Awareness of risk factors associated with any form of impairment is critical for formulating optimal prevention and treatment planning. Millions worldwide suffer from some form of cognitive impairment, with the highest rates amongst Black and Hispanic populations. The latter have also been found to achieve lower scores on standardized neurocognitive testing than other racial/ethnic groups. Understanding the socio-demographic risk factors that lead to this discrepancy in neurocognitive functioning across racial groups is crucial. Adverse childhood experiences (ACEs), are one aspect of social determinants of health. ACES have been linked to a greater risk of future memory impairment, such as dementia. Moreover, higher instances of ACEs have been found amongst racial minorities. Considering the current literature, the purpose of this exploratory research is to better understand how social determinants, more specifically, ACEs, may play a role in the development of cognitive impairment.

This cross-sectional study included data from an urban, public Midwestern academic medical center. There was a total of 64 adult clinical patients that were referred for a neuropsychological evaluation. All patients were administered a standardized neurocognitive battery that included the Montreal Cognitive Assessment (MoCA) as well as a 10-item ACE questionnaire, which measures levels of adverse childhood experiences. The sample was 73% Black and 27% White. The average age was 66 (SD=8.6) and average education was 12.6 years (SD=3.4). A two-way ANOVA was conducted to evaluate the interaction of racial identity (White; Black) and ACE score on MoCA total score. An ACE score >4 was categorized as “high”; ACE <4 was categorized as “low.”

There was not a significant interaction of race and ACE group on MoCA score (p=.929) nor a significant main effect of ACE score (p=.541). Interestingly, there was a significant main effect of Race on MoCA (p=.029). White patients had an average MoCA score of 21.82 (sd=4.77). Black patients had an average MoCA score of 17.54 (sd=5.91).

Overall, Black patients demonstrated statistically lower scores on the MoCA than White patients. There was no significant difference on MoCA score between races when also accounting for ACE scores. Given this study’s findings, one’s level of adverse childhood experiences does not appear to impact one’s cognitive ability later in life. There is a significant difference in cognitive ability between races, specifically Black and White people, which suggests there may be social determinants other than childhood experiences to be explored that influence cognitive impairment.

Parkinson’s disease (PD) is a neurodegenerative disorder affecting over 10 million people worldwide. PD is characterized by both motor (e.g., tremor, rigidity, and bradykinesia) and non-motor (including cognitive impairment and neuropsychiatric symptoms such as apathy, disinhibition, executive dysfunction) symptoms. Caregiver burden is prevalent in those providing care for patients with PD and can result in negative health complications. Past work shows associations between motor symptoms, cognitive impairment, neuropsychiatric symptoms, and caregiver burden in PD. However, their relative contributions are poorly understood. This study examined these relationships, hypothesizing that while motor symptoms, cognitive impairment, and neuropsychiatric symptoms would all affect caregiver burden, neuropsychiatric symptoms would predict burden above and beyond the contribution of the other factors

Participants were 42 people living with PD who were assessed at a hospital-based tertiary movement disorders specialty clinic for deep brain stimulation (DBS) candidacy evaluation with their caregiver. Motor exam was assessed by a PD specialist using the Unified Parkinson’s Disease Rating Scale (UPDRS). The Mini Mental State Examination (MMSE) assessed global cognition. Frontal Systems Behavior Scale (FrSBe) Family Form captured caregiver ratings of neuropsychiatric symptoms under 3 subscales: apathy, disinhibition, and executive dysfunction. The Multidimensional Caregiver Strain Index (MCSI) captured caregiver burden. Linear regression analyses examined relationships between caregiver burden (MCSI) and motor symptoms (UPDRS), cognitive impairment (MMSE), and neuropsychiatric symptoms (FrSBe).

Using linear regression analyses, cognitive impairment (R2=0.08, F(1,41)=4.42, p=0.04) and neuropsychiatric symptoms (R2=0.35, F(1, 41)=21.0, p<0.01) predicted caregiver burden but motor symptoms did not (R2=0.03, F(1,41)=1.30, p=0.26). Hierarchical linear regression revealed that neuropsychiatric symptoms predicted caregiver burden above and beyond the contribution of cognitive impairment (AR2=0.28, AF(1)=12.7, p=0.001), accounting for an additional 28% of the variance in caregiver burden. Follow-up linear regression to examine the relationships between caregiver burden and the FrSBe subscales indicated that apathy (p<0.001), versus disinhibition (p=0.16) and dysexecutive behaviors (p=0.80), was the driver of the significant relationship.

Consistent with our hypothesis, results revealed that cognitive impairment and neuropsychiatric symptoms (specifically apathy) were independent predictors of caregiver burden, with neuropsychiatric symptoms predicting caregiver burden above and beyond the contribution of cognitive impairment. Somewhat surprisingly, motor symptoms were not a predictor of caregiver burden contrary to some previous research, though findings are mixed. Results highlight the importance of assessing for neuropsychiatric symptoms in PD, which may be overlooked by care providers relative to motor or cognitive symptoms, but which appear stressful to caregivers. Future directions include reexamining results in a larger more heterogenous sample including people living with PD at different disease stages (i.e., everyone in the present sample had severe enough symptoms to be considering DBS). Cognitive measures of executive functioning (which are more specific to PD than measures of global cognition) should also be included in future works. Development of supportive caregiver interventions specifically targeting apathy in PD may be useful. Longitudinal designs would be helpful to reexamine relationships following DBS surgery, as there are some reports of increased neuropsychiatric symptoms following the procedure.

Fatigue, which can be classified into physical and cognitive subtypes (Schiehser et al., 2012), is a common non-motor symptom in persons with Parkinson’s disease (PD) that has no clear treatment. Cognitive changes, also common in PD (Litvan et al., 2012), may impact how patients perceive fatigue (Kukla et al., 2021). Grit is a personality trait defined as perseverance and passion towards a long-term goal, and is associated with multiple positive outcomes such as lower fatigue levels in healthy individuals (Martinez-Moreno et al., 2021). However, scarce research has examined the relationship between grit and fatigue in persons with PD. Therefore, we aimed to investigate the relationship between fatigue (cognitive and physical) and grit, as well as the impact of cognitive status (i.e., cognitive normal vs. mild cognitive impairment [MCI]) on this relationship in non-demented individuals with PD.

