Risk factors for cognitive impairment in amyotrophic lateral sclerosis: a systematic review and meta-analysis.

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Cognitive impairment is a common, far-reaching but imperceptible manifestation in patients with amyotrophic lateral sclerosis (ALS). We aimed to identify the risk factors for cognitive impairment in ALS.We searched PubMed and EMBASE for cross-sectional, case-control and cohort studies that reported predictors of cognitive impairment in ALS. The obtained data were meta-analysed to generate overall ORs and 95% CIs.Twenty-seven eligible articles reporting on 6799 individuals were included out of 20 501 records. Nine predictors were identified: C9orf72 (OR 3.62, 95% CI 1.76 to 7.45), dysarthria (OR 2.25, 95% CI 1.20 to 4.22), family history of ALS (OR 1.76, 95% CI 1.18 to 2.61), predominant upper motor neuron (PUMN) phenotype (OR 1.73, 95% CI 1.09 to 2.73) and bulbar onset (OR 1.54, 95% CI 1.28 to 1.87) increased risk factors for cognitive impairment in ALS. ALS Functional Rating Scale-Revised scores, sex, age or education level were not significantly associated with cognitive impairment in ALS. In addition, C9orf72 (OR=5.94) and bulbar onset (OR=2.08) were strong predictors of ALS-frontotemporal dementia. Female sex conferred more susceptibility to executive cognitive impairment than male sex (OR=1.82).Patients with C9orf72 repeat expansion, dysarthria, family history of ALS, PUMN phenotype and bulbar onset had a high risk for cognitive impairment in ALS. These associations may contribute to understanding the heterogeneity of ALS.CRD42020201085.


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