Heart rate variability (HRV) can be an indicator of the flexibility of the central and autonomic nervous systems. Heart rate variability biofeedback (HRV-BF) has been shown to validate the neuro-peripheral relationship and enhance the interaction between top-down and bottom-up processes. Few previous studies have focused on the treatment outcomes of HRV-BF in traumatic brain injury, and such studies have been mostly limited to pilot studies or case reports. The purpose of this study is to investigate the efficacy of HRV-BF for neuropsychological functioning in patients with mild traumatic brain injury (mTBI).

Forty-one patients with mTBI were referred from the neurosurgery outpatient program and randomly assigned to a psychoeducation group or a HRV-BF intervention group. The psychoeducation group received standard medical care and one 60-minute psychoeducation session after brain injury. The HRV-BF group received standard medical care and one 60-minute session of the HRV-BF intervention weekly for 10 weeks. All participants received performance-based and self-reported neuropsychological measures of memory, executive function, mood, and information processing at week 1 of injury (pretest) and week 12 (posttest).

Participants in HRV-BF improved significantly after the intervention compared with the psychoeducation group on the Verbal Learning Test, Frontal Assessment Battery, Verbal Fluency Test, Paced Auditory Serial Addition Test, Trail Making Test, Dysexecutive Questionnaire, Depression Inventory, and Checklist of Post-concussion Symptoms.

HRV-BF was found to be an efficacious and efficient intervention for improving neuropsychological functioning in patients with mTBI and a potential candidate for mTBI rehabilitation.

Executive functions (EFs) are considered to be both unitary and diverse functions with common conceptualizations consisting of inhibitory control, working memory, and cognitive flexibility. Current research indicates that these abilities develop along different timelines and that working memory and inhibitory control may be foundational for cognitive flexibility, or the ability to shift attention between tasks or operations. Very few interventions target cognitive flexibility despite its importance for academic or occupational tasks, social skills, problem-solving, and goal-directed behavior in general, and the ability is commonly impaired in individuals with neurodevelopmental disorders (NDDs) such as autism spectrum disorder, attention deficit hyperactivity disorder, and learning disorders. The current study investigated a tablet-based cognitive flexibility intervention, Dino Island (DI), that combines a game-based, process-specific intervention with compensatory metacognitive strategies as delivered by classroom aides within a school setting.

20 children between ages 6-12 years (x̄ = 10.83 years) with NDDs and identified executive function deficits and their assigned classroom aides (i.e., “interventionists”) were randomly assigned to either DI or an educational game control condition. Interventionists completed a 2-4 hour online training course and a brief, remote Q&A session with the research team, which provided key information for delivering the intervention such as game-play and metacognitive/behavioral strategy instruction. Fidelity checks were conducted weekly. Interventionists were instructed to deliver 14-16 hours of intervention during the school day over 6-8 weeks, divided into 3-4 weekly sessions of 30-60 minutes each. Baseline and post-intervention assessments consisted of cognitive measures of cognitive flexibility (Minnesota Executive Function Scale), working memory (Weschler Intelligence Scales for Children, 4th Edn. Integrated Spatial Span) and parent-completed EF rating scales (Behavior Rating Inventory of Executive Function).

Samples sizes were smaller than expected due to COVID-19 related disruptions within schools, so nonparametric analyses were conducted to explore trends in the data. Results of the Mann-Whitney U test indicated that participants within the DI condition made greater gains in cognitive flexibility with a trend towards significance (p = 0.115. After dummy coding for positive change, results also indicated that gains in spatial working memory differed by condition (p = 0.127). Similarly, gains in task monitoring trended towards significant difference by condition.

DI, a novel EF intervention, may be beneficial to cognitive flexibility, working memory, and monitoring skills within youth with EF deficits. Though there were many absences and upheavals within the participating schools related to COVID-19, it is promising to see differences in outcomes with such a small sample. This poster will expand upon the current results as well as future directions for the DI intervention.

Older adults experiencing mild cognitive difficulties (MCD) may benefit from compensatory cognitive training (CCT) to address cognitive changes. CCT can be delivered over various lengths of time and can focus on a specific cognitive domain (e.g., memory) or multiple domains. Identifying the most relevant and impactful portions of a CCT intervention could allow for more effective and streamlined delivery of compensatory strategies, perhaps allowing this type of training to be included in feedback sessions or brief interventions. This study sought to investigate which factors older adults with MCD found to be most beneficial and applicable to their daily lives after completion of a brief telehealth CCT program.

Adults age 55+ with documented MCD (n=28) and an optional care partner (CP; n=18) were recruited for video-chat delivery of a 6-week, motivationally-enhanced CCT program adapted from CogSMART. The six weeks included content addressing: Education and Lifestyle Strategies (Session 1); Organization, Prioritization, and Prospective Memory (Session 2); Attention, Concentration, and Working Memory (Session 3); Learning and Memory (Session 4); Executive Functions: Decision-Making, Problem-Solving, and Planning (Session 5); and Skills Integration and Next Steps (Session 6). After completing the course, participants (n=25) provided open-ended feedback on course content, including the areas they found most helpful. They were also asked which strategies from the course they had successfully applied in their daily lives, and which they expected to continue using following the course. Qualitative data were coded and analyzed by two researchers.

