Perceived physical and mental fatigability in older adults with and without multiple sclerosis.

BACKGROUND: Fatigue stands out as a prevalent and debilitating symptom in both Multiple Sclerosis (MS) and the aging population. Traditional methods for measuring perceived fatigue may not adequately account for individual activity differences, leading to varied prevalence rates. Perceived fatigability anchors fatigue to specific activities with predetermined intensity and duration, thereby mitigating self-pacing bias. Despite its potential, perceived fatigability is poorly understood in older adults, particularly those with neurological conditions, including MS. This study thus aimed to (1) investigate whether, among older adults, MS was associated with worse perceived physical and mental fatigability; (2) evaluate whether, among older adults with MS (OAMS), greater patient-reported disease-related disability was associated with worse perceived physical and mental fatigability. METHODS: Participants were 96 older adults with a physician-confirmed diagnosis of MS (mean age: 64.6 ± 4.2) and 110 healthy controls (mean age: 68.2 ± 7.2), all confirmed to be dementia-free through established case conference procedures. Physical and mental fatigability were measured using the Pittsburgh Fatigability Scale, a 10-item questionnaire (score range: 0 to 50) designed to assess fatigue levels that individuals expect to feel after engaging in a range of typical activities for older adults. MS disease-related disability was assessed with the Patient Determined Disease Steps scale, which ranges from 0 (normal) to 8 (bedridden), with scores ≥ 2 indicating worse MS-related disability after a median split. Separate linear regression models were performed to investigate associations between group status (MS vs. Control) as the predictor and perceived physical and mental fatigability scores as the outcome variables. Within the MS group, additional linear regression models were performed to explore the relationship between disease-related disability and fatigability levels. All models adjusted for age, sex, race, education, global health, general cognitive function, and depressive symptoms levels. RESULTS: The fully adjusted models yielded the following key findings: OAMS reported significantly higher levels of perceived physical fatigability (M = 25.11 ± 9.67) compared to controls (M = 17.95 ± 8.35) (p = 0.003). Similarly, the perceived mental fatigability in OAMS (M = 16.82 ± 11.79) was significantly greater than that in controls (M = 9.15 ± 7.12) (p = 0.003). Within the MS group, individuals with greater disease-related disability reported significantly greater levels of both physical (M = 30.13 ± 7.71 vs. 18.67 ± 8.00, p < 0.001) and mental fatigability (M = 20.31 ± 12.18 vs. 12.33 ± 9.69, p = 0.009) compared to those with lower MS-related disability. Of note, the significance of these findings persisted in models that adjusted for depressive symptoms. CONCLUSION: Our study provides compelling evidence that OAMS exhibit significantly higher perceived physical and mental fatigability compared to healthy controls. Additionally, worse MS-related disability correlates with worse physical and mental fatigability. These results persist after adjusting for confounders including depressive symptoms. Our findings underscore the necessity of holistic management strategies that cater to both physical and psychological aspects of MS, laying a foundation for future studies to uncover the pathophysiological mechanisms of fatigability in older adults with and without MS.

Disability Moderates Dual Task Walking Performance and Neural Efficiency in Older Adults With Multiple Sclerosis.

