Ecological validity of cognitive fluctuations in dementia with Lewy bodies.

OBJECTIVES: Cognitive fluctuations are a core clinical feature of dementia with Lewy bodies (DLB), but their contribution to the everyday functioning difficulties evident DLB are not well understood. The current study evaluated whether intraindividual variability across a battery of neurocognitive tests (intraindividual variability-dispersion) and daily cognitive fluctuations as measured by informant report are associated with worse daily functioning in DLB. METHODS: The study sample included 97 participants with consensus-defined DLB from the National Alzheimer's Coordinating Center (NACC). Intraindividual variability-dispersion was measured using the coefficient of variation, which divides the standard deviation of an individual's performance scores across 12 normed neurocognitive indices from the NACC neuropsychological battery by that individual's performance mean. Informants reported on daily cognitive fluctuations using the Mayo Fluctuations Scale (MFS) and on daily functioning using the functional activities questionnaire (FAQ). RESULTS: Logistic regression identified a large univariate association of intraindividual variability-dispersion and presence of daily cognitive fluctuations on the MFS (Odds Ratio = 73.27, 95% Confidence Interval = 1.38, 3,895.05). Multiple linear regression demonstrated that higher intraindividual variability-dispersion and presence of daily cognitive fluctuations as assessed by the MFS were significantly and independently related to worse daily functioning (FAQ scores). CONCLUSIONS: Among those with DLB, informant-rated daily cognitive fluctuations and cognitive fluctuations measured in the clinic (as indexed by intraindividual variability-dispersion across a battery of tests) were independently associated with poorer everyday functioning. These data demonstrate ecological validity in measures of cognitive fluctuations in DLB.

Cream of the Crop: Clinical Representativeness of Eligible and Ineligible Cannabis Users in Research.

BACKGROUND: Experts have recommended criteria (Gonzalez et al., 2002) for recruiting pure chronic cannabis users (i.e., those without polysubstance use or psychiatric illness) when evaluating cannabis' non-acute effects on cognition. OBJECTIVES: We sought to demonstrate the implications of using such criteria by examining characteristics of respondents who completed an eligibility screening for a parent study evaluating the cognitive effects of chronic cannabis use. METHODS: Over a 3-year, 8-month period, 612 respondents from the community completed an eligibility screening based on recommendations in the cannabis literature. Using independent samples t-tests and chi-square tests, we examined whether qualified/eligible respondents (n = 219) differed from non-qualified/ineligible respondents (n = 393). RESULTS: Compared to ineligible cannabis users, eligible cannabis-using respondents were significantly younger, used cannabis more frequently, used alcohol less frequently, and were less likely to have a history of other drug use, a psychiatric diagnosis, or to have used psychiatric medication. Conclusions/Importance: Our findings indicate that eligible/pure cannabis users are not representative of typical cannabis users in the general community (i.e., ineligible users with polysubstance use and/or psychiatric diagnoses) who ultimately comprised the majority of our cannabis-using sample (65.2%). Thus, typical cannabis users may be more accurately characterized as polysubstance users, posing a number of challenges related to the generalizability of findings from studies utilizing pure samples of cannabis users. Recruiting samples of typical cannabis users will improve external validity in research. Furthermore, reporting comprehensive characteristics of such samples will enable consumers to gauge the applicability of study findings to populations of interest.

Lifetime marijuana and alcohol use, and cognitive dysfunction in people with human immunodeficiency virus infection.

