Table 2.
Summary of results of studies of comorbidity and radiological outcomes from 2015-2022.
| Reference | Design Sample size |
Demographic and MS characteristics | Comorbidity | Radiological outcome | Summary of Findings |
|---|---|---|---|---|---|
| Vascular and related comorbidities | |||||
| (55) | Longitudinal study 194 PwMS |
Mean age: 46.7y (11.2y) 74% female: 75% RRMS |
Hypertension, hyperlipidemia, CVD, diabetes, obesity/overweight | BPF, WM, GM, T2 lesion volumes, lateral ventricular volume | CVD associated with faster rates of BPF and WM loss. Hypertension was associated with higher lateral ventricle volume change Hyperlipidemia and obesity/overweight were not associated change in outcomes. |
| (34) | Longitudinal study 959 PwMS |
Mean age: 37.9y (SD: 9.6y) 73% female 100% RRMS |
hypertension, dyslipidemia, diabetes, depression, anxiety, and migraine | Combined unique lesion activity | Migraine was associated with a lower risk of combined unique lesion activity. Other comorbidities were not associated with lesion outcomes. |
| (56) | Longitudinal study 489 PwMS |
Mean age: 71% female 59% RRMS |
hypertension, CVD, smoking, obesity, type 1 diabetes |
BPF, WM, GM, cortical GM, T1, and T2 lesion volumes | Hypertension and heart disease were associated with decreased total GM and cortical GM volume. Obesity was associated with increased T1 lesion volume CVD was associated with Increased lateral ventricle volume in CIS |
| (57) | Longitudinal study 98 PwMS |
Mean age: 49.3y (12.8y) 85% female 84% RRMS |
Framingham CVD risk scores, Diabetes, hypertension, hyperlipidemia, CVD, PVD, obesity | BPF | Higher Framingham risk scores were associated with greater brain volume loss over time. The association was strongest for participants with the highest brain volumes at baseline. |
| (58) | Longitudinal study 82 PwMS/CIS |
Mean age: 32.4y (SD: 8.7y) 65% female 100% CIS/RRMS |
Hypertension, hyperlipidemia, diabetes | BPF, WM, GM, cortical GM, thalamic, basal ganglia, and T2 lesion volumes | At baseline, having a vascular risk factor was associated with lower BPF, total GM, cortical GM, and WM volumes. Change in MRI outcomes was similar between PwMS with a vascular risk factor versus those without a vascular risk factor |
| (59) | Cross-sectional study 326 PwMS Longitudinal study 90 PwMS |
Mean age: 44.2y (SD: 10.4) 65% female 90% RRMS |
Diabetes, hypertension | BPF, WM, GM, cortical GM volumes | In cross-sectional analyses, diabetes was associated with lower BPF, GM, and cortical GM, and hypertension was associated with lower cortical GM. Increasing burden of vascular risk factors (diabetes, hypertension, smoking) associated with lower cortical GM. In longitudinal analysis, ≥1 vascular was associated with faster BPF loss. |
| (46) | Longitudinal study 51 PwMS |
Mean age: 58.8y (SD: 6.4y) 55% female 100% PMS |
Hypertension, dyslipidemia, obesity, diabetes, PVD or CVD | GCIPL, RNFL | Vascular comorbidity was not associated with change in GCIPL or RNFL |
| (60) | Cross-sectional study 573 PwMS/CIS |
Mean age: 45.0y (12.4y) 71% female 100% RRMS/CIS |
Migraine | BPF, T2 lesions, Gd+ lesions | Migraine was more common in PwMS or CIS than healthy people Migraine was associated with more Gd+ lesions but not volume of Gd+ lesions in PwMS or CIS |
| (61) | Cross-sectional study 204 PwMS |
Mean age: 44.7y (11.9y) 76% female Subtype not reported |
Migraine | T2 lesion volume, number of T2 lesions, Gd+ lesions, T1 hypointense lesions | Migraine was associated with fewer T1 hypointense lesions but was not associated with other MRI outcomes. |
| (44) | Cross-sectional study 6409 PwMS |