Participants were 70 non-demented individuals with PD who were diagnosed as either cognitively normal (n=20) or MCI (n=50) based on Level II of the Movement Disorder Society PD-MCI criteria. Participants completed the Modified Fatigue Impact Scale (MFIS), which consists of two subscales (cognitive and physical fatigue) that are combined for a total overall fatigue score. Participants also completed the Grit Scale, which consists of items such as ambition, perseverance, and consistency. ANOVAs were conducted to determine differences in grit between PD-cognitively normal vs PD-MCI groups. Correlations and multiple hierarchical regressions controlling for significant demographics (i.e., age, education, sex), mood (i.e., depression, anxiety) and disease variables (i.e., disease duration, Levodopa equivalent dosage) with backwards elimination were conducted to evaluate the relationship between grit and fatigue (MFIS total score and MFIS cognitive and physical fatigue subscales).

There was no significant difference in grit total scores between PD patients who were cognitively normal or MCI (p = .336). Higher grit total scores predicted lower MFIS total (ß = -.290, p = .005) and lower cognitive fatigue (ß = -.336, p < .001) scores in the total sample, above and beyond relevant covariates as well as cognitive status. Grit scores were not significantly associated with physical fatigue (ß = -.206, p = .066). Furthermore, cognitive status was not a significant predictor of fatigue scores in any of the models (all p’s > .28).

Findings indicate that higher levels of grit are associated with lower levels of fatigue, specifically cognitive fatigue, in individuals with PD. These results held true for those who were cognitively normal or with MCI, suggesting that grit may impact fatigue in non-demented PD patients regardless of cognitive status. These findings underscore the importance of considering grit when assessing or treating fatigue, particularly cognitive fatigue, in persons with PD.

Cognitive impairment in Parkinson's disease (CIPD) is present in approximately 40% of patients. Language deficits, evidenced by poor word- retrieval, have historically characterized memory weaknesses in PD. That is, the "retrieval deficit hypothesis," suggests successful memory encoding, but poor retrieval subsequent to language and executive dysfunction, another prominent area of CIPD. However, recent studies suggest that memory impairments in PD are instead at the level of learning. At present, several suggested etiologies to explain learning impairments in PD exist that are not related to language, for example that processing speed deficits (another characteristic of CIPD) impact learning; however, other studies present evidence against this theory. Therefore, we hypothesize that deficits in language continue to be a primary component of memory impairment in PD, but at the level of learning rather than retrieval

85 adults (age M = 61.54, SD = 10.00; %female = 26.7; Dementia Rating Scale M = 137.77, SD = 5.63) diagnosed with Parkinson's disease according to the UK Brain Bank criteria for idiopathic PD, completed a neuropsychological test battery when "off" levodopa medication. The battery included the Boston Naming Test (BNT), verbal fluency tests (Controlled Oral Word Association [COWA] and category fluency), the California Verbal Learning Test, 2nd Edition (CVLT-II), and the Oral Symbol Digit Modalities Test (SDMT). Separate linear regression models were used to examine BNT, COWA, category fluency, and SDMT performance as predictors of total learning (sum of trials 1-5), short-delay free recall, long-delay free recall, and recognition discriminability on the CVLT-II. Analyses were adjusted for age, sex, education, and disease severity (MDS-Unified Parkinson's Disease Rating Scale, part 3 score). Follow up analyses adjusted for processing speed (oral SDMT).

Adjusted linear regression models revealed that both verbal fluencies predicted verbal learning (letter: ß = .37, p < .01; category: ß = .45, p < .01), long-delay free recall (letter: ß = .25, p = .05; category: ß = .34, p = .01), and recognition discriminability (letter: ß = .36, p = .02; category: ß =.33, p = .03) on the CVLT-II. Confrontation naming significantly predicted only long-delay free recall (ß =.31, p = .01). Processing speed predicted verbal learning (ß = .51, p < .01), short-delay free recall (ß = .35, p = .03), and long-delay free recall (ß = .44, p < .01). After adjusting for processing speed, letter fluency significantly predicted learning (ß = .23, p = .05) and discriminability (ß = .33, p = .04). Category fluency significantly predicted learning only (ß = .28, p = .04). Finally, confrontation naming significantly predicted only long-delay free recall (ß= .28, p = .01).

While processing speed was associated with verbal learning and recall, components of language predicted variance in verbal learning in PD that was not accounted for by speed. Additionally, discriminability was related to aspects of language that are more reliant on executive functioning. It is therefore suggested that verbal memory in PD is interpreted within the context of one's language ability. Other potential mechanisms and clinical implications are discussed.

During the COVID-19 pandemic the Oral Trail Making Test (O-TMT) was frequently used as a telehealth-compatible substitute for the written version of the Trail Making Test (W-TMT). There is significant debate among neuropsychologists about the degree to which the O-TMT measures the same cognitive abilities as the W-TMT (i.e., processing speed for part A and set-shifting for part B). Given the continued use of the O-TMT - especially for patients with fine-motor or visual impairments -we examined how O-TMT and W-TMT scores were correlated in patients with movement disorders.

Between April 2021 and July 2022 thirty individuals with movement disorders (n=27 idiopathic Parkinson’s disease [PD]; n=1 drug-induced PD; n=1 progressive supranuclear palsy [PSP]; n=1 possible PSP) completed in-person neuropsychological evaluations at the Emory Brain Health Center in Atlanta, GA. The patients were on average 71.3 years old (SD=7.5 years), had 16 years of education (SD=2.8 years), and the majority were non-Hispanic White (n=27 White; n=3 African American) and male (n=17). In addition to other neuropsychological measures, these patients completed both the O-TMT and the W-TMT. O-TMT and W-TMT administration was counterbalanced across patients and took place thirty-minutes apart. Raw scores (i.e., time in seconds) to complete O-TMT and W-TMT part A and part B, as well as discrepancy scores (part B - part A), were used for statistical analysis; a raw score of 300 seconds was assigned when a participant could not complete that section of the O-TMT or W-TMT. Given the non-normal distribution of the data, Spearman correlations were performed between O-TMT and W-TMT scores.

Ten patients were unable to perform W-TMT part B. Of these, seven patients could also not perform O-TMT part B. Part A scores on O-TMT and W-TMT were not significantly correlated (rs = 0.27, p = .15). In contrast, part B scores were strongly correlated, such that slower performances on O-TMT part B corresponded with slower performances on W-TMT part B (rs = 0.82, p < .001). Discrepancy scores for the O-TMT and W-TMT were also significantly correlated, such that larger part A and part B discrepancy scores on O-TMT corresponded with larger discrepancy scores on W-TMT (rs = 0.78, p <.001). The pattern of results was replicated when examining these correlations only in patients who could complete all parts of O-TMT and W-TMT (n=19); part A scores of the O-TMT and W-TMT were again not correlated (rs = -0.20, p = .41), whereas the part B scores (rs = 0.54, p = .02) and discrepancy scores (rs = 0.59, p = .008) were significantly correlated.

