Stephen M. Meyer

Neuropsychological Functioning in Bipolar Disorder and Schizophrenia

BACKGROUND Some patients with bipolar disorder (BD) demonstrate neuropsychological deficits even when stable. However, it remains unclear whether these differ qualitatively from those seen in schizophrenia (SZ). METHODS We compared the nature and severity of cognitive deficits shown by 106 patients with SZ and 66 patients with BD to 316 healthy adults (NC). All participants completed a cognitive battery with 19 individual measures. After adjusting their test performance for age, sex, race, education, and estimated premorbid IQ, we derived regression-based T-scores for each measure and the six cognitive domains. RESULTS Both patient groups performed significantly worse than NCs on most (BD) or all (SZ) cognitive tests and domains. The resulting effect sizes ranged from .37 to 1.32 (mean=.97) across tests for SZ patients and from .23 to .87 (mean=.59) for BD patients. The Pearson correlation of these effect sizes was .71 (p<.001). CONCLUSIONS Patients with bipolar disorder suffer from cognitive deficits that are milder but qualitatively similar to those of patients with schizophrenia. These findings support the notion that schizophrenia and bipolar disorder show greater phenotypic similarity in terms of the nature than severity of their neuropsychological deficits.

Behavioral aspects of Lesch–Nyhan disease and its variants

Self-injury is a defining feature of lesch-nyhan disease (LND) but does not occur in the less severely affected Lesch-Nyhan variants (LNV). The aim of this study was to quantify behavioral and emotional abnormalities in LND and LNV. Thirty-nine informants rated 22 patients with LND (21 males, 1 female), 11 males with LNV, and 11 healthy controls (HC; 10 males, 1 female) using two well-validated rating scales. The age of patients with LND ranged from 12 years 7 months to 38 years 3 months (mean 22 y 11 mo; sd 7 y 8 mo), whereas the age range of those with LNV was 12 years 9 months to 65 years (mean 30 y 7 mo; sd 15 y 2 mo), and the healthy controls were aged 12 years 4 months to 31 years 3 months (mean 17 y 10 mo; sd 5 y 7 mo). Behavioral ratings were based on the Child Behavior Checklist and the American Association On Mental Retardations Adaptive Behavior Scale--Residential And Community, 2nd edition. Statistical analyses revealed that patients with LND showed severe self-injury together with problematic aggression, anxious-depressed symptoms, distractibility, motor stereotypes, and disturbing interpersonal behaviors. Patients with LNV were rated as being intermediate between the HC and LND groups on all behavior scales. Although the LNV group did not differ from hcs on most scales, their reported attention problems were as severe as those found in LND. We conclude that self-injurious and aggressive behaviors are nearly universal and that other behavioral abnormalities are common in LND. Although patients with LNV typically do not self-injure or display severe aggression, attention problems are common and a few patients demonstrate other behavioral anomalies.

Development, Psychometric Properties, and Validity of the Hopkins Adult Reading Test (HART)

We describe the development of a 35-item, oral word-reading test with two equivalent forms (HART-A and HART-B) designed to estimate premorbid abilities. Both forms show excellent internal consistency (coefficients alpha >.91) and test–retest reliability (Pearson rs >.90). HART performance was combined with demographic variables to generate regression equations that predict IQ scores obtained concurrently and 4–8 years earlier. The resulting models explained 61% of full scale IQ (FSIQ) variability in 327 healthy adults. The FSIQs that can be estimated range from below 73 to above 131. Combined with demographic variables, these two brief word reading tests accurately predict a broader range of IQs than Blair and Spreens (1989) longer version. Equivalent forms make it especially useful for longitudinal studies.

