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.

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.

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.

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.

Antibody response to SARS-CoV-2 vaccination following typical and three-dose dosing schedules in multiple sclerosis patients treated with disease modifying therapies.

BACKGROUND: Immunizations against SARS-CoV-2 virus are now available and recommended, but the effect of additional dosing of the vaccine in immunocompromised MS patients is unknown. METHODS: Part I - A retrospective chart review of MS patients who were vaccinated against SARS-CoV-2 and tested commercially for Sars Covid Spike Protein Antibody between March 1 - June 30, 2021. Part II - Patients on treatment with anti-CD20 infusion medications who received a SARS-CoV-2 third mRNA vaccination dose August 13, 2021 - October 31, 2021 and were subsequently commercially tested for Sars Covid Spike Protein Antibody. RESULTS: Part I - A total of N = 208 MS patients, age range 23-76 were tested, with 49% (102/208) demonstrating a humoral response. Stratified by DMT type, patients treated with interferon, teriflunomide, or a remote history of alemtuzumab (>2 years since last DMT) yielded 100% measurable antibodies; >90% amongst patients treated with natalizumab, fumarates and glatiramer acetate; <50% measurable antibodies following vaccination in S1P modulators and anti-CD20 treated patients. Subsequently, in Part II - N = 40 patients on anti-CD20 treatments (33 ocrelizumab, 7 rituximab) who received 3 mRNA vaccinations yielded 20% humoral response. CONCLUSIONS: MS patients are able to mount a humoral vaccine response to SARS-CoV-2, irrespective of the vaccine type administered; patients treated with S1P modulators and anti-CD20 agents are least likely to mount such a response with a typical dosing schedule. Patients treated with ocrelizumab/rituximab show a similar modest humoral immune system benefit following three doses as with standard dosing.

The presence of SARS-CoV2 antibodies in MS patients.

BACKGROUND: The COVID-19 pandemic has raised novel concerns for people living with MS regarding their safety. METHODS: Observational study of patients at a single comprehensive community MS center. RESULTS: 48 patients with MS were suspected of developing COVID-19 March to May 2020; 2 died. Of the remainder, 17 were tested for COVID-19 antibodies as part of routine care. Average age of this subgroup was 49.8y ± 11.3 (age range 32-67), 76% female. 65% were treated with an anti-CD20 drug, 12% untreated, and 6% each received glatiramer acetate, interferon, natalizumab, or teriflunomide. 59% of patients were antibody negative. CONCLUSIONS: The low incidence of SARS CoV2 antibodies following infection suggests that certain DMTs may alter SARS CoV2-Ab response or persistence.

Motivation in multiple sclerosis cognitive fatigue: An experimental approach.

Introduction: Cognitive fatigue is a common symptom in multiple sclerosis (MS). Recent research has implicated dopaminergic pathways originating in the basal ganglia as neurological correlates of cognitive fatigue in MS. This same system has long been associated with goal-directed behavior and reward-based motivation. While researchers have demonstrated that reward has a reliable impact on performance in tasks of sustained attention in healthy individuals, the effect of reward on fatigue is less clear, as prior research has not adequately controlled for desensitization to reward in a sustained attention task. The primary aims of this study were to examine the effect of reward on attention in MS patients, and to examine the effect of reward on objective cognitive fatigue. Method: The study employed a 3 × 3 repeated measures design to evaluate performance of N = 64 patients with definite MS on a measure of cognitive fatigue across several reward conditions. The study utilized a novel delayed-reward paradigm to better control the measured effect of reward on fatigue. Results: Reward (main effect) displayed a significant effect on overall performance (F = 3.050, p < .05). Reward was also shown to affect fatigue trajectory (Reward × Interval, F = 2.433, p < .05). However, this effect was dependent on the method of reward administration. Conclusions: Study findings support the role of motivation in MS cognitive performance, particularly in objective cognitive fatigue, a behavioral finding that is consistent with current neuropsychological theory. Study findings support the delayed-reward paradigm as an effective method for measuring reward effect on tasks of sustained attention.

