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.

The Technology in Caring Questionnaire: Development and Psychometric Properties.

OBJECTIVE: We developed the Technology in Caring Questionnaire (TCQ) to assess the use of technology-based strategies by dementia caregivers. METHODS: One hundred caregivers completed a survey that included TCQ items along with measures of technology proficiency and patient and caregiver-centered outcomes. RESULTS: The final 34-item TCQ scale had adequate to excellent internal consistency (raw Cronbach alpha = 0.75; standardized Cronbach alpha = 0.95; Guttman lambda-6 = 0.97). TCQ scores demonstrated modest convergent associations with scores from measures of smartphone ( r = 0.265, P < 0.01) and computer proficiency ( r = 0.230, P < 0.05) but a strong association with overall technology experience scores ( r = 0.578, P < 0.001). Elevated TCQ scores were associated with reduced informant-reported cognitive symptoms ( B = -0.003, P < 0.05), increased ability of caregivers to find support and information ( B = 0.03, P < 0.001), and increased direct care strain ( B = 0.03, P < 0.05), after controlling for dementia severity and demographics. CONCLUSION: The TCQ has good psychometric properties for the assessment of technology-based care strategies among dementia caregivers. Findings imply that the use of technologies may aid in symptom management and finding support and information but may also increase caregiver strain.

Recent Advances in Neuropsychological Test Interpretation for Clinical Practice.

Much attention in the field of clinical neuropsychology has focused on adapting to the modern healthcare environment by advancing telehealth and promoting technological innovation in assessment. Perhaps as important (but less discussed) are advances in the development and interpretation of normative neuropsychological test data. These techniques can yield improvement in diagnostic decision-making and treatment planning with little additional cost. Brooks and colleagues (Can Psychol 50: 196-209, 2009) eloquently summarized best practices in normative data creation and interpretation, providing a practical overview of norm development, measurement error, the base rates of low scores, and methods for assessing change. Since the publication of this seminal work, there have been several important advances in research on development and interpretation of normative neuropsychological test data, which may be less familiar to the practicing clinician. Specifically, we provide a review of the literature on regression-based normed scores, item response theory, multivariate base rates, summary/factor scores, cognitive intraindividual variability, and measuring change over time. For each topic, we include (1) an overview of the method, (2) a rapid review of the recent literature, (3) a relevant case example, and (4) a discussion of limitations and controversies. Our goal was to provide a primer for use of normative neuropsychological test data in neuropsychological practice.

Psychometric properties of the Autonomic Symptoms Checklist in the Lewy body disease module of the uniform dataset.

INTRODUCTION: Autonomic dysfunction is an important feature of Lewy Body Dementia (DLB), but measurement of autonomic symptoms has been limited in both previous research and clinical practice. Accurate measurement of autonomic dysfunction has the potential to improve our understanding of the course and progression of DLB, given that autonomic symptoms typically precede cognitive impairment and are associated with functional impairment. The primary aim of this study was to examine the psychometric properties of the two versions (3.0 and 3.1) of the NACC LBD-module Autonomic Symptom Checklist (ASC). METHODS: Psychometric analyses of the ASC (internal consistency, reliability, factor structure, and validity) were conducted on data acquired from 245 individuals with DLB from the NACC database. ASC V3.0 was contrasted on these attributes to V3.1. RESULTS: Results suggested an underlying factor structure for the ASC, and confirmatory factor analysis (CFA) revealed 3 factors, which generally aligned with discrete autonomic systems. The ASC V3.0 and CFA-identified scales were comparable in terms of reliability, which were both improved relative to the ASC V3.1. In terms of ecological validity, CFA-identified items related to gastrointestinal/thermoregulation symptoms were significantly more associated with functional outcomes compared to the unitary ASC. CONCLUSION: Findings underscore the importance of differentiation within the autonomic system. Future research into autonomic symptom classes and lab-based pathophysiological measurement of autonomic dysfunction in DLB has the potential to support early identification and inform treatment planning.

Neuropsychological Equivalence of the Clinical Diagnosis of Mild Cognitive Impairment in the National Alzheimer's Coordinating Center Uniform Data Set and Alzheimer's Disease Neuroimaging Initiative.

