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.

Late-life depression is prevalent among older adults and the presence of depressive symptoms has been shown to be associated cross-sectionally with worse verbal fluency performance. There is limited and mixed evidence as to whether depressive symptoms impact change in verbal fluency performance over time, and whether gender impacts this relationship.

Participants were community-dwelling older adults who were dementia-free at baseline (N = 522; M age = 75.96, SD + 6.46 years). Baseline depressive symptoms were measured using the Geriatric Depression Scale. Category fluency and letter fluency performance, using the Controlled Oral Word Association Test (COWAT), were examined annually. Linear mixed effects models stratified by gender examined whether associations between baseline depressive symptoms and changes in fluency performance over five years were different in female (n = 289) as compared to male (n = 233) participants. Sensitivity analyses excluding participants with prevalent or incident mild cognitive impairment (MCI) (n = 141), excluding participants with incident dementia (n = 28), and excluding participants with prevalent or incident MCI or incident dementia (n = 169) were run. All analyses were adjusted for age, years of education, estimated premorbid functioning, and health comorbidities.

Depression was minimal across participants (m = 4.72, SD + 3.96). A subset of participants (n = 44) reported “possible depression,” namely levels suggestive of subclinical depression, according to clinical cutoffs. The “possible depression” group included 31 females (10.73% of females) and 13 males (5.58% of males), and the “no depression” group included 258 females (89.27% of females) and 220 males (94.42% of males). Baseline levels of depressive symptoms suggestive of subclinical depression were associated with worse decline in category fluency performance during longitudinal follow-up in females (estimate = -0.16, p = .002) but not males (estimate = -0.03, p = .658). Results remained the same when excluding prevalent and incident MCI cases (estimate = -0.19, p = .005), excluding incident dementia cases (estimate = -0.12, p = .017), and excluding prevalent and incident MCI and incident dementia cases (estimate = -0.20, p = .004). Letter fluency performance did not decline over time and was not influenced by levels of depressive symptoms in females (estimate = -0.03, p = .502) or males (estimate = 0.05, p = .452).

Baseline presence of depressive symptoms suggestive of subclinical depression was associated with worse decline in category fluency performance during longitudinal follow-up in female but not male participants. Letter fluency performance did not decline and was not impacted by levels of depressive symptoms. Results remained significant when accounting for covariates and potential confounders. The present study elucidated the combined influence of gender and depressive symptoms on change in fluency performance in older adults and can aid in identifying individuals who may be at a greater risk of cognitive decline.

Pain is a mechanism for attention disruption due, in part, to a shared reliance on the prefrontal cortex (PFC). Amongst older adults, the experience of pain is both prevalent and functionally impactful. Dual-task walking (DTW) paradigms are a useful means of assessing the impact of pain on attentional control and known to be sensitive to changes in the cortical hemodynamic response within the PFC. To date, however, few studies have utilized such paradigms to examine the impact of self-reported pain on attentional control via assessment of cognitive, gait and neuroimaging outcomes. Examining these associations would facilitate a better understanding of the ways in which pain may negatively impact neural efficiency, thereby increasing risk of adverse functional outcomes, in healthy aging.

Study participants (N= 408; mean age = 76 ± 6.5ys; % female =55.4) were grouped into pain (n= 266) and no pain (n= 142) groups based upon their responses on the MOS-PSS and MOS-PES. These questionnaires were also used to assess self-reported levels of pain severity and interference amongst individuals with reported pain. Functional near-infrared spectroscopy was used to measure intraindividual variability (IIV) of the cortical hemodynamic response within the PFC during a DTW paradigm which consisted of Single-Task-Walk (STW), Cognitive Interference (Alpha), and Dual-Task-Walk (DTW) conditions. Participants walked along an electronic walkway and quantitative gait data were extracted in order to assess IIV in stride length during STW and DTW conditions. The rate of correct letter generation was used as a measure of cognitive accuracy during Alpha and DTW conditions. Linear mixed effects models (LMEMs) were used to examine the effects of perceived pain on neural and behavioral responses as well as on the change in these outcomes form single- to dual-task conditions. Stratified LMEMs were used to examine whether these associations differed by gender.

LMEMs revealed that perceived pain presence was associated with reduced IIV in PFC oxygenation (estimate = -0.032, p = 0.037) and reduced IIV in stride length in the DTW condition (estimate = -1.180, p = 0.006). High pain severity was associated with a greater increase in stride length IIV from STW to DTW (estimate = -1.301, p = 0.039). Stratified LMEMs revealed that the association between pain and neural IIV was significant in only males (estimate = -0.049, p = 0.037), while the association between pain and gait IIV was significant in only females (estimate = -1.712, p = .008).

Study results suggest that self-reported pain over one month is associated with differential patterns of neural and behavioral responding amongst healthy, community-dwelling older adults. Furthermore, it appears that males are more susceptible to the neural effects of pain, while females are more susceptible to the behavioral effects under attention-demanding conditions. In this population, these patterns may reflect a tendency towards inefficient neural and behavioral modifications in response to perceived pain. These findings highlight the need for clinical use of routine pain assessments and, when appropriate, the implementation of timely and effective pain treatments in aging.

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.

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.

Increased intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning hemodynamic signal IIV is limited. Cortical thinning occurs during aging and is associated with cognitive decline. Dual-task walking (DTW) performance in older adults has been related to cognition and neural integrity. We examined the hypothesis that reduced cortical thickness would be associated with greater increases in IIV in prefrontal cortex oxygenated hemoglobin (HbO2) from single tasks to DTW in healthy older adults while adjusting for behavioral performance.

Participants were 55 healthy community-dwelling older adults (mean age = 74.84, standard deviation (SD) = 4.97). Structural MRI was used to quantify cortical thickness. Functional near-infrared spectroscopy (fNIRS) was used to assess changes in prefrontal cortex HbO2 during walking. HbO2 IIV was operationalized as the SD of HbO2 observations assessed during the first 30 seconds of each task. Linear mixed models were used to examine the moderation effect of cortical thickness throughout the cortex on HbO2 IIV across task conditions.

Analyses revealed that thinner cortex in several regions was associated with greater increases in HbO2 IIV from the single tasks to DTW (ps < .02).

Consistent with neural inefficiency, reduced cortical thickness in the PFC and throughout the cerebral cortex was associated with increases in HbO2 IIV from the single tasks to DTW without behavioral benefit. Reduced cortical thickness and greater IIV of prefrontal cortex HbO2 during DTW may be further investigated as risk factors for developing mobility impairments in aging.