| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Regional cerebral blood flow (rCBF) was measured in 47 patients with dementia of the Alzheimer type (DAT) with the Xe-133 inhalation technique (HEADTOME : ring type SPECT). The patients were classified into 4 groups depending on the distribution patterns of CBF: the first group consisted of patients with lower CBF values for bilateral temporal areas, the second group consisted of patients with lower CBF values for left temporal area, the third group consisted of patients with lower CBF values for bilateral front-tomporo-parietal areas, the forth group consisted of Patients with normal CBF values. From the aspect of the relation between CBF patterns and levels of monoamino metabolites and acatylcholine esterase (AchE) in CSF, the first group was characterized by significantly lower levels of AchE, HVA AND 5-HIAA. The forth group was characterized by significantly lower levels of 5-HIAA. From the aspect of the EEG record analysis, a significant decrease of alpha activities and a signific
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ant increase of delta activities over bilateral temporal ares were found in the first group. A significant diffuse increase of low frequency was found in the third group. A diffuse increase of fast frequency with low voltage was found in the forth group.
Ten patients with ATD (mean age 60.8 years, mild stave: 4 cases, moderate stage: 6 cases) were treated with the administration of anticholinesterase drug physostigmine for 14 days. These patients received 10 or 15 mg of oral physostigmine. The effects of chronic physostigmine treatment on intellectual function, regional cerebral blood flow and EEG were examined. Each patient's mental status was assessed with Haseoawa's dementia rating scale (HDRS), GBS scale and Miyake's memory test (MMT). The total score of HDRS, GBS and MMT did not show any substantial improvement after the chronic administration of physostigmine. The small increase (20 - 30 % increase) of bilateral frontal blood flow values, bilateral temporal blood flow values and mean CBF values were found after the chronic administration of physostigmine. Especially, these increases of CBF values were found in 6 patients with moderate stage and mainly in the first group. However, since these observations were made in only 10 of the patients with DAT, further investigations of physostigmine treatment will be required to draw a final conclusion.
We investigated the age-related changes in [^3H]IP1 formation in response to 100 M carbachol in rat cerebral cortex slices. There was a clear tendency that the [^3H]IP1 formation was decreased by aging, although the difference was statistically not significant. These results suggested that the significant decrease in postsynaptic muscarinic receptors was not found in the cerebral cortex of the aged rat.
The present study indicated a tendency that physostigmine treatment of DAT was effective. Because a marked decrease in presynaptic cholinergic function as well as a decrease in dopaminargic function and serotinergic function has been found in DAT, the only cholinergic manipulation treatment was presumed not to be enough. Therefore, the mixed now compensatory treatment including not only cholinargic system but also other nourotransmitters systems may be effective in the treatment of dementia of the Alzheimer type. Further trials of this treatment will be required. Less
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