Qian Winnie, Fischer Corinne E, Schweizer Tom A, Munoz David G
Keenan Research Centre for Biomedical Research, The Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON. Canada.
Curr Alzheimer Res. 2018;15(2):187-194. doi: 10.2174/1567205014666170829114346.
Psychosis is a common phenomenon in Alzheimer's disease (AD). The APOE ε4 allele is the strongest genetic risk factor for the development of AD, but its association with psychosis remains unclear.
We investigated the associations between psychosis, subdivided into delusions and hallucinations, as well as APOE ε4 allele on cognitive and functional outcomes. Secondarily, we investigated the associations between APOE ε4, Lewy bodies, and psychosis.
Data from the National Alzheimer's Coordinating Center (NACC) were used. Nine hundred patients with a confirmed diagnosis of AD based on the NIA-AA Reagan were included in the analysis. Global cognition was assessed using the Mini-Mental State Exam (MMSE) and functional status was assessed using the Functional Activities Questionnaire (FAQ). Psychosis status was determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factorial design was used to assess the effects of psychosis and APOE ε4, as well as their interaction.
Psychosis and the presence of APOE ε4 were both associated with lower MMSE scores, while only psychosis was associated with higher FAQ scores. Furthermore, patients with hallucinations had lower MMSE and higher FAQ scores than patients with only delusions. There was a significant interaction effect between psychosis and APOE ε4 on MMSE scores, with APOE ε4 negatively affecting patients with hallucinations-only psychosis. APOE ε4 was positively associated with the presence of Lewy body pathology, and both were found to be more prevalent in psychotic patients, with a stronger association with hallucinations.
Psychosis in AD was associated with greater cognitive and functional impairments. Patients with hallucinations-with or without delusions-conferred even greater deficits compared to patients with only delusions. The APOE ε4 allele was associated with worse cognition, especially for patients with hallucination-only psychosis. APOE ε4 may mediate cognitive impairment in the hallucinations phenotype through the development of Lewy bodies. Our findings support that subtypes of psychosis should be evaluated separately.
精神病是阿尔茨海默病（AD）中的常见现象。APOEε4等位基因是AD发生发展的最强遗传风险因素，但其与精神病的关联尚不清楚。
我们研究了细分为妄想和幻觉的精神病与APOEε4等位基因在认知和功能结局方面的关联。其次，我们研究了APOEε4、路易体与精神病之间的关联。
使用了来自国家阿尔茨海默病协调中心（NACC）的数据。基于NIA-AA里根标准确诊为AD的900名患者纳入分析。使用简易精神状态检查表（MMSE）评估整体认知，使用功能活动问卷（FAQ）评估功能状态。使用神经精神科问卷（NPI-Q）确定精神病状态。采用析因设计评估精神病和APOEε4的影响及其相互作用。
精神病和APOEε4的存在均与较低的MMSE评分相关，而仅精神病与较高的FAQ评分相关。此外，有幻觉的患者比仅有妄想的患者MMSE评分更低、FAQ评分更高。精神病和APOEε4对MMSE评分有显著的交互作用，APOEε4对仅有幻觉性精神病的患者有负面影响。APOEε4与路易体病理的存在呈正相关，且两者在精神病患者中更为普遍，与幻觉的关联更强。
AD中的精神病与更严重的认知和功能损害相关。与仅有妄想的患者相比，有幻觉（无论有无妄想）的患者存在更严重的缺陷。APOEε4等位基因与更差的认知相关，尤其是对于仅有幻觉性精神病的患者。APOEε4可能通过路易体的形成介导幻觉表型中的认知障碍。我们的研究结果支持应分别评估精神病的亚型。
