Research has shown that social support has protective effects against cognitive decline in older adults. No study to date has examined the relationship between social support and cognition in older adults with Multiple Sclerosis (MS). Advances in treatments for MS have resulted in a growing number of aging individuals with MS, making it imperative to identify modifiable risk factors that affect cognition, such as social support. Therefore, this study was designed to examine the association between social support and cognition in older adults with MS and healthy controls.

Participants were older adults with MS (N = 70; M age = 64.71, SD + 3.86 years; 62.9% female) and community-residing older adults (N = 74; M age = 68.42, SD + 5.96 years; 58.1% female). Perceived social support was assessed using the Medical Outcomes Study Modified Social Support Survey (MSSS), which measures emotional/informational support, tangible support, affectionate support, and positive social interaction. Cognition was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which measures immediate and delayed memory, attention, language, and visuospatial abilities. Linear regressions stratified by group status (MS vs. control) assessed the association between perceived social support and cognition.

Linear regressions controlling for age, gender, education, and medical comorbidities showed that higher total MSSS scores were related to higher RBANS scores in the MS group (β = 0.243, p = .046) and marginally in the control group (β = 0.239, p = .053). Examination of MSSS domains showed that emotional/informational support (β = 0.246, p = .044) and positive social interaction (β = 0.279, p = .023) were significant predictors of RBANS performance in the MS group. Positive social interaction (β = 0.262, p = .011) was a significant predictor of RBANS performance in the control group. Analyses that further adjusted for depression scores showed that positive social interaction remained a significant predictor of RBANS performance in the control group (β = 0.361, p = .005). In contrast, depression scores attenuated associations between all aspects of social support and RBANS performance in the MS group (p > .05).

Among older adults, the association between social support and cognition varied as a function of MS status. Overall perceived social support, emotional/informational support, and positive social interaction were significantly associated with cognition in the MS group. However, depressive symptoms attenuated these associations. In contrast, positive social interaction was the key driver of the association between social support and cognition among the healthy controls, and notably, this association remained significant even after adjusting for depressive symptoms.

Prospective memory (PM) is the ability to remember to produce an action at a specific moment in the future signaled by the occurrence of a specific event (EB condition), a time or a time interval (TB condition). Detection of the appropriate moment corresponds to the prospective component (PC), while production of the appropriate action corresponds to the retrospective (RC) component. Although PM difficulties have been reported in healthy aging and in association with Multiple Sclerosis (MS), PM has not been examined in elderly people with MS (PwMS), which is particularly relevant since their life expectancy has improved significantly in recent years due to available treatments, and PM is essential to daily functioning. The main objective of this study was to investigate whether the decline in PM performance with advancing age is influenced by the presence of multiple sclerosis (MS). This study also aimed to clarify the type of PM impairment (PC vs RC in TB and EB conditions) in MS as a function of age.

A total of 80 participants were recruited and separated into four groups: elderly PwMS (n = 20), young PwMS (n = 20), elderly healthy controls (HC) (n = 20) and young HC (n = 20). PM and its components were measured using the TEMP, an experimental ecological tool developed by our laboratory that has been validated in previous studies. In addition, all participants underwent a series of neuropsychological tests specific to MS (MACIFMS) and aging (Boston Naming Test, Clock Drawing Test, Towers of London, Trail making Test, Stroop, MoCA).

On the TEMP total score, a two-way ANOVA showed a main effect of age (F[1,75]=47.4, p<0.001, n2 = .40), a main effect of the presence of MS (F[1,75]=19.51, p<0.001, n2 = .21) as well as a significant Age X Disease interaction (F[2,74] =5.40, p=0.023, n2 = .07). Direct comparison between EB and TB conditions revealed that for the PC, only elderly PwMS had more difficulty in the TB than in the EB condition (Z = -2.51, p = 0.012), whereas RC score was significantly lower in the TB than in the EB condition in all groups except in younger controls (younger PwMS : Z = -2.56, p = 0.01; elderly HC : Z = -3.31, p < 0.001; elderly PwMS :Z = -3.04, p = 0.002).

The TEMP revealed a marked impairment in PM in elderly PwMS compared to elderly HC and young PwMS. This impairment was particularly evident on the PC component in the TB condition. RC difficulties noted in the TB condition in all but younger controls reflect the arbitrary nature of the cue-action link that is particularly sensitive to episodic memory difficulties often observed in aging and MS.

To test whether adherence to treatment in patients with MS is influenced by cognitive variables (executive functions), personality, and social support.

This is a pilot observational, descriptive, cross-sectional study. 60 patients with Relapsing remitting MS ( 73.33% female; age: 41.41 ±14.00) undergoing medical treatment ( 28 dymethilfumarate, 7 ocrelizumab/ rituximab, 6 fingolimod, 5 interferon, 5 natalizumab, 4 cladribine, 3 teriflunomide, 1 alemtuzumab, 1 glatiramer acetate) underwent a comprehensive multi-component evaluation including : cognition, social support (using the self-reported record of social support scale), personality (using the NEO-FFI questionnaire) and evaluation of treatment adherence using the Morisky Green Levine Medication Adherence Scale Participants were divided into two groups according to their adherence to medical treatment, low vs. high adherence was defined using a cutoff score of 4. Differences between groups were evaluated using Student's t-test with a significance level of p<0.05, the effect size was calculated with Cohen's d test.

Groups did not differ significantly in age, sex, type of treatment, Montreal Cognitive Assesments (MoCA) or neuropsychiatric scales of depression and anxiety. Regardless of treatment type, 63.33% of the patients had high treatment adherence. Significant differences between groups were found in the Global Index of Social Support (p=0.016, Cohen's d= 0.73) and the responsibility factor of the NEO-FFI (p=0.048, Cohen's d= 0.20). Conversely, no significant differences were found in executive functions (p=0.8), Openness (p=0.062), Extraversion (p=0.5), Neuroticism (p=0.4) and Agreeableness (p=0.8).

Social support and the responsibility factor of personality are significantly different between MS patients with high and low adherence to medical treatment. The study of social support and personality may be a key component in improving adherence strategies.

