%）、持续性心理困扰（β=-0.12 [-0.23；-0.02]；I2 = 82.5%）和间歇性心理困扰（β=-0.09 [-0.12；-0.05]；I2 = 0%）中均存在这种关联。基线心理困扰与随后的认知衰退率无关。心理困扰与随后的痴呆症有关（比值比=1.12 [1.04；1.20]；I2 = 0%），包括具有临床意义的心理困扰（比值比=1.28 [1.07；1.52]；I2 = 0%）、持续性心理困扰（比值比=1.43 [1.04；1.98]；I2 = 44.0%）和间歇性症状（比值比=1.32 [1.02；1.71]；I2 = 40.3%）。痴呆症与晚年（65 - 75岁）评估的心理困扰有关（比值比：1.29 [1.18；1.40]；I2 = 13.9%），但与中年（45 - 54岁）评估无关（比值比：1.09 [0.93；1.28]；I2 = 34.0%）。
在这项多队列研究中，心理困扰与随后的痴呆症以及较低的随后认知水平有关，包括持续性和间歇性心理困扰。当在老年时评估心理困扰时与痴呆症存在关联，但在45 - 54岁时不存在，这表明这种关联可能部分代表痴呆症神经病理学的早期临床前标志物。研究结果凸显了心理困扰在为痴呆症预防提供信息和支持识别高危人群方面的潜在相关性，而这两者都是全球主要的公共卫生优先事项。