BACKGROUND: Substance use is common among people with human immunodeficiency virus (HIV) infection. Alcohol, marijuana, and HIV can have negative effects on cognition. Associations between current and lifetime marijuana and alcohol use and cognitive dysfunction in people with HIV infection were examined. METHODS: Some 215 HIV-infected adults with Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) substance dependence or ever injection drug use were studied. In adjusted cross-sectional regression analyses associations were assessed between current marijuana use, current heavy alcohol use, lifetime marijuana use, lifetime alcohol use, duration of heavy alcohol use (the independent variables), and 3 measures of cognitive dysfunction (dependent variables): both the (i) memory and (ii) attention domains from the Montreal Cognitive Assessment (MoCA) and the (iii) 4-item cognitive function scale (CF4) from the Medical Outcomes Study HIV Health Survey (MOS-HIV). Analyses were adjusted for demographics, primary language, depressive symptoms, anxiety, comorbidities, antiretroviral therapy, hepatitis C virus (ever), duration of HIV infection (years), HIV-viral load (log copies/mL), CD4 cell count, lifetime and recent cocaine use, and recent illicit and prescribed opioid use. RESULTS: Current marijuana use was significantly and negatively associated with the MOS-HIV CF4 score (adjusted mean difference = -0.40, P = .01). Current marijuana use was not significantly associated with either MoCA score. Lifetime marijuana use and current heavy and lifetime alcohol use and duration of heavy alcohol use were not associated with any measure of cognitive dysfunction. CONCLUSION: Current marijuana use was associated with one measure of cognitive dysfunction, but there was not a consistent pattern of association with lifetime marijuana use or alcohol use and measures of cognitive dysfunction. Understanding the mechanism by which marijuana, with and without alcohol, are associated with worse cognition warrants larger, longer studies with more precise and diverse measurements of cognitive function.

Self-perceived cognitive fluctuations and their relationship to everyday functioning in older adults with and without HIV disease.

Objective: HIV is associated with elevated performance-based cognitive intra-individual variability (IIV) in the laboratory that can reflect difficulty regulating cognitive resources over time (i.e., cognitive fluctuations) and disrupt everyday functioning. Whether persons living with HIV (PLWH) experience appreciable cognitive fluctuations in their daily lives is unclear. This study examined the presence of cognitive fluctuations and their relationship to everyday functioning in PLWH. Methods: Participants were 145 PLWH and 61 seronegative individuals age ≥ 50 years who completed a self-report version of the Mayo Fluctuations Scale (MFS), structured psychiatric interview, medical evaluation, and well-validated measures of mood, cognitive symptoms, and activities of daily living (ADLs). A confirmatory factor analysis of the MFS yielded three factors, including a 7-item cognitive fluctuations scale. Results: Univariable analyses showed that HIV was associated with moderately higher MFS Cognitive Fluctuation subscale scores (d = 0.46), but this effect was no longer significant a multiple regression model that included medical comorbidities and affective disorders, which emerged as unique predictors. Of clinical relevance, higher MFS Cognitive Fluctuation subscale scores were independently associated with more frequent cognitive symptoms and dependence in ADLs in the full sample. Conclusions: Higher frequency of self-perceived cognitive fluctuations disrupts management of ADLs among middle-aged and older adults independent of HIV status and general cognitive symptoms. Future studies are needed to understand the full clinical significance of self-perceived cognitive fluctuations among PLWH and their impact on daily life.

Psychiatric Comorbidities in Women Veterans with Epilepsy.

Background: Women Veterans with epilepsy (WVE) may have unique psychiatric comorbidities that affect presentation, treatment, and outcomes. This large, nationally representative study of Veterans Health Administration (VHA) patients explores sex differences in psychiatric diagnoses and treatment to better characterize WVE. Methods: This study included a retrospective cohort design utilizing VHA Corporate Data Warehouse administrative data. Data from 58,525 Veterans with epilepsy (8.5% women) were obtained. Psychiatric diagnoses and treatment were analyzed, with comparisons between men with epilepsy and WVE. Secondary analyses included further exploration of select gynecological conditions. Results: WVE had higher psychiatric burden than men, as evidenced by higher rates of nearly all psychiatric diagnoses, including depression (59.1% vs. 38.9%; χ2 = 771.6), posttraumatic stress disorder (42.0% vs. 26.5%; χ2 = 549.1), and anxiety disorder (44.9% vs. 24.5%; χ2 = 977.7), as well as higher use of psychotropic medication prescriptions (2.3 vs. 1.4 average number of psychotropics prescribed). Furthermore, higher percentages of women versus men utilized the emergency room for psychiatric purposes (11.7% vs. 6.9%; χ2 = 153.06) and were hospitalized with psychiatric diagnoses (9.8% vs. 6.1%; χ2 = 100.95). Discussion: Veterans with epilepsy represent a unique group with high rates of psychiatric comorbidity. These results suggest that among Veterans, men and women with epilepsy have differing psychiatric comorbidities, leading to disparate health care needs. Based on this study's findings, WVE may require a different approach to care with an increased focus on specialized psychiatric treatment for WVE.