Results suggest that an oral version of the Trail Making Test shows promise as an alternative to the written version for assessing set shifting abilities. These findings are limited to patients with movement disorders, and future research with diverse patient populations could help determine whether O-TMT can be generalized to other patient groups. Additionally, future research should examine whether O-TMT scores obtained via virtual testing correspond with W-TMT scores obtained in-person.

Parkinson’s disease (PD) is typically characterized by unilateral onset of motor symptoms (i.e., tremors, rigidity) which is caused by dopaminergic degeneration of the substantia nigra that influences basal ganglia-prefrontal circuitry. Over time, motor symptoms become more bilateral, though continue to remain asymmetric. Many neuropsychological studies suggest that laterality of motor onset may be linked to hemispheric specific cognitive or mood changes. Namely, worse verbal/language performance may be present in individuals with right body (left hemisphere) onset and conversely for visuospatial performance, with depression symptoms relating more so to individuals with right body (left hemisphere) onset. To date, findings are often inconsistent, with some studies showing evidence for laterality effects and others not. The basis for this inconsistency is unclear, though one possibility relates to small sample sizes and varying methodologies. Thus, the goal of this study was to examine potential cognitive and mood laterality effects in a large clinical sample of individuals with PD.

Participants included a convenience sample of 600 nondemented individuals with idiopathic PD from the University of Florida Fixel Institute Movement Disorders Center. As a group, participants were around 60 years of age (Mean Age=63.9+9.4), well educated (Mean years=14.9+2.7), predominantly male (70%), and white non-Hispanic (93%). Side of initial motor symptom onset was based on self-report: Right (N=337) and Left (N=263). Approximately 79% were tremor predominant. All received mood and neurocognitive measures as part of standard clinical care, including indices of executive function (Stroop Color-Word, Trails B, Letter Fluency), recent verbal memory (delayed recall: Hopkin’s Verbal Learning Test, WMS-III Logical Memory), language (Boston Naming Test, Animal fluency), visuospatial skills (Judgment of Line Orientation, Facial Recognition Test). Evaluation of emotion symptoms included: depression (Beck Depression Inventory-II), apathy (Apathy Scale), and anxiety (State-Trait Anxiety Inventory). Analyses used raw scores from these measures. Due to non-normality of most measures’ distributions, laterality effects were examined using bootstrapped multivariate methods (multivariate analysis of variance [MANOVA]). Separate MANOVA’s were run for each cognitive domain (i.e., EF, language, etc.) and mood measures.

The right and left sided onset groups did not significantly differ in demographic (age, education, sex) or disease characteristics (duration, PD subtype). Results of the MANOVA’s with cognitive variables were all nonsignificant broadly (all with F’s ranging from .33 to .94) and at the single test level. Similarly, the left and right onset groups did not significantly differ (a=0.05) across standard scales of depression (F=0.031), anxiety (Trait F=0.463; State F=3.29), and apathy (F=0.74).

We found no evidence that laterality of initial motor symptoms influenced cognitive or mood symptoms in a large cohort of 600 individuals with PD. These findings raise questions about importance of motor onset laterality for cognitive and emotion related changes in PD. Future studies should move beyond self-report and behavioral motor scales for determining hemispheric contributions. In PD, use of refined metrics for determining the extent of asymmetric dopaminergic degeneration (e.g., DAT scan) at the hemispheric level coupled with sensitive neuropsychological measures may provide clearer understanding of potential neural circuitry relationships.

Subjective cognitive complaints are common in individuals with Parkinson’s disease and Essential Tremor. One scale often used to capture the type and severity of subjective cognitive concerns is the Cognitive Change Index-20 (CCI-20). Created by Saykin et al (2006), the CCI-20 is a questionnaire that assesses perception of cognitive changes in memory, executive function, and language domains. Despite its multidomain structure, previous research has not empirically examined whether the CCI-20's underlying factor structure aligns with the cognitive domains proposed during its original development. Thus, the goal of the current study was to investigate the factor structure of the CCI-20 in individuals with movement disorders (Parkinson’s disease, Essential Tremor) who are known to experience varying degrees of cognitive sequelae as part of their disease progression.

Participants included a convenience sample of 216 non-demented individuals with Parkinson disease (n=149) or Essential Tremor (n=67) who were seen at the University of Florida Fixel Institute Movement Disorders Center. All received the CCI-20 as part of a neuropsychological evaluation. The CCI-20 consists of 20 items, rated on a 5-point Likert scale, that ask questions about change in memory (12 items), executive function (5 items), and language (3 items) over the past 5 years. An exploratory factor analysis was conducted on CCI-20 scores using Promax rotation with factor extraction based on scree plot visual inspection and Kaiser’s rule (eigenvalues >1.0). Cronbach’s alpha was used to assess internal consistency reliability. Finally, Spearman correlations determined associations between factors and mood measures of depression (Beck Depression Inventory-II, BDI-II), apathy (Apathy Scale, AS), and anxiety (State-Trait Anxiety Inventory, STAI).

Because the Parkinson’s disease and Essential Tremor groups did not statistically differ in their CCI-20 total scores, they were combined into a single group for analyses. This resulted in 216 participants who were well-educated (m=15.01±2.92), in their mid-60's (m=67.72±9.33), predominantly male (63%), and non-Hispanic White (93.6%). The factor analysis resulted in 3 factors: factor 1 included 8 memory items (items 1-4, 6, 10-12; loadings from .524 to .920); factor 2 included all executive and language (items 13-20; loadings from .605 to .824), and factor 3 included four remaining memory items (items 5, 7-9; loadings from .628 to .810). Reliability of the 20 CCI items was good (a = .94), and reliability within each factor ranged from adequate (Factor 3, a = .78) to good (Factors 1 and 2, a = .90). All factors showed significant weak to moderate associations with BDI-II, AS, and STAI (state and trait) scores.

