Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

National Norms for Hospitalizations Due to Ambulatory Care Sensitive Conditions among Adults in the US.

BACKGROUND: Ambulatory care sensitive conditions (ACSCs) are acute or chronic health issues that lead to potentially preventable hospitalizations when not treated in the outpatient primary care setting. OBJECTIVE: To describe national hospitalization rates due to ACSCs among adult inpatients in the US. DESIGN: A retrospective cross-sectional analysis of the 2018 US National Inpatient Sample (NIS) dataset from the Healthcare Cost and Utilization Project at the Agency of Healthcare Research and Quality was completed in the year 2022. PARTICIPANTS: Participants were adult inpatients from community hospitals in 48 states of the US and District of Columbia. MAIN MEASURES: ACSC admission rates were calculated using ICD-10 codes and the Purdy ACSC definition. The admission rates were weighted to the US inpatient population and stratified by age, sex, and race. KEY RESULTS: ACSC hospitalization rates varied considerably across age and average number of hospitalizations varied across sex and race. ACSC hospitalization rates increased with age, male sex, and Native American and Black race. The most common ACSCs were pneumonia, diabetes, and congestive heart failure. CONCLUSIONS: Previous studies have emphasized the importance of preventable hospitalizations, however, the national rates for ACSC hospitalizations across all ages in the US have not been reported. The national rates presented will facilitate comparisons to identify hospitals and health care systems with higher-than-expected rates of ACSC admissions that may suggest a need for improved primary care services.

Neuropsychological Functioning in Primary Dystonia: Updated and Expanded Multidomain Meta-Analysis.

BACKGROUND: Primary dystonia is conventionally considered as a motor disorder, though an emerging literature reports associated cognitive dysfunction. OBJECTIVES: Here, we conducted meta-analyses on studies comparing clinical measures of cognition in persons with primary dystonia and healthy controls (HCs). METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and PsycINFO (January 2000-October 2020). Analyses were modeled under random effects. We used Hedge's g as a bias-corrected estimate of effect size, where negative values indicate lower performance in dystonia versus controls. Between-study heterogeneity and bias were primarily assessed with Cochran's Q, I2 , and Egger's regression. RESULTS: From 866 initial results, 20 studies met criteria for analysis (dystonia n = 739, controls n = 643; 254 effect sizes extracted). Meta-analysis showed a significant combined effect size of primary dystonia across all studies (g = -0.56, P < 0.001), with low heterogeneity (Q = 25.26, P = 0.15, I2  = 24.78). Within-domain effects of primary dystonia were motor speed = -0.84, nonmotor speed = -0.83, global cognition = -0.65, language = -0.54, executive functioning = -0.53, learning/memory = -0.46, visuospatial/construction = -0.44, and simple/complex attention = -0.37 (P-values <0.01). High heterogeneity was observed in the motor/nonmotor speed and learning/memory domains. There was no evidence of publication bias. Moderator analyses were mostly negative but possibly underpowered. Blepharospasm samples showed worse performance than other focal/cervical dystonias. Those with inherited (ie, genetic) disease etiology demonstrated worse performance than acquired. CONCLUSIONS: Dystonia patients consistently demonstrated lower performances on neuropsychological tests versus HCs. Effect sizes were generally moderate in strength, clustering around -0.50 SD units. Within the speed domain, results suggested cognitive slowing beyond effects from motor symptoms. Overall, findings indicate dystonia patients experience multidomain cognitive difficulties, as detected by neuropsychological tests. © 2022 International Parkinson and Movement Disorder Society.

Cannabidiol (CBD) and cognition in epilepsy.

