Hormonal contraceptives and the brain: A systematic review on 60 years of neuroimaging, EEG, and biochemical studies in humans and animals.

Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of hormonal contraception. We systematically review human and animal studies on the brain effects of hormonal contraception which employed neuroimaging techniques such as MRI, PET and EEG, as well as animal studies which reported on neurotransmitter and other brain biochemical effects. We screened 1001 articles and ultimately extracted data from 70, comprising 51 human and 19 animal studies. Of note, there were no animal studies which employed structural or functional MRI, MRS or PET. In summary, our review shows hormonal contraceptive associations with changes in the brain have been documented. Many questions remain and more studies are needed to describe the effects of hormonal contraception on the brain.

Genetic Variants and Persistent Impairment Following Mild Traumatic Brain Injury: A Systematic Review.

OBJECTIVE: The purpose of this review is to systematically assess primary research publications on known genetic variants, which modify the risk for symptoms or dysfunction persisting 30 days or more following mild traumatic brain injury (mTBI). SUMMARY OF REVIEW: A search of PubMed and Embase from inception through June 2022 identified 42 studies that associated genetic variants with the presence of symptoms or cognitive dysfunction 30 days or more following mTBI. Risk of bias was assessed for each publication using the Newcastle Ottawa Scale (NOS). Fifteen of the 22 studies evaluating apolipoprotein E ( APOE ) ɛ4 concluded that it was associated with worse outcomes and 4 of the 8 studies investigating the brain-derived neurotrophic factor ( BDNF ) reported the Val66Met allele was associated with poorer outcomes. The review also identified 12 studies associating 28 additional variants with mTBI outcomes. Of these, 8 references associated specific variants with poorer outcomes. Aside from analyses comparing carriers and noncarriers of APOE ɛ4 and BDNF Val66Met, most of the reviewed studies were too dissimilar, particularly in terms of specific outcome measures but also in genes examined, to allow for direct comparisons of their findings. Moreover, these investigations were observational and subject to varying degrees of bias. CONCLUSIONS: The most consistent finding across articles was that APOE ɛ4 is associated with persistent post-mTBI impairment (symptoms or cognitive dysfunction) more than 30 days after mTBI. The sparsity of other well-established and consistent findings in the mTBI literature should motivate larger, prospective studies, which characterize the risk for persistent impairment with standardized outcomes in mTBI posed by other genetic variants influencing mTBI recovery.

Caudate volume and symptoms of apathy in older adults with multiple sclerosis.

BACKGROUND: Apathy is common in multiple sclerosis (MS) and neurological disease, but its presence and underlying brain mechanisms in older adults with MS (OAMS) have not been evaluated. OBJECTIVE: Examine apathy and its association with caudate nuclei volume in OAMS and controls. We hypothesized that compared to controls, OAMS would demonstrate: a) greater apathy; b) stronger associations between apathy and caudate nuclei volumes. METHODS: OAMS (n = 67, mean age = 64.55 ± 3.89) and controls (n = 74, mean age = 69.04 ± 6.32) underwent brain MRI, cognitive assessment, psychological, and motoric testing. Apathy was assessed through the apathy subscale of the 30-item Geriatric Depression Scale. RESULTS: OAMS reported greater apathy compared to controls (ß = 0.281, p = 0.004). Adjusted moderation analyses revealed a significantly stronger association between caudate volume and apathy (left: B = -1.156, p = 0.039, right: B = -1.163, p = 0.040) among OAMS compared to controls. Conditional effects revealed that in adjusted models, lower volume of both the left (b = -0.882, p = 0.037) and right (b = -0.891, p = 0.038) caudate nuclei was significantly associated with greater apathy only among OAMS. CONCLUSION: Caudate nuclei, which are susceptible to adverse MS effects and implicated in mediating cognitive and motor function, may influence the presence and severity of apathy in OAMS.

Deep learning of longitudinal chest X-ray and clinical variables predicts duration on ventilator and mortality in COVID-19 patients.

