The NHANES Biological Age Index demonstrates accelerated aging in MS patients.

Abstract

Chronological age is associated with disability accumulation in multiple sclerosis (MS). Biological age may give more precise estimates of aging pathways associations with MS severity. Both normal aging and accelerated aging from MS may negatively impact disease course. Multi-marker indices of aging, such as the NHANES biological age index (BAI), may be more robust than single biomarkers in capturing biological age and are strongly associated with mortality risk and aging-related diseases. We sought to investigate whether the NHANES BAI, utilizing readily available measures in the clinic, captures accelerating aging and correlates with disability in MS participants. We conducted a prospective, cross-sectional case-control pilot study. Consecutive patients who met the 2017 McDonald's Criteria for MS were recruited from May 2020 to May 2022 along with age-similar healthy controls. BAI components included blood pressure, FEV1, serum creatinine, C-reactive protein, blood-urea nitrogen, albumin, alkaline phosphatase, cholesterol, CMV IgG, and hemoglobin A1c. The index was calculated using the Klemara and Doubal method. Spearman correlation and multivariable linear regression models were used to assess the association between BAI and MS clinical outcomes. A total of 51 MS (68.6% female) and 38 control (68.4% female) participants were recruited. BAI correlated with chronological age (CA) in MS (r2=0.90,p<0.0001) and control participants (r2 =0.87,p<0.0001). The mean BAI was 1.4 years older than CA in MS participants (range +15 to -10.5 years) and 2.2 years younger in control participants (range +11.2 to -14.1 years). In unadjusted Spearman analyses, BAI correlated with the timed 25-foot walk (T25FW, rhos=0.31, p=0.045) and symbol digit modalities test (SDMT rhos=0.35, p=0.018). In a multivariable regression model, a 5-year older BAI was associated with a 1.2-point lower score on SDMT (95%CI -2.2 to -0.25, p=0.014). MS participants were biologically older than their own chronological age and age-similar controls. In this modest-sized pilot sample, there was strongest correlation for MS outcome measures between BAI and the SDMT. These results support further study of the BAI as a marker of biological age variability in MS.