Anecdotal reports of the benefits of cannabis and its components in the treatment of epilepsy have been reported for millennia. However, only recently randomized controlled trial data in support of cannabidiol (CBD) became available resulting in its FDA approval for the treatment of seizures and epilepsy. One of the most common and debilitating comorbidities of epilepsy is cognitive impairment. This impairment has a multifactorial etiology including network dysfunction due to seizures, negative cognitive side effects from anti-seizure medications (ASMs), and mood disturbances. Knowing the effects of a particular ASM (either positive or negative) is vital for providers to counsel patients on expected side effects, and may result in choosing a particular regimen over the other if the patient already suffers from significant cognitive deficits. Unlike most other ASMs and other well-studied cannabinoids such as Δ9-tetrahydrocannabinol, CBD has been shown to have additional mechanisms of action (MOA) that result in neuroprotective, anti-inflammatory, anti-oxidant, and neurogenesis effects. These additional MOAs suggest that the use of CBD could lead to other actions including positive effects on cognition that may be independent of seizure control. This targeted review discusses the currently available data on CBD's effects on cognition in epilepsy. First, we review the proposed mechanisms by which CBD could exert effects on cognition. Then, we present the pre-clinical/animal data investigating cognitive effects of CBD in seizure/epilepsy models. Finally, we discuss the available human data, including the studies in people with epilepsy that included cognitive evaluations pre- and on-CBD, and studies investigating if CBD has any effects on brain structure or function in areas pertinent to memory and cognitive functions.

Relationships between cognitive function, seizure control, and self-reported leisure-time exercise in epilepsy.

Exercise may be a strategy for improvement of cognitive deficits commonly present in people with idiopathic generalized epilepsies (IGE). We investigated the relationship between cognition and level of physical exercise in leisure (PEL) in people with IGE who have been seizurefree for at least 6 months (IGE-) as compared to those who have not been seizurefree (IGE+) and healthy controls (HCs). We hypothesized that higher level of physical exercise is associated with better cognitive functioning in patients with IGE and HCs, and that seizure control affects both PEL levels and cognitive functioning in patients with IGE. We recruited 75 participants aged 18-65: 31 people with IGE (17 IGE-, 14 IGE+) and 44 HCs. Participants completed assessments of quality of life (SF-36), physical activity levels (Baecke questionnaire and International Physical Activity Questionnaire (IPAQ)) and cognition (Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test - Revised (HVLT), and flanker task). Group differences (HCs vs. IGE; HCs vs. IGE+ vs. IGE-) were assessed. Pearson correlations examined linear relationships between PEL and cognitive performance. Groups were similar in age and sex. Compared to HCs, patients with IGE had higher body mass index, fewer years of education, and consistently scored worse on all measures except flanker task accuracy on incongruent trials. When examining IGE- and IGE+ subgroups, compared to HCs, both had higher body mass index, and fewer years of education. Healthy controls scored significantly better than one or both of the IGE groups on SF-36 scores, PEL levels, IPAQ activity level, MoCA scores, HVLT learning and long-delay free-recall scores, and flanker task accuracy on congruent trials. Among patients with IGE, there were no significant differences between age of epilepsy onset, duration of epilepsy, number of anti-seizure drugs (ASDs) currently being used, or the group distribution of type of IGE. In the combined sample (IGE+, IGE- and HCs), PEL positively correlated with MoCA scores (Pearson's r = 0.238; p = 0.0397) and with flanker task accuracy on congruent trials (Pearson's r = 0.295; p = 0.0132). Overall, patients with IGE performed worse than HCs on cognitive and physical activity measures, but the cognitive impairments were more pronounced for IGE+, while physical exercise levels were less for patients with IGE regardless of seizure control. While positive relationships between leisure-time PEL and cognitive performance are promising, further investigations into how exercise levels interact with cognitive functioning in epilepsy are needed.

Effects of highly purified cannabidiol (CBD) on fMRI of working memory in treatment-resistant epilepsy.