BACKGROUND: Mobility and cognitive impairment are prevalent and co-occurring in older adults with multiple sclerosis (OAMS), yet there is limited research concerning the role of disability status in the cognitive control of gait among OAMS. OBJECTIVE: We investigated the levels of prefrontal cortex (PFC) activation, using oxygenated hemoglobin (HbO2), during cognitively-demanding tasks in OAMS with lower and higher disability using functional near-infrared spectroscopy (fNIRS) to: (1) identify PFC activation differences in single task walk and cognitively-demanding tasks in OAMS with different levels of disability; and (2) evaluate if disability may moderate practice-related changes in neural efficiency in OAMS. METHODS: We gathered data from OAMS with lower (n = 51, age = 65 ± 4 years) or higher disability (n = 48, age = 65 ± 5 years), using a cutoff of 3 or more, in the Patient Determined Disease Steps, for higher disability, under 3 different conditions (single-task walk, Single-Task-Alpha, and Dual-Task-Walk [DTW]) administered over 3 counterbalanced, repeated trials. RESULTS: OAMS who had a lower disability level exhibited decreased PFC activation levels during Single-Task-Walk (STW) and larger increases in PFC activation levels, when going from STW to a cognitively-demanding task, such as a DTW, than those with higher disability. OAMS with a lower disability level exhibited greater declines in PFC activation levels with additional within session practice than those with a higher disability level. CONCLUSIONS: These findings suggest that disability moderates brain adaptability to cognitively-demanding tasks and demonstrate the potential for fNIRS-derived outcome measures to complement neurorehabilitation outcomes.

Trait anxiety increases the attentional cost of walking in young adults: A cross-sectional study.

BACKGROUND: Anxiety is a prevalent mental health disorder, with debilitating symptoms causing avoidance and decreased quality of life. Balance impairments during standing and walking are common in anxiety. However, understanding of gait control mechanisms in people with trait anxiety, particularly when walking requires increased attention (dual-task), is still limited. This work examined the attentional cost of walking in people with varying levels of trait anxiety. Since people with anxiety are often prone to Space and Motion Discomfort (SMD), this work also evaluated the potential role of SMD in the attentional cost of walking. METHODS: Fifty-six participants, aged 18-51, classified as anxious and non-anxious, were asked to walk under single- and two dual-task conditions (cognitive: counting backwards; visuomotor: texting on a mobile phone). Task performance (walking, counting and texting) was measured. Prefrontal cortex (PFC) activation was recorded using functional near infrared spectroscopy (fNIRS) for a subset of participants (n = 29). RESULTS: Anxious individuals walked slower under dual-task conditions, with smaller increases in PFC activation from single to dual-task conditions in the cognitive task. Dual-task walking was unrelated to SMD. LIMITATIONS: sample size was limited, particularly for fNIRS data. CONCLUSIONS: To the best of our knowledge, this study is the first to identify anxiety-related deficits in attentional gait control in the general population, including during the everyday task of texting on a mobile phone. Since decrements in dual-task walking are linked to poor health outcomes, results from this work may have functional implications for people with anxiety.

Physical reserve and its underpinning functional neural networks moderate the relationship between white matter hyperintensity and postural balance in older adults with subcortical ischemic vascular cognitive impairment.

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one's capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional networks associated with PR, and examining the relationship between PR, WMH, and postural balance. PR was defined in 22 community-dwelling older adults with SIVCI. Functional networks of PR were computed using general linear model. Subsequent analyses examined whether PR and relevant networks moderated the relationship between WMH and postural balance under two conditions-eyes open while standing on foam (EOF) or on floor (EONF). We found that PR and the relevant networks-frontoparietal network (FPN) and default mode network (DMN)-significantly moderated the association between WMH and postural balance. For individuals with high PR, postural balance remained stable regardless of the extent of WMH load; whereas for those with low PR, postural balance worsened as WMH load increased. These results suggest the attenuated effects of WMH on postural stability due to PR may be underpinned by functional neural network reorganization in the FPN and DMN as a part of compensatory processes.

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.

Frontal-striatal tract integrity and depression in older adults with and without multiple sclerosis.

