Warmer outdoor temperature has been linked to clinical exacerbations1,2
and T2 lesion activity3
in patients with MS. Although approximately 65% of patients with MS experience cognitive deficits,5
the current study is the first to formally investigate the relationship between outdoor temperature and cognition in patients with MS. We found that warmer temperatures are associated with worse cognitive performance across 2 independent samples of patients with MS. Our cross-sectional analysis demonstrated that cognitive status is worse on warmer days in patients with MS equated for level of disease severity (i.e., brain atrophy). This relationship was specific to MS, as cognitive status was unrelated to temperature among matched healthy controls. The longitudinal/within-subjects analysis showed that changes in outdoor temperature are associated with cognitive fluctuations within individual patients with MS. Importantly, results of the longitudinal/within-subjects analysis demonstrate that individual patients have a measurable decline in cognitive status when the outdoor temperature is warmer.
Clinicians frequently rely on sensorimotor symptoms (e.g., optic neuritis, muscle weakness) as clinical indicators of MS disease activity. Such symptoms are most likely to result from a focal disruption of critical white matter tracts underlying these primary functions; as such, sensorimotor symptoms likely underestimate the true extent of MS disease activity throughout cerebral white matter. Indeed, a recent study showed that MS disease activity frequently occurs in the absence of sensorimotor symptoms,3
suggesting that subclinical disease activity is common. The need for more sensitive markers of disease-related activity is therefore critical. Cognition relies on diffusely distributed white matter tracts throughout the brain, making changes in cognitive status uniquely suited to detect otherwise “quiescent” exacerbations.
The association of warmer outdoor temperatures and worse cognitive function in persons with MS holds important implications for treatment. Clinicians should carefully monitor patients with MS for heat-related cognitive exacerbations, which may occur even in the absence of sensorimotor symptomology. Additionally, awareness of heat-related cognitive decline may inform lifestyle decisions by patients with MS, especially when demands for optimal cognitive functioning are high (e.g., taking summer-session courses in college). Researchers investigating cognition in MS must consider/control for temperature, especially in clinical trials where seasonal temperature can differ greatly at baseline and follow-up. (Indeed, the 6-month follow-up within our longitudinal analysis approximates a typical clinical trial.) More generally, the effects of temperature should be considered as a possible confound for any clinical trial using cognition as an outcome of interest, including drug trials; follow-up at warmer temperature may obfuscate the beneficial effects of experimental treatments.
A limitation of the present study is that it does not elucidate the underlying mechanisms for the association of outdoor temperature and cognition. In addition, while the recently reported finding of increased T2 lesion activity during warmer temperatures3
provided the impetus for the present investigation, we did not look at lesion activity in our samples and can therefore draw no conclusions as to whether increased lesion activity occurred. However, future studies examining the neuropathologic changes associated with worse cognition in warmer temperatures are warranted. In addition, putative mechanisms underlying the effect of temperature on cognition remain to be explored in future research. That is, separate lines of research have shown that increased temperature is associated with increased lesion activity3
and slowed or blocked conduction within demyelinated axons (for review, see12
), but it remains unclear whether these mechanisms or an as-yet unidentified mechanism is responsible for the heat-related decrements in cognitive status observed among patients with MS in the current study. It may also be useful to examine individuals with secondary progressive MS, as we may expect to see exaggerated effects of slowed/blocked conduction as a result of demyelination in this more advanced disease subtype.