TY - JOUR
T1 - Associations of Alcohol Consumption and Smoking With Disease Risk and Neurodegeneration in Individuals With Multiple Sclerosis in the United Kingdom
AU - Kleerekooper, Iris
AU - Chua, Sharon
AU - Foster, Paul J.
AU - Trip, S. Anand
AU - Plant, Gordon T.
AU - UK Biobank Eye and Vision Consortium
AU - Petzold, Axel
AU - Patel, Praveen
N1 - Funding Information: Funding/Support: This study was supported by the postdoctoral research fellowship exchange program from the European Committee for Treatment and Research in Multiple Sclerosis (Dr Kleerekooper) and by the University College London Hospital Biomedical Research Centre (Dr Trip). Funding Information: Author Contributions: Dr Kleerekooper had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Kleerekooper, Foster, Trip, Petzold, Patel. Acquisition, analysis, or interpretation of data: Kleerekooper, Chua, Foster, Plant, Petzold, Patel. Drafting of the manuscript: Kleerekooper, Trip, Patel. Critical revision of the manuscript for important intellectual content: Kleerekooper, Chua, Foster, Plant, Petzold. Statistical analysis: Kleerekooper, Petzold. Obtained funding: Foster. Administrative, technical, or material support: Chua, Trip. Supervision: Foster, Trip, Plant, Petzold, Patel. Other (had the original idea for this study): Petzold. Conflict of Interest Disclosures: Dr Foster reported receiving personal fees and grants from Allergan PLC, Carl Zeiss AG, Google/DeepMind Technologies, and Santen Pharmaceutical Co, Ltd, outside the submitted work and receiving support from The Desmond Foundation, London, and the National Institute of Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital. Dr Trip reported receiving nonfinancial support and/or personal fees from Biogen Inc, Merck Serono, Novartis International AG, F. Hoffmann–La Roche AG, and Teva Pharmaceuticals, and involvement with clinical trials run by Biogen Inc and Sanofi Genzyme. Dr Petzold reported being a member of the steering committee for the Optical Coherence Tomography in MS study (Novartis International AG) and the SC Zeiss OCTA Angio-Network; receiving consulting fees for performing ocular coherence tomography quality control for the PASSOS study (Novartis International AG); receiving grant support for the RECOVER trial from University College San Francisco, the RESTORE trial from a Dutch private foundation, and the nimodipine trial from Fight for Sight; receiving nonfinancial support from Moorfields Eye Hospital; institutional research funding from the NIHR; speaker fees from Heidelberg Spectralis Lecture at Heidelberg Academy; and research funding from UK Biobank Eye and Vision Consortium outside the submitted work. Dr Patel reported receiving personal fees from Bayer UK and Roche UK outside the submitted work. No other disclosures were reported. Publisher Copyright: © 2022 Kleerekooper I et al.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85125611620&partnerID=8YFLogxK
U2 - https://doi.org/10.1001/jamanetworkopen.2022.0902
DO - https://doi.org/10.1001/jamanetworkopen.2022.0902
M3 - Article
C2 - 35238934
SN - 2574-3805
VL - 5
SP - e220902
JO - JAMA network open
JF - JAMA network open
IS - 3
M1 - e220902
ER -