The CCI-20 revealed three distinct dimensions of subjective cognitive complaints that did not correspond to the memory, executive function, and language domains. Rather, the CCI-20 was decomposed into two different dimensions of memory complaints and one dimension of non-memory complaints. Mood symptoms played a significant role in driving all dimensions of subjective cognitive complaints. Future studies should confirm this triadic structure in a healthy older adult sample and explore the relationship between factors and objective cognitive performance beyond the contribution of mood. T32-AG061892; T32-NS082168

Individuals with Parkinson's disease (PD) have varying trajectories of cognitive decline. One reason for this heterogeneity may be "cognitive reserve": where higher education/IQ/current mental engagement compensates for increasing brain burden (Stern et al., 2020). With few exceptions, most studies examining cognitive reserve in PD fail to include brain metrics. This study's goal was to examine whether cognitive reserve moderated the relationship between neuroimaging indices of brain burden (diffusion free water fraction and T2-weighted white matter changes) and two commonly impaired domains in PD: executive function and memory. We hypothesized cognitive reserve would mitigate the relationship between higher brain burden and worse cognitive performance.

Participants included 108 individuals with PD without dementia (age mean=67.9±6.3, education mean=16.6±2.5) who were prospectively recruited for two NIH-funded projects at the University of Florida. All received neuropsychological measures of executive function (Trails B, Stroop, Letter Fluency) and memory (delayed recall: Hopkin's Verbal Learning Test-Revised, WMS-III Logical Memory). Domain specific z-score composites were created using data from age/education matched non-PD peer controls (N=62). For the Cognitive Reserve (CR) proxy, a z-score composite included years of education, WASI-II Vocabulary, and Wechsler Test of Adult Reading. At the time of testing, participants completed multiple MRI scans (T1-weighted, diffusion, Fluid Attenuated Inversion Recovery) from which the following were extracted: 1) whole-brain free water within the white matter (a measure of microstructural integrity and neuroinflammation), 2) white matter hyperintensities/white matter total volume (WMH/WMV), and bilaterally-averaged edge weights of white matter connectivity between 3) dorsolateral prefrontal cortex and caudate and 4) entorhinal cortex and hippocampi. Separate linear regressions for each brain metric used executive function and memory composites as dependent variables; predictors were age, CR proxy, respective brain metric, and a residual centered interaction term (brain metric*CR proxy). Identical models were run in dichotomized short and long disease duration groups (median split=6 years).

In all models, a lower CR proxy significantly predicted worse executive function (WMH/WMV: beta=0.49, free water: beta=0.54, frontal edge weight: beta=0.49, p's<0.001) and memory (WMH/WMV: beta=0.42, free water: beta=0.35, temporal edge weight: beta=0.39, p's <0.01). For neuroimaging metrics, higher free water significantly predicted worse executive function (beta=-0.39, p=0.002) but not memory. No other brain metrics were significant predictors of either domain. Accounting for PD duration, higher free water predicted worse executive function for those with both short (beta=-0.49, p=0.04) and long disease duration (beta=-0.48, p=0.02). Specifically in those with long disease duration, higher free water (beta=-0.57 p=0.02) and lower edge weights between entorhinal cortex and hippocampi (beta=0.30, p=0.03) predicted worse memory. Overall, no models contained significant interactions between the CR proxy and any brain metric.

Results replicate previous work showing that a cognitive reserve proxy relates to cognition. However, cognitive reserve did not moderate brain burden's relationship to cognition. Across the sample, greater neuroinflammation was associated with worse executive function. For those with longer disease duration, higher neuroinflammation and lower medial temporal white matter connectivity related to worse memory. Future work should examine other brain burden metrics to determine whether/how cognitive reserve influences the cognitive trajectory of PD.

Hand and arm functions have been associated with cognition in healthy young and older adults (Vasylenko et al., 2018) and in patients with Parkinson's disease (Bezdicek et al., 2014). Music training has been proposed to integrate motor and cognitive functions by engaging motoric, sensory, perceptual, and various cognitive domains (Wan & Schlaug, 2010). In this study, we examined if performance on fine and gross motor tasks is predicted by cognitive measures of memory, attention, and executive functions, and whether this relationship varies by the extent of musical training in healthy young participants.

Forty five healthy young participants were recruited (M = 22.32, SD = 4.10; 78% female). Participants completed fine (Grooved pegboard) and gross motor (Box and Blocks) measures as well as cognitive measures (Rey auditory verbal learning test, Stroop, Trail making, and D2 cancellation), and the musical training subscale of the Goldsmith Musical Sophistication Index. Two multiple regression models were conducted assessing cognitive measures as predictors of fine and gross motor functions, with musical training as a covariate in both models.

Musical training was normally distributed across participants (M = 23.47, SD = 10.28). The results of the first model assessing the role of cognitive measures as predictors of fine motor function indicate a moderate fit (F(5,36) = 3.32, R = 0.55, explaining .32 of variance, p < .05), with memory (B = 2.75, SE = 0.82, p < .005) and sustained attention (B = 0.09, SE = 0.03, p < .01) as moderate predictors. These cognitive measures were also found to predict gross motor function (F(5,36) = 3.06, p < .05, R = 0.55, explaining .30 of the variance), with memory retention (B = 2.49, SE = 0.83, p < .001) and sustained attention (B = 0.07, SE = 0.03, p < .05) as moderate predictors. In both models, musical training was not a significant predictor.

We found that both fine and gross hand motor functions are predicted by cognitive measures of memory retention and sustained attention. Our results support previous findings associating cognition and motor function, with attention being relevant in young adults and memory a predictor in older adults (Vasylenko et al., 2018). We corroborate these findings for hand function, but did not find executive functions to be implicated, which were previously reported as a predictor only for older adults. While musical training has been suggested to enhance the cognitive-motor relationship as it involves motor skills as well as engages various cognitive domains (Wan & Schlaug, 2010), prior musical training was not found to affect this relationship. While music background did not predict better hand motor function, it did account for more interpersonal variance. The results suggest that for most amateur musicians, including those with years of experience, musical training may not affect the association between cognition and both fine and gross hand motor skill. The current findings indicate that while musical training can be an enriching experience, it may not (exclusively) enhance motor-cognitive integration. Different outcomes may be found with more extreme levels of music training, or a different age group.

Cognitive decline is a common non-motor feature of Parkinson's disease (PD). However, the underlying mechanisms of cognitive impairment in PD require further elucidation. FDG PET imaging data analyses have revealed distinct brain metabolic patterns associated with the cognitive features of PD. The PD cognition-related pattern (PDCP) and default mode network (DMN) are two overlapping, but topographically distinct, networks that may serve as biomarkers of cognitive decline in PD. Decreased activity of the resting-state DMN and increased expression of the PDCP are associated with cognitive impairment in PD. Studies have consistently demonstrated the association between neuropsychological memory test performance and PDCP expression. Thus, we examined whether memory performance could offer additional value in predicting PDCP expression in PD patients. We hypothesized that DMN and memory performance would predict greater variance in PDCP expression than the DMN alone.