OBJECTIVES: To use deep learning of serial portable chest X-ray (pCXR) and clinical variables to predict mortality and duration on invasive mechanical ventilation (IMV) for Coronavirus disease 2019 (COVID-19) patients. METHODS: This is a retrospective study. Serial pCXR and serial clinical variables were analyzed for data from day 1, day 5, day 1-3, day 3-5, or day 1-5 on IMV (110 IMV survivors and 76 IMV non-survivors). The outcome variables were duration on IMV and mortality. With fivefold cross-validation, the performance of the proposed deep learning system was evaluated by receiver operating characteristic (ROC) analysis and correlation analysis. RESULTS: Predictive models using 5-consecutive-day data outperformed those using 3-consecutive-day and 1-day data. Prediction using data closer to the outcome was generally better (i.e., day 5 data performed better than day 1 data, and day 3-5 data performed better than day 1-3 data). Prediction performance was generally better for the combined pCXR and non-imaging clinical data than either alone. The combined pCXR and non-imaging data of 5 consecutive days predicted mortality with an accuracy of 85 ± 3.5% (95% confidence interval (CI)) and an area under the curve (AUC) of 0.87 ± 0.05 (95% CI) and predicted the duration needed to be on IMV to within 2.56 ± 0.21 (95% CI) days on the validation dataset. CONCLUSIONS: Deep learning of longitudinal pCXR and clinical data have the potential to accurately predict mortality and duration on IMV in COVID-19 patients. Longitudinal pCXR could have prognostic value if these findings can be validated in a large, multi-institutional cohort.

Registration quality filtering improves robustness of voxel-wise analyses to the choice of brain template.

MOTIVATION: Many clinical and scientific conclusions that rely on voxel-wise analyses of neuroimaging depend on the accurate comparison of corresponding anatomical regions. Such comparisons are made possible by registration of the images of subjects of interest onto a common brain template, such as the Johns Hopkins University (JHU) template. However, current image registration algorithms are prone to errors that are distributed in a template-dependent manner. Therefore, the results of voxel-wise analyses can be sensitive to template choice. Despite this problem, the issue of appropriate template choice for voxel-wise analyses is not generally addressed in contemporary neuroimaging studies, which may lead to the reporting of spurious results. RESULTS: We present a novel approach to determine the suitability of a brain template for voxel-wise analysis. The approach is based on computing a "distance" between automatically-generated atlases of the subjects of interest and templates that is indicative of the extent of subject-to-template registration errors. This allows for the filtering of subjects and candidate templates based on a quantitative measure of registration quality. We benchmark our approach by evaluating alternative templates for a voxel-wise analysis that reproduces the well-known decline in fractional anisotropy (FA) with age. Our results show that filtering registrations minimizes errors and decreases the sensitivity of voxel-wise analysis to template choice. In addition to carrying important implications for future neuroimaging studies, the developed framework of template induction can be used to evaluate robustness of data analysis methods to template choice.

Evaluating the validity of self-report as a method for quantifying heading exposure in male youth soccer.

Assessing heading exposure in football is important when exploring the association between heading and brain alterations. To this end, questionnaires have been developed for use in adult populations. However, the validity of self-report in adolescents remains to be elucidated. Male youth soccer players (n = 34) completed a questionnaire on heading exposure after a two-week period, which included matches and training sessions. Self-reported numbers were compared to observation (considered reference). In total, we observed 157 training sessions and 64 matches. Self-reported heading exposure correlated with observed heading exposure (Spearman's rho 0.68; p < 0.001). Players systematically overestimated their heading exposure by a factor of 3 with the random error of 46%. Area under the curve was 0.87 (95% CI 0.67-1) utilizing self-report for identifying players from high- and low-exposure groups. Thus, in this study, self-reported data could be used to group youth players into high and low heading exposure groups, but not to quantify individual heading exposure.

The Impact of Sleep on the Relationship between Soccer Heading Exposure and Neuropsychological Function in College-Age Soccer Players.

OBJECTIVE: Soccer is the most popular sport worldwide and is the only sport where athletes purposely use their head to deflect the ball during play, termed "heading" the ball. These repetitive head impacts (RHI) are associated with worse neuropsychological function; however, factors that can increase risk of injury following exposure to such head impacts have been largely unexamined. The present study provided a novel examination of the modifying role of sleep on the relationship between RHI exposure and neuropsychological function in college-age soccer players. METHODS: Fifty varsity and intramural college soccer players completed questionnaires assessing recent and long-term heading exposure, a self-report measure of sleep function, and a battery of neuropsychological tests. RESULTS: A high level of recent heading exposure was significantly associated with poorer processing speed, independent of concussion history. With reduced sleep duration, a high level of recent heading exposure was related to worse sustained attention. However, with greater hours of sleep duration, heading exposure was related to preserved neuropsychological outcome in sustained attention. CONCLUSIONS: We replicated our earlier finding of an association between recent head impact exposure and worse processing speed in an independent sample. In addition, we found that sleep may serve as a risk or protective factor for soccer players following extensive exposure to head impacts. Ultimately, this study furthers the understanding of factors impacting neuropsychological function in soccer players and provides empirical support for sleep interventions to help ensure safer soccer play and recovery from injury.

