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Treatment of pathologic emotionality with thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH) has been reported to be effective in some neuropsychiatric diseases. We examined the effect of TRH on the syndrome of pathologic laughing or crying in four patients with multiple cerebral infarction and one with olivo-ponto-cerebellar atrophy (OPCA). We found a marked therapeutic effect of the peptide on pathologic laughing with a slight improvement in ataxia in a patient with OPCA. A marked diminution in frequency of their pathologic crying with TRH was achieved in two patients with multiple cerebral infarction. The two other patients did not respond to TRH. Levodopa was administered to these patients to compare with TRH in therapeutic efficacy on the symptom and was effective in only one of four patients. The concentration of homovanillic acid in cerebrospinal fluid had diminished in two of the four patients. The results suggest that the tripeptide is effective in the control of this syndrome. We discuss the underlying mechanism(s) of the syndrome and the mode(s) of action of TRH.

Affective Symptoms↗

[Triphasic waves in dementia syndromes].

Seventy-one EEGs (0.49%) of 53 patients, out of 14,458 recordings, contained triphasic waves: twenty-nine were patients with metabolic encephalopathies and 24 were demented patients (16 of these had a presumptive diagnosis of Alzheimer's disease and the other eight of mult-infarct dementia). Demented subjects with metabolic disorders are included in the metabolic encephalopathies group. In all of the cases of Alzheimer's disease, triphasic waves were atypical: in 14 they occurred singly or in short bursts, in 10 they had occipital predominance and in 2 they were bilateral but asymmetrical. In 5 cases, triphasic waves were associated with myoclonus and in 2 of them they occurred in long runs with a pseudo-periodic pattern. In these cases the distinction from Creutzfeldt-Jakob disease was based on neuropathologic findings.

Aged↗

[Continuous pattern recognition in the assessment of memory disorders in dementia].

A simple and short method for assessing visual short term memory is presented, based on continuous picture recognition, which is not explicitly dependent on input or output language abilities. The material was gathered from Kimura's Recurring Figures Test (RFT) and Erzigkeit's SKT. Two of three parallel series which are characterized by different levels of "nameability" and familiarity are apt to distinguish between demented patients and patients without memory problems. Objectivity is assured by a simle scoring system which allows rapid transformation into d'-values according to signal detection theory. It is expected that by this procedure not only screening for memory problems in the demented will be facilitated, but also the impact of language disorders will be minimized.

Aged↗

[Diagnosis of the most frequent causes of dementia].

Contemporary diagnosis of the most frequent causes of dementia is far from optimum. It may be influenced by problems in collecting clinical data, investigation, and clinico-pathological correlation at departments of pathology. The study suggests a course of this action. Clinicoanatomical diagnosis of dementia needs to estimate the patient was really demented and evaluate the quantitative morphological finding.

Alzheimer Disease↗

Cerebral blood flow in dementia.

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.

Aged↗

Oxiracetam in dementia: a double-blind, placebo-controlled study.

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.

Aged↗

Binswanger's disease (Part II): Pathogenesis of subcortical arteriosclerotic encephalopathy and its relation to other dementing processes.

Subcortical arteriosclerotic encephalopathy (SAE) is a common though infrequently recognized dementia of the elderly. The unique vascular anatomy of the subcortical white matter and central brain stem probably predisposes those regions to chronic ischemia and incomplete infarction in the presence of various cardiovascular and hemodynamic insults. Recent studies have begun to define the risk factors for SAE, and others have shown it to be a condition frequently comorbid with the dementias of Alzheimer's disease, the multi-infarct state, and normal pressure hydrocephalus. Recent research into the etiologies of these disorders suggest certain pathogenetic links between them, strongly implying that they are not neatly distinct disease entities, as is commonly believed, and accounting for some of the overlap between these dementing illnesses seen clinically.

Alzheimer Disease↗

Coexisting depression and dementia in a community survey of the elderly.