Participants most often endorsed strategies from Session 2 (44% of participants) and Session 3 (44%) as being helpful and applicable in daily life. Session 1 content was also frequently endorsed (36%). Content from Session 5 was noted to have been helpful/applicable least often (12%). Participants also reported having found common factors of the program to be helpful (35%), such as interaction with the clinician, education on relevant resources, or greater self-reflection and self-awareness through the program. A minority of participants reported “all” (22%) or “none” (24%) of the content to be helpful.

Among older adults with MCD, strategies related to prospective memory (e.g., calendar training) and attention (e.g., mindfulness) were most frequently reported as being helpful and applicable in daily life. Participants reported confidence in their ability to continue using these strategies after the program, along with continued implementation of lifestyle factors to promote healthy brain aging (e.g., exercise). Clinicians interested in providing CCT to older adults with MCD may find the most benefit from emphasizing and prioritizing strategies within these domains. Future research could use ecological momentary assessment techniques to gather real-time measures of how these learned strategies are employed in daily life. Continued exploration of the most salient and effective compensatory strategies for older adults with MCD will support effective intervention and promote independence among aging patients.

The goal-control model of the functional impairment in dementia posits two different underlying mechanisms: decay of task goals (reduced task accomplishment) and poor control over goal execution (high error rates). Here we present a case series in which we explore the effects of a performance-based, functional intervention on two participants. Outcomes were evaluated using the goal-control framework.

Two participants with dementia (CS: age 70, 14 years of education; EM: age 93, 18 years of education) completed neuropsychological tests (scored using age, education, and IQ-adjusted norms) and baseline testing with the Naturalistic Action Task (NAT; a validated performance-based task of everyday function including a Breakfast and Lunch task). The Virtual Kitchen (VK) was used to train, through repeated performance, either the Breakfast (CS) or Lunch (EM) tasks for 30 minutes (or 10 total repetitions) per day over 5 days. After VK training, participants performed the NAT Breakfast and Lunch tasks again to evaluate improvement on the trained and untrained tasks. Baseline and post-training NATs were scored for task accomplishment and errors by two coders observing video recordings. Z scores were derived by calculating accomplishment and error change scores for each participant relative to the mean and standard deviations of change scores from a cohort of 36 healthy controls (mean age: 73.3, SD: 6.44; mean education: 17.42, SD: 2.17).

Both participants exhibited similar cognitive profiles: high estimated IQ; low MMSE (total = 19 for both CS and EM; 1st percentile); anterograde amnesia, slowed processing speed and impaired executive function; average scores on tests of attention, language, and self-reported depression. Informant report of daily functioning (FAQ) suggested that EM (FAQ=28) exhibited greater functional impairment than CS (FAQ=9). Both participants completed all VK training sessions. Z scores of the change from pre- to post-training showed significant increases in task accomplishment on the trained task (trained condition change z scores: EM = +27.69; CS =+ 6.06), but significantly less improvement or worse task accomplishment on the untrained task (untrained condition change z scores: EM = +4.06; CS = -13.69). The training did not reduce errors, as error rates increased for both participants on the trained task.

The participants presented in this case study exhibited comparable cognitive profiles, including marked anterograde amnesia. Our results suggest that repeated training in a virtual context can improve specific aspects of functioning on real, life everyday tasks. Further, according to the goal-control framework, repeated practice reduces the decay of the task goal, as represented by greater task accomplishment, but does not improve executive control over the task execution. Important future directions are to determine if people with different cognitive profiles will demonstrate different benefits from VK training and to examine if virtual training of personally relevant, everyday tasks can promote independent living and improve quality of life.

Perceived poor sleep quality is the most commonly reported issue among veterans with a history of mild traumatic brain injury (mTBI). Poor sleep can impact aspects of objective and subjective executive functioning abilities (e.g., planning, organization, decision-making) and lead to decreased societal participation. However, less is known about how perceived executive dysfunction impacts the relationship between perceived poor sleep and societal participation in veterans with a prior history of mTBI. We hypothesized that executive dysfunction mediates the relationship between subjective sleep quality and societal participation.

Participants included sixty-two U.S. veterans [Age: M=41.73 (SD=13.19); Education: M=15.16 (SD=2.20); 14.5% female]. The participants completed the Mayo-Portland Adaptability Inventory - 4 (MPAI-4; total scores), the Behavior Rating Inventory of Executive Function - Adult (BRIEF-A; subscale planning/organizing), and the Pittsburg Sleep Quality Index (PSQI; total scores). 21 participants met diagnostic criteria for Post-traumatic stress disorder (PTSD) [as determined by a cutoff score of 45 on the PTSD Checklist for DSM-5 (PCL-5)]. A mediation analysis was utilized to examine the impact of executive functions on the relationship between perceived sleep quality and societal participation. Mediation analyses were conducted via linear regression modeling using SPSS Version 27. Post hoc analyses were conducted to control for PTSD, which is common in veteran populations.