Theory of mind (ToM) deficits have been reported in patients with multiple sclerosis (pwMS). However, most studies have used pictures or written scenarios as stimuli without distinguishing between cognitive and affective ToM, and no studies have investigated older pwMS. The aims of this study were to determine the impact of MS and age on cognitive and affective ToM using a more ecological video-based task. We also aimed to investigate the relationships between ToM, cognition and emotion reading to understand the nature of ToM deficits in pwMS.

We recruited 13 young healthy controls (HC), 14 young pwMS, 14 elderly HC and 15 elderly pwMS. ToM was measured using an adaptation of the Conversations and Insinuations task (Ouellet et al. 2010). In this task, participants watch four 2-minutes videos of social interactions, which are interrupted by multiple choice questions about either the emotional state (affective ToM; 14 questions) or the intention (cognitive ToM; 14 questions) of the characters. They also underwent a short neuropsychological battery including cognitive tasks (Montreal Cognitive Assessment (MoCA), DKEFS Color-Word Interference Test) and an experimental multimodal emotion recognition task.

We found significant effects of group (pwMS < HC), age (older < younger) and condition (cognitive ToM < affective ToM) on the ToM task. Although no interaction effect was found, the elderly pwMS group showed the largest discrepancy between their cognitive and affective ToM, the cognitive subtask being significantly more affected. ToM significantly correlated with general cognition (MoCA) in all participants, while cognitive inhibition (DKEFS Color-Word Interference Test) correlated with ToM only in elderly pwMS. No significant correlation was observed between ToM and emotion reading.

This study highlights both cognitive and affective ToM deficits in pwMS, and particularly in cognitive ToM in elderly pwMS. These impairments could be underlied by cognitive and executive difficulties, but not by core social cognitive impairments, as observed in the correlation analyses. Future studies should investigate the relationships between ToM impairments and impairments in real-life empathy and social behavior in pwMS.

Research examining co-occurring anxiety and depression in persons with multiple sclerosis (PwMS) is scarce, though an estimated 20% of PwMS experience clinically significant anxiety and depression (Gascoyne et al., 2019). Recent work by Hanna & Strober (2020) found that PwMS with comorbid anxiety and depression reported worse outcomes in all constructs of symptomatology, disease management, psychological well-being, and quality of life. However, it is unclear how co-occurring anxiety and depression symptoms may influence or exacerbate cognitive difficulties in PwMS. Further, considering there are high levels of comorbidity between depression, anxiety, and fatigue in PwMS, this study aims to examine the unique variances of depression, anxiety, co-occurring depression and anxiety, and fatigue on cognitive functioning.

86 PwMS (F=65,M=21) completed a comprehensive neuropsychological battery that included self-report measures of anxiety, depression, and fatigue. An intraindividual variability (IIV) composite score was calculated by combining standardized intraindividual standard deviation and maximum discrepancy scores on measures of attention/processing speed and memory for each participant. Lower scores indicate worse performance (i.e., greater variability). A hierarchical regression was conducted with IIV as the outcome variable and with depression, anxiety, cognitive fatigue, physical fatigue, and the interaction between depression and anxiety as predictors. Expanded Disability Status Scale (EDSS) scores were included as a covariate.

The only model that included a statistically significant predictor of IIV was the final model, which included EDSS, depression, anxiety, cognitive fatigue, physical fatigue, and the interaction between depression and anxiety, F(6,77)=2.97, p=.01, AR2=.08. While the main effects of depression and anxiety were not significant, the interaction between depression and anxiety was significant, F(6,77)=7.20, p=.01, n2=.09. Simple effects tests revealed that the relationship between IIV and anxiety was marginally significant for those at the cutoff for clinical depression (square root BDI-FS=2; BDI-FS=4), F(6,77)=3.52, p=.07, n2=.04. However, the effect of anxiety on IIV increased as depression increased. For example, in those with high levels of depression (1.5 SD above the mean), there was a significant relationship between anxiety and IIV, F(6,77)=4.16, p=.04, n2=.05, though this was not the case for those with low levels of depression (1.5 SD below the mean), F(6,77)=0.01, p=.92, n2=.00.

The interaction between depression and anxiety predicted variability in performance such that those with high levels of depression and anxiety demonstrated significantly greater IIV. Since dispersion is considered a marker for neurocognitive integrity, this may suggest that co-occurring psychological disturbances are associated with poorer cognitive integrity, an important consideration for interventions and outcomes. While interventions aimed at treating co-occurring depression and anxiety have been largely overlooked within the MS literature (Butler et al., 2016), transdiagnostic interventions have been beneficial for general adult populations with co-occurring anxiety and depression (McEvoy et al., 2009). Future work should examine the efficacy of interventions aimed at addressing co-occurring depression and anxiety in PwMS, as this may help to improve cognitive functioning, as well as perception of functioning, which will likely further improve quality of life and overall well-being.

Lower levels of social support in persons with Multiple Sclerosis (PwMS) are associated with myriad poor outcomes including worse mental health, lower quality of life, and reduced motor function (Kever et al., 2021). Social support has also been associated with physical pain (Alphonsus et al., 2021) and sleep disturbance (Harris et al., 2020) in PwMS. Pain is one of the most common symptoms of MS (Valentine et al., 2022) and is also known to be related to sleep disturbance (Neau et al., 2012). With these considerations in mind, the goal of the current study was to examine social support as a possible moderator in the relationship between pain and sleep quality in PwMS.

