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 (P < 0.0001) and 2.76-fold greater adjusted dementia incidence rate (95% CI: 2.27–3.35, P < 0.001); incidence rate in NPS-not-MBI did not differ from No-NPS (hazard ratio 0.97, 95% CI: 0.82–1.14, P = 0.687). Of those with MBI who progressed to dementia, 76.0% developed Alzheimer's disease. Similarly, in the SCD subsample (n = 3485), persons with MBI had 1.99-fold greater dementia incidence versus No-NPS (95% CI: 1.46–2.71, P < 0.001) while NPS-not-MBI did not differ from No-NPS (hazard ratio 0.92, 95% CI: 0.70–1.19, P = 0.511).

Incorporating natural history into assessment of psychiatric symptoms in accordance with MBI criteria enhances dementia prognostication and modelling.

对认知正常的个体进行的精神症状与事件痴呆之间关联的研究并未可靠地区分精神综合征与代表神经退行性的神经精神症状 （NPS）。传统建模经常忽略症状自然病程。轻度行为障碍 （MBI） 是一种综合症，它利用晚年出现的和持续的 NPS 来识别新发痴呆的高危人群。

我们旨在探讨 MBI 和常规测量的 NPS （NPS-not-MBI） 与认知正常个体和认知正常子集与主观认知能力下降 （SCD） 的痴呆事件的关联。

使用国家阿尔茨海默病协调中心的数据，MBI 通过不存在既往精神疾病（症状出现）和痴呆前就诊的 >2/3 出现症状（症状持续）来实施。Kaplan-Meier 生存曲线和 Cox 比例风险回归对 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、种族、APOE-ε4 和认知状态进行调整。

样本包括 1408 名 MBI（年龄 75.2 ± 9.5 岁;54.3% 为女性）、5625 名 NPS-not-MBI（年龄 71.6 ± 8.8 岁;65.5% 为女性）和 5078 名无 NPS（年龄 71.2 ± 8.9 岁;67.6% 为女性）参与者。与无NPS相比，MBI参与者的无痴呆生存率较低（P < 0.0001），调整后的痴呆发生率高2.76倍（95% CI：2.27-3.35，P < 0.001）;NPS-not-MBI 的发生率与无 NPS 的发生率没有差异 （风险比 0.97,95% CI： 0.82–1.14，P = 0.687）。在进展为痴呆的 MBI 患者中，76.0% 发展为阿尔茨海默病。同样，在 SCD 子样本 （n = 3485） 中，MBI 患者的痴呆发病率是无 NPS 的 1.99 倍 （95% CI： 1.46-2.71，P < 0.001），而 NPS 非 MBI 与无 NPS 没有差异 （风险比 0.92,95% CI： 0.70-1.19，P = 0.511）。

根据 MBI 标准将自然病程纳入精神症状评估可增强痴呆预后和建模。