We report here on the coexistence of dementia and depression in a community population aged 75 years and older. Complete information about mood and cognition was available for 286 cognitively intact subjects selected for assessment because of their low scores on the Mini-Mental State, and for 158 mildly and moderately demented subjects. Severely demented subjects, who were incapable of providing information, were excluded. Five percent (8/158) of demented subjects also fulfilled criteria for major depressive disorder Diagnostic and Statistical Manual of Mental Disorders, third edition (DSM-III) compared with 9% (27/286) of cognitively intact subjects. No substantial differences existed in the symptoms reported by demented depressives and nondemented depressives, but subjects who suffered from both disorders were so markedly apathetic that their depression might easily have been overlooked had specific enquiries not been made. Depression was particularly associated with dementia secondary to multi-infarct and Parkinson's disease. When reviewed one year later, 2 of the 18 surviving depressed, nondemented subjects showed evidence of dementia. Both presented unusual diagnostic difficulties, however, and no evidence emerged that large numbers of elderly people will be misclassified in community surveys that include a mental state examination, cognitive testing, and an informant interview.

Aged↗

Brain dopamine D-1 receptors in senile dementia.

Brain dopamine D-1 binding sites were studied by using [3H]flupenthixol in 4 brain regions of 44 senile patients with neuropathologically verified organic dementia and 28 age-matched controls. The D-1 binding sites were decreased in the substantia nigra and nucleus accumbens in patients with Alzheimer's disease, while no change was found in multi-infarct or combined dementia. The striatal D-1 binding sites were unchanged in all groups of patients. Only a few correlations between various clinical and post-mortem variables and the [3H]flupenthixol binding of the dementia patients were found. The findings of this study indicate that there is reduction of brain D-1 binding sites in patients with Alzheimer's disease.

Aged↗

[Brain catecholamines, mental diseases, aging and senile dementia: biochemical and pharmacological aspects].

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.

Aged↗

Cerebrospinal fluid neuropeptides in dementia.

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.

Aged↗

Efficacy and clinical relevance of cognition enhancers.

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.

Acetylcarnitine↗

Nimodipine in the treatment of old age dementias.

1. In a multicenter, placebo-controlled, double-blind clinical study in 178 elderly patients with cognitive decline, nimodipine, a calcium antagonist was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with 90 mg of nimodipine administered orally in divided doses for 12 weeks was significantly superior to an inactive placebo on all outcome measures including the Wechsler Memory Scale, the Mini Mental State Examination, the Global Deterioration Scale, the Sandoz Clinical Assessment Geriatric Scale, the Plutchik Geriatric Rating Scale, the Severity of Illness and Global Improvement Scales of Clinical Global Impression, and the Hamilton Psychiatric Rating Scale for Depression. 3. Adverse effects with nimodipine were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.

Aged↗

Glycosaminoglycan polysulfate in the treatment of old age dementias.

1. In a multicenter, placebo-controlled, double-blind clinical trial in 155 elderly patients with cognitive decline, glycosaminoglycan polysulfate was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the basis of a divided dosage schedule for 12 weeks, was significantly superior to an inactive placebo on several outcome measures including the Wechsler Memory Scale-Russell Revision (Easy Paired Associates Learning and Immediate Visual Reproduction), Mini Mental State Examination, the Sandoz Clinical Assessment Geriatric (Cognitive Dysfunction and Depression), Hachinski Dementia Scale, Brief Psychiatric Rating Scale (Confusion and Depressive Withdrawal) and Global Improvement Scale of the Clinical Global Impression. 3. Adverse effects with glycosaminoglycan polysulfate were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.

Activities of Daily Living↗

Granulomatous angiitis of the central nervous system: protean manifestations and response to treatment.

Granulomatous angiitis is an uncommon necrotising vasculitis of unknown cause restricted to vessels of the central nervous system. Five tissue-proven cases emphasise the protean manifestations of this disease and the difficulties encountered in reaching a diagnosis. One patient presented with a temporoparietal mass, the second, a progressive dementia, the third suggested herpes simplex encephalitis, the fourth mimicked multi-infarct state; and the fifth presented with a cerebellar mass lesion. In four cases with CSF examination, protein was elevated (81-193 gm/l) and three patients had mononuclear pleocytosis (12-800 WBC/mm3). Cerebral arteriogram suggested vasculitis in only one of four cases. Diagnosis was made by brain biopsy in three cases and all three were treated successfully. The diagnosis in the two other cases was made at postmortem examination.

Adult↗