Differentiating Cognitive Decline in Multiple Sclerosis and Alzheimer Disease: Sarah Levy, PhD

WATCH TIME: 5 minutes

"Orientation seems to be a key differentiator in the cognitive profile between [patients with multiple sclerosis and patients with Alzheimer disease]."

Cognitive impairment is a common concern among older adults with multiple sclerosis (MS), often affecting quality of life and independence. However, distinguishing whether cognitive decline is because of MS or other conditions, such as Alzheimer disease (AD), remains challenging. The Montreal Cognitive Assessment (MoCA) is a widely used screening tool for cognitive impairment across neurological disorders, including MS, and thus, comparing MoCA performance patterns between patients with MS and those with AD may offer valuable insights for diagnostic accuracy. Recent research has also suggested that MS may provide a protective effect against AD, potentially reducing the likelihood of co-occurrence.

A recently conducted study aimed to analyze MoCA performance in older adults with MS to identify specific cognitive patterns that differentiate MS-related impairment from AD-related decline. The retrospective analysis included 100 patients with MS over age 60, comparing MoCA scores with normative data from cognitively normal (NC) individuals and patients with AD. All told, the overall MS group had a mean MoCA score of 23.7, lower than the NC group (27.4) but higher than the AD group (16.2). Among patients with MS with impaired scores (n = 19), performance resembled the AD group on tasks such as Trails, Cube Copy, Clock Drawing, Fluency, and Abstraction. However, key differences emerged: patients with MS performed worse on Sentence Repetition, whereas those with AD showed greater impairment in Naming and Orientation. Notably, 90% of impaired patients with MS retained near-perfect Orientation scores. These findings suggest that distinct cognitive profiles reflected differing underlying pathologies, potentially helping to differentiate MS-related cognitive changes from AD. Additionally, they support the notion that MS may confer some protective advantage against AD-related cognitive decline.

These insights were recently presented by coauthor Sarah Levy, PhD, clinical neuropsychologist and assistant professor at Mount Sinai, at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27 to March 1, in West Palm Beach, Florida. During the Forum, Levy sat down for an interview with NeurologyLive^® to discuss how cognitive impairment presents in older adults with MS and how it can sometimes mimic AD. She emphasized that although both conditions may involve deficits in language and episodic memory, orientation remains a distinguishing factor—patients with MS tended to retain awareness of time and place, whereas those with AD often did not. The conversation also highlighted the importance of objective biomarkers, such as blood-based tests and amyloid PET scans, to better differentiate between MS-related cognitive impairment and AD. Additionally, Levy discussed the MS Cognitive Scale, a patient-reported questionnaire designed to track cognitive deficits in MS.

Click here for coverage of 2025 ACTRIMS Forum.

REFERENCES
1. La Rosa F, Dereskewicz EM, Silva JD, et al. Characterizing Longitudinal Brain Age in Multiple Sclerosis. Presented at ACTRIMS Forum 2025; February 27 to March 1; West Palm Beach, Florida. Session PS1. 016.