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Cognitive neurology
Original research
Risk factors for cognitive impairment in amyotrophic lateral sclerosis: a systematic review and meta-analysis
  1. Tianmi Yang,
  2. Yanbing Hou,
  3. Chunyu Li,
  4. Bei Cao,
  5. Yangfan Cheng,
  6. Qianqian Wei,
  7. Lingyu Zhang,
  8. Huifang Shang
  1. Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, Chengdu, Sichuan, China
  1. Correspondence to Professor Huifang Shang, Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, Sichuan University, Chengdu, Sichuan, China, 610041; hfshang2002{at}126.com

Abstract

Objective 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.

Methods 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.

Results 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).

Conclusions 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.

PROSPERO registration number CRD42020201085.

  • cognition
  • ALS
  • meta-analysis
  • C9orf72

https://doi.org/10.1136/jnnp-2020-325701

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    Footnotes

    • Contributors HS, BC and TY conceived and designed the study. TY and YH selected the articles and extracted and cross-checked the data. TY, YC and CL contributed to the statistical analysis. TY, YH and HS wrote the first draft of the manuscript. TY, HS, CL, YH, Q-QW and LZ contributed to the writing of the final version of the manuscript.

    • Funding This work was supported by the National Natural Science Foundation of China (grant number 81 871 000); the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (No. ZYJC18038); the China Postdoctoral Science Foundation (grant number 2019 M653427) and Science and Technology Bureau Fund of Sichuan Province (grant number 2020YFS0220).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article or uploaded as online supplemental information.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.