Chang Zheng, Yao Honghui, Sun Shihua, Zhang Le, Liu Shengxin, Brikell Isabell, D'Onofrio Brian M, Larsson Henrik, Lichtenstein Paul, Kuja-Halkola Ralf, Hägg Sara, Happé Francesca, Taylor Mark J
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Mol Psychiatry. 2025 May 14. doi: 10.1038/s41380-025-03045-6.
There is emerging evidence to suggest that autistic individuals are at an increased risk for cognitive decline or dementia. It is unknown whether this association is due to shared familial influences between autism and dementia. The main purpose of this study was, thus, to investigate the risk of dementia in relatives of autistic individuals. We conducted a family study based on linking Swedish registers. We identified all individuals born in Sweden from 1980-2013, followed until 2020, and clinical diagnoses of autism among these individuals. We linked these index individuals with their parents, grandparents, and aunts/uncles. The risk of dementia (including any type of dementia, Alzheimer's disease, and other types of dementia) in relatives of autistic individuals was estimated using Cox proportional hazards models. Analyses were then stratified by sex of the relatives and intellectual disability in autistic individuals. Relatives of autistic individuals were at an increased risk of dementia. The risk was strongest in parents (hazards ratio [HR] = 1.36, 95% confidence intervals = 1.25-1.49), and weaker in grandparents (HR = 1.08, 1.06-1.10) and aunts/uncles (HR = 1.15, 0.96-1.38). Furthermore, there were indications of a stronger association between autism in index individuals and dementia in mothers (HR = 1.51, 1.29-1.77) compared to dementia in fathers (HR = 1.30, 1.16-1.45). There was only a small difference in relatives of autistic individuals with and without intellectual disability. Our results provide evidence of familial co-aggregation between autism and different types of dementia, and a potential genetic link. Future research now needs to clarify the risk of dementia in autistic individuals.
越来越多的证据表明,自闭症患者认知能力下降或患痴呆症的风险增加。目前尚不清楚这种关联是否是由于自闭症和痴呆症之间存在共同的家族影响。因此,本研究的主要目的是调查自闭症患者亲属患痴呆症的风险。我们基于瑞典登记册的关联进行了一项家族研究。我们确定了1980年至2013年在瑞典出生、随访至2020年的所有个体,以及这些个体中的自闭症临床诊断。我们将这些索引个体与其父母、祖父母和姑姑/叔叔进行了关联。使用Cox比例风险模型估计自闭症患者亲属患痴呆症(包括任何类型的痴呆症、阿尔茨海默病和其他类型的痴呆症)的风险。然后按亲属性别和自闭症个体的智力残疾情况进行分层分析。自闭症患者的亲属患痴呆症的风险增加。这种风险在父母中最强(风险比[HR]=1.36,95%置信区间=1.25-1.49),在祖父母中较弱(HR=1.08,1.06-1.10),在姑姑/叔叔中(HR=1.15,0.96-1.38)。此外,有迹象表明,与父亲患痴呆症(HR=1.30,1.16-1.45)相比,索引个体中的自闭症与母亲患痴呆症之间的关联更强(HR=1.51,1.29-1.77)。有和没有智力残疾的自闭症患者的亲属之间只有很小的差异。我们的结果提供了自闭症与不同类型痴呆症之间家族共同聚集以及潜在遗传联系的证据。现在需要未来的研究来阐明自闭症患者患痴呆症的风险。