Participants included 48 PD patients ages 46-80 (mean (SD) Age: 61.9 (8.1), Education: 15.0 (2.8), IQ: 112.5 (14.9), DRS total: 136.7 (5.8)). All participants completed the FDG PET and neuropsychological evaluation 8-12 hours after their last dose of Levodopa. Neuropsychological memory testing included the California Verbal Learning Test (CVLT) z score of sum of learning trials. PDCP and DMN values were z scores generated from normal controls in previous studies. Data were analyzed using linear regression analyses.

A hierarchical regression was performed to predict PDCP as a function of DMN and CVLT learning performance. Variables were entered in two separate blocks. The first block included DMN as a predictor, and the overall regression was significant (R2 = 0.55, F(1, 39)= 47.0, p < 0.001). As hypothesized, DMN significantly predicted PCDP expression (β= -0.74, p < 0.001). The second block of the regression included CVLT learning memory performance. Both DMN and CVLT performance explained a significant amount of variance in PDCP (R2 change = 0.05, F(2, 39)= 27.6, p < 0.001). CVLT performance significantly predicted PDCP (β= -0.22, p =0.048). The final model accounted for 60.0% of the variance inPDCP.

Disruptions in functional connectivity within brain networks have become increasingly recognized as mechanisms responsible for cognitive impairment in patients. As demonstrated in previous studies, our results indicated that DMN loss is a strong predictor of PDCP expression, likely due to the networks' overlapping spatial regions. However, we found that the addition of memory performance to the model could explain a small amount of variance (5%) over and above DMN expression. Overall, the current findings demonstrate a functional (i.e., learning) distinction between population-specific (PDCP) and more general brain networks (DMN).

Cardiovascular risk factors and white matter hyperintensities predict the progression and severity of cognitive symptoms in PD. While controversial, emerging evidence suggests that cerebrovascular dysfunction is an etiological driver of protein aggregation in neurodegenerative conditions, highlighting a need to understand how cerebrovascular function impacts cognitive function in PD. MRI cerebrovascular reactivity (CVR) paradigms provide an opportunity to measure the ability of the cerebral vessels to dilate or constrict in response to challenges. The current study evaluates whether whole brain CVR measures, degree of response (fit) and delay differ in PD with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) relative to healthy controls (HC). Additionally, we evaluate if these metrics are associated with cognitive performance.

8 PD-NC, 11 PD-MCI and 11 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task force, Level II assessment (comprehensive assessment). Participants were asked to inhale gas enriched in CO2 to elicit a vasodilatory response while undergoing bold oxygen level-dependent magnetic resonance image (MRI). Whole brain fit to an end-tidal CO2 regressor and delay were used to quantify CVR in each participant. An analysis of covariance (ANCOVA) was used to evaluate group differences between HC, PD-NC, and PD-MCI in the whole brain fit and delay CVR measures accounting for age, sex, and education. Multiple regressions were conducted for each cognitive variable with whole brain fit and delay as the dependent variables adjusting for age, sex, and education.

A significant main effect of group was observed for whole brain CVR latency (F(2, 23) = 4.227; p = 0.027). Post hoc tests were not significant, though indicated a trend that PD-NC (18.14 ±1.94) and PD-MCI (18.15 ± 1.55) patients exhibited longer delays relative to HC (15.84 ± 2.37). Regression results indicated limited relationships between CVR measures and cognitive functioning.

PD patients (PD-NC and PD-MCI) exhibited longer CVR delays relative to HC, suggesting a delayed vasodilatory response in PD. Examination of the association between CVR metrics and cognition were not significant, though these results should be interpreted with caution given the small sample size.

Deep Brain Stimulation (DBS) is an FDA-approved treatment for Parkinson's Disease (PD), for which the medical workup includes routine pre- and post- operative neuropsychological assessment to determine potential surgical cognitive risk. Existing research suggests that cognitively normal individuals experience good cognitive outcome, whereas those with pre-existing cognitive deficits are prone to accelerated cognitive decline post-DBS. The goal of this study is to identify characteristics that determine which individuals with PD are at risk for accelerated post-DBS cognitive loss, and to characterize the nature of the decline in this population.

We conducted a retrospective chart review of PD- DBS patients who completed their DBS workup and surgery at Mount Sinai Hospital NYC between 2015 and 2022. Non-English speakers were excluded from this study due to small sample size and use of a neurocognitive battery different from that of English speakers. Using repeated measures t-tests, chi square, and regression analyses, we explored variables related to disease (e.g., duration, L-Dopa burden, DBS target), socio-demographic background (e.g., age onset, current age, education), assessment modality (telehealth vs in-office), neurocognitive performances (e.g., WMS-IV Logical Memory (LM), HVLT-R, WASI-II Matrix & Similarities, WAIS-IV Digit Span), and cognitive diagnosis (amnestic vs non-amnestic MCI) for all individuals in the sample. At the individual level, we utilized Reliable Change Indices (RCI) to identify clinically significant cognitive differences from pre- to post-DBS exam. We considered LM- Delayed Recall (LMDR) as a proxy for memory loss, as this cognitive function is expected to remain generally unchanged post PD-DBS. Therefore, decline on this measure in the first year after DBS could indicate a change in global memory function and possible evidence of accelerated postoperative decline.

Of 65 charts reviewed, 44 patients were native English-speaking and included in our analyses. At the group level, there were no significant differences in disease characteristics, socio-demographic variables, or cognitive classification between those who declined versus those who did not decline on LMDR. Regression statistics for predictors of cognitive decline also were non-significant. Of the eight individuals who declined on LMDR, one patient declined on a total of one neuropsychological measure, four declined on a total of two measures, two declined on a total of three measures, and one declined on a total of four measures. Two of these eight individuals had a diagnosis that changed to amnestic MCI based on concomitant interval history of ADL compromise. Of these two individuals, one declined in two tests and the other declined in four tests. Six of the eight individuals who declined also showed abnormalities in their imaging with either edema or hemorrhage.

Our analysis is unique in that we explored cognitive decline at both the group and individual levels. Despite this, we did not find predictors of post-DBS cognitive decline. Further detailed analysis of additional post-operative factors that might play a greater role in our understanding of this phenomenon is warranted. This said, our data do support that the majority of individuals with non-amnestic MCI did not decline cognitively.

To evaluate changes in neuropsychiatric symptoms among patients with multiple sclerosis (MS) following coronavirus disease of 2019 (COVID-19) infection using the National COVID Cohort Collaborative (N3C). The N3C represents the largest cohort of COVID-19 cases, through the unification of electronic health records from over 60 medical centers.