Assessing the criterion validity of four highly abbreviated measures from the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS).

OBJECTIVE: Cognitive dysfunction is prevalent in multiple sclerosis. As self-reported cognitive functioning is unreliable, brief objective screening measures are needed. Utilizing widely used full-length neuropsychological tests, this study aimed to establish the criterion validity of highly abbreviated versions of the Brief Visuospatial Memory Test - Revised (BVMT-R), Symbol Digit Modalities Test (SDMT), Delis-Kaplan Executive Function System (D-KEFS) Sorting Test, and Controlled Oral Word Association Test (COWAT) in order to begin developing an MS-specific screening battery. METHOD: Participants from Holy Name Medical Center and the Kessler Foundation were administered one or more of these four measures. Using test-specific criterion to identify impairment at both -1.5 and -2.0 SD, receiver-operating-characteristic (ROC) analyses of BVMT-R Trial 1, Trial 2, and Trial 1 + 2 raw data (N = 286) were run to calculate the classification accuracy of the abbreviated version, as well as the sensitivity and specificity. The same methods were used for SDMT 30-s and 60-s (N = 321), D-KEFS Sorting Free Card Sort 1 (N = 120), and COWAT letters F and A (N = 298). RESULTS: Using these definitions of impairment, each analysis yielded high classification accuracy (89.3 to 94.3%). CONCLUSIONS: BVMT-R Trial 1, SDMT 30-s, D-KEFS Free Card Sort 1, and COWAT F possess good criterion validity in detecting impairment on their respective overall measure, capturing much of the same information as the full version. Along with the first two trials of the California Verbal Learning Test - Second Edition (CVLT-II), these five highly abbreviated measures may be used to develop a brief screening battery.

Cognitive and motor functioning in patients with multiple sclerosis: neuropsychological predictors of walking speed and falls.

While motor and cognitive impairments are common in Multiple Sclerosis (MS) patients, research concerning their relationship in this population has been limited. We aimed to evaluate cross-sectional associations between cognitive functions, walking speed, and falls in patients with MS. Through a retrospective chart review of 81 patients with MS, we examined whether measures of cognitive function predicted walking speed on the Timed 25-Foot Walk and self-reported fall frequency. Hierarchical linear regressions showed that after controlling for age, gender, and disease severity, slower processing speed and IQ predicted slower gait speed, while poorer verbal memory predicted increased frequency of falls. Moreover, a binary logistic regression showed that poorer verbal memory also predicted increased risk of multiple falls. Thus, specific cognitive functions are meaningfully related to mobility limitations in patients with MS. These findings suggest that risk assessment for gait decline and falls should include cognitive assessment in patients with MS.

Depression levels and interferon treatment in people with multiple sclerosis.

Multiple sclerosis (MS) is the most common cause of neurologic disease in young and middle-aged adults, and 75% of patients are female. Nearly one in two patients with MS will experience clinically significant depression-approximately three times the prevalence rate in the general population. This study used a cross-sectional approach to examine the link between depression levels and use of interferon medications among individuals with MS. Data were collected from 694 patients of the Multiple Sclerosis Comprehensive Care Center at Holy Name Medical Center in Teaneck, New Jersey. Analysis of variance was used to compare depression scores between patients taking and not taking interferons. Regression analyses with depression scores as the dependent variable were also conducted. The Beck Depression Inventory (BDI) was reduced to a set of dimensions by principal components analysis. Two components were identified, reflecting somatic and cognitive symptoms. The results showed no significant relationship between depression levels and interferon treatment. Significant associations were observed between depression and both age and disability status, with younger, more disabled patients tending to be more depressed.

Suicidal thinking in multiple sclerosis.

