Brain lesions associated with memory loss in multiple sclerosis linked to common brain circuit

Between 30% and 50% of people living with multiple sclerosis (MS) will experience memory problems, but the cause is uncertain. Brain lesions are the hallmark imaging sign used to diagnose MS and are often associated with memory dysfunction. However, increased MS brain lesions are not specific to memory problems, and are also associated with fatigue, walking difficulty and other common MS symptoms. Previous studies that attempted to align the anatomy of lesions associated with memory problems in MS led to conflicting results.

Multiple sclerosis lesions that impair memory map to a connected memory circuit - Journal of Neurology

Background Nearly 1 million Americans are living with multiple sclerosis (MS) and 30–50% will experience memory dysfunction. It remains unclear whether this memory dysfunction is due to overall white matter lesion burden or damage to specific neuroanatomical structures. Here we test if MS memory dysfunction is associated with white matter lesions to a specific brain circuit. Methods We performed a cross-sectional analysis of standard structural images and verbal memory scores as assessed by immediate recall trials from 431 patients with MS (mean age 49.2 years, 71.9% female) enrolled at a large, academic referral center. White matter lesion locations from each patient were mapped using a validated algorithm. First, we tested for associations between memory dysfunction and total MS lesion volume. Second, we tested for associations between memory dysfunction and lesion intersection with an a priori memory circuit derived from stroke lesions. Third, we performed mediation analyses to determine which variable was most associated with memory dysfunction. Finally, we performed a data-driven analysis to derive de-novo brain circuits for MS memory dysfunction using both functional (n = 1000) and structural (n = 178) connectomes. Results Both total lesion volume (r = 0.31, p < 0.001) and lesion damage to our a priori memory circuit (r = 0.34, p < 0.001) were associated with memory dysfunction. However, lesion damage to the memory circuit fully mediated the association of lesion volume with memory performance. Our data-driven analysis identified multiple connections associated with memory dysfunction, including peaks in the hippocampus (T = 6.05, family-wise error p = 0.000008), parahippocampus, fornix and cingulate. Finally, the overall topography of our data-driven MS memory circuit matched our a priori stroke-derived memory circuit. Conclusions Lesion locations associated with memory dysfunction in MS map onto a specific brain circuit centered on the hippocampus. Lesion damage to this circuit fully mediated associations between lesion volume and memory. A circuit-based approach to mapping MS symptoms based on lesions visible on standard structural imaging may prove useful for localization and prognosis of higher order deficits in MS.

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Self-awareness of Memory Function and Clinical Progression in Cognitively Normal Older Adults

This cohort study investigates the association of a novel measure for self-awareness of memory function with future clinical progression toward Alzheimer disease in individuals who were cognitively normal at baseline.

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