OBJECTIVE: We aimed to determine changes in working memory and functional connectivity via functional magnetic resonance imaging (fMRI)-modified Sternberg task after treatment with highly purified cannabidiol (CBD, Epidiolex®; 100 mg/mL) in patients with treatment-resistant epilepsy (TRE). METHODS: Twenty patients with TRE (mean age: 35.8 years; 7 male) performed fMRI Sternberg task before receiving CBD ("PRE") and after reaching stable dosage of CBD (15-25 mg/kg/day; "ON"). Each patient performed 2 runs of the modified Sternberg task during PRE and ON fMRI. Twenty-three healthy controls (HCs; mean age: 25 years; 11 M) also completed the task. All were presented with a sequence of 2 or 6 letters and instructed to remember them (encoding). After a delay, a single letter was shown, and participants recalled if letter was shown in sequence (retrieval). Paired t-tests were used to analyze accuracy/response times. For each subject, event-related modeling of encoding (2 and 6 letters) and retrieval was performed. Paired t-tests controlling for seizure frequency change and scanner type were performed to assess changes in neural recruitment during encoding and retrieval in key regions of interest. RESULTS: There was nonsignificant increase in mean modified Sternberg task accuracy from PRE to ON-CBD (28.6 vs. 32.1%). PRE and ON accuracy was worse than HCs (75.5%, p < 0.001). ON-PRE comparison revealed increased activation in the right inferior frontal gyrus (IFG) during 6-letter encoding. ON-HC comparison revealed increased activation in bilateral IFG and insula during 2-letter encoding. PRE-HC comparison revealed decreased activation in the left middle frontal gyrus during 6-letter encoding. None of these activations were associated with working memory performance. SIGNIFICANCE: Treatment-resistant epilepsy results in poorer working memory performance and lower neural recruitment compared with HCs. Treatment with CBD results in no significant changes in working memory performance and in significant increases in neural activity in regions important for verbal memory and attention compared with HCs during memory encoding.

Cognitive function and adaptive skills after a one-year trial of cannabidiol (CBD) in a pediatric sample with treatment-resistant epilepsy.

OBJECTIVE: Cannabidiol (CBD) is a nonpsychoactive derivative of cannabis. Studies indicate that it is safe and effective in treating certain types of epilepsy. The present study examined the presence of adverse or beneficial cognitive or functional adaptive effects associated with CBD in the treatment of children, adolescents, and teenagers with treatment-resistant epilepsy (TRE) as part of an ongoing prospective, open-label safety study. METHODS: Participants (N = 38) between the age of 3 and 19 years with TRE were enrolled in an open-label study of a pharmaceutical formulation of CBD (Epidiolex®; GW Research Ltd.) as an add-on treatment. In addition to baseline physical, neurological, and laboratory testing, cognitive assessment was completed prior to initiating CBD and after one year, both using the NIH Toolbox Cognition Battery (NIHTB-CB). Many participants were unable to complete the NIHTB-CB because of the magnitude of their cognitive impairment (n = 24), and in these cases, the participant's caregiver was asked to complete the Adaptive Behavior Assessment System - Second Edition (ABAS-II) as a measure of functional adaptive skills. RESULTS: There were no statistically significant changes in cognitive function, as measured by the NIHTB-CB, in those participants who were able to complete such testing, but there was a nonsignificant trend toward improvement in some cognitive domains. For participants who were unable to complete formal standardized cognitive testing because of the magnitude of their cognitive impairment, their functional adaptive skills, as measured by the ABAS-II, were unchanged after a one-year trial of CBD. SIGNIFICANCE: Our findings suggest that CBD, as an add-on drug for TRE in a pediatric sample, does not appear to cause adverse effects (AEs) involving cognition or adaptive function over one year of treatment.

High health care costs in minority groups of older US Medicare beneficiaries with epilepsy.

OBJECTIVE: To examine health care costs in diverse older Medicare beneficiaries with epilepsy. METHODS: Using 2008-2010 claims data, we conducted a longitudinal cohort study of a random sample of Medicare beneficiaries augmented for minority representation. Epilepsy cases (n = 36 912) had ≥1 International Classification of Diseases, Ninth Edition (ICD-9) 345.x or ≥2 ICD-9 780.3x claims, and ≥1 antiepileptic drug (AED) in 2009; new cases (n = 3706) had no seizure/epilepsy claims nor AEDs in the previous 365 days. Costs were measured by reimbursements for all care received. High cost was defined as follow-up 1-year cost ≥ 75th percentile. Logistic regressions examined association of high cost with race/ethnicity, adjusting for demographic, clinical, economic, and treatment quality factors. In cases with continuous 2-year data, we obtained costs in two 6-month periods before and two after the index event. RESULTS: Cohort was ~62% African Americans (AAs), 11% Hispanics, 5% Asians, and 2% American Indian/Alaska Natives. Mean costs in the follow-up were ~$30 000 (median = $11 547; new cases, mean = $44 642; median = $25 008). About 19% white compared to 27% AA cases had high cost. AA had higher odds of high cost in adjusted analyses (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.11-1.29), although this was only marginally significant when adjusting for AED adherence (OR = 1.09, 95% CI = 1.01-1.18, P = 0.03). Factors associated with high cost included ≥1 comorbidity, neurological care, and low AED adherence. Costs were highest at ~$17 000 in the 6 months immediately before and after the index event (>$29 000 for new cases). SIGNIFICANCE: The financial sequelae of epilepsy among older Americans disproportionally affect minorities. Studies should examine contributors to high costs.