Cognitive dispersion and its functional relevance in behavioral variant frontotemporal dementia and prodromal behavioral variant frontotemporal dementia.

OBJECTIVE: Executive dysfunction is characteristic of behavioral variant frontotemporal dementia (bvFTD) but can be challenging to detect. Dispersion-based intraindividual variability (IIV-d) is hypothesized to reflect a sensitive index of executive dysfunction and has demonstrated relevance to functional decline but has not been evaluated in bvFTD. METHOD: We report on 477 demographically matched participants (159 cognitively healthy [CH], 159 clinical Alzheimer's disease [AD], 159 clinical bvFTD/prodromal bvFTD) who completed the Uniform Data Set 3.0 Neuropsychological Battery. IIV-d was measured using the coefficient of variance (CoV; raw and demographically adjusted) across 12 Uniform Data Set 3.0 Neuropsychological Battery indicators and the informant-rated Functional Activities Questionnaire assessed daily functioning. RESULTS: Analysis of covariance showed that participants in the bvFTD/prodromal bvFTD group exhibited higher raw and demographically adjusted CoV compared to CH participants, at a very large effect size (d = 1.28-1.47). Demographically adjusted (but not raw) CoV was lower in the bvFTD/prodromal bvFTD group than the AD group, though the effect size was small (d = .38). Both CoV metrics accurately differentiated the bvFTD/prodromal bvFTD and CH groups (areas under the curve = .84), but not bvFTD/prodromal bvFTD and AD groups (areas under the curve = .59). Regression analyses in the bvFTD/prodromal bvFTD group indicated that higher IIV-d on both metrics was associated with greater daily functioning impairment, over and above covariates. CONCLUSIONS: Compared to healthy adults, individuals with bvFTD/prodromal bvFTD show greater levels of performance variability across a battery of neuropsychological measures, which interferes with everyday functioning. These data demonstrate the clinical utility and ecological validity of IIV-d in bvFTD/prodromal bvFTD, though these findings should be replicated in more diverse samples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The neuropsychological presentation of women with epilepsy: clinical considerations and future directions.

Objective: Cognitive, mood, and behavioral changes are common among persons with epilepsy (PWE), resulting in a complex neuropsychological presentation. Women with epilepsy (WWE) represent a distinct cohort within the broader epilepsy population due to sex and gender-specific factors impacting epilepsy semiology and treatment. However, unique neuropsychological profiles among WWE have not been established. This narrative review aims to further define neuropsychological correlates in WWE and promote meaningful discussion related to enhancing the provision of neuropsychological care within this clinical population. Method: Current literature in PWE examining differences in cognitive function, mental health, and quality of life (QoL) between women and men was critically reviewed, emphasizing considerations for neuropsychological practice. Results: WWE demonstrate a preservation of verbal learning and memory compared to men both pre- and post-surgically, with sex-based, neurobiological mechanisms likely contributing to this association. WWE also have elevated risk for affective disorder psychopathology, suicidality, and traumatic experiences. Epidemiology related to psychotic and bipolar spectrum disorders is less clear, and findings are mixed regarding sex-specific behavioral side effects of antiseizure and psychotropic medication. Finally, hormonal and obstetric factors are highlighted as important contributors to neuropsychological symptoms in WWE, with elevated risk for low QoL and increased stigma associated with greater medical and psychiatric comorbidities compared to men. Conclusions: While emerging literature has begun to characterize the neuropsychological presentation of WWE, future research is needed to define sex and gender differences in neuropsychological sequalae among PWE to ensure consistency and quality of care for WWE.