Personality and Risk Taking in Sports: A Focus on Unintentional and Intentional Head Impacts in Amateur Soccer Players.

OBJECTIVE: In soccer, unintentional and intentional (heading) head impacts are associated with concussive symptoms and cognitive dysfunction. We examined whether personality traits were associated with these behaviors in soccer players. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Participants completed study visits at the Albert Einstein College of Medicine. A total of 307 adult amateur soccer players, recruited from New York City and the surrounding area, completed 737 HeadCount-2w questionnaires. PREDICTOR VARIABLES: Personality traits (intellect/imagination, conscientiousness, extraversion, agreeableness, and neuroticism) were assessed with the Mini-International Personality Item Pool questionnaire at the baseline study visit. MAIN OUTCOME MEASURES: Participants completed an online questionnaire (HeadCount-2w) to ascertain frequency of intentional head impacts and occurrence of unintentional head impacts every 3 to 6 months. Generalized estimating equations repeated-measures regressions determined whether personality predicted unintentional and intentional impacts. RESULTS: Personality traits were not associated with unintentional head impact(s) or frequency of intentional head impacts. CONCLUSIONS: These findings have important clinical implications, suggesting that personality is not driving the association between high levels of unintentional and intentional head impacts and worse neuropsychological functioning and concussive symptoms.

The neurobiological effects of repetitive head impacts in collision sports.

It is now recognized that repetitive head impacts (RHI) in sport have the potential for long-term neurological impairments. In order to identify targets for intervention and/or pharmacological treatment, it is necessary to characterize the neurobiological mechanisms associated with RHI. This review aims to summarize animal and human studies that specifically address Blood Brain Barrier (BBB) dysfunction, abnormal neuro-metabolic and neuro-inflammatory processes as well as Tau aggregation associated with RHI in collision sports. Additionally, we examine the influence of physical activity and genetics on outcomes of RHI, discuss methodological considerations, and provide suggestions for future directions of this burgeoning area of research.

Implantable Electronic Stimulation Devices from Head to Sacrum: Imaging Features and Functions.

Electronic stimulation devices are implanted in various locations in the body to decrease pain, modulate nerve function, or stimulate various end organs. The authors describe these devices using a craniocaudal approach, first describing deep brain stimulation (DBS) devices and ending with sacral nerve stimulation (SNS) devices. The radiology-relevant background information for each device and its imaging appearance are also described. These devices have a common design theme and include the following components: (a) a pulse generator that houses the battery and control electronics, (b) an insulated lead or wire that conveys signals to the last component, which is (c) an electrode that contacts the end organ and senses and/or acts on the end organ. DBS electrodes are inserted into various deep gray nuclei, most commonly to treat the symptoms of movement disorders. Occipital, trigeminal, and spinal nerve stimulation devices are used as second-line therapy to control craniofacial or back pain. For cardiac devices, the authors describe two newer devices, the subcutaneous implantable cardioverter defibrillator and the leadless pacemaker, both of which avoid complications related to having leads threaded through the venous system. Diaphragmatic stimulation devices stimulate the phrenic nerve to restore diaphragmatic movement. Gastric electrical stimulation devices act on various parts of the stomach for the treatment of gastroparesis or obesity. Finally, SNS devices are used to modulate urinary and defecatory functions. Common complications diagnosed at imaging include infection, hematoma, lead migration, and lead breakage. Understanding the components, normal function, and normal imaging appearance of each device allows the radiologist to identify complications. ©RSNA, 2019.

MRI-defined White Matter Microstructural Alteration Associated with Soccer Heading Is More Extensive in Women than Men.