The total PSQI scores significantly predicted MPAI-4 total scores F(1, 53) = 16.740, p < .001 (R2= .55) when controlling for PTSD diagnoses. A mediation analysis showed that BRIEF-A Planning/Organizing T-scores partially mediate the relationship between PSQI scores and MPAI-4 scores when controlling for PTSD diagnoses F(2, 54) = 12.055, p < .001 (R2 = .61).

Results suggest that per000eived sleep quality impacts societal participation. However, how patients perceive their executive functioning abilities partially mediates the relationship between perceived sleep quality and societal participation, such that perceived poor sleep quality leads to reduced societal participation when there is subjective executive dysfunction. Therefore, clinical interventions should focus on the cognitive rehabilitation of executive functioning among veterans with a history of mTBI to improve their subjective experience. Ultimately, these efforts may improve veterans’ participation and utilization of healthcare services.

I-InTERACT-North is a stepped-care telepsychological parenting intervention designed to promote positive parenting skills and improve child behaviour. Initially developed for children with traumatic brain injury, our pilot study has shown efficacy in increasing positive parenting skills and reducing problem behaviours for children with early brain injury (e.g., stroke, encephalopathy). Recently, the program has expanded to include children with neurodevelopmental disorders, including Autism Spectrum Disorder. Although positive parenting programs (e.g., Parent-Child Interaction Therapy) can be effective for autistic children, it is unknown whether the goals most important to these families can be addressed with IInTERACT-North program. An examination of suitability and preliminary efficacy was conducted.

Parent participants of autistic children between 3 and 9 years (n= 20) were recruited from the neonatal, neurology, psychiatry, or cardiology clinics at The Hospital for Sick Children and the Province of Ontario Neurodevelopmental Disorders (POND) Network. Top problems, as reported by parents at baseline, were analyzed qualitatively through a cross-case analysis procedure in order to identify common themes and facilitate generalizations surrounding concerning behaviours. Parent-reported intensity of their children’s top problem behaviours on a scale from 1 (“not a problem”) to 8 (“huge problem”) were quantified. To explore preliminary program efficacy, t-tests were used to compare pre- and post-intervention problems and intensity on the Eyberg Child Behavior Inventory (ECBI) (n=16).

A total of 56 top problem data units were examined, with convergent thematic coding on 53 of 56 (94.6% inter-coder reliability). Four prevalent, high-agreement themes were retained: emotion dysregulation (19; 33.9%), non-compliance (12; 21.4%), sibling conflict (7; 12.5%), and inattention and hyperactivity (7; 12.5%). Average problem intensity for these themes ranged from 5.85 to 6.53 (where 8 is greatest impairment) with emotion dysregulation having the highest intensity (6.53) compared to the others. Scores on the ECBI were lower post-intervention (Intensity scale: M= 59.06, SD= 8.1; Problem scale: M= 60.69, SD= 11.5) compared to pre-intervention (Intensity scale: M= 61.19, SD= 10.4; Problem scale: M= 64.31, SD= 11.7), but small sample size precluded detecting statistical significance (p’s = .16 and .07, respectively).

Thematic analysis of top problems identified by parents of autistic children suggested that concerns were transdiagnostic in nature, and represent common treatment targets of the I-InTERACTNorth program. Though challenging behaviours related to restricted interests or repetitive behaviours may exist in our sample, parental behavioural goals appeared to align with the types of concerns traditionally raised by participants of the program, supporting a transdiagnostic approach. Preliminary data point to positive treatment outcomes in these families.

Lateralization and localization of neuropathology helps determine the extent to which eloquent cortex and diseased brain tissue share loci, important information for neurosurgical decision-making, and predicting neurocognitive outcomes. Emerging data suggest that lateralization and localization can inform specific neurorehabilitation approaches following acquired brain injury (ABI). In recent years, computerized cognitive remediation (CCR) of attention and working memory (WM) has been included among treatment guidelines to enhance cognition in post-acute recovery following ABI. Although CCR has shown promise for improving attention and executive functioning in ABI, it is unknown how treatment response may be predicted by locus of ABI. Even less is known about the effects of CCR following neurosurgery. The current study explores neurosurgical lateralization and localization as potential variables for predicting treatment response to CCR.

Adult patients with a variety of neurological diagnoses (N = 17; ∼47% women) completed a full course of Cogmed Working Memory Training (CWMT) s/p neurosurgical intervention. All participants engaged in 30 sessions of CWMT over eight weeks, as well as neuropsychological (NP) assessment at pre-training baseline, immediate post-training, and at 3-month follow-up. Objective and subjective indices of attention, working memory, executive functioning, and emotional well-being were evaluated at three time-points. Neurosurgical loci included left-hemisphere frontal, temporal, and temporoparietal lobes, as well as right-hemisphere frontal, frontotemporal, and temporal lobes.