The use of word-reading to estimate "premorbid" ability in cognitive domains other than intelligence

Diagnostic neuropsychological assessment requires the clinician to estimate a patients premorbid abilities. Word reading tests, such as the National Adult Reading Test-Revised (NART-R), provide reasonably accurate estimates of premorbid IQ, but their capacity to benchmark other premorbid cognitive abilities remains unclear. In this extension of an earlier report, we administered the NART-R, an abbreviated Wechsler Adult Intelligence Scale (WAIS-R or WAIS-III), and 26 other cognitive measures to 322 reasonably healthy adults. While NART-R performance correlated robustly (rs > or = .72) with concurrent Verbal and Full Scale IQ, its correlation with all other cognitive measures was significantly lower. Thus, while it is appealing to use word reading as a proxy for premorbid functioning in other cognitive domains, the NART-R has limited utility for this because it does not predict current performance on other cognitive tests as well as it predicts IQ in healthy adults.

Interrater and Test–Retest Reliability of a Fixed Condition Design Fluency Test

Despite its potential as a unique neuropsychological test, the emergence of a psychometrically sound research foundation for Jones-Gotman and Milners (1977) Design Fluency Test (DFT) has been constrained by the lack of consistent administration and scoring practices and limited information about its reliability. Here we describe an approach to administering and scoring the fixed condition DFT that is modeled on Jones-Gotman and Milners original method and that clarifies procedural ambiguities. Results include interrater and long-term test-retest reliability analyses using this approach. First, based on five raters who scored 50 DFT protocols, good to excellent intra-class correlation coefficients were obtained for all DFT scores. Second, in a broadly representative sample of 87 healthy adults who were tested twice over an average of 5½ years, the test–retest reliabilities for total and novel design scores ranged from good to excellent. This study demonstrates that the fixed condition DFT can be scored reliably using these procedures and that the reliability coefficients for DFT total and novel designs scores are comparable to those of other commonly used neuropsychological tests.

The relationship between CRA ADAS-Cog training and performance on monitoring ADAS-Cogs at clinical sites in an Alzheimer's disease clinical trial

Background:A phase II 12-month trial of resveratrol for mild-moderate dementia due to Alzheimer’s disease (AD) will determine its safety and tolerability and putative effects on clinical outcomes, volumetric MRI, Aband tau levels in cerebrospinal fluid, and metabolic profiles. A history of metabolic syndrome or type 2 diabetes mellitus (T2D), particularly during midlife, is a well-known risk factor for AD in late life but underlying mechanisms are unknown.Methods: Exclusionary criteria include individuals consuming any resveratrol-containing supplement and subjects treated for T2D. Eligible subjects (50-90 year old men and women recruited from and/or referred to specialty clinics) with mild-moderate AD (MMSE 1226) were administered a baseline oral glucose tolerance test (OGTT, 75 g) after an overnight fast. Results will be compared to a repeat OGTT on the maximally tolerated resveratrol dose after 12 months. Resveratrol was synthesized, encapsulated, and packaged by Aptuit Laurus (now Catalent), initiated at 500 mg bymouth once daily, and will end with 1 g twice daily (with 500 mg increments every 3 months). Results: Five subjects (5/128 or 4%) revealed impaired fasting glycemia (110-125 mg/dl) and 38 subjects (38/ 125 or 30%) revealed impaired glucose tolerance at 2 hours (140-200 mg/ dl). Three subjects (3/128 or 2%) had findings consistent with a diagnosis of T2D (fasting glucose > 125 mg/dl) and 16 subjects (16/125 or 13%) had results consistent with T2D (glucose > 200 mg/dl) at 2 hours. The mean fasting glucose (+/S.E.) was 92 +/1 mg/dl. The mean glucose at 2 hours was 143 +/5 mg/dl. These data revealed a prevalence of impaired fasting glycemia or T2D at baseline of 6%. The prevalence of impaired glucose tolerance or T2D at 2 hours was 43%. Six subjects screen-failed due to newly-diagnosed or treated T2D.Conclusions:Due to this high prevalence, the OGTT may be considered for individuals with AD in order to optimize medical management of borderline or undiagnosed T2D. AD, a chronic inflammatory disorder may increase risk of co-incident impaired fasting glycemia, glucose intolerance, and T2D. Conversely, a glucoregulatory disturbance may promote AD. Treatment of this study cohort with resveratrol or placebo is in progress.