Ferkauf Graduate School of Psychology: Faculty Publications
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Item Open Access The relationship of tobacco use and migraine: A narrative review(Springer, 2023) Weinberger, A. H.; Seng, Elizabeth K.; 0000-0002-8938-4949•Purpose of Review Tobacco use is associated with significant health consequences especially for people with medical conditions. Although lifestyle strategies (e.g., sleep, diet) are commonly recommended as part of migraine treatment, tobacco related strategies (e.g., smoking cessation) are rarely included. This review is aimed at elucidating what is known about tobacco use and migraine and at identifying gaps in the research. •Recent Findings The prevalence of smoking is higher among people with migraine, and people with migraine believe that smoking makes migraine attacks worse. There is also evidence that smoking may exacerbate migraine-related consequences (e.g., stroke). Very few studies have examined other aspects of smoking and migraine or tobacco products other than cigarettes. •Summary There are significant gaps in our knowledge of smoking and migraine. More research is needed to understand the relationship of tobacco use to migraine and potential benefits of adding smoking cessation efforts into migraine care.Item Open Access Migraine-related stigma and its relationship to disability, interictal burden, and quality of life: Results of the OVERCOME (US) Study(Kluwer Heath, 2024) Seng, Elizabeth K.; Shapiro, Robert E.; Nicholson, Robert A.; Buse, Dawn C.; Reed, Michael L.; Zaga, Anthony J.; Muenzel, E. Jolanda; Hutchinson, Susan; Pearlman, Eric M.; Lipton, Richard B.; 0000-0002-8938-4949•Background and Objectives This population-based analysis characterizes the relative frequency of migraine-related stigma and its cross-sectional relationship to migraine outcomes. We hypothesized that migraine-related stigma would be inversely associated with favorable migraine outcomes across headache day categories. •Methods OVERCOME (US) is a web-based observational study that annually recruited a demographically representative US sample and then identified people with active migraine using a validated migraine diagnostic questionnaire. It also assessed how frequently respondents experienced migraine-related stigma using a novel 12-item questionnaire (Migraine-Related Stigma, MiRS) that contained 2 factors; feeling that others viewed migraine as being used for Secondary Gain (8 items, α = 0.92) and feeling that others were Minimizing disease Burden (4 items, α = 0.86). We defined 5 groups: (1) MiRS-Both (Secondary Gain and Minimizing Burden often/very often; (2) MiRS-SG (Secondary Gain often/very often); (3) MiRS-MB (Minimizing Burden often/very often); (4) MiRS-Rarely/Sometimes; (5) MiRS-Never. Using MiRS group as the independent variable, we modeled its cross-sectional relationship to disability (Migraine Disability Assessment, MIDAS), interictal burden (Migraine Interictal Burden Scale-4), and migraine-specific quality of life (Migraine Specific Quality of Life v2.1 Role Function-Restrictive) while controlling for sociodemographics, clinical features, and monthly headache day categories. •Results Among this population-based sample with active migraine (n = 59,001), mean age was 41.3 years and respondents predominantly identified as female (74.9%) and as White (70.1%). Among respondents, 41.1% reported experiencing, on average, ≥4 monthly headache days and 31.7% experienced migraine-related stigma often/very often; the proportion experiencing migraine-related stigma often/very often increased from 25.5% among those with <4 monthly headache days to 47.5% among those with ≥15 monthly headache days. The risk for increased disability (MIDAS score) was significant for each MiRS group compared with the MiRS-Never group; the risk more than doubled for the MiRS-Both group (rate ratio 2.68, 95% CI 2.56–2.80). For disability, interictal burden, and migraine-specific quality of life, increased migraine-related stigma was associated with increased disease burden across all monthly headache day categories. •Discussion OVERCOME (US) found that 31.7% of people with migraine experienced migraine-related stigma often/very often and was associated with more disability, greater interictal burden, and reduced quality of life.Item Open Access Changes in cognitive appraisal in a randomized controlled trial of mindfulness-based cognitive therapy for patients with migraine(2023) Seng, Elizabeth K.; Kruse, Jessica A.; 0000-0002-8938-4949•Objective: This study is a secondary analysis evaluating changes in cognitive fusion and pain catastrophizing over 8 weeks of mindfulness-based cognitive therapy for mi- graine (MBCT-M) intervention versus waitlist/treatment as usual. •Background: Migraine is a common