Home›Neurology› Brain age gap correlates with slower cognitive processing speed in patients with Multiple Sclerosis
Brain age gap correlates with slower cognitive processing speed in patients with Multiple SclerosisBrain Age Gap Linked to Slower Processing in MS
medRxivPublished August 24, 2026Study authors: Lea, R.; Lea, S.; Al-Iedani, O.; Ramadan, S.; Maltby, V.; Lechner-Scott, J.DOI ↗Editorial oversight: Dr. Ji-eun Park, MD · Brain, Mind & Pain
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Key Takeaway
Note that brain age gap may serve as an adjunctive MRI marker for cognitive processing speed in Multiple Sclerosis.
This meta-analysis synthesizes data from five independent clinical cohorts (n=1,250) and a large observational cohort from the UK Biobank to evaluate the relationship between brain age gap (BAG) and cognitive processing speed (CPS). The study specifically examines how BAG relates to cognitive outcomes in patients with Multiple Sclerosis (MS) compared to a normative reference group.
The analysis found a moderate negative association between BAG and CPS in the UK Biobank MS cohort (r=-0.35, 95% CI -0.52 to -0.17, P<.001). In contrast, the normative reference group showed a negligible association (r=-0.05, 95% CI -0.07 to -0.04, P<.001). A significant MS-specific correlation was identified in the interaction analysis (beta=-0.19, 95% CI -0.29 to -0.09, P<.001). Furthermore, a pooled correlation across five independent clinical cohorts showed a negative association between BAG and CPS (r=-0.25, 95% CI -0.33 to -0.18, P<.001).
The authors note that these are cross-sectional findings. Therefore, the study does not establish a mechanism, prognosis, or clinical decision utility at this time. While BAG may serve as an adjunctive MRI marker for cognitive processing speed in MS, further research is required to determine its specific role in clinical management.
How this fits prior evidence
This meta-analysis addresses a gap in identifying objective imaging markers for cognitive decline in Multiple Sclerosis. While previous coverage has focused on the prevalence of neurogenic bladder and autonomic gastrointestinal dysfunction in MS patients, this study provides evidence regarding the potential use of brain age gap as an MRI marker for cognitive processing speed.
Researchers analyzed data from several groups of people with Multiple Sclerosis (MS) to look at how brain age relates to mental speed. They compared these results against a large group of healthy individuals to see if the patterns were specific to MS.
The study found that for those with MS, a larger gap between their actual age and their brain's estimated age was linked to slower cognitive processing speeds. In contrast, this link was not seen in the healthy group. This suggests that the brain age gap might be a specific marker for how MS affects mental processing.
Because these findings come from cross-sectional data, they only show a link between these two factors. The study does not explain why this happens or how it might change future health. It also does not provide a way to make clinical decisions at this time. Doctors may eventually use brain age as an extra tool on MRIs to help track cognitive changes in patients.
What this means for you:
A larger gap between actual and brain age is linked to slower processing speeds specifically in people with MS.
Common questions
What is the brain age gap?
The brain age gap refers to the difference between a person's actual chronological age and the age of their brain as estimated by imaging. In this study, researchers found that for people with Multiple Sclerosis, a larger gap was linked to slower cognitive processing speeds.
Is this finding specific to Multiple Sclerosis?
Yes, the results suggest it is specific to MS. While people with MS showed a link between brain age and processing speed, the healthy group in the study showed almost no link at all.
Can this be used to treat Multiple Sclerosis?
The study does not show that it can be used for treatment. It only shows a link between brain age and processing speed. More research is needed to understand the cause or how it might help in clinical decisions.
Background and Objectives: Cognitive impairment is common in multiple sclerosis (MS), but whether brain age gap (BAG) has greater cognitive relevance in MS than in people without brain disease is not known. We tested whether BAG was more strongly associated with cognitive processing speed (CPS) in MS. Methods: We performed a cross-sectional analysis of MRI-derived BAG and CPS from a UK Biobank study consisting of 21,117 normative reference subjects with no recorded brain disease and 97 subjects with MS. BAG and CPS were standardized to the normative reference distribution, and an age- and sex-adjusted interaction tested whether the association differed between groups. Separately, a meta-analysis of the relationship of BAG and CPS was performed using published data from five independent MS cohorts (n=1,250 subjects in total). Correlation statistics were pooled to establish the effect size, 95% confidence intervals and p-values. Results: In UK Biobank, there was a moderate negative association between BAG and CPS in MS (r=-0.35, 95% CI -0.52 to -0.17; P<.001), whereas the association in the normative reference group was negligible (r=-0.05, 95% CI -0.07 to -0.04; P<.001). There was a BAG-by-MS interaction indicating an MS-specific correlation (beta =-0.19, 95% CI -0.29 to -0.09; P<.001). Across five independent clinical MS cohorts, the pooled BAG-CPS correlation was r=-0.25 (95% CI -0.33 to -0.18; P<.001). Overall, the magnitude of the association between BAG and CPS was at least five-fold greater in MS than in the normative population. Conclusion: BAG was substantially more strongly associated with CPS in MS than in the normative population. These cross-sectional findings support further evaluation of BAG as an adjunctive MRI marker. Further studies are required to establish mechanism, prognosis, or clinical decision utility.