Cognitive functioning following long-term cannabidiol use in adults with treatment-resistant epilepsy.

Cognitive dysfunction is a common comorbidity in adults with treatment-resistant epilepsy (TRE). Recently, cannabidiol (CBD) has demonstrated efficacy in epilepsy treatment. However, our understanding of CBD's cognitive effects in epilepsy is limited. We examined long-term cognitive effects of CBD in adults with TRE as part of an ongoing prospective, open-label safety study. Twenty-sevenadults with TRE (mean age: 34[SD +14], female 52%) enrolled in the UAB CBD program completed standardized cognitive testing (NIH Toolbox Cognition Battery (NIHTB-CB)) at pre-CBD administration baseline and at one-yearfollow-up. Participants were receiving stable CBD dose at the time of one-year testing (mean=36.5mg/kg/day). The NIHTB-CB consisted of two global composite scales (Fluid and Crystallized) and seven individual tests measuring aspects of working memory, episodic memory, executive function, processing speed, and language. All participants had recorded Chalfont Seizure Severity Scale (CSSS) scores at each visit. Statistical analyses consisted of t-test, Pearson correlation coefficient, and linear regression. At baseline, cognitive test performance was below average for both global composite scales (Fluid: 71 [±18] range: 46-117) and Crystallized (76 [±15] range: 59-112)]. Longitudinal analysis revealed no significant group change across the two global composite scales. Of the seven individual cognitive tests, none changed significantly over time. No correlation was found between the cognitive change scores and CBD dose (all P's≥0.21). Change in cognitive test performance was not associated change in seizure severity rating. These findings are encouraging and indicate that long-term administration of pharmaceutical grade CBD is overall cognitively well-tolerated in adults with TRE.

A pilot study of combined endurance and resistance exercise rehabilitation for verbal memory and functional connectivity improvement in epilepsy.

Memory impairment is common in persons with epilepsy (PWE), and exercise may be a strategy for its improvement. In this pilot study, we hypothesized that exercise rehabilitation would improve physical fitness and verbal memory and induce changes in brain networks involved in memory processes. We examined the effects of combined endurance and resistance exercise rehabilitation on memory and resting state functional connectivity (rsFC). Participants were randomized to exercise (PWE-E) or control (PWE-noE). The exercise intervention consisted of 18 supervised sessions on nonconsecutive days over 6 weeks. Before and after the intervention period, both groups completed self-report assessments (Short Form-36 (SF-36), Baecke Questionnaire (BQ) of habitual physical activity, and Profile of Mood States (POMS)), cognitive testing (California Verbal Learning Test-II (CVLT-II)), and magnetic resonance imaging (MRI); PWE-E also completed exercise performance tests. After completing the study, PWE-noE were offered cross-over to the exercise arm. There were no differences in baseline demographic, clinical, or assessment variables between 8 PWE-noE and 9 PWE-E. Persons with epilepsy that participated in exercise intervention increased maximum voluntary strength (all strength tests p < 0.05) and exhibited nonsignificant improvement in cardiorespiratory fitness (p = 0.15). Groups did not show significant changes in quality of life (QOL) or habitual physical activity between visits. However, there was an effect of visit on POMS total mood disturbance (TMD) measure showing improvement from baseline to visit 2 (p = 0.023). There were significant group by visit interactions on CVLT-II learning score (p = 0.044) and total recognition discriminability (d') (p = 0.007). Persons with epilepsy that participated in exercise intervention had significant reductions in paracingulate rsFC with the anterior cingulate and increases in rsFC for the cerebellum, thalamus, posterior cingulate cortex (PCC), and left and right inferior parietal lobule (IPL) (corrected p < 0.05). Change in CVLT-II learning score was associated with rsFC changes for the paracingulate cortex (rS = -0.67; p = 0.0033), left IPL (rS = 0.70; p = 0.0019), and right IPL (rS = 0.71; p = 0.0015) while change in d' was associated with change in cerebellum rsFC to angular/middle occipital gyrus (rS = 0.68; p = 0.0025). Our conclusion is that exercise rehabilitation may facilitate verbal memory improvement and brain network functional connectivity changes in PWE and that improved memory performance is associated with changes in rsFC. A larger randomized controlled trial of exercise rehabilitation for cognitive improvement in PWE is warranted.