OBJECTIVE: Lower white matter integrity of frontal-subcortical circuitry has been associated with late-life depression in normally aging older adults and with the presence of multiple sclerosis (MS). Frontal-striatal white matter tracts involved in executive, cognitive, emotion, and motor function may underlie depression in older adults with MS. The present study examined the association between depression score and frontal-striatal white matter integrity in older adults with MS and controls. METHODS: Older adults with MS (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. Depression was assessed through the 30-item Geriatric Depression Scale. Fractional anisotropy (FA) was extracted from two bilateral tracts: dorsolateral prefrontal cortex to putamen nucleus (DLPFC-pn) and dorsolateral prefrontal cortex to caudate nucleus (DLPFC-cn). RESULTS: OAMS reported significantly worse (i.e., higher) depression symptoms (ß = .357, p < .001) compared to healthy controls. Adjusted moderation analyses revealed, via group by FA interactions, significantly stronger associations between FA of the left DLPFC-pn tract and total depression (B = - 61.70, p = .011) among OAMS compared to controls. Conditional effects revealed that lower FA of the left DLPFC-pn was significantly associated with worse (i.e., higher) depression symptoms (b = - 38.0, p = .028) only among OAMS. The other three tracts were not significant in moderation models. CONCLUSIONS: We provided first evidence that lower white matter integrity of the left DLPFC-pn tract was related to worse depression in older adults with MS.

Brain control of dual-task walking can be improved in aging and neurological disease.

The peak prevalence of multiple sclerosis has shifted into older age groups, but co-occurring and possibly synergistic motoric and cognitive declines in this patient population are poorly understood. Dual-task-walking performance, subserved by the prefrontal cortex, and compromised in multiple sclerosis and aging, predicts health outcomes. Whether acute practice can improve dual-task walking performance and prefrontal cortex hemodynamic response efficiency in multiple sclerosis has not been reported. To address this gap in the literature, the current study examined task- and practice-related effects on dual-task-walking and associated brain activation in older adults with multiple sclerosis and controls. Multiple sclerosis (n = 94, mean age = 64.76 ± 4.19 years) and control (n = 104, mean age = 68.18 ± 7.01 years) participants were tested under three experimental conditions (dual-task-walk, single-task-walk, and single-task-alpha) administered over three repeated counterbalanced trials. Functional near-infrared-spectroscopy was used to evaluate task- and practice-related changes in prefrontal cortex oxygenated hemoglobin. Gait and cognitive performances declined, and prefrontal cortex oxygenated hemoglobin was higher in dual compared to both single task conditions in both groups. Gait and cognitive performances improved over trials in both groups. There were greater declines over trials in oxygenated hemoglobin in dual-task-walk compared to single-task-walk in both groups. Among controls, but not multiple sclerosis participants, declines over trials in oxygenated hemoglobin were greater in dual-task-walk compared to single-task-alpha. Dual-task walking and associated prefrontal cortex activation efficiency improved during a single session, but improvement in neural resource utilization, although significant, was attenuated in multiple sclerosis participants. These findings suggest encouraging brain adaptability in aging and neurological disease.

The impact of music making on neural efficiency & dual-task walking performance in healthy older adults.

Music making is linked to improved cognition and related neuroanatomical changes in children and adults; however, this has been relatively under-studied in aging. The purpose of this study was to assess neural, cognitive, and physical correlates of music making in aging using a dual-task walking (DTW) paradigm. Study participants (N = 415) were healthy adults aged 65 years or older, including musicians (n = 70) who were identified by current weekly engagement in musical activity. A DTW paradigm consisting of single- and dual-task conditions, as well as portable neuroimaging (functional near-infrared spectroscopy), was administered. Outcome measures included neural activation in the prefrontal cortex assessed across task conditions by recording changes in oxygenated hemoglobin, cognitive performance, and gait velocity. Linear mixed effects models examined the impact of music making on outcome measures in addition to moderating their change between task conditions. Across participants (53.3% women; 76 ± 6.55 years), neural activation increased from single- to dual-task conditions (p < 0.001); however, musicians demonstrated attenuated activation between a single cognitive interference task and dual-task walking (p = 0.014). Musicians also displayed significantly smaller decline in behavioral performance (p < 0.001) from single- to dual-task conditions and faster gait overall (p = 0.014). Given evidence of lower prefrontal cortex activation in the context of similar or improved behavioral performance, results indicate the presence of enhanced neural efficiency in older adult musicians. Furthermore, improved dual-task performance in older adult musicians was observed. Results have important clinical implications for healthy aging, as executive functioning plays an essential role in maintaining functional ability in older adulthood.