This cross-sectional study included 91 PwMS (females = 76). A neuropsychological battery and psychosocial questionnaires were administered. For sleep quality a composite was created from the sleep and rest scale of the Sickness Impact Profile (SIP), sleep-related items on the Multiple Sclerosis-Symptom Severity Scale (MS-SSS) (i.e., sleeping too much or sleep disturbance, fatigue or tiredness, and not sleeping enough), and an item from the Sleep Habits Questionnaire (SHQ) ("How many nights on average are you troubled by disturbed sleep?"). This composite (a = .76) has been used in prior research. Lower scores were indicative of worse sleep quality. Pain intensity and pain interference were measured using the Brief Pain Inventory (BPI). Pain intensity was calculated from four pain indices (i.e., pain at its worst in the last 24 hours, at its least in the last 24 hours, on average, and current pain at the time of the assessment) and pain interference was calculated from seven indices (i.e., general activity, mood, walking ability, normal work, relationships with others, sleep, and enjoyment of life). The Social Support Questionnaire (SSQ) measured average satisfaction with supports. A series of hierarchical linear regressions were conducted with the sleep quality index as the outcome variable and satisfaction with social supports, both indices of pain (intensity and interference), and their interactions as predictors. Then, simple effects tests were used to clarify the pattern of any significant interactions.

Regression analysis revealed that the interaction between pain interference and satisfaction with social support was significant (p = .034). Simple effects tests revealed that when satisfaction with social support was high, pain interference was associated with better sleep quality (p < .001). The interaction between pain intensity and satisfaction with social supports was also significant (p = .014). Simple effects test revealed that at high levels of satisfaction with social supports, pain intensity was associated with better sleep quality (p < .001).

Satisfaction with social support moderated the relationship between pain interference and pain intensity on sleep quality in PwMS. Specifically, high satisfaction with social support buffers against the negative effects of pain interference and pain intensity on sleep quality in PwMS. This provides evidence that interventions aimed at increasing social supports in PwMS may lead improvements in sleep quality and reduce the impact of pain on sleep quality.

Depression is highly prevalent in persons with multiple sclerosis (pwMS). A reformulated version of the learned helplessness theory posits that individuals who attribute the cause of negative events to personal factors (internal), perceive that the cause persists for a long period of time (stable), and believe it is present in all situations (global) are at an increased risk for depression. As such, it is critical to examine possible modifiable factors that buffer against the deleterious effects of negative attributional style. Therefore, the current study investigated whether stress moderates the relationship between negative attributional style and depression symptoms in an MS sample.

Thirty-six pwMS (30 Female, 6 Male) completed a comprehensive neuropsychological test battery and psychosocial questionnaires that assessed cognitive attributional style, daily stressors, and depression symptoms. The Attributional Style Questionnaire (ASQ) was used to create internal, stable, and global attribution dimension scores, as well as an overall attributional style score combining the three dimensions. Stress was quantified as the total score of perceived hassles from the Hassles and Uplifts Scale (HUS). Depression symptoms were measured using the Beck Depression Inventory-Fast Screen (BDI-FS). Hierarchical linear regressions were conducted with depression symptoms as the outcome variable. Each dimension of attributional style (internal, stable, global, or overall ASQ), stress, and their interactions were included as predictors. Simple effects tests were used to clarify the pattern of any significant interaction.

Regression analyses revealed that the interaction between overall attributional style and stress was significant (p = .025). Simple effects tests revealed that overall attributional style was associated with depression symptoms only in pwMS with high levels of stress (p = .015). For the individual dimensions of the ASQ, several interactions were also significant. The interaction between the internal dimension and stress was significant (p= .009), such that internal attributions were associated with depression symptoms only in pwMS with high levels of stress (p = .002). The interaction between the stable dimension and stress was also significant (p = .01); stable attributional style was associated with depression symptoms only in pwMS with high levels of stress (p = .009). The interaction between the global dimension and stress was not significant.

Stress moderated the relationship between negative attributional style and depression symptoms in pwMS. Specifically, the internal and stable dimensions and overall attributional style were associated with increased depression symptoms only in pwMS who reported high levels of stress, but not in those with low levels of stress. Interventions aimed at reducing and managing stress may help protect against the effects of negative cognitive schemas on depression symptoms in MS. Additionally, previous research demonstrates that attributional style may be a malleable target of evidence-based psychotherapy (Seligman et al., 1988; Proudfoot et al., 2009). Our findings suggest that cognitive therapy specifically targeting the internal and stable dimensions of attributional style may be effective in modifying attributional style, perceptions of stress and, subsequently, improve depression outcomes in MS.

The current study aimed to examine real-time associations between non-cognitive symptoms and cognitive dysfunction (latter measured both objectively and subjectively in real-time) using ecological momentary assessment (EMA).

Forty-five persons with MS completed EMA four times per day for three weeks. For each EMA, participants completed mobile versions of the Trail-Making Test part B (mTMT-B) and a finger tapping task, as well as surveys about symptom severity. Trait (usual levels of a symptom) and state (when symptom level was higher or lower than the individual's usual levels) aspects of each symptom's severity were calculated. Multilevel models were conducted to account for within-person clustering, with performance on the mTMT-B and self-reported rating of cognitive dysfunction as primary outcomes.

A total of 3,174 EMA sessions were collected; compliance rate was 84%. There was significant intra-day variability in mTMT-B performance, anxiety, fatigue, and pain. More severe state depressive symptoms predicted lower performance on the mTMT-B in real-time. Self-reported difficulties with sleeping the night before predicted mTMT-B performance the following day. In contrast, state (but not trait) fatigue, depression, anxiety, and pain all predicted self-reported cognitive dysfunction in real time. Further, state self-reported cognitive dysfunction (but not mTMT-B performance) was associated with a higher perceived sense of accomplishment.

Self-reported cognitive dysfunction was more susceptible to influences of other MS symptoms (especially when the symptom is more severe than the individual's usual levels) and better predicted perceived sense of accomplishment than objectively measured executive functioning in real-time. Objective executive functioning performance was sensitive to effects of depressive symptoms and sleep difficulties. The current study demonstrated the feasibility of assessing real-time associations among MS symptoms using smartphone-administered EMA.

Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease of the central nervous system. Apathy is significantly higher in adults with MS compared to healthy populations. Apathy is a lack of motivation that can cause dysfunctions in each step of goal-directed behaviors. Apathy is associated with diminished ability to perform activities of daily living, tasks requiring normal executive function, and quality of life. Across various neurodegenerative disorders, apathy has been regarded as a predictor of poor cognition and functional outcomes. However, the severity of apathy and its association with cognitive function in older adults with MS have not been reported. This study's objective was to address this gap of knowledge. Hence, we evaluated: 1) the severity of apathy symptoms in older adults with MS compared to healthy older adults and, 2) the association of apathy symptoms and global cognitive functioning in older adults with MS compared to controls.