Purpose To examine the role of sex in abnormal white matter microstructure after soccer heading as identified by using the diffusion-tensor imaging (DTI) metric fractional anisotropy (FA). Materials and Methods In this prospective cross-sectional study, 98 individuals who were enrolled in a larger prospective study of amateur soccer players (from 2013 to 2016) were matched 1:1 for age and history of soccer heading in the prior 12 months. Among the subjects, 49 men (mean age, 25.7 years; range, 18-50 years) and 49 women (mean age, 25.8 years; range, 18-50 years) with median total soccer headings per year of 487 and 469, respectively, underwent 3.0-T DTI. Images were registered to the Johns Hopkins University template. A voxelwise linear regression was fitted for FA with terms for the number of headings during the previous 12 months and its interaction with sex after controlling for the following potential confounders: age, years of education, number of lifetime concussions, and handedness. In the resulting statistical maps, P < .01 indicated a statistically significant difference, with a threshold cluster size larger than 100 mm3. Results Among men, three regions were identified in which greater heading exposure was associated with lower FA; eight such regions were identified among women (>100 contiguous voxels, P < .01). In seven of the eight regions identified in women, the association between heading and FA was stronger in women than in men. There was no significant difference of heading with FA between the sexes for any region in which heading was associated with FA among men (P > .01, <100 contiguous voxels). Conclusion With similar exposure to heading, women exhibit more widespread evidence of microstructural white matter alteration than do men, suggesting preliminary support for a biologic divergence of brain response to repetitive trauma. © RSNA, 2018 Online supplemental material is available for this article.

Recent and Long-Term Soccer Heading Exposure Is Differentially Associated With Neuropsychological Function in Amateur Players.

OBJECTIVES: The present study examined the relative contribution of recent or long-term heading to neuropsychological function in amateur adult soccer players. PARTICIPANTS AND METHODS: Soccer players completed a baseline questionnaire (HeadCount-12m) to ascertain heading during the prior 12 months (long-term heading, LTH) and an online questionnaire (HeadCount-2w) every 3 months to ascertain heading during the prior 2 weeks (recent heading, RH). Cogstate, a battery of six neuropsychological tests, was administered to assess neuropsychological function. Generalized estimating equations were used to test if LTH or RH was associated with neuropsychological function while accounting for the role of recognized concussion. RESULTS: A total of 311 soccer players completed 630 HeadCount-2w. Participants had an average age of 26 years. Participants headed the ball a median of 611 times/year (mean=1,384.03) and 9.50 times/2 weeks (mean=34.17). High levels of RH were significantly associated with reduced performance on a task of psychomotor speed (p=.02), while high levels of LTH were significantly associated with poorer performance on tasks of verbal learning (p=.03) and verbal memory (p=.04). Significantly better attention (p=.02) was detectable at moderately high levels of RH, but not at the highest level of RH. One hundred and seven (34.4%) participants reported a lifetime history of concussion, but this was not related to neuropsychological function and did not modify the association of RH or LTH with neuropsychological function. CONCLUSION: High levels of both RH and LTH were associated with poorer neuropsychological function, but on different domains. The clinical manifestations following repetitive exposure to heading could change with chronicity of exposure. (JINS, 2018, 24, 147-155).

White matter microstructural abnormalities in blast-exposed combat veterans: accounting for potential pre-injury factors using consanguineous controls.

PURPOSE: Assess the prevalence of white matter microstructural changes in combat veterans, within the context of a highly matched control group comprising unexposed close relatives. METHODS: This prospective study had institutional review board approval, included written informed consent, and is HIPAA-compliant. Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18 unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous relationship to a member of the subject group. Whole-brain voxel-based comparison of fractional anisotropy (FA) was performed using both group and individual analyses. Areas where effects on FA were detected were subsequently characterized by extracting radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) from the regions of abnormal FA. RESULTS: Controls did not differ from veterans on any background demographic factor. In voxel-based group comparison, we identify high fractional anisotropy (FA) in veterans compared to controls (p < 0.01). Within individual veterans, we find multiple areas of both abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent with multifocal traumatic axonal injury. In individualized analyses, low FA areas demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in both group and individual analyses. CONCLUSIONS: Combat-related blast exposure is associated with microstructural white matter abnormalities, and the nature of the control group decreases the likelihood that the findings reflect underlying background differences. Abnormalities are heterogeneously distributed across patients, consistent with TAI, and include areas of low and high FA.

Heading and unintentional head impacts have opposing associations with Patient Reported Outcomes in amateur soccer players.