Anosognosia of financial ability in mild cognitive impairment.

OBJECTIVES: Although financial ability has been well-studied in mild cognitive impairment (MCI) and Alzheimer's disease (AD) using performance-based financial capacity assessment instruments, research is limited investigating everyday financial problems and declines in persons with AD and MCI and the insight of people with MCI to recognize that financial capacity declines are occurring. To address this gap in the research, we investigated everyday financial activities and skills in a sample of older adults representing the dementia spectrum. METHODS: Participants were 186 older adults in three diagnostic classifications: cognitively healthy, MCI likely due to AD, and mild AD dementia. Everyday financial ability was assessed using the Current Financial Activities Report (CFAR). The CFAR is a standardized report-based measure which elicits participant and study partner ratings about a participant's everyday financial abilities. RESULTS: Results showed that both CFAR self- and study partner-report distinguished diagnostic groups on key financial capacity variables in a pattern consistent with level of clinical pathology. Study partner-report indicated higher levels of financial skill difficulties in study participants than did the self-report of the same study participants. Study partner-ratings were more highly correlated with participant scores on a performance-based measure of financial capacity than were participant self-ratings. Results also showed that loss of awareness of financial decline is emerging at the MCI stage of AD. CONCLUSIONS: People with MCI represent a group of older adults at particular risk for financial missteps and-similar to people with AD-are in need of supervision of their financial skills and activities.

Risk of pharmacokinetic interactions between antiepileptic and other drugs in older persons and factors associated with risk.

OBJECTIVE: To determine the frequency of older Americans with epilepsy receiving concomitant prescriptions for antiepileptic drugs (AEDs) and non-epilepsy drugs (NEDs) which could result in significant pharmacokinetic (PK) interaction, and to assess the contributions of racial/ethnic, socioeconomic, and demographic factors. METHODS: Retrospective analyses of 2008-2010 Medicare claims for a 5% random sample of beneficiaries ≥67 years old in 2009 augmented for minority representation. Prevalent cases had ≥1 ICD-9 345.x or ≥2 ICD-9 780.3x, and ≥1 AED. Among them, incident cases had no seizure/epilepsy claim codes nor AEDs in preceding 365 days. Drug claims for AEDs, and for the 50 most common NEDs within +/- 60 days of the index epilepsy date were tabulated. Interacting pairs of AEDs/NEDs were identified by literature review. Logistic regression models were used to examine factors affecting the likelihood of interaction risk. RESULTS: Interacting drug pairs affecting NED efficacy were found in 24.5% of incident, 39% of prevalent cases. Combinations affecting AED efficacy were found in 20.4% of incident, 29.3% of prevalent cases. Factors predicting higher interaction risk included having ≥ 1 comorbidity, being eligible for Part D low Income Subsidy, and not living in the northeastern US. Protective factors were Asian race/ethnicity, and treatment by a neurologist. SIGNIFICANCE: A substantial portion of older epilepsy patients received NED-AED combinations that could cause important PK interactions. The lower frequency among incident vs. prevalent cases may reflect changes in prescribing practices. Avoidance of interacting AEDs is feasible for most persons because of the availability of newer drugs.

What does the U.S. Medicare administrative claims database tell us about initial antiepileptic drug treatment for older adults with new-onset epilepsy?

