Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis.

OBJECTIVES: The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT). METHODS: Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18-59 years, clinically definite multiple sclerosis (MS), and performance ≤ ½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT). Neuropsychological assessments were performed at baseline and 24 weeks. Primary outcomes were change on the Selective Reminding Test (SRT) of verbal memory and the participant's impression of memory change. Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician's impression of memory change. RESULTS: A total of 120 participants were enrolled and randomized to either donepezil or placebo. No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes. A trend was noted for the clinician's impression of memory change in favor of donepezil (37.7%) vs placebo (23.7%) (p = 0.097). No serious or unanticipated adverse events attributed to study medication developed. CONCLUSIONS: Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average.

A comparison of administration procedures for the Rey-Osterrieth Complex Figure: flowcharts versus pen switching.

The Rey-Osterrieth Complex Figure (ROCF) is commonly used to assess visuospatial skills, visuoconstruction, visual memory, and executive functioning. Two different methods are traditionally used to record the order in which the figure is drawn: the flowchart method and the pen-switching method. Although it has been suggested that pen switching may interfere with performance, to date no research has been conducted to assess whether ROCF performance significantly differs due to administration method. As part of routine neuropsychological evaluation, 100 inpatients and outpatients were randomly assigned to either method. Using the Boston Qualitative Scoring System and the traditional 36-point scoring method, the authors unexpectedly found that the pen-switching group generally performed better than the flowchart group, and productions drawn with pen switching were also significantly faster to score.

Practice effects, test-retest stability, and dual baseline assessments with the California Verbal Learning Test in an HIV sample.

Repeated neuropsychological assessments have been recently employed to investigate the natural course and effects of interventions in individuals with human immunodeficiency virus (HIV) infection. Important considerations when interpreting serial assessments are the roles of practice effects and test-retest reliability on follow-up performance. Although several statistical and methodological controls have been proposed for minimizing practice effects, they have not been empirically tested in HIV samples. Three groups (HIV+/symptomatic, HIV+/asymptomatic, HIV- "at risk" controls) were administered the California Verbal Learning Test (CVLT) twice with a brief test-retest interval. Significant practice effects were observed on six of the CVLT measures. Test-retest stability coefficients were reported. A third and fourth administration of the CVLT was conducted to observe the impact of the dual baseline assessment approach on test performance. Trend analyses indicated that the dual baseline approach is a viable method for minimizing practice effects. The dual baseline approach also lead to improvement in a number of the stability coefficients. Limitations and future directions are discussed.

Serial neuropsychological assessment with the National Institute of Mental Health (NIMH) AIDS Abbreviated Neuropsychological Battery.

The effect of repeated administration of the (NIMH) AIDS Abbreviated Neuropsychological Battery was evaluated in a group of "at risk" individuals who served as control subjects in a larger research project. Subjects' performance across five assessment points was evaluated by repeated measures analysis. Statistically significant trends were obtained on the California Verbal Learning Test, the Paced Auditory Serial Addition Task, and the State scale of the State-Trait Anxiety Inventory. No discernable trends were detected on the Vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised, total time or errors on the Visual Search Task, the Hamilton Depression Rating Scale, or the Trait scale of the State-Trait Anxiety Inventory. The implications of these findings in both clinical and research settings are discussed.

Longitudinal analysis of olfactory deficits in HIV infection.

The presence and degree of odor identification deficits in 55 HIV-infected (30 asymptomatic, 25 symptomatic) and 29 HIV-negative at-risk control volunteers were examined longitudinally using the University of Pennsylvania Smell Identification Test (UPSIT). Factors other than HIV infection that could account for olfactory loss (i.e., sinusitis or upper respiratory infection) were also considered by obtaining MRI scans of the nasal passages and information from an olfaction questionnaire. No differences were found among groups at the first administration of the UPSIT, with significant differences among groups emerging at the 1-year and 2-year follow-ups. The symptomatic group showed a significant decline in odor identification scores across time, while means for the asymptomatic and control groups remained stable. The presence of sinusitis or an upper respiratory infection appeared to have no effect on odor identification. The implications for these findings in relationship to cognitive decline in neurodegenerative diseases are discussed.

Issues associated with repeated neuropsychological assessments.

Distinguishing practice effects from other factors in repeated neuropsychological assessments are discussed in the context of research studies and clinical/forensic assessments. Potential methodological procedures for reducing the impact of practice effects in research settings are outlined. In contrast, the potential clinical utility and interpretation of practice effects in clinical assessments and forensic evaluations are highlighted.

Practice effects with the NIMH AIDS abbreviated neuropsychological battery.

The degree of practice effects with the Brief NIMH Neuropsychological Battery for HIV Infection and AIDS is reported using a 7-10 day test-retest interval. The patient groups were asymptomatic and symptomatic of HIV while the control group was made up of "at risk" volunteers. Statistically significant practice effects were obtained on the California Verbal Learning Test, the Paced Auditory Serial Addition Task and the Visual Search Test among the infected individuals. The controls subjects demonstrated statistically significant practice effects on all of the neuropsychological tests. The implications of these findings in prospective studies are discussed.