Out of 5,631,225 COVID-19 confirmed positive patients, we identified a cohort of patients with MS who were diagnosed with COVID-19. Conditions were searched using terms denoting common neuropsychiatric comorbid diagnoses, including anxiety, depression, pain, sleep disorders, fatigue, and cognitive disorders. We examined descriptively the percentages of patients who were newly diagnosed with each comorbid condition after COVID-19 infection. Additionally, we searched for various patient-reported outcome measures in the N3C dataset; only the Patient Health Questionnaire-9 (PHQ-9) had an adequate sample size in our cohort for analysis. To control for variability due to non-COVID-19 factors, we only included PHQ-9 scores that were reported one year before and after COVID-19 infection. A repeated-measures analysis of variance (ANOVA) was conducted to analyze the difference between PHQ-9 scores before and after COVID-19 diagnosis among MS patients.

In our final dataset, there were 40,690 patients who were diagnosed with MS and COVID-19. Among patients without pre-existing anxiety conditions, 9.18% were diagnosed with an anxiety disorder after COVID-19 infection. Among those who did not have a pre-existing cognitive disorder, 1.73% had such diagnoses after COVID-19 infection. Among those without previous depressive disorders, 8.89% were diagnosed with a depressive disorder after COVID-19 infection. Of those without fatigue conditions prior to COVID-19 in their medical records, 8.81% had documented fatigue in their records after contracting COVID-19. Of those without pain conditions in their medical records, 11.37% had documented pain in their records after COVID-19 infection. Finally, among patients without pre-existing sleep disorders, 8.71% were diagnosed with sleep disorders after COVID-19 infection. Regarding PHQ-9 scores, 50 patients had documented scores before their COVID-19 diagnosis and 50 after COVID-19 diagnosis (17 had scores for both before and after COVID-19 diagnosis). There was no significant difference in PHQ-9 scores before and after COVID-19 diagnosis (F(df) = 0.326, p = 0.572; meanbefore = 8.77, meanafter = 9.32).

Approximately 2-11% of MS patients developed new neuropsychiatric conditions after COVID-19 infection, with pain being the most common, followed by anxiety, fatigue, depression, and sleep disorders. Cognitive disorders were the least prevalent new onset neuropsychiatric sequelae of COVID-19 in this cohort. Additionally, there was a non-significant increase in severity of depressive symptoms, as indicated by a 1.36-point increase in PHQ-9 scores. These results suggest that patients with MS who have also been diagnosed with COVID-19 may be at risk for developing newly onset neuropsychiatric symptoms.

Pediatric acquired demyelinating syndromes (PADS) include a heterogeneous group of diagnoses, including acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), optic neuritis (ON) and transverse myelitis (TM). Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is often associated with demyelinating conditions, but may also present with encephalopathy without demyelinating lesions. Approximately 30% of patients diagnosed with MOGAD experience a relapse. Neurocognitive outcomes in PADS have reduced performance on tasks related to attention, processing speed, visual motor, and fine motor functioning. Psychosocial problems include anxiety, depression, and fatigue. Neurocognitive and psychosocial impacts of MOGAD events for the pediatric population are sparse. The current study sought to characterize neurocognitive sequelae from MOGAD (MAGAD+) compared to patients diagnosed withPADS without MOGAD (MOGAD-).

Twenty children and adolescents (6–18 years) diagnosed with PADS were recruited using a clinic convenience sample of patients. Study participants completed a neurocognitive battery and parents completed questionnaires of behavioral and emotional functioning. Demographic and medical variables were collected via retrospective chart review. Chi square and t-test analyses were used to compare MOGAD+ and MOGAD- groups. Performance on neuropsychological and behavioral questionnaires were compared to established sex and age norms to assess the degree to which group means deviate from normative expectations.

MOGAD+ and MOGAD- groups did not significantly differ based on demographic, neurocognitive, or parent reported social and behavioral functioning. Neurocognitive testing documented mean scores that were in the average range between groups. Notable variability in performance was observed within both MOGAD+ and MOGAD- groups. Bilateral fine motor deficits, visual motor, visual perception attention, and executive functioning deficits were notable for the combined PADS group, with 30-50% performing >1.5 SD below the mean. The number of white matter lesions or hospital duration were not significantly associated with performance on neurocognitive measures. However, older age of onset of PADS was significantly correlated with lower performance on visual motor integration and visual perception tasks (r(18) = -.50 p = .026; r(18) = -.53 p = .016). Findings also revealed associations of shorter hospitalization stays with higher behavioral symptoms on a parent measure of social/behavioral functioning (r(18) = -.47 p = .037).

Consistent with the PADS literature, relative to control norms, lower performance on tasks related to attention, executive functioning, visual motor, and fine motor skills, irrespective of MOGAD status, are observed in the current study. The variability of functioning and heterogeneity observed across PADS diagnoses warrants further study to better understand the impact of clinical course, treatment outcomes, and neuropsychological sequelae over time in this population. Higher behavioral distress with shorter hospital stays may indicate a potential opportunity for patient and family education preparing for return to home/community. The current study was limited by small sample size, variable time since hospitalization, and heterogeneous diagnoses within PADS that make it difficult to generalize findings. Future studies could prospectively follow patients over time to better understand the trajectory of recovery, identify predictors for relapse, and those at greatest risk of neurocognitive and behavioral deficits.

Social support is an emerging protective factor against cognitive decline. However, the relationship between social support and cognitive functioning in the multiple sclerosis (MS) population is not well understood. The present study aimed to investigate the associations between different aspects of social support and cognitive performance among persons with MS.

A volunteer sample of 63 persons with MS (% female = 88.9, mean age = 48.16) completed measures assessing perceived levels of social support measured by the Medical Outcomes Study Support Social Survey 5-item short form (MSSS-5), and social network (social network diversity and total size of social network) measured by the Social Network Index (SNI). Cognitive functioning was assessed by a brief virtual examiner-administered neuropsychological test battery (using a teleconferencing platform), including the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test, animal naming, and the Symbol Digit Modalities Test. Participants also completed brief, self-paced, virtual cognitive tests through the testmybrain.org platform, which consisted of digit span and the Trail-Making Test. A principal component analysis (PCA) was carried out to reduce the number of neuropsychological outcomes into fewer dimensions. Multiple linear regressions were conducted to examine the associations between social support measures and cognitive performance. Regression models were adjusted by the levels of depressive symptoms (operationalized by the Chicago Multiscale Depression Inventory or the Hospital Anxiety and Depression Scale) and premorbid functioning (measured by the Test of Premorbid Functioning).

