Psychometric evaluation of ADAS-Cog and NTB for measuring drug response.

AIMS: To conduct a psychometric analysis to determine the adequacy of instruments that measure cognition in Alzheimer's disease trials. BACKGROUND: Both the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and the Neuropsychological Test Battery (NTB) are validated outcome measures for clinical trials in Alzheimer's disease and are approved also for regulatory purposes. However, it is not clear how comparable they are in measuring cognitive function. In fact, many recent trials in Alzheimer's disease patients have failed and it has been questioned if ADAS-Cog still is a sensitive measure. MATERIALS AND METHODS: The present paper examines the psychometric properties of ADAS-Cog and NTB, based on a post hoc analysis of data from a clinical trial (NCT01024660), which was conducted by AstraZeneca, in mild-to-moderate Alzheimer's disease (AD) patients, with a Mini Mental State Examination (MMSE) Total score 16-24. Acceptability, reliability, different types of validity and ability to detect change were assessed using relevant statistical methods. Total scores of both tests, as well as separate domains of both tests, including the Wechsler Memory Scale (WMS), Rey Auditory Verbal Learning Test (RAVLT) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Condition, were analyzed. RESULTS: Overall, NTB performed well, with acceptable reliability and ability to detect change, while ADAS-Cog had insufficient psychometric properties, including ceiling effects in 8 out of a total of 11 ADAS-Cog items in mild AD patients, as well as low test-retest reliability in some of the items. DISCUSSION: Based on a direct comparison on the same patient sample, we see advantages of the NTB compared with the ADAS-Cog for the evaluation of cognitive function in the population of mild-to-moderate AD patients. The results suggest that not all of ADAS-Cog items are relevant for both mild and moderate AD population. CONCLUSIONS: This validation study demonstrates satisfactory psychometric properties of the NTB, while ADAS-Cog was found to be psychometrically inadequate.

Cognitive impairment and white matter damage in hypertension: a pilot study.

OBJECTIVES: Hypertension has been associated with impaired cognition. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy were applied to assess white matter abnormalities in treated vs untreated hypertension and if these correlated with neuropsychological performance. METHODS: Subjects were 40 patients with medically treated hypertension (mean age 69.3 years), 10 patients with untreated hypertension (mean age 57.6 years) and 30 normotensive controls (mean age 68.2 years). Hypertension was defined as a previous diagnosis and taking hypertensive medication, or a resting blood pressure of >140/90 mmHg on the day of assessment. RESULTS: Patients with treated hypertension performed worse on immediate (P = 0.037) as well as delayed memory tasks (P = 0.024) compared with normotensive controls. Cognitive performance was worse in untreated compared with treated hypertension on executive functions (P = 0.041) and psychomotor speed (P = 0.003). There was no significant correlation between cognition and any of the imaging parameters in treated hypertension. However, in untreated hypertension the results revealed a positive correlation between an executive functioning and attention composite score and DTI mean diffusivity values (P = 0.016) and between psychomotor speed and spectroscopy NAA/tCr levels (P = 0.015). CONCLUSIONS: These results suggest there is cognitive impairment in hypertension. Treated hypertension was associated with deficits in memory while untreated hypertension revealed a more 'subcortical' pattern of cognitive impairment.