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The cognitive efficacy of the M1-selective muscarinic agonist xanomeline in mild-to-moderate Alzheimer disease (AD) was measured using the Computerized Neuropsychological Test Battery (CNTB) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) in this 17-center, double-blind, placebo-controlled study. Three hundred forty-three patients were randomly assigned to receive 25, 50, or 75 mg xanomeline tartrate or placebo three times daily (t.i.d.) for 24 weeks, followed by placebo for 4 weeks in a single-blind washout phase. Cognitive function was assessed at randomization and after 4, 8, 12, 24, and 28 weeks. Three hundred nineteen patients were included in an intent-to-treat (ITT) analysis; 209 completers had evaluable data at week 24. ITT analysis showed a significant (por = 0.05) dose-response trend and a significant (por = 0.05) between-group comparison favoring 75 mg t.i.d. over placebo for the CNTB summary score but not for the ADAS-cog. In the completer analysis, however, the ADAS-cog showed a significant (por = 0.05) dose-response trend and between-group comparison, whereas the CNTB Summary Score did not. The ADAS-cog was less sensitive to treatment effects in mildly impaired patients (ADAS-cog21) than in moderately impaired patients (ADAS-cogor = 21), whereas the CNTB was sensitive in the entire study population (mean ADAS-cog = 22.5+/-9.6). Significant (por = 0.05) beneficial treatment effects were seen in measures of simple reaction time and delayed verbal recall, which are included in the CNTB but not in the ADAS-cog. During the single-blind placebo washout period, the ADAS-cog score of the placebo group worsened dramatically (change of 2.63 points; por = 0.001), whereas the CNTB score remained stable (change of 1.04 points; p=0.694). Thus, the CNTB appears to be more objective than the ADAS-cog.

imaging was conducted followingz 12 mCi of [11 C] PIB and 60 min dynamic PET scan in 3D mode (septa retracted). Mean cortical binding potential (MCBP) was determined as previously described. Results: Pearson correlation revealed the following correlations and trends between MCBP (for amyloid) and hippocampal subvolumes: left CA2-3 r 1⁄4 -0.29 (p 1⁄4 0.05); right CA2-3 r1⁄4 -0.25 (p1⁄4 0.09); left CA1 r1⁄4 -0.20 (p1⁄4 0.18); right CA1 r 1⁄4 -0.27 (p 1⁄4 0.07). No other regional volumes were correlated with MCBP. Conclusions: In this young healthy cognitively normal population there were trends towards the same pattern seen recently in an amnestic MCI population, with significantly smaller subfield volumes in CA 2-3 and subiculum compared with controls. In our study group only 8/46 participants had elevated MCBP (> 0.18 BP). We will extend our sample to a larger and older population, which can be expected to have higher numbers of participants with elevated amyloid.

In an administration of the Computerized Neuropsychological Test Battery (CNTB), stable schizophrenic outpatients (n = 26) showed significant impairment (P < 0.05) relative to normal control subjects (n = 28) in overall function and measures of verbal learning. Except on tests of motor speed, the performance profile of schizophrenic patients was similar to that of elderly normal control subjects (n = 33). This profile of deficits is consistent with findings of other investigators in similar patient populations. In addition to displaying sensitivity to the mild impairments found in outpatients, the CNTB showed high test-retest reliability (r = 0.76, P < 0.0001). It should be useful for evaluating cognitive impairment in clinical trials of prospective treatments.

This pilot clinical trial was a 15-week, double-blind, controlled, three-way crossover study evaluating cognitive effects of ceranapril in subjects with dementia of the Alzheimer type (age range 50-75 years). Computerized (CNTB) and noncomputerized cognitive test batteries revealed no significant results (p > 0.05). On further analysis of the data, however, a study of longer duration and/or higher dosages may be warranted.

The Computerized Neuropsychological Test Battery (CNTB), a new assessment tool for neuropsychopharmacologic research, is based on a neuropsychological approach. While it is based on tests previously shown to be sensitive to subtle changes in neuropsychological functioning, it differs from currently available tools for measuring central nervous system effects of new compounds. It has sensitivity to a broader range of cognitive functioning and is more comprehensive than other measurements in its sampling of neuropsychological functions, providing wider application to diverse clinical populations. The CNTB is valid, reliable, and has two alternative forms. Use of the computer as an expert system maximizes standardization and ease of CNTB administration and data analysis. Using this assessment tool, three groups of subjects were compared: young and elderly neurologically normal subjects and elderly subjects with the dementia syndrome of Alzheimer's disease (AD). The AD subjects' summary score on the CNTB correlated significantly with the Blessed Information Memory Concentration Test score. The CNTB summary score was significantly higher in young subjects than in neurologically normal elderly subjects, demonstrating sensitivity to the effects of aging. The CNTB summary score also was significantly higher in neurologically normal elderly subjects than in elderly subjects with AD dementia. ( J Geriatr Psychiatry Neurol 1991;4:211-217).

The presence of lateral ventricular enlargement in some manic-depressive subjects, as assessed by ventricular-brain ratios (VBRs), has been reported. A study of 27 bipolar patients and 27 individually matched normal controls confirmed that finding. Bipolar patients had significantly larger VBRs than did controls. Clinical measures associated with the presence of ventricular enlargement in the bipolar patients included more frequent hospitalizations and histories of persistent unemployment. Other measures of illness severity or social deterioration were not significantly associated with large VBR.

The authors evaluate current thinking as to when psychiatrists should call for computed tomography (CT). They discuss changes in the CT scan in CNS disorders likely to be seen by psychiatrists. The CT scan can be of considerable aid when the diagnosis is uncertain, especially since studies have shown that organic brain disease is underrecognized in psychiatric patients. Six case histories illuminate how CT provides diagnostic assistance.