OBJECTIVE: Disparities in epilepsy treatment are not uncommon; therefore, we examined population-based estimates of initial antiepileptic drugs (AEDs) in new-onset epilepsy among racial/ethnic minority groups of older US Medicare beneficiaries. METHODS: We conducted retrospective analyses of 2008-2010 Medicare administrative claims for a 5% random sample of beneficiaries augmented for minority representation. New-onset epilepsy cases in 2009 had ≥1 International Classification of Diseases, Ninth Revision (ICD-9) 345.x or ≥2 ICD-9 780.3x, and ≥1 AED, AND no seizure/epilepsy claim codes or AEDs in preceding 365 days. We examined AED use and concordance with Quality Indicators of Epilepsy Treatment (QUIET) 6 (monotherapy as initial treatment = ≥30 day first prescription with no other concomitant AEDs), and prompt AED treatment (first AED within 30 days of diagnosis). Logistic regression examined likelihood of prompt treatment by demographic (race/ethnicity, gender, age), clinical (number of comorbid conditions, neurology care, index event occurring in the emergency room (ER)), and economic (Part D coverage phase, eligibility for Part D Low Income Subsidy [LIS], and ZIP code level poverty) factors. RESULTS: Over 1 year of follow-up, 79.6% of 3,706 new epilepsy cases had one AED only (77.89% of whites vs. 89% of American Indian/Alaska Native [AI/AN]). Levetiracetam was the most commonly prescribed AED (45.5%: from 24.6% AI/AN to 55.0% whites). The second most common was phenytoin (30.6%: from 18.8% Asians to 43.1% AI/AN). QUIET 6 concordance was 94.7% (93.9% for whites to 97.3% of AI/AN). Only 50% received prompt AED therapy (49.6% whites to 53.9% AI/AN). Race/ethnicity was not significantly associated with AED patterns, monotherapy use, or prompt treatment. SIGNIFICANCE: Monotherapy is common across all racial/ethnic groups of older adults with new-onset epilepsy, older AEDs are commonly prescribed, and treatment is frequently delayed. Further studies on reasons for treatment delays are warranted. Interventions should be developed and tested to develop paradigms that lead to better care.

Quality Indicator for Epilepsy Treatment 15 (QUIET-15): Intervening after recurrent seizures in the elderly.

In this study, we examined the provision of care to older adults with epilepsy and compliance with the "Quality Indicator for Epilepsy Treatment 15" (QUIET-15) measure. We analyzed 2008-2010, 5% random sample of Medicare beneficiaries augmented with data from all beneficiaries who identified as a minority with claims related to seizures (780.3x) or epilepsy (345.xx). Of 36,912 identified epilepsy cases, 12.6% had ≥1 emergency room (ER) visit for seizure(s). For those who presented to ER, among those taking anti-epileptic drugs (AEDs), AED was changed in 15.4%, dose adjusted in 19.7%, and stopped in 14.9%; among those not taking AED, therapy was initiated in 68.5%. In adjusted logistic regressions, African-Americans were more likely to have recurrent seizures than Whites (OR 1.41, 95%CI 1.27-1.56), while Asians were less likely to have recurrent seizures (OR 0.71, 95%CI 0.57-0.89). There were no significant racial/ethnic differences in the likelihood of a post-seizure intervention. The chance of seizure recurrence leading to ER visit decreased with age and increased with the number of comorbidities. Patients with seizure recurrence were more likely to be taking an enzyme-inducing AED (OR 1.69, 95%CI 1.57-1.82) and receiving Part D Low Income Subsidy (OR 1.36, 95%CI 1.22-1.51). The probability of AED change after a seizure was higher for patients with ≥4 comorbidities (OR 1.69, 95%CI 1.25-2.27), patients who saw a neurologist (OR 1.49, 95%CI 1.30-1.70), and patients who were taking an enzyme-inducing AED (OR 1.47, 95%CI 1.27-1.71). Overall, a minority of Medicare beneficiaries experienced seizure recurrence that resulted in an ER visit. However, only half of them received treatment concordant with QUIET-15. Though racial differences were observed in occurrence of seizures, none were noted in the provision of care.

Neurocognitive Predictors of Declining Financial Capacity in Persons with Mild Cognitive Impairment.

