Hippocampus pathology in dementia: post-mortem assessed cation shifts and amino acid transmitter contents and its possible neuroimaging in vivo.
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The term leuko-araiosis as predicted by Hachinski may now have outlived its usefulness. Careful delineation of the white matter changes seen in MR imaging by use of the MR characteristics and by the location of the lesions may reduce the apparent heterogeneity of the associate clinical and neuropathological findings. As currently defined, leuko-araiosis is seen in aggregate more commonly in subjects with cerebro-vascular disease or with cerebro-vascular risk factors but it is a common finding associated with aging in otherwise normal, healthy elderly subjects. Its clinical significance as an isolated finding in these populations should therefore be treated cautiously. Its appearance should alert the physician however to seek for and treat potential cerebro-vascular risk factors.
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Lacunae are small deep cerebral infarcts which are believed to occur in hypertensive patients, producing characteristic clinical syndromes. Previous reports suggested to differentiate this type of stroke from other cerebrovascular diseases, but failed to provide any evidence that this classification is useful in clinical practice. We reviewed the present literature concerning pathogenesis, clinical features, diagnostic, and therapeutic aspects of lacunae and we established that current concepts in lacunar stroke are inadequately supported. Although lacunar syndromes are reported to be correlated with lacunar infarcts, these syndromes are also described in patients with different pathological findings. The assumption that lacunae always result from a distinct and specific small-vessel arteriopathy is not confirmed; in fact, an atheroma may occlude a single perforating artery at the base of the brain as well as larger arteries. Lipohyalinosis, initially referred to as the underlying pathologic vascular lesion specific for lacunae, is found most commonly in a subset of patients with severe hypertension associated with multilacunar dementia. Large infarcts and hemorrhages are reported to coexist with lacunae in autoptic and neuroradiological studies; intracranial atherosclerosis is associated with lacunae as well as with large superficial infarcts. The percentage of patients with hypertension is approximately the same regardless of type of the infarct, lacunar or cortical. Diagnostic criteria are not clear-cut: clinical onset, neurological examination, and assessment of risk factors are unable to take lacunae apart from other infarcts; the size of the lesion, but not the site or the pathogenesis, determines clinical course, degree of motor deficit, and prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
While there are several types of stroke, the sudden or rapidly developing loss of one or more cerebral functions is the hallmark of the condition. Although classic manifestations include hemiparesis, hemianaesthesia, hemianopia, dysphasia, ataxia and cranial nerve palsies, several less typical stroke syndromes occur regularly.
We analysed the construction of neuropsychological disorders in the group of 50 demented patients diagnosed according the DSM III. Examination included clinical state, eeg, CT, observations of Hachinski's test and some psychological methods estimating social or occupational functioning, orientation, memory, thinking, perception and copying figures, emotional state. We have not found synonymous agreement between a degree of dementia and movement, CT and eeg disorders. From the psychical functions impairment most frequently were: disorders of recent memory, perception and copying figures as well as thinking. Emotional difficulty not be a rule.
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The rCBF in a group of 120 patients with cerebrovascular disease (CVD) diagnosed clinically as well as with CT scans and a group of 120 healthy subjects as controls was measured with the 133Xenon inhalation method. The result showed that the rCBF of the CVD group was significantly lower than that of the control group (P less than 0.01). The tally rate between the rCBF reduction areas and the lesion sites was 85 per cent. The areas of rCBF reduction measured with 133Xenon inhalation were larger than the extents of the lesions shown by CT scans in 47 cases of cerebral infarction. The rCBF reductions of bilateral cerebral hemispheres were found in 16 cases of cerebral infarction. The average hemispheric rCBF obviously decreased in 12 cases of multiple cerebral infarction with dementia, but showed no decrease of rCBF in 18 cases of small focal cerebral infarction.
The medical histories and postmortems of 30 patients with neuropathologically verified Alzheimer's disease were compared with a group of 20 patients suffering from vascular dementia and a group of 10 patients with other forms of dementia. The total numbers of clinically or pathologically diagnosed medical disorders did not show significant differences between the different forms of dementia. Metabolic, infectious, degenerative, and malignant disorders occurred with similar frequency in all investigated groups. Cardiovascular diseases were only slightly more common in patients with vascular dementia. In contrast to several earlier clinical or epidemiological studies, it has to be concluded that patients with Alzheimer's dementia cannot be considered physically "healthier" than patients with other forms of dementia. Therefore, they need the same medical attention as do other elderly demented patients.
We studied the relationship between P300 latency and regional cerebral blood flow (rCBF) in nondemented patients with cerebral infarction. Subjects were 24 nondemented patients (mean age 64.1 years) who had a CT-proven infarct in the territory of the deep perforators of the internal carotid artery system and 53 controls (mean age 64.1 years). Prolongation of P300 latency with advancing age was observed in the both groups. There was no significant difference in P300 latency and rCBF between the two groups. There was a negative correlation between P300 latency and rCBF, especially in the bilateral fronto-parietal regions in the patient group. These results indicate that cognitive function assessed by P300 latency may be related to rCBF in the fronto-parietal region in the nondemented patients with lacunar infarctions.