Utilization of epilepsy care among Women Veterans: A population-based study.

OBJECTIVE: Higher healthcare utilization in epilepsy correlates with better clinical and quality of life outcomes. Women Veterans with epilepsy (WVE) have unique characteristics that may affect access and utilization of care. This study investigates epilepsy care in WVE, with respect to utilization of outpatient, inpatient, and emergency room care. METHODS: Data were collected from 58,525 Veterans with epilepsy using the Veterans Health Administration (VHA) Corporate Data Warehouse administrative data. Overall, 8.5% of the sample were women (n = 4983). Neurology visits, comprehensive epilepsy care, neuroimaging, ASM prescription and hospital and emergency care were analyzed, and comparisons were made with men Veterans with epilepsy to identify gender differences. RESULTS: Compared to men, a greater proportion of WVE utilized services including neurology (73.8% vs. 62.0%), comprehensive epilepsy care (16.1% vs. 11.7%), epilepsy monitoring unit evaluation (EMU; 6.1% vs. 2.9%), neuroimaging (CT: 39.1% vs. 36.6%; MRI: 43.7% vs. 32.5%), and electroencephalograms: (EEG: 36.5% vs. 29.1%). WVE also evidenced higher percentages of seizure-related emergency room care usage vs. men (15.2 vs. 12.6) and hospitalizations (12.3 vs. 10.0) and were prescribed a greater number of ASMs (average:2.3 vs. 1.9). Valproate was prescribed to 17.6% of WVE, despite potential teratogenic concerns. SIGNIFICANCE: WVE have greater utilization of epilepsy care within the VHA system compared to men, which could lead to better epilepsy management and quality of life. However, higher rates of emergency care, hospitalizations, and concurrent ASMs among WVE highlight the clinical complexity and raise concern for potentially comorbid conditions including psychogenic non-epileptic seizures.

A Longitudinal Examination of Alcohol-Related Blackouts as a Predictor of Changes in Learning, Memory, and Executive Function in Adolescents.

Introduction: In adolescents, the relationship between alcohol-related blackouts (ARBs) and distinct cognitive changes lasting beyond intoxication is unclear. We examined ARBs as a predictor of persistent changes in the development of learning, memory, and executive function in participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. Methods: Descriptive analyses of the NCANDA sample (N = 831, 50.9% female, 12-21 years at baseline) identified ARB patterns within participants with an ARB history (n = 106). Latent growth curve modeling evaluated ARB-related performance changes on four neuropsychological measures across five years, excluding baseline data to reduce the magnitude of practice effects over time (n = 790). Measures included the Penn Conditional Exclusion Test (PCET), Penn Letter N-back Test (PLBT), Penn Facial Memory Test immediate (PFMTi), and delayed (PFMTd) recognition trials, and the Rey Complex Figure Test copy (RCFTc), immediate recall (RCFTi), and delayed recall (RCFTd) trials. Multivariate models were fit for raw accuracy scores from each measure, with ARB history (i.e., presence of past-year ARBs) as the main independent variable. Age, sex, race, socioeconomic status, assessment site, and alcohol use (i.e., past-year frequency) were included as covariates. Interaction effects between ARB history and alcohol use frequency were tested. Results: By year five, 16% of participants had experienced at least one ARB (59% of whom reported > 1 ARB and 57% of whom had an ARB lasting > 1 h). After controlling for demographics and alcohol use, ARB history predicted attenuated PFMTd performance growth at year one. Interaction effects between ARB history and alcohol use frequency predicted attenuated PFMTd performance growth at years one and two. ARB history predicted attenuated RCFTi and RCFTd performance growth by year four, but not PCET or PLBT performance over time. By contrast, greater past-year alcohol use predicted attenuated PFMTi and PFMTd performance growth between years two and four in adolescents without an ARB history. Conclusion: We found that ARBs predict distinct, lasting changes in learning and memory for visual information, with results suggesting that the developing brain is vulnerable to ARBs during adolescence and emerging adulthood.