NP data were reviewed and yielded a clinical impression of cognitive and affective functioning for a cohort of patients with heterogeneous diagnoses (e.g., brain tumor, epilepsy, NPH). Preliminary NP findings suggested that treatment response to CCR for WM was consistent with extant literature on brain-behavior relationships according to lateralization and localization of neurosurgical intervention.

Neurosurgical patients experience neurocognitive and affective dysfunction that may respond well to cognitive rehabilitation (CR) that includes CCR. Additionally, it is possible that lateralization and localization of surgical intervention may contribute to individual differences in treatment response. Further neurorehabilitation research is warranted to identify patients most likely to benefit from CCR and better tailor CR modalities to optimize recovery s/p neurological surgery.

Preterm birth (gestational age < 37 weeks) is associated with delays in the development of executive functions and their precursors, including controlling attention and retaining task-relevant information. In the current study, we aim to examine the potential therapeutic effects of a novel cognitive tablet game, Dino Island (DI), and its implementation through a parent-delivered intervention program on cognitive development in preterm children.

In total, 34 participants (M = 4.99 years old) were recruited from a perinatal follow-up clinic or through the community in Calgary, AB. Participants were randomly assigned to either the DI intervention (n = 20) or tablet-based educational control games (C; n = 14). Parents completed a 2-hour training program that included information about how to support their child through the intervention using behavioural supports and metacognitive strategies. Neuropsychological assessment was done prior to beginning the intervention and after 12 weeks of intervention. Various tests were used to assess near transfer measures of sustained attention, shifting attention, executive function, verbal working memory and inhibition, and to assess far transfer measures of language skills and early numeracy. Families tracked weekly progress using journals, with the goal of 3-4 30-minute sessions per week. Multiple ANCOVA analyses were run to analyze quantitative data using the pre-test score as a covariate.

A total of 21 participants completed the 12 weeks of intervention (DI: n = 11 and C: n = 10). Those who did not complete the intervention withdrew from the study or were unable to make a follow-up assessment due to COVID-19 restrictions. Groups did not significantly differ in age (DI: M = 4.92, C: M = 4.61), sex (DI: Female = 6, C: Female = 6), or in weeks preterm (DI: M = 29.49 weeks, C: M = 32.7 weeks).

Multiple ANCOVAs were run to determine the effect of either the DI or Control intervention on the cognitive measures after controlling for the pre-intervention score of participants. As compared to the Control group, the DI intervention group showed near transfer gains in sustained attention (F(1,7) = 5.1, p = 0.043), and executive functions (F(2,18) = 5.41, p = 0.014), as well as far transfer gains in phonetic awareness (F(2,16) = 11.63, p = 0.001), vocabulary and oral language skills (F(2,7) = 5.54, p = 0.014), and number identification fluency (F(2,17) = 11.37, p = 0.001). Detailed analyses will be discussed in the poster.

This study provides preliminary support for the potential efficacy of the DI intervention when delivered by parents to children born preterm. Pre-post testing after 12 weeks of intervention indicated both near and far transfer gains. These results highlight the benefits of utilizing a tablet game format to facilitate collaborative parent-child interactions in cognitive intervention. This intervention provides a potential affordable and engaging alternative to existing cognitive interventions. Further investigation with a larger and more diverse sample is required.

Children with neurodevelopmental disorders (NDDs) commonly experience attentional and executive function (EF) difficulties that are negatively associated with academic success, psychosocial functioning, and quality of life. Access to early and consistent interventions is a critical protective factor and there are recommendations to deliver cognitive interventions in schools; however, current cognitive interventions are expensive and/or inaccessible, particularly for those with limited resources and/or in remote communities. The current study evaluated the school-based implementation of two game-based interventions in children with NDDs: 1) a novel neurocognitive attention/EF intervention (Dino Island; DI), and 2) a commercial educational intervention (Adventure Academy; AA). DI is a game-based attention/EF intervention specifically developed for children for delivery in community-based settings.

Thirty five children with NDDs (ages 5-13 years) and 17 EAs participated. EAs completed on-line training to deliver the interventions to assigned students at their respective schools (3x/week, 40-60 minutes/session, 8 weeks, 14 hours in total). We gathered baseline child and EA demographic data, completed pre-intervention EA interviews, and conducted regular fidelity checks throughout the interventions. Implementation data included paper-pencil tracking forms, computerized game analytic data, and online communications.

Using a mixed methods approach we evaluated the following implementation outcomes: fidelity, feasibility, acceptability, and barriers. Overall, no meaningful between-group differences were found in EA or child demographics, except for total number of years worked as an EA (M = 17.18 for AA and 9.15 for DI; t (22) = - 4.34, p < .01) and EA gender (χ2 (1) = 6.11, p < .05). For both groups, EA age was significantly associated with the number of sessions played [DI (r = .847, p < .01), AA (r = .986, p < .05)]. EAs who knew their student better completed longer sessions [DI (r = .646), AA (r = .973)], all ps < .05]. The number of years worked as an EA was negatively associated with the total intervention hours for both groups. Qualitative interview data indicated that most EAs found DI valuable and feasible to deliver in their classrooms, whereas more implementation challenges were identified with AA. Barriers common to both groups included technical difficulties (e.g., game access, internet firewalls), environmental barriers (e.g., distractions in surroundings, time of the year), child factors (e.g., lack of motivation, attentional difficulties, frustration), and game-specific factors (e.g., difficulty level progression). Barriers specific to DI included greater challenges in motivating children as a function of difficulty level progression. Furthermore, given the comprehensive nature of training required for delivery, EAs needed a longer time to complete the training for DI. Nevertheless, many EAs in the DI group found the training helpful, with a potential to generalize to other children in the classroom.