INTRODUCTION: Our understanding of Alzheimer's disease may be improved by harmonizing data from large cohort studies of older adults. Differences in the way clinical conditions, like mild cognitive impairment (MCI), are diagnosed may lead to variability among participants that share the same diagnostic label. This variability presents a challenge for cohort harmonization and may lead to inconsistency in research findings. Little research to date has explored the equivalence of the diagnostic label of MCI across 2 of the largest and most influential cohort studies in the USA: the National Alzheimer's Coordinating Center (NACC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS: Participants with MCI due to presumed Alzheimer's disease from the NACC Uniform Data Set (n = 789) and ADNI (n = 131) were compared on demographic, psychological, and functional variables, as well as on an abbreviated neuropsychological battery common to the 2 data sets. RESULTS: Though similar in terms of age, education, and functional status, the NACC sample was more diverse (17.4% non-White participants vs. 7.6% in ADNI; χ2 = 7.923, p = 0.005) and tended to perform worse on some cognitive tests. In particular, participants diagnosed with MCI in NACC were more likely to have clinically significant impairments on language measures (26.36-31.18%) than MCI participants in ADNI (16.03-19.85%). DISCUSSION: The current findings suggest important differences in cognitive performances between 2 large MCI cohorts, likely reflective of differences in diagnostic criteria used in these 2 studies, as well as differences in sample compositions. Such diagnostic heterogeneity may make harmonizing data across these cohorts challenging. However, application of shared psychometric criteria across studies may lead to closer equivalence of MCI groups. Such approaches could pave the way for cohort harmonization and enable "big data" analytic approaches to understanding Alzhei-mer's to be developed.

An Initial Empirical Operationalization of the Earliest Stages of the Alzheimer's Continuum.

PURPOSE: The Alzheimer's Continuum (AC) includes 2 preclinical stages defined by subjective cognitive complaints, transitional cognitive declines, and neurobehavioral symptoms. Operationalization of these stages is necessary for them to be applied in research. METHODS: Cognitively normal individuals with known amyloid biomarker status were selected from the National Alzheimer's Coordinating Center Uniform Data Set. Participants and their caregivers provided information on subjective cognitive complaints, neurobehavioral features, and objective cognitive functioning. PATIENTS: The sample included 101 amyloid positive (A+) and 447 amyloid negative (A-) individuals. RESULTS: Rates of subjective cognitive complaints (A+: 34.90%, A-: 29.90%) and neurobehavioral symptoms (A+: 22.40%, A-: 22.40%) did not significantly differ between A+/- individuals. However, the frequency of transitional cognitive decline was significantly higher among A+ (38.00%) than A- participants (24.90%). We explored various empirical definitions for defining the early stages of the AC among A+ participants. Rates of classification into AC stage 1 versus AC stage 2 varied depending on the number of symptoms required: 57.40% versus 42.60% (1 symptom), 28.70% versus 71.30% (2 symptoms), and 6.90% versus 93.10% (all 3 symptoms). CONCLUSION: The presence of 2 of the proposed symptom classes to separate AC stage 2 from stage 1 seems to provide a good empirical balance.

The Role of Trait Impulsivity in the Associations between Rumination and Alcohol-Related Outcomes.

Background/Purpose: Emerging adults engage in high rates of alcohol consumption, which contribute to negative alcohol-related consequences and alcohol-related aggression. Rumination, or repetitive thinking about negative experiences, predicts greater negative alcohol-related consequences and alcohol-related aggression. Mechanisms of these associations are not well understood. We examined whether impulsivity mediates the effect of rumination on alcohol-related outcomes. We also tested an alternative model in which impulsivity moderates the effect of rumination on these outcomes. Methods: In a cross-sectional study with 202 undergraduates, we assessed trait rumination, four facets of impulsivity (urgency, premeditation, perseverance, and sensation seeking), recent alcohol use, negative alcohol-related consequences, and alcohol-related aggression. Results: Mediational analyses revealed that rumination indirectly predicted greater negative alcohol-related consequences and alcohol-related aggression via more urgency. Moderational analyses yielded nonsignificant interactions. Conclusion: Although cross-sectional data cannot suggest causality, the pattern of correlations suggests that rumination may lead to more clinically relevant alcohol-related outcomes because it triggers rash responding to negative affect.

Empirically defining the preclinical stages of the Alzheimer's continuum in the Alzheimer's Disease Neuroimaging Initiative.

