Neuropsychological investigation of anterior and posterior cortical function in early-stage probable Alzheimer's disease.

In vivo neuroimaging studies have generally indicated a greater involvement of posterior cortical areas in early-stage dementia of the Alzheimer type (DAT) relative to frontal involvement. By contrast, some recent neuropsychological studies have shown that DAT patients perform poorly in frontal lobe tasks even in the early stages of the disease, although there is disagreement as to whether this necessarily implicates frontal pathology. The main aim of this study was to examine the hypothesis prompted by both neuroimaging studies and the traditional clinical conception of the disease, that, compared with the functioning of posterior association cortex, executive functions (thought to depend on frontal lobe integrity) are relatively spared in the early stages of DAT. A group of patients with a diagnosis of early-stage, probable DAT (n = 17) was compared with age- and IQ-matched controls (n = 17) across a range of neuropsychological tasks presumed to exercise frontal or temporoparietal functions. A profile of strengths and weaknesses was observed across 'anterior' and 'posterior' cognitive tests, including dissociations among some tests of temporoparietal function, in particular visual object perception (impaired) and spatial analysis skills (intact). Thus there was little support for the notion that the disease progresses cortically in a posterior-to-anterior direction. Possible reasons for the discrepancy between neurophysiological and neuropsychological observations are discussed, including the possibility that neuropsychological tests do not provide a valid indication of regional brain function when used in the context of DAT. Caution is urged in the clinical application of 'frontal lobe tests' for the differential diagnosis of DAT.

Aggression in boat builders: a search for altered mood states in boat builders exposed to styrene.

Published reviews and industrywide anecdotal reports have suggested an association between exposure to some volatile organic compounds (VOCs) and altered mood states. In this paper we report a unique study of boat-builders exposed to styrene. Two hundred and thirteen employees exposed to solvents and 144 who were not exposed completed questionnaires related to mood states. Additionally, for 23 of the 213 employees, the air concentrations of styrene were measured at their workplaces, and urinary concentrations of mandelic acid (a metabolite of styrene) were determined in order to assess biological exposure. Special features of this study included the use of the Prolife of Mood States (POMS) questionnaire and the availability of sound historical data. A weak association is demonstrated between styrene exposure and aggression/hostility. That this is found to be most marked in the earliest years of exposure suggests that selection characteristics might be a more important association than solvent exposure.

Cholecystokinin and anxiety in normal volunteers: an investigation of the anxiogenic properties of pentagastrin and reversal by the cholecystokinin receptor subtype B antagonist L-365,260.

1. Two studies were undertaken to develop a model of experimentally induced anxiety in normal volunteers based on cholecystokinin (CCK) receptor agonism/antagonism. 2. In Study 1 rapid intravenous injections of the CCK receptor subtype B (CCKB) agonist pentagastrin (0.15, 0.3 and 0.6 micrograms kg-1) were found to produce dose-related increases in subjective ratings of anxiety compared with placebo. 3. In Study 2 the effects of pre-treatment with two doses of the CCKB receptor antagonist L-365,260 (10 mg, 50 mg p.o.) on the anxiety induced by pentagastrin 0.3 micrograms kg-1 i.v. were investigated. Detailed measurements of blood pressure and pulse rate were also undertaken. Pentagastrin produced changes in blood pressure and pulse rate which had a similar time course to that observed for subjective anxiety ratings. L-365,260 reversed both the autonomic and anxiogenic effects of pentagastrin. 4. The pentagastrin model would appear to be a useful tool for investigating potential anxiolytics in normal volunteers.