Cortical thickness moderates intraindividual variability in prefrontal cortex activation patterns of older adults during walking.

OBJECTIVE: Increased intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning hemodynamic signal IIV is limited. Cortical thinning occurs during aging and is associated with cognitive decline. Dual-task walking (DTW) performance in older adults has been related to cognition and neural integrity. We examined the hypothesis that reduced cortical thickness would be associated with greater increases in IIV in prefrontal cortex oxygenated hemoglobin (HbO2) from single tasks to DTW in healthy older adults while adjusting for behavioral performance. METHOD: Participants were 55 healthy community-dwelling older adults (mean age = 74.84, standard deviation (SD) = 4.97). Structural MRI was used to quantify cortical thickness. Functional near-infrared spectroscopy (fNIRS) was used to assess changes in prefrontal cortex HbO2 during walking. HbO2 IIV was operationalized as the SD of HbO2 observations assessed during the first 30 seconds of each task. Linear mixed models were used to examine the moderation effect of cortical thickness throughout the cortex on HbO2 IIV across task conditions. RESULTS: Analyses revealed that thinner cortex in several regions was associated with greater increases in HbO2 IIV from the single tasks to DTW (ps < .02). CONCLUSIONS: Consistent with neural inefficiency, reduced cortical thickness in the PFC and throughout the cerebral cortex was associated with increases in HbO2 IIV from the single tasks to DTW without behavioral benefit. Reduced cortical thickness and greater IIV of prefrontal cortex HbO2 during DTW may be further investigated as risk factors for developing mobility impairments in aging.

Depressive Symptoms are Associated with Decline Over Time in Verbal Fluency Performance in Female but Not Male Community-Dwelling Older Adults.

OBJECTIVE: The current study was designed to examine associations between depressive symptoms and longitudinal declines in category and letter fluency performance in a gender-stratified sample of older adults. METHOD: Participants were community-residing older adults (females: n = 289; males: n = 233) followed annually (2011-2018) as part of a cohort study conducted at Albert Einstein College of Medicine in New York. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). Standard forms assessed category and letter fluency performance. Participants were dementia-free during study enrollment. RESULTS: The presence of baseline depressive symptoms suggestive of subclinical depression was associated with a worse longitudinal decline in category fluency performance in female but not male participants. These associations remained significant when excluding participants with prevalent and incident mild cognitive impairment and incident dementia. Irrespective of gender, letter fluency performance did not decline over time and was not influenced by the presence of depressive symptoms. DISCUSSION: The present study's results can aid in identification of older adults who may be at greater risk for cognitive decline, and add to the limited literature examining the influence of gender on longitudinal associations between depressive symptoms and verbal fluency performance.

Initial validation of the university of Alabama Birmingham study of aging life-space assessment in older adults with multiple sclerosis.

BACKGROUND: Older adults with multiple sclerosis (OAMS) have declines in walking and physical performance that may erode community mobility defined as the spatial extent of mobility in one's daily life and environment. OBJECTIVE: This study provided the first application and validation of the University of Alabama Birmingham Study of Aging Life-Space Assessment (UAB LSA) as a measure of community mobility in OAMS. METHODS: The sample included 97 OAMS and 108 healthy controls (HCs) who completed baseline assessments as part of an ongoing, longitudinal study. The primary assessments included the UAB LSA and timed 25-foot walk (T25FW), short physical performance battery (SPPB), global health score (GHS), and geriatric depression scale (GDS) in both OAMS and HCs, and patient determined disease steps (PDDS) scale in only OAMS. RESULTS: OAMS had significantly lower UAB LSA scores than HCs (p < .001). UAB LSA scores had strong correlations with T25FW(rs = -.641) and SPPB(rs = 0.507) in OAMS, and moderate correlations in HCs (rs = -.300 & rs = 0.384). The correlations between UAB LSA and GHS and GDS scores were significant, but small in OAMS (rs = -.239 & rs = -.231), and not statistically significant in HCs (rs = -.009 & rs = -.166). There was a strong correlation between UAB LSA and PDDS scores in the OAMS sample (rs = -.605). CONCLUSION: We provided initial evidence for UAB LSA scores as a measure of community mobility in OAMS.

