Multiple Sclerosis and Healthy Aging: a Comparative Analysis of Structure and Function

The relationship between healthy, normal aging and the neurodegenerative disease Multiple Sclerosis (MS) is a subject of ongoing debate. Parallels between the two include vascular and metabolic decline in addition to cognitive decline. In particular, processing speed declines are seen in both aging and MS. In aging, previous work has suggested that processing speed decline is thought to be the basis for all age-related cognitive decline. Whereas neurovascular and neurovascular effects of MS and aging have previously been studied separately, they have not been studied in parallel. In addition, the relationships between these effects and MS- and age- related cognitive decline have not previously been investigated. In the studies presented here, I explore the relationships between neurovascular and neurometabolic function in aging and in MS as well as their effects on cognitive and brain volume using multiple regression analysis. I found that cerebrovascular reactivity is associated with cognitive decline in aging, but not in MS, despite significantly lower arterial reactivity in MS. I also found that task-evoked neurovascular and neurometabolic dynamics are associated with brain volume in MS, but not in aging. Lastly, I do not find any relationships between processing speed and white matter integrity in any group. These results indicate that processing speed decline is a diffuse phenomenon that can arise from the dysfunction of many different systems. It is also indicative of divergent effects of vascular pathology and signaling dysfunction on MS patients and older adults. This work shows that despite similarities in pathological processes, vascular and metabolic associations with cognitive decline and brain volume differ between MS and aging.