The availability of affordable, accessible, and effective cognitive intervention is important for children with NDDs. We found that delivery of a novel cognitive intervention by EAs was feasible and acceptable, with similarities and differences in implementation facilitators/barriers between the cognitive and commercialized academic intervention. Recommendations regarding strategies for successful school-based implementation of neurocognitive intervention will be elaborated on in the poster.

Studies have reported that athletic conditioning or training may have neuropsychological benefits for adult athletes, including enhanced processing speed, executive function, and working memory and attention. However, others have reported that these benefits may be attenuated by an athlete’s level of exposure to repetitive, subconcussive head impacts, such as heading the ball in soccer. Neurocognitive dispersion, or intraindividual variability (IIV), has become an increasingly popular tool to assess neuropsychological performance in various clinical populations. Less dispersion is typically associated with more consistent and better overall performance (i.e., fewer lapses of reaction time and accuracy). However, few studies have utilized these measures in healthy young adults. The objective of this study was to determine if athletes and non-athletes exhibited different levels of neurocognitive dispersion on a battery of neuropsychological tasks. It was hypothesized that athletes would exhibit less neurocognitive dispersion compared to non-athletes, despite their exposure to repetitive subconcussive head impacts.

Division 1 varsity and club team university athletes (n = 74, Mage = 19.93, female = 55%), and non-athlete undergraduate students (N = 154, Mage = 20.12, female = 69%) completed a neuropsychological battery consisting of 13 cognitive tests. Outcomes for each test were converted to standard scores and combined for overall neuropsychological performance. Two measures of IIV, intraindividual standard deviation (ISD) and maximum discrepancy (MD), were calculated across all 13 cognitive tests for each participant. Intraindividual standard deviation was calculated by taking the standard deviation of the mean performance across each task for each participant. Maximum discrepancy was calculated by subtracted the lowest standard score from the highest standard score per participant across all 13 cognitive tests.

Controlling for the impact of premorbid functioning, depressive symptoms, and gender, an analysis of covariance (ANCOVA) found significantly less ISD in athletes (M = 11.28, SD = 2.76) compared to non-athletes (M = 12.56, SD = 3.61) across all 13 neuropsychological tasks (η2 = 0.04, p = .004). Similarly, significantly lower MD scores were found in athletes (M = 40.25, SD = 11.14) compared to non-athletes (M = 44.69, SD = 14.07) across all 13 neuropsychological tasks (η2 = 0.03, p = .008). Post-hoc analyses revealed no significant differences when athletes were divided into contact and non-contact athletes.

Similar to prior findings that aerobic exercise may enhance cognitive performance, both contact and non-contact college athletes exhibited less neurocognitive dispersion (as measured by ISD and MD) compared to non-athlete college students. However, no significant differences were found between non-contact athletes and contact athletes (soccer players) who were exposed to repetitive subconcussive heading events. These findings suggest that athletic performance in college-aged athletes may lead to more consistent and therefore overall better neuropsychological performance despite exposure to repetitive subconcussive head impacts.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of cerebral small vessel disease leading to early cerebrovascular changes. These changes result from mutations in the NOTCH3 gene that cause progressive accumulations of granular osmiophilic material (GOM) deposits, thickening arterial walls and reducing or restricting blood flow in the brain. The clinical presentation of CADASIL is characterized by migraines with aura, early and recurrent strokes, progressive cognitive impairment, and psychiatric disturbances. CADASIL is rare but frequently underrecognized or misdiagnosed. A genetic condition with a 50% risk of inheritance from an affected parent, the gold standard for diagnosis is genetic testing to determine the presence of mutations in the NOTCH3 gene. This presentation aims to familiarize neuropsychologists with the condition of CADASIL through a unique case study highlighting important psychological, social, and ethical considerations raised by genetic testing.

This case study presents a 67-year-old, right-handed, married female diagnosed with CADASIL who was referred for neuropsychological evaluation of cognitive function and low mood concerns following multiple ischemic events.

Results revealed severe cognitive deficits in domains of attention, learning, and memory. Her superior verbal abilities and executive function remained largely intact. Assessment of mood revealed elevations in symptoms of depression and anxiety. The patient was aware of CADASIL in her father, paternal aunt, and younger brother, but elected to forego any genetic testing to confirm whether she had the condition until she experienced a stroke at age 61. She has two adult children who have also elected to forego testing and currently remain asymptomatic. Cognitive profile, mood disturbances, and patient perspectives on refraining from pre-symptomatic genetic testing for CADASIL diagnosis will be discussed.