A PCA reduced neuropsychological outcomes into 3 components representing cognitive domains of 1) processing speed/executive functioning, 2) verbal memory, and 3) verbal fluency / simple attention. In the unadjusted models, both perceived social support (i.e., to what extent one receives assistance from their social network) as well as total size of social network (i.e., total number of people one regularly talks to) were significant predictors of the processing speed/executive functioning component score of moderate strength, where F(1, 59) = 11.93, p = .001, β = 0.41 and F(1, 59) = 11.57, p = .001, β = 0.41, respectively. These associations were maintained after adjusting for depressive symptoms and level of premorbid functioning (F(4, 55) = 3.31, p = .003 and F(4, 55) = 3.31, p = .006, respectively). On the other hand, social network diversity (i.e., number of different types of close social relationships one has) was not a significant predictor of the processing speed/executive functioning component score (p > 0.05). None of the social support measures were significantly associated with the verbal memory and verbal fluency/simple attention component scores.

Greater social support (specifically, perceived levels of assistance and total size of social network) is associated with better performance on processing speed/executive functioning measures among persons with MS, independent of effects from depressive symptoms and premorbid functioning. Maintaining a strong social support network may be an important factor in optimizing cognitive health in MS.

Multiple Sclerosis (MS) affects up to 500,000 adults in the United States, with cognitive impairment present in 45%-65% of people. Studies showed hippocampal atrophy in MS, but the underlying mechanisms remain unknown. Inflammation has been proposed to play a significant role, and associations between systemic inflammatory biomarkers and hippocampal atrophy have been shown in other neurological conditions. However, research exploring serum biomarker and volumetric associations in MS are lacking. Given that conventional imaging methods lack resolution for hippocampal internal architecture (HIA), new protocols were developed. We used the High-Resolution Multiple Image Co-Registration and Averaging (HR-MICRA) method to visualize the HIA subfields. We investigated the relationship between subfield volumes generated from HR-MICRA scans and systemic serum biomarkers in MS.

Patients with MS were recruited (N= 34, mean age= 54.6, 35.3% Black) underwent Magnetic Resonance Imaging (MRI), and serum biomarkers were obtained, specifically chosen for their potential role in MS. Inflammatory biomarkers included; granulocyte colony stimulating factor (G-CSF), interleukin-10 (IL-10), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor- a (TNF- a), and growth factors; vascular endothelial growth factor (VEGF); insulin-like growth factor-1 (IGF-1), and brain derived growth factor (BDNF). Imaging was performed in a Siemens Prisma 3T scanner with a 64-channel head coil using the HR-MICRA method. Hippocampal subfields were calculated using the Automated Segmentation of Hippocampal Subfields (ASHS) package. We used the Magdeburg Young Adult 7T Atlas for sub-hippocampal structures and Penn Temporal Lobe Epilepsy T1-MRI Whole Hippocampus ASHS Atlas for general hippocampal structure and segmentation. Pearson's product-moment analyses provided correlations between biomarkers and hippocampal subfield volumes for each cerebral hemisphere. A statistical significance level of p < 0.05 was used for all analyses.

Correlations emerged between left hemisphere Cornu Ammonis (CA) 2 and G-CSF (r = -.384; p = .025); IL-10 (r = -.342; p = .048); VEGF (r = -.371; p= .031); and CA3 with IL-10 (r = -.488, p = .003); G-CSF (r = -.386; p= .024); VEGF (r = -.352; p= .041). Dentate gyrus correlated with MMP-9 (r =.416; p=.014); IL-10 (r = -.365; p =.034). BDNF was correlated with right hemisphere CA1 (r = -.417, p = .014), CA2 (r = -.497; p= .003) and CA3 (r = -.451; p=.007).

In our sample of persons with MS, left hemisphere hippocampal subfield volumes were negatively correlated with inflammatory biomarkers, supporting previous reports linking inflammation to reduced brain volumes in other neurological conditions. In the right hemisphere, we found negative correlations between HIA and BDNF, suggesting a neuroprotective function for BDNF in this neurodegenerative disease. These findings in a representative sample of patients with MS highlight the need for further research exploring the relationship between HIA and systemic serum biomarkers in MS.

To investigate the relationship between systematic inflammatory biomarkers and cognition in patients with Multiple Sclerosis (MS).

We recruited 36 patients diagnosed with MS (31 with relapsing-remitting and 5 with progressive) who presented for treatment at the University of Alabama at Birmingham (UAB). Patients underwent a comprehensive neuropsychological battery, and serum blood samples were collected. Cognitive data was divided into an overall Cognitive Composite score and seven cognitive domains (i.e., Attention, Verbal Memory, Visual Memory, Visuospatial Ability, Language, Processing Speed, and Executive Function) using z-score averages. Pearson's product-moment correlations were conducted to determine the relationship between cognitive performance and 14 inflammatory biomarkers specifically chosen for their potential role in MS.

Granulocyte Colony Stimulating Factor (G-CSF) was significantly correlated with Executive Function (r= -.355; p=.039) and Processing Speed (r= -.528; p= .001) scores. Additionally, Interleukin-10 (IL-10) was significantly correlated with Visual Memory (r= -.346; p= .041) scores. Finally, Tumor Necrosis Factor (TNF-a) was significantly correlated with Visual Memory (r= -.347; p= .041).

Studies investigating associations between inflammation and cognition in MS are lacking. In our sample of persons with Multiple Sclerosis, G-CSF biomarkers were negatively correlated with Executive Function as well as Processing Speed. In addition, IL-10 and TNF-a biomarkers were negatively correlated with Visual Memory scores. These findings in a representative sample of patients with MS highlight the need for further research exploring the relationship between systematic inflammatory biomarkers and cognition in MS.

Multiple sclerosis (MS), an inflammatory autoimmune disease of the central nervous system, is characterized by damage to white matter via myelin degeneration with resulting sclerotic plaques and lesions. Upwards of 70% of people with MS show cognitive changes in multiple domains including verbal memory. Advances in disease-modifying therapies have increased the expected lifespan of people with MS, making aging with MS a critical emerging area of study. Memory declines during normal aging, yet the specific impact of MS on verbal memory in aging is inconclusive and understudied. To address this gap in knowledge, we examined whether MS was associated with verbal learning slope, total learning, delayed recall, and recognition performance in older adults. We further explored whether MS disease severity influenced these memory operations.

