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Visual Pathway Measures are Associated with Neuropsychological Function in Multiple Sclerosis.

ABSTRACT: PURPOSE:To determine the relationships between visual function and ganglion cell and inner plexiform layer thickness and neuropsychological measures in multiple sclerosis (MS). METHODS:Ninety-five relapsing-remitting MS (RRMS) and 36 progressive MS patients underwent 100%-contrast visual acuity (VA), 2.5%- and 1.25%-contrast letter acuity (LA) testing, Cirrus-HD-optical coherence tomography, and neuropsychological assessments. Mixed-effects regression models were used to assess relationships. RESULTS:Across the cohort, 1.25%-contrast LA was associated with Symbol Digit Modalities Test (SDMT; ? = 2.17, p = 0.005) and Brief Visuospatial Memory Test-Revised (BVMT-R) total recall (TR) and delayed recall (DR) scores (? = 0.31, p < 0.001; ? = 0.15, p = 0.039, respectively). 2.5%-contrast LA was associated with BVMT-R TR scores (? = 0.27, p = 0.006). In the RRMS cohort, 1.25%-contrast LA was generally more significantly associated with cognitive measures: SDMT (? = 2.97, p = 0.001) and BVMT-R TR (? = 0.32, p < 0.001) and DR (? = 0.22, p = 0.012). CONCLUSION:This study suggests that visual pathway measures, particularly visual function measures, reflect aspects of cognitive function in MS, further supporting their roles as complementary outcomes in MS neuroprotection trials.

SUBMITTER: Nguyen J

PROVIDER: S-EPMC6298605 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Visual Pathway Measures are Associated with Neuropsychological Function in Multiple Sclerosis.

Nguyen James J Rothman Alissa A Fitzgerald Kathryn K Whetstone Anna A Syc-Mazurek Stephanie S Aquino Jannelle J Balcer Laura J LJ Frohman Elliot M EM Frohman Teresa C TC Crainiceanu Ciprian C Beier Meghan M Newsome Scott D SD Calabresi Peter A PA Saidha Shiv S

Current eye research 20180501 7

<h4>Purpose</h4>To determine the relationships between visual function and ganglion cell and inner plexiform layer thickness and neuropsychological measures in multiple sclerosis (MS).<h4>Methods</h4>Ninety-five relapsing-remitting MS (RRMS) and 36 progressive MS patients underwent 100%-contrast visual acuity (VA), 2.5%- and 1.25%-contrast letter acuity (LA) testing, Cirrus-HD-optical coherence tomography, and neuropsychological assessments. Mixed-effects regression models were used to assess re ...[more]

PMID: 29634379

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Project description:Multiple sclerosis is a heterogeneous disease with an unpredictable course and a wide range of severity; some individuals rapidly progress to a disabled state whereas others experience only mild symptoms. Though genetic studies have identified variants that are associated with an increased risk of developing multiple sclerosis, no variants have been consistently associated with multiple sclerosis severity. In part, the lack of findings is related to inherent limitations of clinical rating scales; these scales are insensitive to early degenerative changes that underlie disease progression. Optical coherence tomography imaging of the retina and low-contrast letter acuity correlate with and predict clinical and imaging-based outcomes in multiple sclerosis. Therefore, they may serve as sensitive phenotypes to discover genetic predictors of disease course. We conducted a set of genome-wide association studies of longitudinal structural and functional visual pathway phenotypes in multiple sclerosis. First, we assessed genetic predictors of ganglion cell/inner plexiform layer atrophy in a discovery cohort of 374 patients with multiple sclerosis using mixed-effects models adjusting for age, sex, disease duration, optic neuritis and genetic ancestry and using a combination of single-variant and network-based analyses. For candidate variants identified in discovery, we conducted a similar set of analyses of ganglion cell/inner plexiform layer thinning in a replication cohort (n = 376). Second, we assessed genetic predictors of sustained loss of 5-letters in low-contrast letter acuity in discovery (n = 582) using multivariable-adjusted Cox proportional hazards models. We then evaluated candidate variants/pathways in a replication cohort. (n = 253). Results of both studies revealed novel subnetworks highly enriched for connected genes in early complement activation linked to measures of disease severity. Within these networks, C3 was the gene most strongly associated with ganglion cell/inner plexiform layer atrophy (P = 0.004) and C1QA and CR1 were top results in analysis of sustained low-contrast letter acuity loss. Namely, variant rs158772, linked to C1QA, and rs61822967, linked to CR1, were associated with 71% and 40% increases in risk of sustained LCLA loss, respectively, in meta-analysis pooling discovery and replication cohorts (rs158772: hazard ratio: 1.71; 95% confidence interval 1.30-2.25; P = 1.3 × 10-4; rs61822967: hazard ratio: 1.40; 95% confidence interval: 1.16-1.68; P = 4.1 × 10-4). In conclusion, early complement pathway gene variants were consistently associated with structural and functional measures of multiple sclerosis severity. These results from unbiased analyses are strongly supported by several prior reports that mechanistically implicated early complement factors in neurodegeneration.

Dataset Information

Visual Pathway Measures are Associated with Neuropsychological Function in Multiple Sclerosis.

Publications

Visual Pathway Measures are Associated with Neuropsychological Function in Multiple Sclerosis.

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