Aspects of this case are consistent with a small body of literature evidencing distinct psychological, emotional, and social challenges among families carrying genetic risk of CADASIL. While providing an example of an often underrecognized neurological disorder with which neuropsychologists should be familiar, this case uniquely raises ethical questions relevant to care providers and current treatment guidelines regarding genetic testing among families carrying highly heritable neurological conditions. In particular, personal ethical challenges around deciding to pursue or forego pre-symptomatic testing, and implications for family planning, highlight the importance of genetic counseling for affected families.

Poor cardiovascular health occurs with age and is associated with increased dementia risk, yet its impact on frontotemporal lobar degeneration (FTLD) and autosomal dominant neurodegenerative disease has not been well established. Examining cardiovascular risk in a population with high genetic vulnerability provides an opportunity to assess the impact of lifestyle factors on brain health outcomes. In the current study, we examined whether systemic vascular burden associates with accelerated cognitive and brain aging outcomes in genetic FTLD.

166 adults with autosomal dominant FTLD (C9orf72 n= 97; GRN n= 34; MAPT n= 35; 54% female; Mage = 47.9; Meducation = 15.6 years) enrolled in the Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Longitudinal FTD study (ALLFTD) were included. Participants completed neuroimaging and were screened for cardiovascular risk and functional impairment during a comprehensive neurobehavioral and medical interview. A vascular burden score (VBS) was created by summing vascular risk factors (VRS) [diabetes, hypertension, hyperlipidemia, and sleep apnea] and vascular diseases (VDS) [cerebrovascular disease (e.g., TIA, CVA), cardiac arrhythmia (e.g., atrial fibrillation, pacemaker, defibrillator), coronary artery disease (e.g., myocardial infarction, cardiac bypass, stent), and congestive heart failure] following a previously developed composite (range 0 to 8). We examined the interaction between each vascular health metric (VBS, VDS, VRS) and age (vascular health*age) on clinical severity (CDR plus NACC FTLD-SB), and white matter hyperintensity (WMH) volume outcomes, adjusting for age and sex. Vascular risk, disease, and overall burden scores were examined in separate models.

There was a statistically significant interaction between total VBS and age on both clinical severity (ß=0.20, p=0.044) and WMH burden (ß=0.20, p=0.032). Mutation carriers with higher vascular burden evidenced worse clinical and WMH outcomes for their age. When breaking down the vascular burden score into (separate) vascular risk (VRS) and vascular disease (VDS) scores, the interaction between age and VRS remained significant only for WMH (ß=0.26, p=0.009), but not clinical severity (ß=0.04, p=0.685). On the other hand, the interaction between VDS and age remained significant only for clinical severity (ß=0.20, p=0.041) but not WMH (ß=0.17, p=0.066).

Our results demonstrate that systemic vascular burden is associated with an “accelerated aging” pattern on clinical and white matter outcomes in autosomal dominant FTLD. Specifically, mutation carriers with greater vascular burden show poorer neurobehavioral outcomes for their chronological age. When separating vascular risk from disease, risk was associated with higher age-related WMH burden, whereas disease was associated with poorer age-related clinical severity of mutation carriers. This pattern suggests preferential brain-related effects of vascular risk factors, while the functional impact of such factors may be more closely aligned with fulminant vascular disease. Our results suggest cardiovascular health may be an important, potentially modifiable risk factor to help mitigate the cognitive and behavioral disturbances associated with having a pathogenic variant of autosomal dominant FTLD. Future studies should continue to examine the neuropathological processes underlying the impact of cardiovascular risk in FTLD to inform more precise recommendations, particularly as it relates to lifestyle interventions.

Cerebral amyloid angiopathy (CAA) is one of the most frequent causes of non-traumatic intracerebral hemorrhage (ICH). ICH recurrence risk is significantly higher in patients with CAA than for those without the condition, and CAA is a risk factor for the development of dementia, particularly Alzheimer’s disease. There is a growing body of research describing neuropsychological impairment observed in patients with CAA. Among patients with a history of CAA-related ICH, the most commonly identified cognitive impairments include attention, processing speed, executive functioning, and episodic memory. However, little is known about potential additive or synergistic effects of each CAA-related lesion (such as recurrent ICHs) on cognitive functioning.

We present a case of a 74-year-old female with sporadic CAA, who had recurrent ICHs involving the left occipitoparietal lobe, left frontoparietal lobe, right occipital lobe, and left frontal lobe. She experienced residual visual impairment and probable Charles Bonnet Syndrome. Her clinical presentation and cognitive functioning were tracked with an inpatient neuropsychological evaluation completed after each ICH occurrence within the past year, as well as an outpatient neuropsychological evaluation completed approximately 3-months post-discharge from her most recent hospital admission. Record review, including clinical notes, lab tests, and imaging results supplement her performance on serial inpatient and outpatient neuropsychological evaluations.