Participants included two cohorts: older adults with MS recruited from MS centers and patient registries, and healthy controls recruited from the community. A total of 164 adults age 60 and older without dementia were included in the current study, 79 in the MS group (mean age = 65.05 + 4.72; %female = 62) and 85 in the control group (mean age = 69.53 + 6.65; %female = 65.9). All participants were administered a neuropsychological battery including the Hopkins Verbal Learning Test-Revised (HVLT-R). The Patient Determined Disease Steps (PDDS), a patient-rated score of disability severity in MS comprised of eight steps related to walking ability, was used to operationalize MS severity. Using a median split, the PDDS was dichotomized into low (PDDS = 0-2) versus high (PDDS = 3-5) MS severity groups. Linear regression models were run to examine the effect of group (MS vs. control) and disease severity (PDDS) on four operations from the HVLT-R: learning slope, total learning, delayed recall, and recognition. Statistical analyses adjusted for age, years of education, and sex.

Linear regression models revealed that older adults with MS showed lower total learning compared to healthy controls (β = -.18, p = .03). Learning slope, delayed recall, and recognition did not differ by group (p > .05). Compared to healthy controls, older adults with high MS severity performed worse on total learning (β = -.21; p = .01) and delayed recall (β = -.18; p = .03). Group differences on learning slope and recognition were not significant (p > .05).

The presence of MS was associated with worse total learning. Moreover, high severity of MS was associated with worse total learning and delayed recall in older adults. These results delineate the influence of MS on specific memory operations and emphasize the potential utility of disease severity on cognitive performance in aging.

The relationship between frontotemporal dementias (FTDs) and amyotrophic lateral sclerosis (ALS) is well established and is believed to be more pronounced in those with bulbar onset ALS (B-ALS). This study compared cognitive and behavioral symptoms among persons with B-ALS to those of individuals with nonbulbar phenotypes (NB-ALS).

Outpatient clinic data collected during an initial neuropsychology consultation at an ALS interdisciplinary clinic in an academic medical center was retroactively analyzed. All individuals were diagnosed with ALS by neurologists specializing in movement and neuromuscular disorders based on results of neurological/motor examination, electromyographies, and (when available) genotypic data. Total scores on the short form of the Montreal Cognitive Assessment (MoCA-SF) and scores on the ALS Cognitive Behavioral Screen (ALS-CBS) and ALS CBS Caregiver questionnaire were of focus. 22 B-ALS and 44 NB-ALS individuals were compared on said measures using univariate analyses while controlling for ALS symptoms duration.

B-ALS individuals scored significantly lower on the MoCA-SF (F(2)=3.15, p=0.05, n2=0.13) and the tracking subscale of the ALS-CBS (F(2)=3.50, p=0.04, n2=0.17). The groups were not significantly different on other ALS-CBS measures, including caregiver-rated behavior questionnaire.

Consistent with previous research, this study found lower total scores on a brief screener of global cognition and tasks of tracking requiring cognitive control in those with B-ALS relative to NB-ALS individuals. Interestingly, despite behavioral variant being the most prevalent FTD phenotype, the groups did not differ significantly in terms of caregiver-rated behavioral changes. It is hypothesized that the absence of these differences could reflect effects of gradual loss of speech and functionality that secondarily limit caregivers' abilities to observe behavioral changes concerning for possible behavioral variant FTD. That said this could reflect limitations of the sample and/or study design, and further exploration is therefore needed. Recommendations for future studies of neuropsychological/behavioral variables in B-ALS as well as development of more targeted instruments for use in this population are discussed.

Verbal memory deficits are present in multiple sclerosis (MS), but neither inflammatory T2 lesion volume nor cerebral atrophy (generalized or localized hippocampal atrophy) fully explain disease-related verbal memory changes. Importantly, the hippocampus does not function in a vacuum; memory encoding and retrieval requires interactions between the hippocampus and cortical areas where information is processed and represented. Indeed, we have previously shown that lexical access speed (a language function assessed by rapid automatized naming) independently predicted delayed recall of verbal information (word list) for persons with MS, even when controlling for total learning. Informed by this work and recent ultra high field (7.0 Tesla) MRI research reporting high cortical lesion count in regions associated with phonological processing (e.g., plenum temporale, superior temporal gyrus), we assessed whether phonological processing independently explains verbal memory deficits in persons with MS.

Analyses were performed on a clinical sample of persons withMS aged 18 to 59 years (n=60: 49 relapsing, 11 progressive). Word-list memory was assessed by the Hopkins Verbal Learning Test, Revised (HVLT-R), which yielded scores for Total Learning (TL) and Delayed Recall (DR). Phonological processing was assessed with WIAT-4 Phonemic Proficiency. WIAT-4 Sentence Repetition was utilized as a non-phonological language control task, and WIAT-4 Word Reading was administered to control for premorbid verbal ability. CANTAB Paired Associate Learning served as a nonverbal memory comparison. Performance on tasks was standardized using published age-adjusted norms. Primary analyses used partial correlations to assess relationships between Phonemic Proficiency and (a) HVLT-R TL and DR controlling for WIAT-4 Word Reading, and (b) HVLT-R DR controlling for WIAT-4 Word Reading and HVLT-R TL. To assess specificity to phonological processing, the same partial correlations assessed relationships between Sentence Repetition and HVLT-R variables, and between Phonemic Proficiency and nonverbal memory (CANTAB PAL).

When controlling for premorbid verbal ability, Phonemic Proficiency performance accounted for 7.8% of the variance in HVLT-R TL (rpartial=0.28, p=0.031) and 16% of the variance in HVLT-R DR (rpartial=0.40, p=0.002). Moreover, when additionally controlling for HVLT-R TL, Phonemic Proficiency still accounted for 10% of the variance in HVLT-R DR (r partial— 0.32, p=0.016). Showing specificity to phonological processing ability, performance on Sentence Repetition was not significantly related to HVLT-R DR when controlling for premorbid verbal ability (WIAT-4 Word Reading) and HVLT-R TL (rpartial=0.09, p=0.510). Showing specificity to verbal memory, neither Phonemic Proficiency nor Sentence Repetition performance were reliably related to CANTAB PAL for any variance in performance in nonverbal memory (Ps>0.9).

Results suggest that language ability, specifically phonological processing, contributes to delayed recall of word lists independent of premorbid verbal ability and initial total learning scores in persons with MS. These findings demonstrate contributions of language ability to verbal memory and highlight the need for further research into language ability changes in persons with MS. This may have implications for verbal memory rehabilitation in MS.