Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: Preliminary findings

a Kessler Foundation Research Center , West Orange , NJ , USA.
Neurocase (Impact Factor: 1.12). 10/2013; 20(6). DOI: 10.1080/13554794.2013.841951
Source: PubMed


Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp(2) = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp(2) = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp(2) = 0.126) and memory (p = 0.037, ηp(2) = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS.
    Neurology 04/2014; 82(20). DOI:10.1212/WNL.0000000000000433 · 8.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Cognitive impairment is a highly prevalent, poorly managed, and disabling consequence of multiple sclerosis (MS). Exercise training that improves physical fitness represents a promising approach for managing cognitive impairment in persons with MS. There is limited evidence that physical fitness is associated with multiple domains of cognitive dysfunction across levels of MS disability. Objective: This cross-sectional study examined the associations among aerobic capacity, lower limb muscle strength, and cognitive functions in persons with mild, moderate, and severe MS disability. Methods: The sample included 62 persons with mild (n=20), moderate (n=21), and severe (n=21) MS disability. The participants underwent neuropsychological assessments of cognitive processing speed (CPS; Symbol Digit Modalities Test (SDMT)), verbal memory (California Verbal Learning Test-2 (CVLT-2)), and visual memory (Brief Visuospatial Memory Test-Revised (BVMT-R)). All participants further underwent testing for measuring aerobic capacity (i.e., peak oxygen consumption) and muscular strength (i.e., peak torque of knee flexors and extensors). Results: Aerobic capacity and muscular strength outcomes were associated with SDMT (r’s=.35-.41), but not CVLT-2 or BVMT-R (r’s<.19) scores in the overall sample. Aerobic capacity (r=.42) and knee flexor peak torque (r=.39) were associated with SDMT scores in persons with mild disability, but not in those with moderate (r’s<.06) and severe (r’s<.14) disability. Conclusions: These results support examining aerobic and resistance exercise training programs for improving CPS, particularly among persons with mild MS disability.
    Neurorehabilitation and Neural Repair 07/2014; 29(3). DOI:10.1177/1545968314541331 · 5.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Memory impairment affects 50% of multiple sclerosis (MS) patients. Altered resting-state functional connectivity (FC) has been observed in the default network (DN) of MS patients. No study to date has examined the association of DN FC to its behavioral concomitant, memory. The approach of the present study represents a methodological shift allowing straightforward interpretation of FC alterations in MS, as it presupposes specificity of a network to its paired cognitive function. We examined FC from fMRI collected during rest in the DN of 43 MS patients with and without memory-impairment. Memory-intact patients showed increased DN FC relative to memory-impaired patients. There were no regions of higher FC in memory-impaired patients. DN FC was positively correlated with memory function, such that higher FC was associated with better memory performance. Results were unchanged after controlling for cognitive efficiency, supporting specificity of the DN to memory and not cognitive status more generally. These findings support DN FC as a marker of memory function in MS patients that can be targeted by future treatment interventions. Pairing a functional network with its behavioral concomitant represents a straightforward method for interpreting FC alterations in patients with MS. (JINS, 2014, 20, 1-8).
    Journal of the International Neuropsychological Society 09/2014; 20(9):1-8. DOI:10.1017/S1355617714000800 · 2.96 Impact Factor
Show more