Deep Learning Based Walking Tasks Classification in Older Adults Using fNIRS.

Decline in gait features is common in older adults and an indicator of increased risk of disability, morbidity, and mortality. Under dual task walking (DTW) conditions, further degradation in the performance of both the gait and the secondary cognitive task were found in older adults which were significantly correlated to falls history. Cortical control of gait, specifically in the pre-frontal cortex (PFC) as measured by functional near infrared spectroscopy (fNIRS), during DTW in older adults has recently been studied. However, the automatic classification of differences in cognitive activations under single and dual task gait conditions has not been extensively studied yet. In this paper, by considering single task walking (STW) as a lower attentional walking state and DTW as a higher attentional walking state, we aimed to formulate this as an automatic detection of low and high attentional walking states and leverage deep learning methods to perform their classification. We conduct analysis on the data samples which reveals the characteristics on the difference between HbO2 and Hb values that are subsequently used as additional features. We perform feature engineering to formulate the fNIRS features as a 3-channel image and apply various image processing techniques for data augmentation to enhance the performance of deep learning models. Experimental results show that pre-trained deep learning models that are fine-tuned using the collected fNIRS dataset together with gender and cognitive status information can achieve around 81% classification accuracy which is about 10% higher than the traditional machine learning algorithms. We present additional sensitivity metrics such as confusion matrix, precision and F1 score, as well as accuracy on two-way classification between condition pairings. We further performed an extensive ablation study to evaluate factors such as the voxel locations, channels of input images, zero-paddings and pre-training of deep learning model on their contribution or impact to the classification task. Results showed that using pre-trained model, all the voxel locations, and HbO2 - Hb as the third channel of the input image can achieve the best classification accuracy.

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.

The association between perceived social support and cognition in older adults with and without multiple sclerosis.

BACKGROUND: Advances in treatments for Multiple Sclerosis (MS) have resulted in a growing number of aging individuals with MS. Research has shown that perceived social support has protective effects against age-related cognitive decline but no study to date has examined the relationship between perceived social support and cognition in older adults with MS. The current study addressed this gap in knowledge examining the association between perceived social support and cognition in older adults with and without MS. METHODS: Participants were older adults with MS (n = 67, mean age = 64.75 years;%female =  64.2) and controls (n = 71, mean age = 68.25 years;%female = 57.7) Linear regression models examined the associations of total and domain scores of perceived social support with cognition in the entire sample, and then stratified by group status. RESULTS: Analyses revealed that total perceived social support, emotional/informational support, and positive social interaction were associated with cognition in the total sample. In stratified analyses, emotional/informational support was significantly associated with cognition in the MS group; however, this association became insignificant when analyses adjusted for depressive symptoms. Positive social interaction was significantly associated with cognition in the control group. Notably, this association remained significant even after adjusting for depressive symptoms. CONCLUSION: These findings suggest that distinct dimensions of perceived social support may have differential relationships with cognitive function in older adults with MS and healthy controls.

Presence and Persistence of Perceived Subjective Cognitive Complaints and Incident Mild Cognitive Impairments Among Community-Residing Older Adults.