Data from three inpatient neuropsychological screenings and one lengthier outpatient evaluation are presented. With each inpatient evaluation, her profile demonstrated further cognitive decline involving visuospatial skills, semantic fluency, and episodic memory. In fact, results from her last inpatient screening raised concern for an underlying cortical degenerative process. In contrast, her follow-up outpatient evaluation, after three separate ICH events within one year, demonstrated an isolated set-shifting impairment, with intact performance across all other domains, which ruled out the prior suspicion of a cortical process.

While specific domains of cognition are more vulnerable in CAA, it is difficult to identify a specific and expected cognitive pattern given the extensive number of varied neurological insults patients typically develop throughout the disease course. This case demonstrates the wide range effects of repeated ICH, as well as the contrast between the acute effects of new lesions and the lasting effects of these lesions on cognitive ability after a period of recovery and stabilization. Given that our service was able to perform neuropsychological assessment in the acute phase of each ICH and in the subacute phase after a period of stabilization, this case adds to the literature by providing an example of the additive or synergistic effects of each CAA-related lesion over time.

Stroke is a prevalent disease and often produces cognitive impairment. Post-stroke cognitive impairment has been associated with challenges returning to interpersonal and occupational activities. Knowing what factors are associated with cognitive impairment post-stroke can be useful for predicting outcomes and guiding rehabilitation strategies. One such factor is gender. Previous research has not led to definitive conclusions as to whether there are gender differences in cognitive outcomes following stroke. This may be because other factors, including age at stroke onset, years of education, premorbid intelligence, and lesion volume, may account for apparent gender differences in cognitive outcomes of stroke. Here, we sought to examine whether there are gender differences in general and specific cognitive functions following stroke, beyond what can be accounted for by age at stroke onset, years of education, premorbid intelligence, and lesion volume.

Participants were 237 individuals in the chronic epoch (> 3 months) following ischemic stroke. Using multivariate linear regression, we examined gender as a predictor of overall cognitive functioning and specific cognitive functions, while controlling for age at stroke onset, years of education, premorbid intelligence, and lesion volume. To quantify overall cognitive functioning, we used a measure of general cognitive ability (g) and Full Scale IQ score from the WAIS. To quantify specific cognitive functions, we used scores from 16 individual neuropsychological tests.

After controlling for demographic and lesion factors, men and women did not show any significant differences in overall cognitive functioning following stroke as measured by g (ß = -0.01, 95% CI: -0.14 - 0.12, p = .887) or Full Scale IQ (ß = -0.01, 95% CI: -2.93 - 2.27, p = .801). There were some significant gender differences on specific cognitive tests after controlling for demographic and lesion factors. Specifically, women performed better than men on the Rey Auditory Verbal Learning Test (ps < .001) and men performed better than women on the WAIS Information subtest (ß = -.65, 95% CI: -0.97 - -0.33, p < .001).

Our findings suggest that although men and women have similar overall cognitive functioning after stroke, they show some differences in specific cognitive functions even after accounting for demographic and lesion factors. Namely, women demonstrated better performance on a test of learning while men demonstrated better performance on a test of verbal knowledge/comprehension. This information is important for clinicians as they assess cognitive outcomes in patients post-stroke and plan rehabilitation strategies.

Blood pressure variability (BPV), independent of traditionally targeted average blood pressure levels, is an emerging vascular risk factor for stroke, cerebrovascular disease, and dementia, possibly through links with vascular-endothelial injury. Recent evidence suggests visit-to-visit (e.g., over months, years) BPV is associated with cerebrovascular disease severity, but less is known about relationships with short-term (e.g., < 24 hours) fluctuations in blood pressure. Additionally, it is unclear how BPV may be related to angiogenic growth factors that play a role in cerebral arterial health.

We investigated relationships between short-term BPV, white matter hyperintensities on MRI, and levels of plasma vascular endothelial growth factor (VEGF) in a sample of community-dwelling older adults (n = 57, ages 55-88) without history of dementia or stroke. Blood pressure was collected continuously during a 5-minute resting period. BPV was calculated as variability independent of mean, a commonly used index of BPV uncorrelated with average blood pressure levels. Participants underwent T2-FLAIR MRI to determine severity of white matter lesion burden. Severity of lesions was classified as Fazekas scores (0-3). Participants also underwent venipuncture to determine levels of plasma VEGF. Ordinal logistic regression examined the association between BPV and Fazekas scores. Multiple linear regression explored relationships between BPV and VEGF. Models controlled for age, sex, and average blood pressure.

Elevated BPV was related to greater white matter lesion burden (i.e., Fazekas score) (systolic: OR = 1.17 [95% CI 1.01, 1.37]; p = .04; diastolic: OR = 2.47 [95% CI 1.09, 5.90]; p = .03) and increased levels of plasma VEGF (systolic: ß = .39 [95% CI .11, .67]; adjusted R2 = .16; p = .007; diastolic: ß = .48 [95% CI .18, .78]; adjusted R2 = .18; p = .003).

Findings suggest short-term BPV may be related to cerebrovascular disease burden and angiogenic growth factors relevant to cerebral arterial health, independent of average blood pressure. Understanding the role of BPV in cerebrovascular disease and vascular-endothelial health may help elucidate the increased risk for stroke and dementia associated with elevated BPV.

