Clinical Evolution of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia With Lewy Bodies in a Post-Mortem Cohort

IF 2.8 3区医学 Q2 GERIATRICS & GERONTOLOGY

International Journal of Geriatric Psychiatry Pub Date : 2025-04-28 DOI:10.1002/gps.70084

Lucy L. Gibson, Ragnhild Eide Skogseth, Tibor Hortobagyi, Audun Osland Vik-Mo, Clive Ballard, Dag Aarsland

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Abstract

Background

Almost all patients with neurodegenerative dementias experience neuropsychiatric symptoms (NPS) but the timing and clinical course is highly variable.

Methods

In a prospective cohort study in Western Norway, patients with a new diagnosis of mild dementia were assessed annually in the Neuropsychiatric Inventory (NPI) for up to 9 years until death. Patients with post-mortem neuropathological diagnoses of Alzheimer's disease (pAD) (n = 37), Lewy body disease (pLBD) (n = 14) or meeting criteria for both AD and LBD (mixed AD+LBD) (n = 11) were included in this study. Neuropathological assessment was performed according to standardised protocols and blind to clinical information. In mixed effects logistic regression, longitudinal change in NPS was explored across neuropathological diagnoses and substrates. Additionally, the odds of NPS early and late in disease was evaluated in logistic regression.

Results

Early onset hallucinations were significantly more common in pLBD than pAD (OR 0.069 [95% CI 0.012–0.397], p = 0.003) or mixed AD+LBD (OR 0.09 [95% CI 0.010–0.771], p = 0.028) and there was a greater increase in the odds of hallucinations over time in pAD and AD+LBD than pLBD such that there was was no difference in the prevalence of late-onset hallucinations between pLBD, pAD or AD+LBD. Hallucinations early in disease were associated with higher LBD α-synuclein stages and neocortical LBD, in addition and sparser amyloid distribution. Higher density of amyloid plaques, tau tangles, cerebrovascular disease and increasing additional co-pathologies were associated with increasing odds of hallucinations over time.

Conclusions

LBD, without significant comorbid AD pathology, is associated with hallucinations early in the course of disease while multiple other pathologies may be implicated in aetiology of late-onset hallucinations. Hallucinations increase in AD+LBD as disease progresses, a trajectory more closely aligned with AD than LBD.

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死后队列中阿尔茨海默病和路易体痴呆患者神经精神症状的临床演变

背景：几乎所有的神经退行性痴呆患者都会出现神经精神症状（NPS），但时间和临床病程变化很大。方法在挪威西部的一项前瞻性队列研究中，新诊断为轻度痴呆的患者每年在神经精神量表（NPI）中进行评估，长达9年，直到死亡。本研究纳入了死后神经病理学诊断为阿尔茨海默病（pAD）（n = 37）、路易体病（pLBD）（n = 14）或同时符合AD和LBD（混合型AD+LBD）标准的患者（n = 11）。神经病理评估按标准化方案进行，不考虑临床资料。在混合效应逻辑回归中，NPS的纵向变化在神经病理诊断和基质中进行了探讨。此外，通过logistic回归评估疾病早期和晚期NPS的几率。结果早发性幻觉在pLBD中明显多于pAD （OR 0.069 [95% CI 0.012-0.397], p = 0.003）或AD+LBD混合组（OR 0.09 [95% CI 0.010-0.771], p = 0.028），并且随着时间的推移，pAD和AD+LBD出现幻觉的几率比pLBD增加更多，因此pLBD、pAD或AD+LBD出现晚发性幻觉的几率没有差异。疾病早期的幻觉与较高的LBD α-突触核蛋白阶段和新皮质LBD有关，此外淀粉样蛋白分布较少。随着时间的推移，淀粉样斑块、tau蛋白缠结、脑血管疾病和其他疾病的增加与幻觉的几率增加有关。结论：无明显AD共病的LBD在病程早期与幻觉有关，而多种其他病理可能与迟发性幻觉的病因有关。随着疾病进展，AD+LBD患者的幻觉增加，与LBD相比，其轨迹与AD更接近。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Geriatric Psychiatry 医学-精神病学

CiteScore

6.10

自引率

2.50%

发文量

168

审稿时长

4-8 weeks

期刊介绍： The rapidly increasing world population of aged people has led to a growing need to focus attention on the problems of mental disorder in late life. The aim of the Journal is to communicate the results of original research in the causes, treatment and care of all forms of mental disorder which affect the elderly. The Journal is of interest to psychiatrists, psychologists, social scientists, nurses and others engaged in therapeutic professions, together with general neurobiological researchers. The Journal provides an international perspective on the important issue of geriatric psychiatry, and contributions are published from countries throughout the world. Topics covered include epidemiology of mental disorders in old age, clinical aetiological research, post-mortem pathological and neurochemical studies, treatment trials and evaluation of geriatric psychiatry services.