AIM: The National Institute on Aging and the Alzheimer's Association published new research criteria defining the Alzheimer's continuum (AC) by the presence of positive amyloid-ß biomarkers. Symptom severity of those on the AC is staged across six levels, including two preclinical stages (stages 1 and 2). AC stage 2 is defined by the presence of at least one of the following: (i) transitional cognitive decline; (ii) subjective cognitive decline; or (iii) neurobehavioural symptoms. In contrast, AC stage 1 is defined by the absence of symptoms. METHODS: Initial empirical definitions for each symptom class were developed. These empirical criteria were then applied in a sample of 285 cognitively normal, amyloid-positive individuals from the Alzheimer's Disease Neuroimaging Initiative for purposes of AC stage 1 and 2 classification. RESULTS: In this sample, 56.10% of participants were asymptomatic and classified as AC stage 1. In contrast, 42.46% of individuals were positive for at least one symptom class: 22.11% for transitional cognitive decline, 20.35% for subjective cognitive decline, and 14.74% for neurobehavioural symptoms. AC stage was a predictor of cognitive/functional decline over 4 years of follow up in a longitudinal growth model (B = 0.33, P < 0.001). CONCLUSIONS: Results provide a methodology to operationalize the National Institute on Aging and the Alzheimer's Association AC stage 1 and 2 criteria and include preliminary evidence of the validity of this approach. The methods outlined in this manuscript can be used to test hypotheses regarding prodromal Alzheimer's disease, as well as implemented in clinical trial selection procedures.

The Uniform Dataset 3.0 Neuropsychological Battery: Factor Structure, Invariance Testing, and Demographically Adjusted Factor Score Calculation.

OBJECTIVE: The goals of this study were to (1) specify the factor structure of the Uniform Dataset 3.0 neuropsychological battery (UDS3NB) in cognitively unimpaired older adults, (2) establish measurement invariance for this model, and (3) create a normative calculator for factor scores. METHODS: Data from 2520 cognitively intact older adults were submitted to confirmatory factor analyses and invariance testing across sex, age, and education. Additionally, a subsample of this dataset was used to examine invariance over time using 1-year follow-up data (n = 1061). With the establishment of metric invariance of the UDS3NB measures, factor scores could be extracted uniformly for the entire normative sample. Finally, a calculator was created for deriving demographically adjusted factor scores. RESULTS: A higher order model of cognition yielded the best fit to the data χ2(47) = 385.18, p < .001, comparative fit index = .962, Tucker-Lewis Index = .947, root mean square error of approximation = .054, and standardized root mean residual = .036. This model included a higher order general cognitive abilities factor, as well as lower order processing speed/executive, visual, attention, language, and memory factors. Age, sex, and education were significantly associated with factor score performance, evidencing a need for demographic correction when interpreting factor scores. A user-friendly Excel calculator was created to accomplish this goal and is available in the online supplementary materials. CONCLUSIONS: The UDS3NB is best characterized by a higher order factor structure. Factor scores demonstrate at least metric invariance across time and demographic groups. Methods for calculating these factors scores are provided.

A Survey of Payer Perspectives on Cannabis Use Disorder.

BACKGROUND: Cannabis use disorder (CUD) as described/defined in DSM 5, is characterized by impaired control of marijuana use and related personal, health, and legal consequences. CUD is a serious public health problem, affecting nearly 6 million individuals in the United States. There are no FDA approved medications to treat this disorder. The lack of available treatment options contributes to uncertainties by drug sponsors about formulary and reimbursement decision-making for CUD pharmacotherapies. OBJECTIVE: To addresses this gap by presenting the first findings on managed care payers' perceptions of CUD treatments and clinical trial end points. METHODS: An online survey was conducted with 50 payers from managed care organizations. The survey inquired about perceptions of unmet need in CUD treatment, relevant clinical trial end points, disease knowledge, and likelihood of review of new pharmacotherapies. RESULTS: The majority of payers (62%) reported that they were at least moderately familiar with CUD treatment end points. Most (80%) rated the unmet need for new pharmacotherapies for CUD as at least moderately important. Payers rated the most important end points for clinical trials as abstinence and decreased resource utilization. Most participants said an FDA approved CUD treatment would be formally reviewed by payers within 6 months (58%) or a year (36%). CONCLUSIONS: Based on these findings, payers see an unmet need for CUD treatment. Furthermore, FDA-approved pharmacotherapies for CUD will likely be reviewed quickly by payers, especially if data are provided on the likelihood of achieving abstinence and reduced resource utilization.