Global cognitive impairment should be taken into account in SPECT-neuropsychology correlations: the example of verbal memory in very mild Alzheimer's disease.

PURPOSE: To examine the impact of severity of global cognitive impairment on SPECT-neuropsychology correlations, we correlated a verbal memory test with brain perfusion in patients with very mild Alzheimer's disease (AD), taking into account the Mini-Mental State Examination (MMSE) score as an index of global cognitive impairment. METHODS: Twenty-nine outpatients (mean age 78.2+/-5.5 years) affected by very mild, probable AD underwent brain SPECT with 99mTc-ethylcysteinate dimer and a word list learning test. SPM99 was used for voxel-based correlation analysis after normalisation to mean cerebellar counts (height threshold: p<0.01). In a first analysis, only age and years of education were inserted as nuisance covariates, while in a second analysis the MMSE score was inserted as well. RESULTS: In the first analysis, two clusters of significant correlation were found in both hemispheres, mainly including regions of the right hemisphere, such as the inferior parietal lobule, the middle temporal gyrus and the posterior cingulate. Significant correlation in the left hemisphere was observed in the lingual lobule, the parietal precuneus and the posterior cingulate. After taking into consideration the MMSE, the largest cluster of correlation was found in the left hemisphere, including the parietal gyrus angularis, the posterior cingulate and the middle temporal gyrus. CONCLUSION: The wide differences observed between the correlations achieved with and without taking into account the MMSE score indicate that severity of global cognitive impairment should be considered when searching for brain perfusion-neuropsychology correlations. In the present case, this strategy resulted in correlations that more closely matched neuropsychological models of verbal memory deficit.

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.

Unilateral voluntary hand movement and regional cerebral uptake of technetium-99m-exametazime in human control subjects.

The study examines the sensitivity of a region of interest approach to detect functional changes in brain metabolism with SPECT and split-dose 99mTc-exametazime by replicating a simple hand movement experiment previously carried out with PET. Regional uptake of 99mTc-exametazime was determined in 12 healthy controls before and during a thumb-digit opposition task. Analysis of regional uptake was carried out blind to the hand used in the opposition task and showed a significant unilateral activation effect in a pericentral region of interest with opposite results in left- and right-handed activation. The maximum contralateral increase in tracer uptake was 16% before and 26% after correction for back diffusion. This is in good agreement with previous results employing absolute cerebral blood flow determination with PET and confirms the usefulness of 99mTc-exametazime SPECT for the examination of functional metabolic changes.