Twenty-four patients of comparable age, blood pressure, and degree of dementia were classified by an "Ischemic Score" based on clinical features into "multi-infarct" and "primary degenerative" dementia. Regional cerebral blood flow (CBF) was measured by the intracarotid xenon 133 method. Both groups showed a decreased proportion of rapidly clearing brain tissue (largely gray matter). Cerebral blood flow per 100 gm brain per minute was normal in the primary degenerative group but low in the multi-infarct group. This suggests the blood flow is adequate for metabolic needs of the brain in patients with primary degenerative dementia but inadequate for those with multi-infarct dementia. There was no correlation between degree of dementia and CBF in the primary degenerative group but an inverse relationship existed in the multi-infarct group. Reactivity of blood vessels to reduction of arterial carbon dioxide pressure was normal in both groups.
A multicentre, double-blind, between-patient study was carried out to evaluate the efficacy and tolerability of oxiracetam (800 mg tablet), in comparison with placebo, each given twice daily for 12 weeks to patients suffering from primary degenerative, multi-infarct or mixed dementia. Efficacy was assessed by a neuropsychological battery (simple reaction time, controlled associations, short story, Raven's Progressive Matrices, token test, digit span, word list learning), administered at the beginning and at the end of the study, and by a quality of life scale, administered at entry and after 6 and 12 weeks treatment. Sixty-five patients (28 men, 37 women, mean age 71 yrs) were enrolled; 58 completed the study: 2 on oxiracetam were withdrawn because of poor tolerability, 2 (one in each group) were withdrawn for poor compliance, one (on oxiracetam) for the occurrence of a transient ischaemic attack (defined as not related to the treatment) and 2 for administrative reasons. A significantly (p < 0.01) different effect in favour of oxiracetam was observed on the quality of life scale, and confirmed by significant (defined according to the Bonferroni technique) differences in some neuropsychological tests (e.g. controlled associations, short story). Four patients in the oxiracetam group complained of a total of 5 unwanted effects, and 1 on placebo complained of 3 unwanted effects, but none of them was withdrawn from the study.
Catecholamines (CA) are among the most well known neurotransmitters (NT) which act in a wide range of brain structures and are involved in many important functions, such as general arousal, autonomic, neuroendocrine and motor control and possible in emotion and mentation. The neuropharmacology of the brain CA synapses has played a crucial role in understanding the complex phenomena of the central neurotransmission and the feed-back mechanisms by which the central neurones adapt optimally to the functional needs at any time. The model of neurotransmission, as well as the mechanism by which various substances act at the synaptic level are briefly outlined. Due to the fact that the CA are implicated in many important functions of the brain, it has been suggested that certain mental diseases such as depression, as well as mental and behavioral manifestations of the ageing brain might have their origin in an impairment and particularly in a functional deficiency of the CA occurring at various structures. The available evidence in support to this view is outlined and the hypothesis that senile mental deterioration and the mental impairment encountered in various types of dementia (senile, presenile and multi-infarct) may be due to deficiency of the brain CA is discussed. Since the CA and particularly the dopamine deficiency seems to be a common denominator in depression and in senile mental deterioration, it is suggested that the dopaminergic drugs may serve as useful therapeutic means on one hand and important tools for testing the validity of the above hypotheses on the other.
Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) were measured in 77 female inpatients with moderate to extreme dementia and in 17 elderly female controls. Both multi-infarct (MID) and Alzheimer-type (SDAT) demented patients had equally elevated CSF CRH and TRH but not SRIF levels as compared with the controls. This elevation was, however, not seen in patients with simple dementia while it was most prominent in those exhibiting marked depressive symptoms. It is concluded that depression rather than dementia itself may be associated with CSF CRH and TRH elevation in elderly patients with cognitive impairment.
Changes from the end of 4-week placebo (washout) baselines to the end of 3-month therapy with three chemically different cognition enhancers (CEs) [i.e., piracetam, acetyl-L-carnitine, and nimodipine (NIM)], and parallel changes in placebo controls, were compared to determine the influence of the severity of disease at study entry. Four trials published elsewhere, showing significant treatment differences between active drugs and placebo, were selected according to their (a) sharing at least one global measure for treatment outcome and having shown effects on at least one additional scale or test, and (b) presenting an obvious rank order in the severity of disease. Each study was a standard-controlled clinical phase III trial with greater than 100 psychogeriatric in-or outpatients. The patients' symptoms met the criteria for mild to moderate/severe age-related organic brain syndrome, a core syndrome of senile dementia, either from the primary degenerative, mixed, or multi-infarct type. The extent of changes on placebo was clearly influenced by the mean pretreatment severity of disease. On the whole, the improvements on active drugs reached or exceeded the baseline variability of psychogeriatric scales and tests.