Mean age: 47.6y (SD: 11.7y) 74% female 89% RRMS |
Diabetes, Hypertension, Hyperlipidemia | BPF, GM, WM, thalamic volumes | Dyslipidemia and diabetes were associated with lower BPF Those with 2+ comorbidities had lower BPF, GM, cortical GM and deep GM volumes when compared to those with no comorbidity |
| (62) | Longitudinal study 469 PwMS/CIS |
Mean age: 42 (SD: 10y) 70% female 100% CIS/RRMS |
BMI, obesity (BMI ≥ 30) | BPF, GM | Higher BMI was associated with higher BMI was associated with faster BPF and GM atrophy |
| (63) | Longitudinal study 464 PwMS/CIS |
Mean age: 30.8y (SD: 7.4y) 70% female 100% CIS/RRMS |
BMI, obesity | Number of T2 lesions, number of Gd+ lesions, T2 lesion volume, Brain volume | No associations observed between obesity and any MRI outcomes in overall population Larger reduction in brain volume over time among obese smokers relative to normal weight smokers |
| (64) | Longitudinal study 768 PwMS |
Mean age: 38.2y (SD: 9.4y) 73% female 100% RRMS |
BMI, obesity | WM, GM, CSF | Higher BMI was associated with faster rates of GM loss, when BMI was modeled as a continuous covariate. Findings were less clear when BMI was modeled using standard cut-points. |
| (65) | Cross-sectional 3,046 PwMS |
Mean age: 45.9y (SD: 11.7y) 73% female 70% RRMS |
BMI | BPF, GM, WM, thalamic and T2 lesion volumes | No correlations between BMI and MRI outcomes |
| (66) | Cross-sectional 64 PwMS |
Mean age: 39.8y (SD: 11.1y) 56.2% female 93.8% RRMS |
BMI, obesity, TC, LDL | T2 lesion volume, Gd+ lesions | No association between BMI, TC, or LDL with lesion outcomes |
| (67) | Longitudinal study 522 PwMS |
Mean age: 43.1y (SD: 11.9y) 72% female 70% RRMS |
BMI, obesity | GCIPL, INL, ONL, pRNFL | Higher BMI was associated with faster rates of change in GCIPL. Obesity was associated with faster rates of change in GCIPL BMI/obesity were not associated with changes in the other retinal layers. |
| Psychiatric comorbidity | |||||
| (59) | Cross-sectional study 61 PwMS |
Mean age: 40.2y (SD: 9.2y) 77% female 92% RRMS |
Bipolar disorder | BPF, WM, GM, deep GM substructures (nucleus accumbens, putamen, pallidus, caudate, hippocampus, thalamus) | No differences in BPF, WM, and cortical GM volumes were observed between PwMS with bipolar disorder versus PwMS without bipolar disorder Lower putamen and nucleus accumbens observed in PwMS with bipolar disorder |
| Other autoimmune conditions | |||||
| (68) | Cross-sectional study 815 PwMS |
Mean age: 45.7y (10.3y) 77% female 67% RRMS |
Thyroid disease, asthma, type 2 diabetes, psoriasis, and rheumatoid arthritis | BPF, WM, cortical GM, MTR | Having an autoimmune comorbidity was associated with a lower BPF, cortical GM, MTR of normal appearing brain tissue and gray matter. Psoriasis, thyroid disease, and diabetes were associated with decreased BPF, cortical GM, and total GM volumes |
| (69) | Cross-sectional study 286 PwMS |
Mean age: 42.4y (10.6y) 71% RRMS 92% RRMS |
Type 1 diabetes, autoimmune thyroiditis, celiac disease | BPF, WM, GM, cortical GM volumes | Type 1 diabetes was associated with lower total GM and CM volume. |
PwMS, people with MS; CIS, Clinically isolated syndrome; RRMS, relapsing-remitting MS; PMS, progressive MS; Gd+, Gadolinium enhancing; BPF, brain parenchymal fraction, GM, gray matter; WM, white matter; MTR, magnetization transfer ratio; GCIPL, ganglion cell inner plexiform layer; INL, inner nuclear layer; ONL, outer nuclear layer; pRNFL, peri-papillary retinal nerve fiber layer; RNFL, retinal nerve fiber layer. TC, total cholesterol; BMI, body mass index in kg/m2; LDL, low density lipoprotein; CVD, cardiovascular disease; PVD, peripheral vascular disease.