Participants were community-residing older adults (age >60ys) enrolled in a cohort study, “Brain Predictors of Mobility and Falls in Older Adults with Multiple Sclerosis.” Healthy controls (n=59; mean age=66.25± 3.37; %female=47.5) and persons with MS (n=69; mean age=64.58± 3.88; %female=62.3) were included in the analysis. Using McDonald criteria, MS diagnosis was physician-confirmed by medical record review, apathy symptoms were assessed through 4 apathy symptom questions on the 30-item Geriatric Depression Scale (GDS), and global cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Covariates included age, gender, years of education, global health score (GHS), and depression (GDS w/out apathy questions). For the first objective, a linear regression model was used with a bi-level group status variable (MS vs controls) serving as a predictor of apathy symptoms. For the second objective, two linear regression models stratified by group status were run with apathy symptoms as a predictor of global cognitive functioning.

The presence of MS was significantly associated with worse apathy (β=.34, p < .001) and it remained significant after adjusting for covariates (β=.19, p=.03). Additionally, apathy was negatively associated with global cognition in persons with MS (β=-.32, p =.01) and this association remained significant after adjusting for covariates (β=-.33, p =.01) except depression (β=-.27, p =.08). The association of apathy and global cognitive functioning was not significant in healthy controls (β=.01, p=.95).

This study is the first to report worse apathy symptoms in older persons with MS compared to healthy controls. Additionally, worse apathy symptoms were associated lower global cognitive functioning in older adults with MS but not in healthy controls.

Word finding difficulty is a prevalent cognitive symptom in multiple sclerosis (MS). Word finding relies on retrieving concepts and word forms from the long-term store. Neuropsychological assessment of word finding difficulty in persons with MS (pwMS) is typically characterized by semantic errors and decreased speed in naming tests, along with decreased semantic verbal fluency scores. Despite this, there is significant heterogeneity in the detection of verbal fluency deficits across studies in the MS literature. This may be partially due to disease-related heterogeneity and/or low sensitivity of commonly used scoring approaches. We investigate the latter in the present study. Semantic network analysis, derived from graph theory, provides a fine-grained approach to understanding semantic retrieval by utilizing information about the co-occurrence of words produced on semantic verbal fluency tasks. Analysis results in a graphical quantification of the conceptual-lexical store. A preliminary study found that semantic networks from Spanish-speaking pwMS had fewer associative connections and more central connective pathways, which if affected, may lead parts of the network to become inaccessible for retrieval. However, their investigation was limited in the generalizability of their findings, as they excluded pwMS who have cognitive impairment (CI), which represents a significant proportion of pwMS. We sought to investigate network differences in an English-speaking MS sample, without exclusion based on CI, using widely-used metrics of micro-, meso-, and macroscopic structure. We hypothesize the MS network will be less efficiently organized, thus characterized by higher average shortest path length (ASPL), lower clustering coefficient (CC) and lower modularity (Q).

53 persons with MS and 44 neurologically healthy controls (HC) were recruited as a part of an ongoing study (NMSS RG-1907-34364 & RG-1901-33304). As a part of a larger battery, participants were administered the semantic verbal fluency subtest of the Controlled Oral Word Association Test. Responses were analyzed using a network-analysis R suite.

The MS and HC networks were characterized by having similar average shortest path lengths (ASPL MS =2.466, ASPL HC=2.463, F(1,1997)=0.281, p=0.596), indicating they require similar numbers of edges to be traversed to reach other nodes in the network. This suggests similar efficiency of information transfer. Clustering coefficient was not significantly different between the MS and HC networks (CC MS = 0.742, CC HC =0.742, F(1,1997)=0.10, p=0.919), suggesting similar local interconnectivity. The MS network had significantly lower modularity compared to the HC network (Q MS =0.497, Q HC = 0.502, F(1,1997)=16.678, p<0.001). This means that sub-communities of the network were less segregated into densely connected sub-graphs.

Contrary to expectation, ASPL and CC were not significantly different between groups. The absence of finding lower CC was consistent with prior findings. Consistent with our hypothesis, the MS network had lower modularity. This may suggest that pwMS were unable to use categorical clustering to aid in retrieval from the lexicon. Specifically, low modularity coupled with similar CC may suggest the structure of the MS lexicon is characterized by intact clustering on a microscopic scale but less strong organization into distinct clusters on a larger scale.

Fatigue is common in pediatric-onset multiple sclerosis (POMS), yet causal factors and correlates of fatigue are poorly understood in this population. A 2016 review suggested an association between fatigue and emotional difficulties, sleep disturbance, and reduced quality of life in POMS. Information regarding the potential association between fatigue and cognitive challenges is limited and mixed. Through this systematic review, we searched for relationships between fatigue, cognition, and mental health.

Systematic review methodology and PRISMA guidelines were followed. Five electronic databases were searched: Ovid: Medline, Ovid: EMBASE, Ovid: PsycInfo, Web of Science and CINAHL. Search terms were specific to each database. Reference lists of included studies were also hand-searched. We included empirical studies that were published in English after 2001, included a sample with confirmed diagnoses of POMS using McDonald criteria, and measured fatigue, cognition and clinical factors including mental health outcomes. Cognition had to be assessed using a standardized assessment tool and studies must have examined associations between outcomes of interest either descriptively or by assessing bivariate or multivariate relationships. Covidence was used to complete the screening, extraction, and quality assessment. Two independent researchers (i.e., T.L.F, and/or S.D, and/or M.G) reviewed each paper included in the title and abstract screen and full text review. S.D and M.G completed the extraction and quality assessments. Conflicts at all stages were resolved by the lead author (T.L.F). The University of Adelaide JBI critical appraisal checklist for analytical cross-sectional studies was used to ensure the scientific rigor of each included study. Sample characteristics and measures of fatigue, clinical and cognitive variables were extracted. A narrative synthesis was conducted.