The effects of soccer-related head impacts, beyond overt concussions, on Patient Reported Outcomes (PROs) have not been explored to date. Generalized estimating equations were employed to determine the association between soccer-related head impacts (headers in the prior 2 weeks, unintentional head impacts in the prior 2 weeks, headers in the prior 12 months and lifetime concussions) on PROs including depression, anxiety, sleep disturbance and sleep impairment. Compared to players with no unintentional head impacts in the prior 2 weeks, players with one unintentional exposure reported more symptoms of anxiety (p = 0.002) and players with 2+ exposures reported more symptoms of depression (p = 0.006) and anxiety (p < 0.001). In contrast, players in the 3rd Quartile of 12 mo. headers reported less anxiety (p = 0.001), sleep disturbance (p = 0.002) and sleep impairment (p < 0.001) compared to those in the 1st quartile. Unintentional head impacts are associated with worse PROs while more headers are paradoxically associated with better PROs.

Neuroimaging in Blast-Related Mild Traumatic Brain Injury.

OBJECTIVE: To summarize imaging findings in blast-related mild traumatic brain injury. DESIGN: Our structured review of the literature yielded 5 structural magnetic resonance imaging (sMRI), 18 diffusion tensor imaging, 9 functional magnetic resonance imaging (fMRI), 3 positron emission tomography, 4 magnetoencephalography, 2 electroencephalography, and 1 single-positron emission computerized tomography studies. RESULTS: Four of the 5 sMRI studies reported decreased cortical thickness and decreased thalamus and amygdala volume. Diffusion tensor imaging studies showed abnormal diffusion within white matter tracts commonly associated with traumatic brain injury, including the corpus callosum (8 of the 18) and superior longitudinal fasciculus (8 of the 18). Resting-state fMRI studies reported a variety of functional network differences. Other functional imaging studies showed diffuse changes in activity, especially in the frontal, parietal, temporal, and cingulate regions. CONCLUSION: Vast variation in the sample, design, and measurement features across studies precludes salient conclusions regarding the effectiveness of neuroimaging to assess outcomes and elucidate pathomechanisms. The inherent spatial heterogeneity of mild traumatic brain injury pathology presents a major challenge to meaningful convergence across and generalizable inferences. Approaches to standardize methodology and facilitate access to data and integration across studies hold promise for enhancing our understanding of this complex brain disorder, but can only bear fruit if they are actually consistently implemented.

Laminar Profile and Physiology of the α Rhythm in Primary Visual, Auditory, and Somatosensory Regions of Neocortex.

The functional significance of the α rhythm is widely debated. It has been proposed that α reflects sensory inhibition and/or a temporal sampling or "parsing" mechanism. There is also continuing disagreement over the more fundamental questions of which cortical layers generate α rhythms and whether the generation of α is equivalent across sensory systems. To address these latter questions, we analyzed laminar profiles of local field potentials (LFPs) and concomitant multiunit activity (MUA) from macaque V1, S1, and A1 during both spontaneous activity and sensory stimulation. Current source density (CSD) analysis of laminar LFP profiles revealed α current generators in the supragranular, granular, and infragranular layers. MUA phase-locked to local current source/sink configurations confirmed that α rhythms index local neuronal excitability fluctuations. CSD-defined α generators were strongest in the supragranular layers, whereas LFP α power was greatest in the infragranular layers, consistent with some of the previous reports. The discrepancy between LFP and CSD findings appears to be attributable to contamination of the infragranular LFP signal by activity that is volume-conducted from the stronger supragranular α generators. The presence of α generators across cortical depth in V1, S1, and A1 suggests the involvement of α in feedforward as well as feedback processes and is consistent with the view that α rhythms, perhaps in addition to a role in sensory inhibition, may parse sensory input streams in a way that facilitates communication across cortical areas. SIGNIFICANCE STATEMENT: The α rhythm is thought to reflect sensory inhibition and/or a temporal parsing mechanism. Here, we address two outstanding issues: (1) whether α is a general mechanism across sensory systems and (2) which cortical layers generate α oscillations. Using intracranial recordings from macaque V1, S1, and A1, we show α band activity with a similar spectral and laminar profile in each of these sensory areas. Furthermore, α generators were present in each of the cortical layers, with a strong source in superficial layers. We argue that previous findings, locating α generators exclusively in the deeper layers, were biased because of use of less locally specific local field potential measurements. The laminar distribution of α band activity appears more complex than generally assumed.

The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI.