OBJECTIVES: To examine whether Subjective Cognitive Complaints (SCCs) predicted incident mild cognitive impairment (MCI). DESIGN: Prospective Study. SETTING: Central Control of Mobility and Aging (CCMA), a cohort study of community-residing older adults. PARTICIPANTS: Participants were dementia-free community-residing older adults. MEASUREMENTS: SCCs were assessed at the baseline and via bi-monthly structured phone interviews during the first year using the Ascertain Dementia 8 (AD8). Nonpersistent status required one or two SCCs endorsements and Persistent status required three or more SCCs endorsements. Outcome, presence of mild cognitive impairments (MCI) was determined by established case conference diagnostic procedures. Participants were followed annually. Generalized estimating equations (GEE), logistic model type, were used to determine the odds of developing MCI during follow-up. SCCs served as the three-level predictor (no/nonpersistent/persistent) and cognitive status (MCI versus normal) as the binary outcome. Analyses were adjusted for age, sex, education, race, health status, depressive symptoms, and global cognition. RESULTS: The sample (n=454; mean age=75.67 ± 6.43; %female=55.3) included 245 participants who reported no SCCs, 156 who reported 1-2 SCCs, and 53 who reported 3 or more SCCs. Sixty-eight participants developed MCI during follow-up. Results showed that compared to no SCCs, persistent SCCs, and nonpersistent SCCs were significantly associated with increased odds of developing MCI during follow-up. CONCLUSIONS: The presence of SCCs regardless of their persistence was associated with increased odds of developing MCI even when adjusting for objectively-assessed cognitive performance.

Differential Associations of Mobility With Fronto-Striatal Integrity and Lesion Load in Older Adults With and Without Multiple Sclerosis.

BACKGROUND: Mobility impairment is common in older persons with multiple sclerosis (MS), and further compounded by general age-related mobility decline but its underlying brain substrates are poorly understood. OBJECTIVE: Examine fronto-striatal white matter (WM) integrity and lesion load as imaging correlates of mobility outcomes in older persons with and without MS. METHODS: Fifty-one older MS patients (age 64.9 ± 3.7 years, 29 women) and 50 healthy, matched controls (66.2 ± 3.2 years, 24 women), participated in the study, which included physical and cognitive test batteries and 3T MRI imaging session. Primary imaging measures were fractional anisotropy (FA) and WM lesion load. The relationship between mobility impairment, defined using a validated short physical performance battery cutoff score, and neuroimaging measures was assessed with stratified logistic regression models. FA was extracted from six fronto-striatal circuits (left/right): dorsal striatum (dStr)-to-anterior dorsolateral prefrontal cortex (aDLPFC), dStr-to-posterior DLPFC, and ventral striatum (vStr)-to-ventromedial prefrontal cortex (VMPFC). RESULTS: Mobility impairment was significantly associated with lower FA in two circuits, left dStr-aDLPFC (P = .003) and left vStr-VMPFC (P = .004), in healthy controls but not in MS patients (P > .20), for fully adjusted regression models. Conversely, in MS patients but not in healthy controls, mobility impairment was significantly associated with greater lesion volume (P < .02). CONCLUSIONS: Comparing older persons with and without MS, we provide compelling evidence of a double dissociation between the presence of mobility impairment and two neuroimaging markers of white matter integrity, fronto-striatal fractional anisotropy, and whole brain lesion load.

Gray matter volume and within-task verbal fluency performance among older adults.

The current study examined the relationship between gray matter volume (GMV) and rate of word generation over the course of three consecutive 20-sec intervals in 60-sec letter and category verbal fluency (VF) tasks. Attenuated rate of within-person word generation in VF provides incremental information beyond total scores and predicts increased risk of incident Mild Cognitive Impairment (MCI). No studies to date, however, have determined the structural neural substrates underlying word generation rate in VF. Participants were 70 community-residing adults ≥ 65 years, who completed the letter and category VF tasks and a 3 T structural MRI scan. Linear mixed effects models (LMEMs) were used to determine the moderating effect of GMV on word generation rate. Whole brain voxel-wise LMEMs, adjusted for age, gender, education, Wide-Range Achievement Test - reading subtest score (WRAT3), and global health score, were run using permutation methods to correct for multiple comparisons. Lower GMV, primarily in frontal regions (superior frontal, rostral middle frontal, frontal pole, medial orbitofrontal, and pars orbitalis), were related to attenuated word generation rate, especially for letter VF. We propose that lower frontal GMV underlies inefficient executive word search processes reflected by attenuated word generation slope in letter VF amongst older adults.