We identified 1025 abstracts through our initial search and retained 119 articles for full text review. One hundred and six of these studies were excluded during the full text review including six studies which did not examine the relationship between the outcomes of interest. Fifty-one additional studies were identified from hand-searching reference lists of included studies, of which 24 were retained for full text review. A total of 15 studies were extracted and analyzed. Overall, a positive relationship was found between fatigue and mental health outcomes (i.e., anxiety and depression), whereas results were mixed regarding the association between fatigue and performance-based measures of cognition as well as fatigue and other clinical characteristics (e.g., disease duration, EDSS, treatment with DMDs, relapse rate, age at disease onset). In some studies, fatigue and executive functioning performance were negatively related; the relationship was less clear in others (e.g., both fatigued and non-fatigued MS patients demonstrated cognitive challenges, an association between fatigue and executive functioning was identified at follow-up but not baseline). Eleven of the 15 included studies (73%) did not identify associations between fatigue and cognition.

While studies are mixed, fatigue in children has been associated with aspects of cognition. Understanding the relationship between fatigue, cognition, and mental health and identifying gaps in the existing literature, have implications for informing interventions for this clinical population.

Depression is common in persons with MS (PwMS), substantially contributing to morbidity and mortality. Depression can dually impact PwMS as both a psychosocial reaction to living with the disease and a neurological effect of it. Cardinal features of depression include reduced ability to seek and experience pleasure, often attributed to dysregulation of the brain's reward system. People with depression exhibit atypical reward processing, as do fatigued PwMS. However, it is unclear whether MS itself affects reward processing, and whether it interacts with depression. The current study explored the associations of depression, MS, and their interaction on reward responsiveness. We hypothesized that depression and MS would independently be associated with poorer reward responsiveness and that they would interact synergistically to impair reward responsiveness.

Forty PwMS and 40 healthy age- and education-matched healthy controls (HC) participated in a computerized switching task with high- and low-reward manipulations. The Chicago Multiscale Depression Inventory (CMDI) Mood subscale measured depressive symptoms. The Behavioral Inhibition/Activation Scales (BIS/BAS) measured self-reported reward responsiveness and behavioral inhibition. Switching task performance was measured as response time (RT) and accuracy. Performance differences between the high- and low-reward conditions represented performance-based reward responsiveness. Linear mixed effects models were used to estimate the associations of MS and depression with reward responsiveness, behavioral inhibition, and task performance.

Depression, but not MS, was associated with higher BIS scores (p=.007). Neither depression nor MS was associated with BAS subscales. On the switching task, participants who reported lower depression responded to reward such that they were slightly faster in the high-reward condition compared to the low-reward condition (p=.07). By contrast, in participants who reported higher depression, there was no effect of reward on response time. Additionally, MS (p=.009) and depression (p=.018) were each associated with slower response times. Regarding accuracy, no effects of reward were observed; however, there was an interaction between MS and depression. Among HC participants, depression was not related to accuracy. In comparison, PwMS who reported higher depression were more accurate than PwMS who reported less depression (p=.043).

Consistent with hypotheses, higher depressive symptoms were associated with increased behavioral inhibition. Depression was not associated with self-reported reward responsiveness, but it was associated with reduced reward responsiveness on a cognitive task. Contrary to hypotheses, MS was not associated with reduced reward responsiveness. Additionally, higher depression and an MS diagnosis were related to slower response time, consistent with prior findings that psychomotor slowing is a hallmark feature of both disorders. Interestingly, we observed a unique behavioral trend in PwMS, such that PwMS with higher depressive symptoms were more accurate than PwMS with lower depressive symptoms, whereas this relationship was not present among HCs. Altogether, depression in both PwMS and cognitively healthy individuals may be associated with blunted reward responsiveness, but MS does not exacerbate this relationship. In fact, PwMS with depression may be more conscientious in their functioning and therefore perform better on cognitive task accuracy. Continued work should examine how reward processing and its underlying mechanisms may differ in depressed PwMS.

Parkinson’s disease (PD) affects the person’s quality of life, but the comorbidity of PD and impulsive control disorder (ICD), which has an average prevalence of 23%, can enhance the disruption of quality of life for the patients and their caregivers. The effects of ICD in PD on brain morphology and cognition have been little studied. Thus, this study proposes to investigate the differences in the evolution of cognitive performance and brain structures between PD patients with ICD (PD-ICD) vs. without ICD (PD-no-ICD).

Parkinson’s Progression Markers Initiative (PPMI) data of 58 patients with idiopathic PD, including their MRI data at baseline and three years later, were analyzed. The MRIs were processed with FreeSurfer (7.1.1) to extract cortical volumes, areas, thicknesses, curvatures and folding index as well as volumes of subcortical segmentations. All participants underwent cognitive evaluations. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease was used to differentiate those with at least one ICD from those without any ICD. 12 of the 58 patients had an ICD at their first visit and 19 had an ICD at their visit three years later. There was no significant difference between PD-ICD and PD-no-ICD with respect to sex, use of overall medication, age, age of onset, age at diagnosis, years of education and the Montreal cognitive assessment score. Two-way mixed ANOVAs were performed for each neuropsychological test and brain structure extracted from MRIs with the time of the visit as the repeated independent variable (within participants) and the presence or absence of an ICD as the other independent variable (between participants).

The mixed ANOVA revealed that PD-ICD had their performance decline after three years, for the Hopkins Verbal Learning Test delayed recall and the Symbol Digit Modalities Test while PD-no-ICD saw their performance increase. A whole brain analysis showed that PD-ICD had a significant decrease after three years of the right cortex area total brain volume in comparison to PD-no-ICD. Specific brain structures also underwent significant changes over three years. Cortical changes in PD-ICD were: (1) increased surface area in the left temporal parahippocampus and (2) decreased surface areas of the right insula, right middle and superior temporal regions, left occipital lingual as well as left cingulate isthmus. Furthermore, in the subcortical nuclei, PD-ICD showed (1) increased volumes of the paratenial thalamic nucleus and whole right amygdala and (2) decreased volumes of the right amygdalian basal nucleus and thalamic ventromedial nucleus.

