Associations of Alcohol Consumption and Smoking With Disease Risk and Neurodegeneration in Individuals With Multiple Sclerosis in the United Kingdom

Abstract

Importance: Understanding the effects of modifiable risk factors on risk for multiple sclerosis (MS) and associated neurodegeneration is important to guide clinical counseling.

Objective: To investigate associations of alcohol use, smoking, and obesity with odds of MS diagnosis and macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness.

Design, setting, and participants: This cross-sectional study analyzed data from the community-based UK Biobank study on health behaviors and retinal thickness (measured by optical coherence tomography in both eyes) in individuals aged 40 to 69 years examined from December 1, 2009, to December 31, 2010. Risk factors were identified with multivariable logistic regression analyses. To adjust for intereye correlations, multivariable generalized estimating equations were used to explore associations of alcohol use and smoking with mGCIPL thickness. Finally, interaction models explored whether the correlations of alcohol and smoking with mGCIPL thickness differed for individuals with MS. Data were analyzed from February 1 to July 1, 2021.

Exposures: Smoking status (never, previous, or current), alcohol intake (never or special occasions only [low], once per month to ≤4 times per week [moderate], or daily/almost daily [high]), and body mass index.

Main outcomes and measures: Multiple sclerosis case status and mGCIPL thickness.

Results: A total of 71 981 individuals (38 685 women [53.7%] and 33 296 men [46.3%]; mean [SD] age, 56.7 [8.0] years) were included in the analysis (20 065 healthy control individuals, 51 737 control individuals with comorbidities, and 179 individuals with MS). Modifiable risk factors significantly associated with MS case status were current smoking (odds ratio [OR], 3.05 [95% CI, 1.95-4.64]), moderate alcohol intake (OR, 0.62 [95% CI, 0.43-0.91]), and obesity (OR, 1.72 [95% CI, 1.15-2.56]) compared with healthy control individuals. Compared with the control individuals with comorbidities, only smoking was associated with case status (OR, 2.30 [95% CI, 1.48-3.51]). High alcohol intake was associated with a thinner mGCIPL in individuals with MS (adjusted β = -3.09 [95% CI, -5.70 to -0.48] μm; P = .02). In the alcohol interaction model, high alcohol intake was associated with thinner mGCIPL in control individuals (β = -0.93 [95% CI, -1.07 to -0.79] μm; P < .001), but there was no statistically significant association in individuals with MS (β = -2.27 [95% CI, -4.76 to 0.22] μm; P = .07). Smoking was not associated with mGCIPL thickness in MS. However, smoking was associated with greater mGCIPL thickness in control individuals (β = 0.89 [95% CI, 0.74-1.05 μm]; P < .001).

Conclusions and relevance: These findings suggest that high alcohol intake was associated with retinal features indicative of more severe neurodegeneration, whereas smoking was associated with higher odds of being diagnosed with MS.

Figure 1.. Study Flowchart

Individuals with multiple sclerosis (MS) were defined as those with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), disease code of G35, indicating clinician-diagnosed MS. Healthy control individuals were those who had 0 ICD-10 disease codes registered, whereas control individuals with comorbidities had 1 or more (non-MS) ICD-10 disease codes registered. GCIPL indicates ganglion cell and inner plexiform layer; SD-OCT, spectral domain optical coherence tomography; and UKBB, UK Biobank study.

Figure 2.. Line Plots Visualizing Associations of Modifiable Risk Factors With Multiple Sclerosis (MS) Risk and Macular Ganglion Cell and Inner Plexiform Layer (mGCIPL) Thickness

A, Multivariable logistic regression results visualizing factors associated with risk of being diagnosed with MS. Circles represent odds ratios; whiskers represent 95% CIs. Analysis is adjusted for age, sex, and Townsend deprivation score. The x-axis is log-transformed. B, Multivariable generalized estimating equations (GEEs) results visualizing the associations with smoking status and alcohol intake (adjusted for age, sex, Townsend deprivation score, and intraocular pressure [IOP]) with mGCIPL thickness in individuals with MS. Reference groups include individuals who never smoked, had low alcohol use, and had a healthy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Alcohol consumption was classified as never or special occasions only (low), once per month to no more than 4 times per week (moderate), or daily or almost daily (high); BMI was classified as underweight or healthy weight (<18.0 to 24.9), overweight (25.0-30.0), and obesity (>30.0). OR indicates odds ratio.

Figure 3.. Differences in Associations With Macular Ganglion Cell and Inner Plexiform Layer (mGCIPL) Thickness Based on Multiple Sclerosis (MS) Diagnosis Status

Modeled estimates of the associations of mGCIPL with alcohol consumption and smoking status for the entire cohort, plotted for individuals with MS and control individuals separately. A, Interaction model including interaction term for smoking status and MS diagnosis. B, Interaction model including interaction term for alcohol intake and MS diagnosis. Whiskers represent 95% CIs.