Case-control study of neurocognitive function in euthymic patients with bipolar disorder: an association with mania.

BACKGROUND: Neurocognitive impairments in euthymic patients with bipolar disorder may represent trait rather than state variables. AIMS: To test the hypothesis that euthymic patients with bipolar disorder would exhibit impairment in verbal learning and memory and executive function compared with healthy controls matched for age, gender and premorbid IQ. METHOD: Twenty euthymic patients with bipolar disorder were matched, on a case-by-case basis, to twenty healthy community controls. Cases and controls were tested with a battery of neuropsychological tests. RESULTS: Impairments were found in cases compared with controls in tests of verbal learning and memory. Verbal learning and memory correlated negatively with the number of manic episodes. CONCLUSIONS: Impaired verbal learning and memory may be a trait variable in bipolar disease. There are implications for adherence to medication and relapse and for the role of early treatment interventions. Prospective designs and targeting first-episode groups may help to differentiate trait v. disease process effects.

A double-blind, placebo-controlled study of tacrine in patients with Alzheimer's disease using SPET.

BACKGROUND: the effect of single-dose and long-term cholinergic enhancement with tacrine on regional cerebral perfusion was examined in patients with Alzheimer's disease using single-photon emission tomography (SPET). METHOD: 23 patients with probable Alzheimer's disease (DSM-III-R and NINCDS-ADRDA criteria) were scanned before and after a single oral dose of tacrine at the start of the study and again after 12 weeks of randomized, double-blind treatment with tacrine or placebo, using high resolution (99m)Tc-Exametazime SPET. Patients also underwent neuropsychological testing with the CAMCOG, the Mini-Mental State Examination and the Rivermead Behavioural Memory Test before and after 12 weeks of treatment. RESULTS: occipital count ratios in all regions of interest declined by 3% over 12 weeks, indicating a progression of the disease. Acute tacrine challenge resulted in a 16% increase in the superior frontal and a 11% decrease in the anterior temporal cortex. The acute effects of tacrine were modified by 12 weeks of treatment, particularly in the medial frontal (cingulate) cortex where active treatment was associated with a reduced acute tacrine response. There were no changes in cognitive function associated with active treatment. CONCLUSION: the study demonstrates the sensitivity of cerebral perfusion measures to changes during acute and medium-term tacrine treatment.

Further evidence that reading ability is not preserved in Alzheimer's disease.

BACKGROUND: Pre-morbid intelligence level is routinely assessed in Alzheimer's disease using the National Adult Reading Test (NART). This practice is based on the assumption that pronunciation of irregular words remains unaffected by the disease process. Recent reports have suggested that reading ability may become compromised in moderately demented subjects. METHOD: Sixty-eight probably Alzheimer patients were classified into stages of severity (minimal, mild and moderate) using the Mini-Mental State Examination (MMSE). NART and demographic equations were used to estimate pre-morbid ability. RESULTS: A significant correlation emerged between dementia severity and reading ability, NART v. MMSE scores, r = 0.46, P < 0.01. When the total sample was subdivided into moderate, mild and minimal subgroups, significant between-group differences emerged, despite the groups being well matched for age, sex, and years of full-time education. Pre-morbid IQ, as estimated by demographic regression equations, did not correlate with dementia severity. CONCLUSION: NART performance is compromised in moderate Alzheimer disease, and the measure provides a serious underestimate of pre-morbid IQ in patients with an MMSE of 13 or less.

Laterality of visuo-spatial attention in acute and chronic schizophrenia, major depression and in healthy controls.

Previous studies have suggested that schizophrenia is characterized by an asymmetry of visuo-spatial attention, in particular that acute unmedicated schizophrenics demonstrate relative inattention to right hemispace, whereas chronically medicated patients demonstrate the opposite pattern. In the present study, 30 unmedicated schizophrenic patients, 32 chronically medicated schizophrenic patients, 30 patients suffering from major depression and 60 healthy controls were assessed using two measures of hemispatial attentional neglect, namely letter and star cancellation. The results demonstrated that the chronic schizophrenic group made more total omissions for star cancellation (in both right and left hemispace), but that there was no difference between the groups in terms of omission asymmetry for either letter or star cancellation.

A single photon emission computerised tomography study of regional brain function in elderly patients with major depression and with Alzheimer-type dementia.

The uptake, at rest, of 99mTc-exametazime into different brain regions was compared using SPECT for 20 elderly subjects with major depressive disorder, 20 with Alzheimer-type dementia, and 30 age-matched normal volunteers. Uptake was referred to calcarine-occipital cortex as a reference sensory area. Cross-sectional differences between the three groups were highly statistically significant, but reflected primarily the reductions in cortical uptake in the Alzheimer group. A detailed comparison of depressed patients and controls identified decrements in anterior cingulate, temporal and frontal cortex and in caudate and thalamus in men only. These decrements were correlated with impairment of performance on a trail-making task, but were also associated with continuing treatment with antidepressants or benzodiazepines. However, most depressed patients had quantitatively normal scans for posterior parietal association cortex, and this suggests that SPECT may find a limited role in the differential diagnosis of depression and dementia. The reduced brain function in some depressed patients may parallel the findings from studies of brain structure in elderly depressives; there was between good outcome at 6-18 months and increased tracer uptake in subcortical areas.

A single photon emission computerised tomography study of regional brain function underlying verbal memory in patients with Alzheimer-type dementia.

Ten patients with Alzheimer-type dementia and nine age-matched normal controls were examined with SPECT, using split-dose 99mTc-labelled exametazime. The baseline condition involved repetition of the word 'yes' or 'no'. The activation condition involved recognition (indicated by a 'yes' or 'no') of words from a previously learned list presented along with distractor words. Patients who performed this task successfully were selected, and efforts were made to match the patients with controls according to their performance on the task, although this was not fully achieved. Uptake of 99mTc-exametazime was estimated at baseline and during the word-recognition task for predetermined regions of interest drawn from a standard neuroanatomical atlas. The baseline task appeared to normalise tracer uptake for frontal, temporal and parietal cortex in the patient group. However, during the recognition task, controls but not patients showed activation effects. These were most prominent in dorsolateral frontal cortex and adjacent anterior cingulate cortex. Among patients, successful performance was correlated with activation of dorsolateral frontal and parietal cortex on the left side. The results confirm the central role of frontal mechanisms in a recognition memory task. The study highlights some of the difficulties of using cognitive challenge tests in clinical groups.

The effect of anxiety induction on the regional uptake of 99mTc-exametazime in simple phobia as shown by single photon emission tomography (SPET).

Ten patients suffering from DSM-III-R simple phobia were studied under two conditions: (a) while listening to a 4 min relaxation tape, and (b) while listening to a 4 min audio tape describing exposure to the phobic stimulus. During each condition, subjects were injected with 99mTc-Exametazime, a marker of regional cerebral blood flow. Subjective and psychophysiological measures indicated a marked effect of the anxiety induction procedure. Ratio analysis of the SPET data revealed reductions in tracer uptake largely confined to posterior cerebral regions bilaterally. Analysis of brain regions of interest normalised to the whole brain slice showed reductions confined to right temporal/occipital regions. In general there was no clear association between subjective and physiological variables and changes in regional uptake of tracer as a consequence of the anxiety induction procedure. The changes in tracer uptake were dissimilar to those previously reported for other cognitive activation paradigms, providing some reassurance that those functional brain changes were not artefacts of non-specific changes in state anxiety. These posterior brain changes may reflect alterations in activation of the GABA/benzodiazepine complex.