This study suggests that PD patients who also have ICD might be prone to develop over three years: (1) significant changes in cognitive performance (memory, attention), (2) morphological changes in the amygdala and thalamic nuclei and (3) significant atrophy and area shrinkage in the temporal and insula regions.

Anxiety is very common in Parkinson’s disease (PD) where according to a systematic review, the average prevalence is 31%, surprisingly higher than the average 17% of depressive disorders found in PD. Only a few studies have investigated the impact of anxiety on cognitive performance and brain morphology in PD. They demonstrated anxiety to be a significant predictor of cognitive impairment, where PD patients with anxiety have shown to be twice more likely to have deficits in the memory domain compared to those without anxiety. Furthermore, poorer cognitive performance in all cognitive domains was reported to be a significant risk factor for increased anxiety the following year. Anxiety in PD has also shown reduced volume/thinning in the fronto-cingulate, anterior cingulate cortex, left parietal cortices and the precuneus, despite the scant number of studies on this topic. Hence, the objective of this study aims to determine the evolution of cognitive performance and brain morphology in PD patients with and without anxiety over a three-year span.

We analyzed the baseline and three-year follow-up Parkinson’s Progression Markers Initiative (PPMI) data of 58 PD patients. MRI 3T was processed with FreeSurfer 7.1.1 on the Compute Canada cluster “Cedar” and we extracted cortical (Desikan-atlas-based volumes, thickness, area, folding index, curvature) and volumes of subcortical structures. Additionally, anxiety subscores from the State-trait anxiety inventory as well as neuropsychological tests were analyzed. PD patients were classified in two groups: PD-no-anxiety (n=46) and PD-anxiety (n=12) (subscore of > 40 on the State anxiety scale). Two-way mixed ANOVA models were established with presence/absence of anxiety as a between-subjects factor, time (baseline and three year) as a within-subjects factor and neuropsychological and MRI data were regarded as dependent variables.

Mixed ANOVA revealed that PD-anxiety saw a significantly greater decline in performance on the Montreal Cognitive Assessment test compared to PD-no-anxiety. In addition, PD-anxiety saw their performance decline over time in the Hopkins Verbal Learning test (HVLT) immediate recall, HVLT retention and HVLT delayed recall while PD-no-anxiety saw an increase in performance. In terms of brain morphology, over the three years, PD-anxiety had a greater decrease in the frontal precentral thickness, cingulate isthmus area and thickness, and temporal regions (transverse area and inferior folding) all in the left hemisphere compared to PD-no-anxiety. In subcortical regions, PD-anxiety had a greater decrease in volume of the hippocampal cornu ammonis-1 and pallidum compared to PD-no-anxiety. By contrast, PD-anxiety showed a greater increase in curvature of the frontal middle rostral, frontal pole, parietal supramarginal, and insula cortex as well as in the folding of the parietal superior and occipital pericalcarine of the right hemisphere in comparison to PD-no-anxiety.

This study highlights the importance of taking into consideration anxiety symptoms in PD, as they contribute to poorer cognitive performance and frontal, parietal and temporal differences over time. More studies with a larger sample size are needed in order to confirm these results.

The presence of cognitive impairment corresponds with declines in adaptive functioning (Cahn-Weiner, Ready, & Malloy, 2003). Although memory loss is often highlighted as a key deficit in neurodegenerative diseases (Arvanitakis et al., 2018), research indicates that processing speed may be equally important when predicting functional outcomes in atypical cognitive decline (Roye et al., 2022). Additionally, the development of performance-based measures of adaptive functioning offers a quantifiable depiction of functional deficits within a clinical setting. This study investigated the degree to which processing speed explains the relationship between immediate/delayed memory and adaptive functioning in patients diagnosed with mild and major neurocognitive disorders using an objective measure of adaptive functioning.

Participants (N = 115) were selected from a clinical database of neuropsychological evaluations. Included participants were ages 65+ (M = 74.7, SD = 5.15), completed all relevant study measures, and were diagnosed with Mild Neurocognitive Disorder (NCD; N = 69) or Major NCD (N = 46). They were majority white (87.8%) women (53.0%). The Texas Functional Living Scale was used as a performance-based measure of adaptive functioning. The Coding subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS-CD) was used to measure information processing speed. Composite memory measures for Immediate Recall and Delayed Recall were created from subtests of the RBANS (List Learning, Story Memory, and Figure Recall) and the Wechsler Memory Scale-IV (Logical Memory and Visual Reproduction). Multiple regressions were conducted to evaluate the importance of memory and information processing speed in understanding adaptive functioning. Age and years of education were added as covariates in regression analyses.

Significant correlations (p < .001) were found between adaptive functioning and processing speed (PS; r = .52), immediate memory (IM; r = .43), and delayed memory (DM; r = .32). In a regression model with IM and DM predicting daily functioning, only IM significantly explained daily functioning (rsp = .24, p = .009). A multiple regression revealed daily functioning was significantly and uniquely associated with IM (rsp = .28, p < .001) and PS (rsp = .41, p < .001). This was qualified by a significant interaction effect (rsp = -.29, p = .001), revealing that IM was only associated with adaptive functioning at PS scores lower than the RBANS normative 20th percentile.

Results suggest that processing speed may be a more sensitive predictor of functional decline than memory among older adults with cognitive disorders. These findings support further investigation into the clinical utility of processing speed tests for predicting functional decline in older adults.

A common assumption in clinical neuropsychology is that cerebrovascular risk is adversely associated with executive function, while Alzheimer’s disease (AD) primarily targets episodic memory. The goal of the present study was to determine the cross-sectional and longitudinal validity of these assumptions using validated markers of cerebrovascular and AD burden.