OBJECTIVE: To identify cognitive predictors of declining financial capacity (FC) in persons with mild cognitive impairment (MCI). METHODS: Participants were 66 cognitively normal older adults and 49 persons with MCI who completed neuropsychological testing and a performance measure of financial capacity (Financial Capacity Instrument; FCI) at baseline and two-year follow-up. We calculated two-year change scores for neuropsychological tests and FCI total score. We examined bivariate correlations between demographic/clinical variables and FCI change score, and between neuropsychological and FCI change scores. The five strongest bivariate correlates were entered into a linear regression analysis to identify longitudinal predictors of financial decline within group. RESULTS: Persons with MCI showed significant decline on the FCI and most cognitive variables, while controls demonstrated relatively stable performance. For persons with MCI, education correlated with FCI change score. The top four cognitive variable-FCI change score correlations were written arithmetic, confrontation naming, immediate visual memory, and visual attention. In the regression model, written arithmetic was the primary predictor and visual memory and visual attention were secondary predictors of two-year FCI change scores. CONCLUSION: Semantic arithmetic knowledge, and to a lesser extent visual memory and attention, are key longitudinal cognitive predictors of financial skill decline in individuals with MCI. CLINICAL IMPLICATIONS: Clinicians should consider neurocognitive abilities of written arithmetic, visual memory, and processing speed in their assessments of financial capacity in person with MCI.

Neurocognitive Models of Medical Decision-Making Capacity in Traumatic Brain Injury Across Injury Severity.

OBJECTIVE: To identify neurocognitive predictors of medical decision-making capacity (MDC) in participants with mild and moderate/severe traumatic brain injury (TBI). SETTING: Academic medical center. PARTICIPANTS: Sixty adult controls and 104 adults with TBI (49 mild, 55 moderate/severe) evaluated within 6 weeks of injury. DESIGN: Prospective cross-sectional study. MAIN MEASURES: Participants completed the Capacity to Consent to Treatment Instrument to assess MDC and a neuropsychological test battery. We used factor analysis to reduce the battery test measures into 4 cognitive composite scores (verbal memory, verbal fluency, academic skills, and processing speed/executive function). We identified cognitive predictors of the 3 most clinically relevant Capacity to Consent to Treatment Instrument consent standards (appreciation, reasoning, and understanding). RESULTS: In controls, academic skills (word reading, arithmetic) and verbal memory predicted understanding; verbal fluency predicted reasoning; and no predictors emerged for appreciation. In the mild TBI group, verbal memory predicted understanding and reasoning, whereas academic skills predicted appreciation. In the moderate/severe TBI group, verbal memory and academic skills predicted understanding; academic skills predicted reasoning; and academic skills and verbal fluency predicted appreciation. CONCLUSIONS: Verbal memory was a predictor of MDC in controls and persons with mild and moderate/severe TBI. In clinical practice, impaired verbal memory could serve as a "red flag" for diminished consent capacity in persons with recent TBI.

Capacity of patients with brain metastases to make treatment decisions.

OBJECTIVE: The aim of this study was to investigate medical decision-making capacity (MDC) in patients with brain metastases. METHODS: Participants were 41 adults with brain metastases with Karnofsky Performance Status scores of ≥70 who were recruited from an academic medical center and 41 demographically matched controls recruited from the community. We evaluated MDC using the Capacity to Consent to Treatment Instrument and its four clinically relevant consent standards (expressing a treatment choice, appreciation, reasoning, and understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, and severe impairment) on the consent standards were also assigned to each participant with brain metastasis using cutoff scores derived statistically from the performance of the control group. RESULTS: The brain metastasis patient group performed significantly below controls on consent standards of understanding and reasoning. Capacity compromise was defined as performance ≤1.5 standard deviations below the control group mean. Using this definition, approximately 60% of the participants with brain metastases demonstrated capacity compromise on at least one MDC standard. CONCLUSION: When defining capacity compromise as performance ≤1.5 standard deviation below the control group mean, over half of patients with brain metastases have reduced capacity to make treatment decisions. This impairment is demonstrated shortly after initial diagnosis of brain metastases and highlights the importance of routine clinical assessment of MDC following diagnosis of brain metastasis. These results also indicate a need for the development and investigation of interventions to support or improve MDC in this patient population.

Psychiatric and neurologic risk factors for incident cases of new-onset epilepsy in older adults: data from U.S. Medicare beneficiaries.

