Department of Neurology, Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.
Global Brain Health Institute, University of California, San Francisco, California, USA.
Eur J Neurol. 2022 Apr;29(4):957-967. doi: 10.1111/ene.15203. Epub 2021 Dec 20.
The faster rates of cognitive decline and predominance of atypical forms in early-onset Alzheimer's disease (EOAD) suggest that neuropsychiatric symptoms could be different in EOAD compared to late-onset AD (LOAD); however, prior studies based on non-biomarker-diagnosed cohorts show discordant results. Our goal was to determine the profile of neuropsychiatric symptoms in EOAD and LOAD, in a cohort with biomarker/postmortem-confirmed diagnoses. Additionally, the contribution of co-pathologies was explored.
In all, 219 participants (135 EOAD, 84 LOAD) meeting National Institute on Aging and Alzheimer's Association criteria for AD (115 amyloid positron emission tomography/cerebrospinal fluid biomarkers, 104 postmortem diagnosis) at the University of California San Francisco were evaluated. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was assessed at baseline and during follow-up. The NPI-Q mean comparisons and regression models adjusted by cognitive (Mini-Mental State Examination) and functional status (Clinical Dementia Rating Sum of Boxes) were performed to determine the effect of EOAD/LOAD and amnestic/non-amnestic diagnosis on NPI-Q. Regression models assessing the effect of co-pathologies on NPI-Q were performed.
At baseline, the NPI-Q scores were higher in EOAD compared to LOAD (p < 0.05). Longitudinally, regression models showed a significant effect of diagnosis, where EOAD had higher NPI-Q total, anxiety, motor disturbances and night-time behavior scores (p < 0.05). No differences between amnestics/non-amnestics were found. Argyrophilic grain disease co-pathology predicted a higher severity of NPI-Q scores in LOAD.
Anxiety, night-time behaviors and motor disturbances are more severe in EOAD than LOAD across the disease course. The differential patterns of neuropsychiatric symptoms observed between EOAD/LOAD could suggest a pattern of selective vulnerability extending to the brain's subcortical structures. Further, co-pathologies such as argyrophilic grain disease in LOAD may also play a role in increasing neuropsychiatric symptoms.
认知衰退速度较快且早发性阿尔茨海默病（EOAD）中以非典型形式为主，这表明与晚发性 AD（LOAD）相比，神经精神症状可能不同；然而，基于非生物标志物诊断队列的先前研究结果不一致。我们的目标是确定在具有生物标志物/死后确诊的队列中，EOAD 和 LOAD 的神经精神症状特征。此外，还探讨了共病的作用。
总共纳入了 219 名参与者（135 名 EOAD，84 名 LOAD），他们符合加利福尼亚大学旧金山分校国家老龄化研究所和阿尔茨海默病协会 AD 标准（115 名淀粉样蛋白正电子发射断层扫描/脑脊液生物标志物，104 名死后诊断）。在基线和随访时使用神经精神问卷-问卷（NPI-Q）进行评估。进行 NPI-Q 均值比较和回归模型调整，以确定 EOAD/LOAD 和遗忘型/非遗忘型诊断对 NPI-Q 的影响，调整认知（简易精神状态检查）和功能状态（临床痴呆评定量表总评分）。评估共病对 NPI-Q 影响的回归模型。
基线时，EOAD 的 NPI-Q 评分高于 LOAD（p<0.05）。纵向回归模型显示，诊断有显著影响，其中 EOAD 的 NPI-Q 总分、焦虑、运动障碍和夜间行为评分更高（p<0.05）。遗忘型和非遗忘型之间无差异。颗粒状淀粉样蛋白病共病预测 LOAD 的 NPI-Q 评分更严重。
在疾病过程中，EOAD 的焦虑、夜间行为和运动障碍比 LOAD 更严重。EOAD/LOAD 之间观察到的神经精神症状的不同模式可能表明选择性易感性扩展到大脑的皮质下结构。此外，LOAD 中的共病，如颗粒状淀粉样蛋白病，也可能在增加神经精神症状方面发挥作用。
