Optimizing ADAS-Cog Worksheets: A Survey of Clinical Trial Rater s' Perceptions.

BACKGROUND: The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADASCog) remains the most widely used test of longitudinal cognitive functioning in Alzheimer's disease (AD) clinical trials. Unlike most neuropsychological tests, the ADAS-Cog source documentation worksheets are not uniform across clinical trials, and vary by document layout, inclusion of administration and/or scoring instructions, and documentation of subtest scoring (e.g., recording correct versus incorrect scores), among other differences. Many ADAS-Cog test administrators (raters) participate in multiple AD trials and switching between different ADAS-Cog worksheets may increase the likelihood of administration and/or scoring mistakes that lessen the reliability of the instrument. An anonymous online survey sought raters' experiences with ADAS-Cog worksheets and their opinions on the design and content of the worksheets. RESULTS: Results of the survey indicated preference for structure and standardization of the ADASCog worksheets, which has been considered in the development of a standard ADAS-Cog source document by the Alzheimer's Disease Cooperative Study (ADCS) Working Group.

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 Spreen's (1989) longer version. Equivalent forms make it especially useful for longitudinal studies.

Neuropsychological impairment in deficit vs. non-deficit schizophrenia.

This study aimed to assess the severity and specificity of cognitive impairments that affect individuals with deficit versus non-deficit schizophrenia. We compared 26 patients with the deficit subtype of schizophrenia (SZ-D) and 79 with non-deficit schizophrenia (SZ-ND) to 316 healthy adults (NC). All study participants completed a battery with 19 individual cognitive 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 derived cognitive domains including attention, psychomotor speed, executive function, verbal fluency, visual memory, and verbal memory. Multivariate analyses of variance revealed significant group effects for every individual measure and domain of cognitive functioning (all ps<0.001). Post hoc comparisons revealed that patients with SZ-D performed significantly worse than NCs in every cognitive domain. They also produced lower scores than the SZ-ND group in every domain, but only the difference for verbal fluency reached statistical significance. The correlations of the effect sizes shown by the SZ-D and SZ-ND patients were of intermediate magnitude for the individual tests (r=0.56, p<0.01) and higher, but not statistically significant for the cognitive domains (r=0.79, p=0.06). Patients with SZ-D demonstrate cognitive deficits that are both common and distinct from those shown by patients with SZ-ND. Their impairment of verbal fluency is consistent with the observation that poverty of speech is a clinically significant feature of patients with SZ-D.

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.

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 Milner's (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 Milner's 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 5 1/2 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 use of word-reading to estimate "premorbid" ability in cognitive domains other than intelligence.

Diagnostic neuropsychological assessment requires the clinician to estimate a patient's 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.

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 Retardation's 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.