OBJECTIVE: Neurologic diseases such as stroke are risk factors for new-onset epilepsy in older adults. Recent evidence suggests that psychiatric disorders independently predict epilepsy in older male veterans. Our aim was to examine the relationship between these disorders in a population-based study of older adults that also included women and minorities. METHODS: We used a national 5% random sample of 2005 Medicare beneficiaries including all 50 US states and Washington, DC. Beneficiaries were 65 years of age or older, with continuous Medicare Part A and Part B coverage and not in managed care plans. Epilepsy cases were identified from claims for physician visits, hospitalizations, and outpatient procedures. We used logistic regressions for the overall sample and stratified by gender to determine whether risk of new-onset epilepsy was associated with prior history of psychiatric (i.e., depression, psychosis, bipolar disorder, schizophrenia, posttraumatic stress disorder (PTSD), adjustment disorder, and substance abuse/dependence) and neurologic conditions (i.e., cerebrovascular disease, dementia, traumatic brain injury, brain tumor, metastatic cancer). RESULTS: Preexisting psychiatric disorders were significantly associated with new-onset epilepsy in the study population as were the neurologic conditions evaluated. Five of the seven psychiatric disorders examined were independently associated with new-onset epilepsy; substance abuse, psychosis, bipolar disorder, schizophrenia, and depression. Gender interaction effects were found for substance abuse/dependence and brain tumors. SIGNIFICANCE: Both neurologic and psychiatric factors significantly predicted new-onset epilepsy in a population-based sample of male and female older adults. These results support earlier findings and extend the understanding of risk models for new-onset epilepsy in broader older adult populations.

Cognition in patients with newly diagnosed brain metastasis: profiles and implications.

Cognitive impairment is a common symptom in patients with brain metastasis, and significant cognitive dysfunction is prevalent in a majority of patients who are still able to engage in basic self-care activities. In the current study, the neurocognitive performance of 32 patients with brain metastasis and 32 demographically-matched controls was examined using a battery of standardized neuropsychological tests, with the goal of comprehensively examining the cognitive functioning of newly diagnosed brain metastasis patients. The cognition of all patients was assessed within 1 week of beginning treatment for brain metastasis. Results indicated impairments in verbal memory, attention, executive functioning, and language in relation to healthy controls. Performance in relation to appropriate normative groups was also examined. Overall, cognitive deficits were prevalent and memory was the most common impairment. Given that cognitive dysfunction was present in this cohort of patients with largely minimal functional impairment, these results have implications for patients, caregivers and health care providers treating patients with brain metastasis.

Recovery over 6 months of medical decision-making capacity after traumatic brain injury.

OBJECTIVE: To investigate recovery of medical decision-making capacity (MDC) over 6 months in persons with traumatic brain injury (TBI) stratified by injury severity. DESIGN: Longitudinal study comparing controls and patients with TBI 1 month after injury (t1) and 6 months after injury (t2). SETTING: Inpatient TBI rehabilitation unit and outpatient neurology department. PARTICIPANTS: Participants (N=151) consisted of control subjects (n=60) and patients with TBI (n=91) stratified by injury severity: mild TBI (mTBI; n=27), complicated mild TBI (cmTBI; n=20), and moderate/severe TBI (msevTBI; n=44). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We used the Capacity to Consent to Treatment Instrument to evaluate MDC performance on 5 consent standards (expressing choice, reasonable choice, appreciation, reasoning, and understanding). We also assigned capacity impairment ratings on the consent standards to each participant with TBI using cut scores referenced to control performance. RESULTS: Control performance was stable across time on the consent standards. Patients with mTBI and cmTBI performed below controls on the understanding standard at t1 but not t2. Patients with msevTBI performed below controls on appreciation, reasoning, and understanding at t1, and on appreciation and understanding at t2, but showed substantial improvement over time. CONCLUSIONS: Regardless of injury severity, all groups with TBI demonstrated baseline impairment of MDC with subsequent partial or full recovery of MDC over a 6-month period. However, a sizeable proportion of individual patients with TBI in each group continued to demonstrate capacity compromise at 6 months postinjury. Clinically, this finding suggests that individuals with TBI, regardless of injury severity, need continued monitoring regarding MDC for at least 6 months after injury.