PURPOSE: Studies demonstrate that suicidal ideation (SI) is greater in persons with multiple sclerosis (MS) than in the general population. SI may offer some MS patients a mechanism for feeling in control of their lives, in the face of a daunting, unpredictable disease. In this study, we determined what specific mental constructs or perceptual themes occur for MS patients experiencing SI, while also examining the construct of 'control' as a central theme. METHODS: Individual interviews (N = 16) were audiotaped, transcribed and qualitatively analysed by two independent raters to test for key themes in MS patients reporting SI. RESULTS: In relation to SI, eight key themes were identified by both raters as having been expressed in interviews: perceived loss of control, increased family tension, loneliness, hopelessness and frustration, physical and psychological impact of MS, loss of perceived masculinity or femininity, regaining control and failure to achieve desired or expected role functioning. We created a model to explain the emergence of these themes as they contribute to SI among patients with MS. All participants indicated that perceived loss of control elicited thoughts of suicide. CONCLUSION: Perceived loss of control appears to be a major disease related burden associated with SI in MS patients.

Quality of life in MS: does aging enhance perceptions of mental health?

PURPOSE: This study was designed to examine the relationship between age and quality of life in middle aged and older adults with MS. METHOD: Individuals with MS, recruited through a Comprehensive Care Centre and local registries of the National Multiple Sclerosis Society, completed a telephone interview which incorporated several scales of the MS Quality of Life Inventory. Participants were divided into three age groups reflective of developmental transitions in adulthood, from midlife transition to late adulthood. RESULTS: Between group comparisons controlling for physical functioning and duration of MS revealed that the oldest age group (age 65 and above) reported significantly better mental health than the middle age group (age 50-64), but not the youngest age group (age 35-49). Differences between the middle and youngest age group were not significant. CONCLUSIONS: Results suggest that perhaps the process of getting older, or factors related to being older, enhance perceptions of mental health in individuals with MS. Results are discussed within the context of social comparison theory, which might be an adaptive strategy that could underlie response shift in older individuals with MS.

A qualitative investigation of adaptation in older individuals with multiple sclerosis.

PURPOSE: This qualitative investigation was designed to identify themes that underlie adaptation in older individuals with multiple sclerosis (MS). METHOD: Thirteen individuals (age 60 and above) with MS were recruited from an MS Comprehensive Care Centre and local chapters of the National Multiple Sclerosis Society. Participants completed The Perceptions of Aging Interview by telephone. This open-ended interview was developed to explore two lines of inquiry: MS: Perceptions of Aging, which was based on the literature on adaptation in MS, and Life Strengths, which was adapted from Kivnick's Life Strengths Inventory. RESULTS: The majority of participants reported having adapted to MS and aging. They described several themes and subthemes that seemed to influence their levels of adaptation: Social comparisons, mobility/independence, integration of MS into self-identity, acceptance, pacing and planning, finding meaning/cognitive reframing, social support, religion/spirituality and generativity. CONCLUSIONS: The themes identified in this investigation are generally supported by the literatures on adaptation to MS and adaptation to aging. However, this is the first study to examine these factors in an older MS sample. Moreover, many of these themes are potentially modifiable through clinical intervention, and should be examined in future research with this population.

Reliability and validity of the multiple sclerosis quality of life inventory in older individuals.

PURPOSE: Despite the increasing number of older individuals with multiple sclerosis (MS), there is a paucity of research on this subpopulation. Health-related quality of life (HRQOL) has received extensive attention in MS; however samples tend to be young. The present study assesses the internal consistency reliability and construct validity of the MS Quality of Life Inventory (MSQLI), a widely employed measure of HRQOL, in older individuals. METHOD: Select subscales of the MSQLI and other measures of mental health and physical functioning were administered by telephone to 30 randomly selected older ( >or= 60) individuals and a gender-matched sample of younger ( < 60) individuals. Reliability estimates were calculated separately for each group. Construct (convergent) validity was assessed by examining the pattern of correlations between MSQLI subscales and measures of related constructs in the two groups. RESULTS: Reliability estimates were similar in the two groups. With few exceptions, the correlations measuring convergent validity were in the expected direction, and of considerable magnitude, in both groups. CONCLUSIONS: Results provide preliminary evidence that the MSQLI is a reliable and valid instrument for use with older individuals. The slightly different pattern of results observed in the validity analysis might be explained by an adjustment hypothesis. Future research on HRQOL in this subpopulation is encouraged.