disabling neurological condition. MBCT-M com- bines elements of cognitive behavioral therapy with mindfulness-based approaches and has demonstrated efficacy in reducing migraine-related disability. •Methods: A total of 60 adults with migraine completed a 30-day run-in before ran- domization into a parallel design of either eight weekly individual MBCT-M sessions (n = 31) or waitlist/treatment as usual (n = 29): participants were followed for 1 month after. Participants completed the Pain Catastrophizing Scale (PCS) and the Cognitive Fusion Questionnaire (CFQ) at Months 0, 1, 2, and 4. •Results: The PCS scores decreased more in the MBCT-M group (mean [SD] at base- line = 22.5 [9.6]; at Month 4 = 15.1 [8.8]) than in the waitlist/treatment as usual group (mean [SD] at baseline = 24.9 [9.0]; at Month 4 = 22.5 [10.4]) from Month 0 to 4 (β = −7.24, p = 0.001, 95% confidence interval [CI] −11.39 to −3.09). The CFQ (mean [SD] baseline = 27.6 [8.0]; at Month 4 = 25.0 [8.0]) did not change significantly from Month 0 to 4 (β = −1.2, p = 0.482, 95% CI −4.5 to 2.1). Parallel mediation analyses indi- cated that decreases in the PCS and CFQ together (β = −6.1, SE = 2.5, 95% CI −11.6 to −1.8), and the PCS alone (β = −4.8, SE = 2.04, 95% CI −9.1 to −1.1), mediated changes in headache disability in the MBCT-M treatment completer group (n = 19). •Conclusion: In this study, pain catastrophizing showed strong promise as a potential mechanism of MBCT-M. Future research should continue to explore cognitive ap- praisal changes in mindfulness-based interventions.Item Open Access Headache: The Journal of Head and Face Pain(Wiley, 2023) Seng, Elizabeth; Butler, Nicole; Snyder, Ivy C.; Korn, Talia G.; Nicholson, Robert A.; Robbins, Matthew S.; 0000-0002-8938-4949Abstract •Objective: In this secondary analysis of mobile health headache diary data, we evaluated the relationship between adherence to medication used for the acute treatment of migraine and lifetime history of an anxiety or depression disorder. •Background: Medication non-adherence can produce poor clinical efficacy and may be associated with medication overuse. Medication overuse was defined by taking a migraine-specific medication (MSM) for ≥10 days/month, an opioid or barbiturate for ≥10 days/month, or a nonsteroidal anti-inflammatory drug for ≥15 days/month and having ≥15 headache days/month. Extant literature predominantly evaluates fixed schedule medication adherence. Little is known about predictors of adherence to as needed medication such as those used for the acute treatment of migraine. •Methods: Adults with prior migraine diagnosis and at least 4 headache days/month completed baseline questionnaires assessing lifetime history of depression or anxiety disorder diagnoses and were asked to record 90 days of once-daily electronic headache diaries soliciting: Headache occurrence; symptoms; medication taken, if any, for the acute treatment of migraine; and their pain level (mild, moderate, severe) when the medication was taken. The 193 participants who completed ≥30 days of headache diary were included in this secondary analysis. •Results: A MSM was used as the first medication taken on 45.7% (2825/6176) of headache days. Nearly a quarter of the sample (45/193, 23.3%) overused medications for acute treatment of migraine. Medication overuse was more common in patients with a history of an anxiety disorder, odds ratio (OR) 2.01 (95% confidence interval [CI] 1.01–3.69), but this relationship was not significant when headache days were accounted for, OR 2.02 (95% CI 0.83–4.91). Neither a history of a depression disorder, OR 1.40 (95% CI 0.90–2.16), nor an anxiety disorder, OR 1.11 (95% CI 0.71–1.72), was associated with taking medications early; however, duration of self-monitoring was associated with taking MSM early, OR 1.006 (95% CI 1.004–1.009). •Conclusion: Lifetime history of depression and anxiety were not associated with taking a MSM early. Medication overuse may be more common in patients who have both migraine and anxiety. Taking a MSM early improved over time for all participants, even when adjusting for a history of an anxiety and or a depression disorder.Item Open Access Depressive symptoms are associated with decline over time in verbal fluency performance in female but not male community-residing older adults(Routledge ; Taylor & Francis, 2023) Holtzer, Roee; Wasserman, J.; 0000-0001-6639-0724•Objective: The current study was designed to examine associations between depressive symptoms and longitudinal declines in category and letter fluency performance in a gender-strati ed 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.Item Open Access Differential associations of mobility with fronto-striatal integrity and lesion load in older adults with and without multiple sclerosis(SAGE, 