Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Department of Neurology, Alzheimer Center Amsterdam, Amsterdam University Medical Centers, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
Alzheimers Res Ther. 2022 Apr 4;14(1):48. doi: 10.1186/s13195-022-00991-z.
Neuropsychiatric symptoms (NPS) are common in individuals with Alzheimer's disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia.
Literature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021. Study selection, data extraction, and quality assessment were conducted in duplicate. Effect sizes were calculated as odds ratios (OR) for NPS prevalence and Hedges' g for NPS severity. Data were pooled using random-effects models. Sources of heterogeneity were examined using meta-regression analyses.
Sixty-two studies were eligible representing 21,554 patients (61.2% females). The majority of the included studies had an overall rating of fair quality (71.0%), with ten studies of good quality (16.1%) and eight studies of poor quality (12.9%). There was no sex difference in the presence of any NPS (k = 4, OR = 1.35 [95% confidence interval 0.78, 2.35]) and overall NPS severity (k = 13, g = 0.04 [- 0.04, 0.12]). Regarding specific symptoms, female sex was associated with more prevalent depressive symptoms (k = 20, OR = 1.60 [1.28, 1.98]), psychotic symptoms (general psychosis k = 4, OR = 1.62 [1.12, 2.33]; delusions k = 12, OR = 1.56 [1.28, 1.89]), and aberrant motor behavior (k = 6, OR = 1.47 [1.09, 1.98]). In addition, female sex was related to more severe depressive symptoms (k = 16, g = 0.24 [0.14, 0.34]), delusions (k = 10, g = 0.19 [0.04, 0.34]), and aberrant motor behavior (k = 9, g = 0.17 [0.08, 0.26]), while apathy was more severe among males compared to females (k = 11, g = - 0.10 [- 0.18, - 0.01]). There was no association between sex and the prevalence and severity of agitation, anxiety, disinhibition, eating behavior, euphoria, hallucinations, irritability, and sleep disturbances. Meta-regression analyses revealed no consistent association between the effect sizes across studies and method of NPS assessment and demographic and clinical characteristics.
Female sex was associated with a higher prevalence and greater severity of several specific NPS, while male sex was associated with more severe apathy. While more research is needed into factors underlying these sex differences, our findings may guide tailored treatment approaches of NPS in AD dementia.
神经精神症状（NPS）在阿尔茨海默病（AD）痴呆患者中很常见，但 NPS 的表现存在很大的异质性。性别差异可能解释了这种临床变异性。我们旨在研究 AD 痴呆中 NPS 的患病率和严重程度的性别差异。
从成立到 2021 年 2 月，我们在 Embase、MEDLINE/PubMed、Web of Science 核心合集、Cochrane 对照试验中心注册库、PsycINFO 和 Google Scholar 中进行了文献检索。我们进行了重复的研究选择、数据提取和质量评估。效应大小计算为 NPS 患病率的优势比（OR）和 NPS 严重程度的 Hedges'g。使用随机效应模型对数据进行汇总。使用荟萃回归分析检查异质性的来源。
62 项研究符合纳入标准，代表了 21554 名患者（61.2%为女性）。纳入的研究大多数总体质量评分为中等（71.0%），其中 10 项研究质量良好（16.1%），8 项研究质量较差（12.9%）。在存在任何 NPS（k=4，OR=1.35[95%置信区间 0.78，2.35]）和总体 NPS 严重程度（k=13，g=0.04[-0.04，0.12]）方面，性别之间没有差异。关于特定症状，女性更易出现抑郁症状（k=20，OR=1.60[1.28，1.98]）、精神病症状（一般精神病 k=4，OR=1.62[1.12，2.33]；妄想 k=12，OR=1.56[1.28，1.89]）和异常运动行为（k=6，OR=1.47[1.09，1.98]）。此外，女性的抑郁症状（k=16，g=0.24[0.14，0.34]）、妄想（k=10，g=0.19[0.04，0.34]）和异常运动行为（k=9，g=0.17[0.08，0.26]）更严重，而男性的淡漠更严重（k=11，g=-0.10[-0.18，-0.01]）。在激越、焦虑、抑制障碍、饮食行为、欣快、幻觉、易怒和睡眠障碍的患病率和严重程度方面，性别之间没有关联。荟萃回归分析显示，研究之间的效应大小与 NPS 评估方法以及人口统计学和临床特征之间没有一致的关联。
女性更易出现几种特定的 NPS，包括抑郁、精神病和异常运动行为，且这些症状更严重。而男性更易出现淡漠。虽然需要进一步研究这些性别差异的潜在因素，但我们的研究结果可能有助于指导 AD 痴呆患者 NPS 的针对性治疗方法。
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