19271 longitudinally-followed participants from the National Alzheimer Coordinating Center (NACC) database (Mean age= 72.25; SD age= 10.42; 58% women; 51.6% CDR= 0, 33.7% CDR= 0.5, 14.7% CDR> 1) were included. Cognitive outcomes were a composite memory score and an executive function composite score (UDS3-EF; Staffaroni et al., 2020). Baseline presence of cerebrovascular disease was indexed by the presence of moderate to severe white matter hyperintensities or lacunar infarct on brain MRI (yes/no), while baseline AD pathology was indexed by the presence of a positive amyloid PET scan or elevated CSF AD biomarkers (yes/no). We used linear mixed effect models to assess the effects of baseline cerebrovascular disease, baseline AD pathology, and their interactions with time in study (years post baseline) controlling for baseline age, sex, education, and baseline MoCA score.

Baseline cerebrovascular disease was significantly associated with a lower intercept on executive functioning (between-person effect) (p < -0.001, 95% CI -0.37, -0.14) but not memory, while presence of AD biomarkers was associated with a lower memory intercept (p < -0.001, 95% CI -0.52, -0.39) but not executive function. However, only presence of AD pathology at baseline was associated with faster longitudinal decline on both memory and executive functioning over time. Baseline cerebrovascular disease did not independently relate to rate of cognitive decline.

Consistent with widely held assumptions, our between-person analyses showed that MRI evidence of cerebrovascular disease was associated with worse executive functioning but not memory, while biomarker evidence of AD pathology was associated with worse memory but not executive function. Longitudinally, however, AD is the primary driver of decline in both executive and memory function. These results extend our understanding of how pathology impacts cognition in aging cohorts and highlight the importance of using longitudinal models.

Face-to-face administration is the “gold standard” for both research and clinical cognitive assessments. However, many factors may impede or prevent face-to-face assessments, including distance to clinic, limited mobility, eyesight, or transportation. The COVID19 pandemic further widened gaps in access to care and clinical research participation. Alternatives to face-to-face assessments may provide an opportunity to alleviate the burden caused by both the COVID-19 pandemic and longer standing social inequities. The objectives of this study were to develop and assess the feasibility of a telephone- and video-administered version of the Uniform Data Set (UDS) v3 cognitive batteries for use by NIH-funded Alzheimer’s Disease Research Centers (ADRCs) and other research programs.

Ninety-three individuals (M age: 72.8 years; education: 15.6 years; 72% female; 84% White) enrolled in our ADRC were included. Their most recent adjudicated cognitive status was normal cognition (N=44), MCI (N=35), mild dementia (N=11) or other (N=3). They completed portions of the UDSv3 cognitive battery, plus the RAVLT, either by telephone or video-format within approximately 6 months (M:151 days) of their annual in-person visit, where they completed the same in-person cognitive assessments. Some measures were substituted (Oral Trails for TMT; Blind MoCA for MoCA) to allow for phone administration. Participants also answered questions about the pleasantness, difficulty level, and preference for administration mode. Cognitive testers provided ratings of perceived validity of the assessment. Participants’ cognitive status was adjudicated by a group of cognitive experts blinded to most recent inperson cognitive status.

When results from video and phone modalities were combined, the remote assessments were rated as pleasant as the inperson assessment by 74% of participants. 75% rated the level of difficulty completing the remote cognitive assessment the same as the in-person testing. Overall perceived validity of the testing session, determined by cognitive assessors (video = 92%; phone = 87.5%), was good. There was generally good concordance between test scores obtained remotely and in-person (r = .3 -.8; p < .05), regardless of whether they were administered by phone or video, though individual test correlations differed slightly by mode. Substituted measures also generally correlated well, with the exception of TMT-A and OTMT-A (p > .05). Agreement between adjudicated cognitive status obtained remotely and cognitive status based on in-person data was generally high (78%), with slightly better concordance between video/in-person (82%) vs phone/in-person (76%).

This pilot study provided support for the use of telephone- and video-administered cognitive assessments using the UDSv3 among individuals with normal cognitive function and some degree of cognitive impairment. Participants found the experience similarly pleasant and no more difficult than inperson assessment. Test scores obtained remotely correlated well with those obtained in person, with some variability across individual tests. Adjudication of cognitive status did not differ significantly whether it was based on data obtained remotely or in-person. The study was limited by its’ small sample size, large test-retest window, and lack of randomization to test-modality order. Current efforts are underway to more fully validate this battery of tests for remote assessment. Funded by: P30 AG072947 & P30 AG049638-05S1

Associative memory is impacted early in Alzheimer’s disease (AD). Poorer performance on associative memory tests has been related to greater amyloid and regional tau burden in preclinical AD. Our group previously examined the association of brain pathology and performance on the Free and Cued Selective Reminding Test (FCSRT) in Autosomal Dominant Alzheimer’s Disease (ADAD), finding that associative memory summary scores distinguished non-demented mutation carriers from non-carriers several years before clinical onset of cognitive impairment. In the current study, we examined whether FCSRT learning slopes were associated with brain pathology in a sample of ADAD carriers and non-carriers.

There were 119 participants including 57 non-demented carriers of the Colombian kindred with the Presenilin1 E280A mutation and 62 non-carrier family members (mean age= 36.3, 60% female). Participants were administered the Mini-Mental State Examination (MMSE), a measure of global cognitive status, and the FCSRT, which consists of three trials in which participants are asked to freely recall the same list of 16 items. It is a well-established measure known to be sensitive to early changes in AD. A subsample of 69 participants (32 carriers and 37 non-carriers) underwent positron emission tomography (PET) to measure in vivo cortical amyloid-beta (Pittsburgh compound B, PiB), and regional tau (Flortaucipir, FTP) burden in entorhinal and precuneus regions, which are among the earliest sites of tau accumulation in this ADAD population. Mann Whitney U tests, Spearman correlations, and chi-square tests were used to examine group differences and relations among variables of interest. Learning slope was calculated by subtracting the number of items freely recalled in FCSRT Trial 1 from the number of items freely recalled in Trial 3.