Individual reserve in aging and neurological disease.

BACKGROUND AND OBJECTIVE: Cognitive and physical functions correlate and delineate aging and disease trajectories. Whereas cognitive reserve (CR) is well-established, physical reserve (PR) is poorly understood. We, therefore, developed and evaluated a novel and more comprehensive construct, individual reserve (IR), comprised of residual-derived CR and PR in older adults with and without multiple sclerosis (MS). We hypothesized that: (a) CR and PR would be positively correlated; (b) low CR, PR, and IR would be associated with worse study outcomes; (c) associations of brain atrophy with study outcomes would be stronger in lower compared to higher IR due to compensatory mechanisms conferred by the latter. METHODS: Older adults with MS (n = 66, mean age = 64.48 ± 3.84 years) and controls (n = 66, mean age = 68.20 ± 6.09 years), underwent brain MRI, cognitive assessment, and motoric testing. We regressed the repeatable battery for the assessment of neuropsychological status and short physical performance battery on brain pathology and socio-demographic confounders to derive independent residual CR and PR measures, respectively. We combined CR and PR to define a 4-level IR variable. The oral symbol digit modalities test (SDMT) and timed-25-foot-walk-test (T25FW) served as outcome measures. RESULTS: CR and PR were positively correlated. Low CR, PR and IR were associated with worse SDMT and T25FW performances. Reduced left thalamic volume, a marker of brain atrophy, was associated with poor SDMT and T25FW performances only in individuals with low IR. The presence of MS moderated associations between IR and T25FW performance. CONCLUSION: IR is a novel construct comprised of cognitive and physical dimensions representing collective within-person reserve capacities.

Physical reserve: construct development and predictive utility.

BACKGROUND: Physical reserve (PR) refers to one's ability to maintain physical functioning despite age, illness, or injury. The measurement and predictive utility of PR, however, are not well established. AIMS: We quantified PR using a residual measurement approach by extracting standardized residuals from gait speed, while accounting for demographic and clinical/disease variables, and used it to predict fall-risk. METHODS: Participants (n = 510; age ≥ 70ys) were enrolled in a longitudinal study. Falls were assessed annually (in-person) and bimonthly (via structured telephone interview). RESULTS: General Estimating Equations (GEE) revealed that higher baseline PR was associated with reduced odds of reporting falls over repeated assessments in the total sample, and incident falls among those without fall's history. The protective effect of PR against fall risk remained significant when adjusting for multiple demographic and medical confounders. DISCUSSION/CONCLUSION: We propose a novel framework to assessing PR and demonstrate that higher PR is protective against fall-risk in older adults.

Asthma history influences gait performance and associated prefrontal cortex activation patterns in older adults.

Walking and cognition are interrelated due to dependence on shared brain regions that include the prefrontal cortex (PFC). Limited literature indicates that asthma is associated with poor mobility in older adults but the mechanisms underlying this relationship are unknown. Therefore, we tested the hypothesis that asthma history was associated with poor gait performance due to limited attention resources and neural inefficiency. Participants, older adults age ≥ 65 years reporting positive (n = 36) and negative (n = 36) history of asthma, walked under single and dual-task conditions with a functional near-infrared-spectroscopy (fNIRS) sensor placed on their forehead to assess task-related changes in PFC oxygenated hemoglobin (HbO2). Results showed that positive asthma history was associated with slower gait and higher fNIRS-derived HbO2 under dual-task walking. These findings suggest that limited attention resources and neural inefficiency underlie the association between asthma and poor walking performance in older adults.