Association between vascular risk factors and cognitive impairment in amyotrophic lateral sclerosis: a case-control study

Abstract

Objective

The disease-modifying effects of type 2 diabetes mellitus (T2DM), and hyperlipidemia on the risk and prognosis of amyotrophic lateral sclerosis (ALS) have gained significant attention. We aim to evaluate the association between common vascular risk factors and cognitive impairment in patients with ALS.

Methods

Patients with ALS were consecutively recruited between June 2012 and November 2019 from a tertiary referral center for ALS at the West China Hospital. Vascular risk factors (hypertension, T2DM, hyperlipidemia, overweight, and smoking) were confirmed based on clinical data. Cognitive function was evaluated by the Chinese version of Addenbrooke’s Cognitive Examination-revised. With careful confounder adjustment, multivariable logistic regression analysis was performed separately and accumulatively to determine the association between cognitive impairment and vascular risk factors in ALS.

Results

Of 870 patients, 266 (30.6%) had cognitive impairment. No cognitive burden from vascular risk factors was found in patients with ALS. On the contrary, we first observed that T2DM (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.25–0.98; p = 0.04) and hyperlipidemia (OR, 0.50; 95% CI, 0.26–0.97; p = 0.04) showed protective effects against cognitive decline in ALS, adjusted for age, sex, educational level, site of onset, Revised-ALS Functional Rating Scale score, predominant upper motor neuron phenotype, family history of ALS, and the remaining vascular risk factors. Sensitivity analyses of sex did not substantially reverse the risk estimates.

Conclusions

T2DM and hyperlipidemia decrease the risk of cognitive impairment in patients with ALS. The fitness hypothesis in ALS has been tested and expanded in our work.

Keywords:

• Vascular risk factors
• cognitive impairment
• amyotrophic lateral sclerosis
• diabetes mellitus
• hyperlipidemia

Acknowledgments

The authors thank the patients and their families for their participation in the study.

Author contributions

HFS, TMY, and QQW conceived and designed the study. QQW, BC, RWO, YBH, LYZ, YPC, and TMY collected the data. QQW, TMY, and RWO contributed to the statistical analysis. TMY wrote the first draft of the manuscript. TMY, HFS, CYL, and QQW contributed to the writing of the final version of the manuscript. All authors read and approved the final manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability statement

Data and materials are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the National Key Research and Development Program of China under grant number 2016YFC0901504; the National Natural Science Foundation of China under grant number 81871000; Sichuan Science and Technology Program under grant number 2020YFS0220; the China Postdoctoral Science Foundation under grant number 2019M653427.