Compared to non-carriers, carriers had greater cortical amyloid-ß and regional tau burden, lower MMSE scores (mean [SD]: carriers= 27.5 [2.7]; non-carriers= 28.8 [1.0]), and lower scores on total immediate/ delayed free/ cued recall scores on the FCSRT (all p<.01). The groups did not differ on age, sex, or education level (all p> 0.05). In the whole sample and in carriers only, we found that higher MMSE scores were associated with higher learning slope, meaning faster learning (whole group p= 0.25, p= 0.006; carriers p= 0.30, p=0.029). In the whole sample, we found that lower learning slope was associated with higher levels of amyloid (p=-.34, p=.006) and tau in the left, right, and bilateral precuneus region (p=-.43, p<.001; p=-.46, p<.001; p=-.45, p<.001). In carriers only, lower learning slope was associated with higher tau burden in the left, right, and bilateral precuneus specifically (p=-.43, p=.017; p=-.48, p=.008; p=-.46, p=.010, respectively). No significant associations were found in non-carriers.

These findings suggest that learning curves on an associative memory test may be sensitive to preclinical pathological changes in AD, specifically within the precuneus, a brain region known to be involved in cue reactivity, episodic memory retrieval, and mental imagery strategies. Future studies with larger samples are warranted to further examine associations between the FCSRT learning curves and regional tau accumulation in individuals with ADAD.

Laterality of motor symptom onset in Parkinson’s disease (PD) is well-known and under-appreciated. It is still unclear though if this laterality might have an influence on other symptoms. Specifically, REM sleep behavior disorder has been shown to be a factor that has a high probability to be lined to PD. In this study we analyzed the longitudinal effect of REM symptomatology on brain lateralization in PD.

We used the baseline and 3-year visit data of 116 participants (67 without REM (PD-non-REM), 49 with REM (PD-REM)) aged 37-81 years from the Parkinson’s Progression Markers Initiative (PPMI) dataset. Statistical 3T MRI data (cortical thicknesses, areas, foldings of cortical Desikan atlas and volumes of subcortical regions) were obtained via FreeSurfer 7.1.1. Lateralization was computed using the formula: (left-right)/(lef +right). Mixed ANOVAs were performed on each region of interest.

Our findings showed an increased right asymmetry of the paracentral lobule area and of the pars orbitalis area and volume in PD-REM. There was a reduced right asymmetry of the parietal inferior volume at baseline in PD-REM, whereas REM symptomatology had a stable effect at the 3 years visit. At baseline, there was an increased left asymmetry of the thickness of the caudal anterior cingulate, pars orbitalis and pars triangularis regions in PD-REM. After 3 years, there was an increased right asymmetry in those regions. The precentral, frontal superior and transversal temporal gyri showed inverse results: an increased right asymmetry of the thickness at baseline and an increased left asymmetry after 3 years. Finally, REM symptomatology is associated with more significant increases of the left asymmetry of the frontal superior gyrus volume and of the right asymmetry of the supramarginal gyrus volume after 3 years than at baseline.

These results provide evidence of the modulating effect of the disease progression on the relationship between REM symptoms and brain lateralization in PD.

Huntington’s disease (HD) is a neurodegenerative disease characterised by motor, psychiatric and cognitive decline. Currently, no treatments have been identified in HD for slowing down cognitive decline or improving cognitive function. We are interested in identifying potentially modifiable factors in HD that can be targeted to improve or maintain cognitive function. Sleep and circadian disruption stand out as possible modifiable targets because sleep and circadian symptoms are common in HD, and such disruptions are known to impact cognition in the general population. Despite some emerging evidence that sleep quality correlates with cognition in manifest HD, whether these same relationships exist in the premanifest period is unknown. Further, whether circadian rhythms relate to cognition in premanifest HD remains open. Therefore, we aimed to determine whether sleep and circadian parameters relate to cognitive performance in premanifest HD.

To date, we have recruited 27 premanifest HD participants to a two-week remote sleep study. During the study, participants wore an Actiwatch-2 and completed a sleep diary for 14 consecutive days to assess their sleep and rest-activity patterns. Participants also completed online sleep and mood questionnaires and a cognitive assessment using videoconference. We calculated Pearson correlations to examine whether cognitive performance relates to subjective sleep quality, objective sleep parameters and circadian rest-activity rhythms. Thus far, we have analysed data from 15 female participants with premanifest HD (Mage = 43.20, SD = 11.58).

Preliminary results indicate that measures of subjective sleep quality, insomnia severity, daytime sleepiness, and fatigue severity in premanifest HD do not correlate with cognitive performance. Increases in objectively measured sleep efficiency, however, strongly correlated with better performance on the Hopkins-Verbal Learning Test-Revised (HVLT-R) immediate (r = 0.562, p < 0.05) and delayed recall trials (r = 0.597, p < 0.05) and the Trail Making Test Part B (TMT-B; r = 0.550, p < 0.05). More time spent awake (i.e., wake after sleep onset) was strongly linked to reduced performance on the TMT-B (r = -0.542, p < 0.05) and Symbol Digit Modalities Test (r = -0.556, p < 0.05). Further, increases in total sleep time were associated with better performance on the HVLT-R immediate (r = 0.682, p < 0.05) and delayed recall trial (r = 0.616, p < 0.05). For our circadian parameters, less fragmented day-today rest-activity rhythms (i.e., higher intra-daily variability) strongly correlated with higher scores on the HVLT-R immediate (r = 0.768, p < 0.001) delayed recall trials (r = 0.7276, p < 0.05) and TMT-B (r = 0.516, p < 0.05), whereas consistent and stable day-to-day rest-activity rhythms (i.e., higher inter-daily stability) was associated with poorer performance on ERT (r = -0.587, p < 0.05).

Preliminary results suggest that fragmented sleep, sleep inefficiency, reduced total sleep time, rest-activity rhythm stability and fragmentation relate to poorer cognitive performance in people with premanifest HD. Should analysis of our whole sample confirm these preliminary findings, targeting sleep in HD (e.g., through sleep hygiene and/or psychoeducation) may be a useful strategy to improve or maintain cognition.