How Multiple Sclerosis Symptoms Vary by Age, Sex, and Race/Ethnicity

Discussion

Disability and symptom burden increased with age in men and women of every race/ethnicity groups, as would be expected in a progressive neurologic disorder. The largest increase occurred between ages 40 and 60 years, perhaps a reflection of the transition from the relapsing phase to the progressive phase during this period in most patients. The change in symptom burden score between 50–60 and 60+ years' age groups was less pronounced, possibly because of the relatively slower progression in the older patients or because of psychologic accommodation to physical limitations (as reflected in lower anxiety and depression scores in patients aged 60+ years compared with the 50–60 age group). Immortal time bias, whereby older and severely disabled patients would be more likely to have died or be too impaired to follow up in the clinic, may also have contributed to the apparent flattening in total SyMS scores in the older groups. With the exception of anxiety, individual domain scores all showed an increase with age, but the pattern of increase differed between spinal domains, such as walking and bladder function, which steadily increased, and cognitive and affective domains, which tended to increase before age 40 years, but not thereafter. Worsening of physical disability with age and stabilization of mental health scores has been observed by others as well.^3,13,14

Men and women had similar total symptom scores and similar SRH. Younger women (aged <40 years) tended to have higher total symptom scores than men of the same age, perhaps a reflection of a higher rate of relapse and enhancing lesion formation in women compared with men.^15,-,17 Higher anxiety scores among women with MS may reflect a well-known predisposition of women to anxiety disorders.¹⁸ Women also had higher fatigue scores compared with men; similar findings of higher fatigue in women were reported in a recent multicenter study of Chinese patients with MS.¹⁹ Men had higher overall disability (PDDS), and worse walking and dexterity scores, which is also consistent with the survey of Chinese patients with MS¹⁹ and the literature documenting higher burden of spinal disability and higher load of destructive, T1 hypointense lesions in men compared with women (reviewed in reference 20).

African ancestry is a known risk factor for worse outcomes in MS.^21,22 African Americans have faster disease progression,²³ especially early in the disease,²⁴ and more brain,^25,26 spinal cord,²⁷ and optic nerve²⁸ atrophy. In line with these reports, we found that symptom scores were higher in AAs compared with Whites in every domain even after adjusting for age and sex. The literature on MS in Hispanic Americans is sparse. Our prior work showed that HAs have higher disability scores than Whites.²⁹ In the present work, we show that HAs had worse scores than Whites in every domains and even higher than in AAs in several domains of invisible disability—pain, cognition, depression, and anxiety.

Given the differences in symptom burden across race/ethnic groups, we hypothesized that race would be an independent predictor of good SRH. However, race/ethnicity was a strong predictor of SRH only if domain scores are not taken into account. In a multivariable model that accounted for age, sex, race/ethnicity, self-reported disability, and individual domain symptom scores, only body pain, depression, fatigue, and PDDS—in the order of decreasing contribution—were predictive of good SRH. Sensitivity of the model was 82% and specificity 76%. Thus, what determines how patients view their health is not their demographics but symptom severity in domains of invisible disability and, to a much lesser extent, their overall physical disability score (PDDS).

One limitation of our study is that the racial self-identification does not reveal the extent of genetic admixtures in patients' ancestry³⁰ and may even conflict with the genetic data.³¹ One can overcome this limitation using ancestry informative genetic markers, but this approach is not feasible in a retrospective, clinic-based study. Another limitation is that clinician-rated measures were not available for our sample; prior studies have validated domain SyMS scores against clinician-rated metrics.^12,32,33 Third, we did not collect information on patients' socioeconomic status (SES) and are not able determine how much of variance in symptom burden among race/ethnic groups may be due to differences in SES. In our prior work on disability differences in patients with MS from the different racial groups, adjusting for insurance status as a surrogate for SES did not change the results.²⁹ However, others have found that failure to account for SES differences may lead to overestimation of differences between racial groups.³⁴ We propose that the future observational studies comparing outcomes across ethno-ancestries use Area Deprivation Index, which can be derived from patient's address (neighborhoodatlas.medicine.wisc.edu/), as a more nuanced surrogate of SES, and address social determinants of health, which may disproportionately affect minoritized populations that extend beyond SES.³⁵ Another limitation is that we did not systematically collect data on disease-modifying (DMT) and symptomatic therapies. In our prior work, we did not find differences in overall rates of DMT use across ethnic groups,²⁷ and in a recent audit of NYU MS Center data, a higher proportion of AAs were receiving high-efficacy therapies (natalizumab and anti-CD20 therapies) compared with Whites (data on file) likely in response to their higher disease severity. Thus, it is highly unlikely that observed differences in disease severity are due to undertreatment of minority populations. Finally, the potential impact of various forms of selection bias must be considered. If the more disabled minority patients are preferentially referred to tertiary centers, while milder cases are managed by community neurologists, our minority populations may be skewed toward the more severe end of the spectrum.⁸ Conversely, if the more impaired minority patients are less likely to follow up in the referral center given socioeconomic disparities, the results would be skewed in the opposite direction. The racial representation in our clinics with respect to Whites, AAs, and HAs is reflective of our catchment area, so a considerable referral bias is not likely. Still, clinic patients with MS may differ from the general MS population, and population-based studies covering diverse geographic locales are needed to confirm whether our findings are generalizable.

In conclusion, AA and HA race/ethnicity was associated with higher overall disability, higher symptom severity in each of the 12 domains commonly affected by MS, and lower SRH scores relative to Whites. Importantly, race/ethnicity was not a predictor of SRH, rather SRH was mainly predicted by severity of body pain, depression, and fatigue. Our work suggests that improvement in managing these symptoms will be most likely to improve patients' quality of life and to reduce the disparities in SRH among race/ethnic groups. High symptom burden in non-White minorities with MS warrants investigation into its biologic and sociologic causes.