INTRODUCTION: While cortical processes play an important role in controlling locomotion, the underlying structural brain changes associated with slowing of gait in aging are not yet fully established. Our study aimed to examine the relationship between cortical gray matter volume (GM), white matter volume (WM), ventricular volume (VV), hippocampal and hippocampal subfield volumes, and gait velocity in older adults free of dementia. METHODS: Gait and cognitive performance was tested in 112 community-residing adults, age 70 years and over, participating in the Einstein Aging Study. Gait velocity (cm/s) was obtained using an instrumented walkway. Volumetric MRI measures were estimated using a FreeSurfer software. We examined the cross-sectional relationship of GM, WM, VV, and hippocampal total and subfield volumes and gait velocity using linear regression models. In complementary models, the effect of memory performance on the relationship between gait velocity and regional volumes was evaluated. RESULTS: Slower gait velocity was associated with smaller cortical GM and total hippocampal volumes. There was no association between gait velocity and WM or VV. Among hippocampal subfields, only smaller presubiculum volume was significantly associated with decrease in gait velocity. Addition of the memory performance to the models attenuated the association between gait velocity and all volumetric measures. CONCLUSIONS: Our findings indicate that total GM and hippocampal volumes as well as specific hippocampal subfield volumes are inversely associated with locomotor function. These associations are probably affected by cognitive status of study population.

Neck strength alone does not mitigate adverse associations of soccer heading with cognitive performance in adult amateur players.

OBJECTIVES: Soccer heading is adversely associated with neurocognitive performance, but whether greater neck strength or anthropometrics mitigates these outcomes is controversial. Here, we examine the effect of neck strength or anthropometrics on associations of soccer heading with neurocognitive outcomes in a large cohort of adult amateur players. METHODS: 380 adult amateur league soccer players underwent standardized measurement of neck strength (forward flexion, extension, left lateral flexion, right lateral flexion) and head/neck anthropometric measures (head circumference, neck length, neck circumference and neck volume). Participants were assessed for heading (HeadCount) and cognitive performance (Cogstate) on up to 7 visits over a period of two years. Principal components analysis (PCA) was performed on 8 neck strength and anthropometric measures. We used generalized estimating equations to test the moderation effect of each of the three PCs on 8 previously identified adverse associations of 2-week and 12-month heading estimates with cognitive performance (psychomotor speed, immediate verbal recall, verbal episodic memory, attention, working memory) and of unintentional head impacts on moderate to severe central nervous system symptoms. RESULTS: 3 principal components (PC's) account for 80% of the variance in the PCA. In men, PC1 represents head/neck anthropometric measures, PC2 represents neck strength measures, and PC3 represents the flexor/extensor (F/E) ratio. In women, PC1 represents neck strength, PC2 represents anthropometrics, and PC3 represents the F/E ratio. Of the 48 moderation effects tested, only one showed statistical significance after Bonferroni correction, which was not robust to extensive sensitivity analyses. CONCLUSION: Neither neck strength nor anthropometrics mitigate adverse associations of soccer heading with cognitive performance in adult amateur players.

Life space assessment and falls in older adults with multiple sclerosis.

BACKGROUND/OBJECTIVE: Falls research in older adults with MS (OAMS) is scarce, and no studies have reported on the association between life-space mobility and falls in this group. Herein, we hypothesized that higher baseline life-space scores would be associated with reduced odds of reporting falls during follow-up, and explored whether the association differed by MS subtype (progressive vs. relapsing-remitting). METHODS: OAMS (n = 91, mean age = 64.7 ± 4.3ys, %female = 66.9,%progressive MS = 30.7) completed the University of Alabama at Birmingham Life-Space-Assessment (UAB-LSA) scale and reported falls during a structured monthly telephone interview during follow-up (mean = 16.39 ± 11.44 months). General Estimated Equations (GEE) models were utilized to determine whether UAB-LSA scores predicted falls during follow-up. RESULTS: GEE models revealed that higher UAB-LSA scores were associated with a significant reduction in the odds of falling during follow-up (OR = 0.69, p = 0.012, 95 %CI = 0.51 to 0.92). Stratified analyses revealed that this association was significant in progressive (OR = 0.57, p = 0.004, 95 %CI = 0.39 to 0.84), but not relapsing-remitting (OR = 0.93, p = 0.779, 95 %CI = 0.57 to 1.53) MS. CONCLUSION: Higher life-space mobility was associated with lower odds of falling among OAMS with progressive subtype. The UAB-LSA may complement existing mobility measures for predicting fall risk.