Gibson Lucy L, Skogseth Ragnhild Eide, Hortobagyi Tibor, Vik-Mo Audun Osland, Ballard Clive, Aarsland Dag
Department of Psychological Medicine, King's College London, Centre of Healthy Brain Ageing, Institute of Psychiatry, Psychology, and Neuroscience, London, UK.
Department of Geriatric Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
Int J Geriatr Psychiatry. 2025 May;40(5):e70084. doi: 10.1002/gps.70084.
Almost all patients with neurodegenerative dementias experience neuropsychiatric symptoms (NPS) but the timing and clinical course is highly variable.
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.
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.
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.
几乎所有神经退行性痴呆患者都会出现神经精神症状（NPS），但其出现时间和临床过程差异很大。
在挪威西部进行的一项前瞻性队列研究中，对新诊断为轻度痴呆的患者每年进行一次神经精神量表（NPI）评估，长达9年直至死亡。本研究纳入了经尸检神经病理学诊断为阿尔茨海默病（pAD）（n = 37）、路易体病（pLBD）（n = 14）或符合AD和LBD两者标准（混合性AD + LBD）（n = 11）的患者。神经病理学评估按照标准化方案进行，且对临床信息保密。在混合效应逻辑回归中，探讨了神经病理学诊断和底物之间NPS的纵向变化。此外，在逻辑回归中评估了疾病早期和晚期出现NPS的几率。
与pAD（比值比0.069 [95%置信区间0.012 - 0.397]，p = 0.003）或混合性AD + LBD（比值比0.09 [95%置信区间0.010 - 0.771]，p = 0.028）相比，早发性幻觉在pLBD中显著更常见，并且随着时间推移，pAD和AD + LBD中幻觉出现几率的增加幅度大于pLBD，以至于pLBD、pAD或AD + LBD之间晚发性幻觉的患病率没有差异。疾病早期的幻觉与更高的LBD α-突触核蛋白阶段和新皮质LBD有关，此外还与更稀疏的淀粉样蛋白分布有关。更高密度的淀粉样斑块、tau缠结、脑血管疾病以及增加的其他合并病理学改变与随着时间推移幻觉出现几率的增加有关。
无明显合并AD病理学改变的LBD与疾病早期的幻觉有关，而多种其他病理学改变可能与晚发性幻觉的病因有关。随着疾病进展，AD + LBD中的幻觉会增加，这一轨迹与AD比与LBD更为接近。