2023) Wagshul, M.; Foley, F. W.; Chaudhary, K.; Lipton, M. L.; Motl, R.W.; Izzetoglu, M.; Hernandez, M. E.; Picone, M. A.; Holtzer, R.; 0000-0001-6639-0724•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.Item Open Access Cortical thickness moderates intraindividual variability in prefrontal cortex activation patterns of older adults during walking(2023) Holzer, Roee; Ross, D.; Wagshul, M.E.; Izzetoglu, M.; 0000-0001-6639-0724•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.Item Open Access Gray matter volume and within-task verbal fluency performance among older adults(Elsevier, 2023) Holtzer, R.; Pace, B.; Wagshul, M.; https://orcid.org/orcid-search/search?searchQuery=roee%20holtzerThe 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 3T 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.Item Metadata only Physical reserve: Construct development and predictive utility(Springer, 2023) Holtzer, Roee; O'Brien, C.; 0000-0001-6639-0724•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.Item Open Access Initial validation of the University of Alabama Birmingham study of aging life-space assessment in older adults with multiple sclerosis(2023) Holtzer, Roee; Motl, R. W.; Foley, F. W.; Picone, M. A.; Lipton, M. L.; Izzetoglu, M.; Hernandez, M. E.; 0000-0001-6639-0724•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.Item Open Access Deep learning based walking tasks classification in older adults using fNIRS(2023) Ma, D.; Izzetoglu, M.,; Holtzer, R.; Jiao, X.; 0000-0001-6639-0724Decline 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 pretrained model, all the voxel locations, and HbO2 - Hb as the third channel of the input image can achieve the best classification accuracy.Item Open Access The impact of music making on neural efficiency & dual-task walking performance in healthy older adults(Routledge ; Taylor & Francis, 2023) Jacobs, S.; Izzetoglu, M.; Holtzer, R.; 0000-0001-6639-0724ABSTRACT 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.Item Open Access Asthma history influences gait performance and associated prefrontal cortex activation patterns in older adults(Springer, 2023) Holtzer, Roee; Feldman, J. M.; Jariwala, S. P.; Izzetoglu, M.; 0000-0001-6639-0724Walking 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.Item Open Access Brain control of dual-task walking can be improved in aging and neurological disease(Springer, 2024) Holtzer, Roee; Choi, J.; Motl, R.; Foley, F. W.; Wagshul, M. E.; Hernandez, M. E.; Izzetoglu, M.; 0000-0001-6639-0724The 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. Dualtask- 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 dualtask- 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 singletask- 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. Dualtask 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.Item Open Access Individual reserve in aging and neurological disease(Springer, 2023) Holtzer, Roee; Choi, J.; Motl, R.; Foley, F. W.; Picone, M. A.; Lipton, M.; Lee, J. S.; Izzetoglu, M.; Hernandez, M. E.; 0000-0001-6639-0724•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.Item Metadata only Frontal-striatal tract integrity and depression in older adults with and without multiple sclerosis(Springer Nature Journals, 2024) Cote, S. E.; Wagshul, M.; Foley, F. W.; Lipton, M. L.; Holtzer, R.; Picone, M. A.; Lee, J. S.; 0000-0001-6639-0724•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 (β = .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.Item Open Access Caudate volume and symptoms of apathy in older adults with multiple sclerosisate volume and symptoms of apathy in older adults with multiple sclerosis(SAGE, 2023) Holtzer, Roee; Cote, S. E.; Wagshul, M. E.; Foley, F. W.; Lipton, M. L.; 0000-0001-6639-0724•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 (β = 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.Item Open Access The association between perceived social support and cognition in older adults with and without multiple sclerosis(Elsevier, 2023) Holtzer, Roee; Cohen, Hannah R.; 0000-0001-6639-0724•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.Item Open Access Presence and persistence of perceived subjective cognitive complaints and incident mild cognitive impairments among community-residing older adults(Elsevier, 2023) Holtzer, Roee; Brundage, Katie; 0000-0001-6639-0724•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.Item Open Access Dierential associations of mobility with fronto-striatal integrity and lesion load in older adults with and without multiple sclerosis(SAGE Publishers, 2023) Wagshul, M.; Foley, F. W.; Chaudhary, K.; Motl, R.; Izzetoglu, M.; Hernandez, M. E.; Picone, M. A.; Holtzer, R.; 0000-0001-6639-0724 (Holtzer); 0000-0003-1529-8842 (Foley)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.