Ghahremani Maryam, Smith Eric E, Ismail Zahinoor
Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Br J Psychiatry. 2025 Mar;226(3):129-136. doi: 10.1192/bjp.2024.136. Epub 2024 Dec 16.
Studies in cognitively normal individuals on associations between psychiatric symptomatology and incident dementia have not reliably differentiated psychiatric syndromes from neuropsychiatric symptoms (NPS) that represent neurodegeneration. Conventional modelling often overlooks symptom natural history. Mild behavioural impairment (MBI) is a syndrome that leverages later-life emergent and persistent NPS to identify a high-risk group for incident dementia.
We aimed to explore associations of MBI, and conventionally-measured NPS (NPS-not-MBI), with incident dementia in cognitively normal individuals and the cognitively normal subset with subjective cognitive decline (SCD).
Using National Alzheimer's Coordinating Center data, MBI was operationalised by the absence of past psychiatric disorders (symptom emergence) and the presence of symptoms at >2/3 of pre-dementia visits (symptom persistence). Kaplan-Meier survival curves and Cox proportional hazards regressions modelled dementia incidence across NPS groups and MBI domains, adjusted for age, gender, education, race, APOE-ε4, and cognitive status.
The sample comprised 1408 MBI (age 75.2 ± 9.5; 54.3% female), 5625 NPS-not-MBI (age 71.6 ± 8.8; 65.5% female) and 5078 No-NPS (age 71.2 ± 8.9; 67.6% female) participants. Compared with No-NPS, MBI participants had lower dementia-free survival ( < 0.0001) and 2.76-fold greater adjusted dementia incidence rate (95% CI: 2.27-3.35, < 0.001); incidence rate in NPS-not-MBI did not differ from No-NPS (hazard ratio 0.97, 95% CI: 0.82-1.14, = 0.687). Of those with MBI who progressed to dementia, 76.0% developed Alzheimer's disease. Similarly, in the SCD subsample ( = 3485), persons with MBI had 1.99-fold greater dementia incidence versus No-NPS (95% CI: 1.46-2.71, < 0.001) while NPS-not-MBI did not differ from No-NPS (hazard ratio 0.92, 95% CI: 0.70-1.19, = 0.511).
Incorporating natural history into assessment of psychiatric symptoms in accordance with MBI criteria enhances dementia prognostication and modelling.
针对认知正常个体的研究，探讨精神症状与新发痴呆症之间的关联时，并未可靠地区分精神综合征与代表神经退行性变的神经精神症状（NPS）。传统模型往往忽略了症状的自然史。轻度行为损害（MBI）是一种利用晚年出现并持续存在的NPS来识别新发痴呆症高危人群的综合征。
我们旨在探讨MBI以及传统测量的NPS（非MBI的NPS）与认知正常个体以及有主观认知下降（SCD）的认知正常亚组中新发痴呆症之间的关联。
利用国家阿尔茨海默病协调中心的数据，通过无既往精神疾病（症状出现）以及在痴呆前就诊的2/3以上时间存在症状（症状持续）来定义MBI。采用Kaplan-Meier生存曲线和Cox比例风险回归模型，对各NPS组和MBI领域的痴呆发病率进行建模，并根据年龄、性别、教育程度、种族、APOE-ε4和认知状态进行调整。
样本包括1408名MBI参与者（年龄75.2±9.5岁；54.3%为女性）、5625名非MBI的NPS参与者（年龄71.6±8.8岁；65.5%为女性）和5078名无NPS参与者（年龄71.2±8.9岁；67.6%为女性）。与无NPS参与者相比，MBI参与者的无痴呆生存期更低（P<0.0001），调整后的痴呆发病率高出2.76倍（95%CI：2.27-3.35，P<0.001）；非MBI的NPS参与者的发病率与无NPS参与者无差异（风险比0.97，95%CI：0.82-1.14，P = 0.687）。在进展为痴呆的MBI参与者中，76.0%患阿尔茨海默病。同样，在SCD亚样本（n = 3485）中，MBI患者的痴呆发病率是无NPS参与者的1.99倍（95%CI：1.46-2.71，P<0.001），而非MBI的NPS参与者与无NPS参与者无差异（风险比0.92，95%CI：0.70-1.19，P = 0.511）。
根据MBI标准将自然史纳入精神症状评估可增强痴呆症的预后预测和模型构建。