Patient-reported outcome measures provide valuable insights into health status after neurologic disease, but their relationships with function-based outcome measures remain incompletely understood. Here we evaluate the relationship between these two classes of measure using dimensionality-reduction techniques in patients after acute stroke and examine their associated patterns of neuroanatomical injury.

Fifty-four adults with upper extremity motor deficits were serially assessed at four time points after stroke with functional outcome measures (Upper Extremity Fugl-Meyer, Barthel Index, modified Rankin Scale, Box and Blocks, 9- Hole Peg, Grip Strength) as well as patient-reported measures (PROMIS-Global Physical, Mental, and Social Health, Patient Health Questionnaire-9) of health status. At each timepoint after stroke, exploratory and confirmatory factor analysis were performed to identify and confirm the underlying factorial structure of the entire battery of outcome measures. Multivariate linear regression analysis was used to determine the amount of variance explained by clinical and demographic characteristics on extracted factors. Voxel-Based Lesion Symptom Mapping was used to examine the relationship between factors and patterns of neuroanatomical injury.

In the battery of stroke outcome measures, two factors were identified and retained, accounting for >78% of the overall variance across outcomes at every timepoint. Function-based measures loaded onto Factor 1 separately from patient-reported measures which loaded onto Factor 2. Results were consistent at each serial timepoint after stroke. Pre-stroke disability (p=0.03) and amount of damage to the corticospinal tract (p=0.001), explained significant variance in performance on Factor 1 (function-based outcomes), whereas education (p=0.01) and socioeconomic status (p=0.04) explained significant variance in performance on Factor 2 (PROMs). While function-based measures were related to injury to subcortical brain regions known to be important for motor function, patient-reported measures were related to injury to cortical brain regions including the insula and inferior parietal lobe, known to be important for affective processing and social cognition.

Two distinct factors representing function-based and patient-reported measures of health status were extracted from the study battery of stroke outcome measures scored across the first year post-stroke. Each factor was associated with injury to brain regions concordant with the content of the represented assessments. These findings emphasize the distinct behavioral elements and neuroanatomical underpinnings of function-based and patient-reported outcome measures after stroke and have potential implications for precision rehabilitation.

Essential tremor (ET) is the most common movement disorder, characterized by bilateral action tremors of the upper extremities. Surgical interventions can be considered for severe cases that are refractory to medication. Magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus of the thalamus (Vim) is a recently approved, minimally invasive treatment for unilateral tremor. While patients are generally pleased with unilateral treatment, many patients are bothered by tremor on the untreated side. Historically, bilateral thalamotomy has been associated with a higher rate of adverse events, including cognitive impairment. MRgFUS Vim thalamotomy for bilateral tremor is currently being investigated. The goal of the present study was to evaluate the effect of bilateral MRgFUS Vim thalamotomy on cognition.

Twelve patients with medication-refractory essential tremor (mean age = 68.77 +/- 11.78 years, mean education = 14.34 +/- 2.71 years, 8 male) were included in the present study. Three of the 12 patients met criteria for mild cognitive impairment (MCI). All patients successfully underwent unilateral MRgFUS thalamotomy at least 48 weeks before the second thalamotomy. A battery of neuropsychological tests was administered to patients before (considered baseline in the present study) and three months following the second thalamotomy. Baseline evaluations occurred on average 144.64 +/- 91.53 weeks (range: 55.00 - 346.58) after the first thalamotomy. The neuropsychological battery assessed domains of processing speed (Oral Symbol Digit Modalities Test, D-KEFS Color-Word Naming and Reading), attention (WAIS-IV Digit Span Forward), executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching), working memory (WAIS-IV Digit Span Backward and Sequencing), verbal fluency (D-KEFS Letter Fluency and Animal Fluency), confrontation naming (Boston Naming Test), verbal memory (Hopkins Verbal Learning Test-Revised), and visuospatial perception (Judgment of Line Orientation). Alternate versions of tests were used when possible. Cognitive changes were analyzed at the group and individual level. Group level changes were assessed with paired sample t-tests (corrected for multiple comparisons). At the individual level, postoperative declines > 1.5 SD from baseline were considered clinically significant.

Participants’ baseline intellectual functioning ranged from low average to superior (as measured by the WTAR). The mean baseline score on the Montreal Cognitive Assessment was 24.58 (range: 17 - 30). At the group level, there were no significant changes in cognitive scores from baseline to follow-up (all p values > 0.635). At the individual level, one patient with MCI declined > 1.5 SD on the verbal memory composite. No other patients showed declines > 1.5 SD.

Our preliminary findings suggest that bilateral MRgFUS Vim thalamotomy is relatively safe from a cognitive perspective. However, a single patient with MCI exhibited clinically significant postoperative decline in verbal memory. Future studies with larger sample sizes are needed to investigate the factors that increase the risk of postoperative cognitive decline, including pre-existing cognitive impairment, older age, and lesion size.