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Cerebrospinal fluid neuropeptides in mood disorder and dementia.

Cerebrospinal fluid (CSF) concentrations of immunoreactive corticotropin-releasing hormone (CRH) and somatostatin (SRIF) were measured in female psychiatric inpatients with DSM-III-R diagnoses of major depression, mania, generalized anxiety and somatization disorder. In addition, elderly patients with dementia disorders, with or without concomitant major depression, were also investigated. CSF SRIF was not significantly different among these groups; on the other hand, mean CSF CRH concentrations were significantly higher in major depression and in dementia with depression as compared with neurological controls with no psychiatric disorders. CSF CRH levels in mania, simple dementia, or anxiety or somatization disorder were not significantly different from the controls. Background physical or clinical variables did not account for the differences in CRH concentrations. It is concluded that CSF CRH elevation may be present in some patients with major depression independent of age and an underlying dementia disorder.

Adult

The use of positron emission tomography in the clinical assessment of dementia.

A number of reasons can be cited for performing a test that identifies patients early in their course who have fatal and currently untreatable neurological disorders. At this stage of illness there is clinical ambiguity. The patient, family, and physician are typically faced with a battery of negative test results and an ambiguous clinical impression that can lead to periodic repetition of tests that involve cost, inconvenience, potential morbidity to the patient, and lack of definitive diagnosis. An accurate test would lead to the avoidance of these low-yield, repetitive, and costly evaluations. In addition, such studies can identify homogeneous groups of individuals with degenerative disorders leading to dementia who could be enrolled in experimental therapeutic programs. In these programs therapies could be monitored in an objective and noninvasive fashion using positron emission tomography (PET). The magnitude of the health problems resulting from the dementing illnesses is great in terms of medical practice, economics, and family hardship. The number of individuals with these disorders is predicted to increase dramatically in the future. The ability to provide an accurate diagnosis and more clear prognosis early in the disease course should diminish ambiguity for patients, families, and physicians. Ample evidence is cited in this article to show that PET has the ability to provide such information objectively and noninvasively.

Alzheimer Disease

Safety and effectiveness of low-dose clozapine in psychogeriatric patients: a preliminary study.

The short- and long-term treatment tolerance of low-dose clozapine was retrospectively investigated in 18 psychogeriatric patients. Discontinued use of the drug because of side effects or inefficiency was required for only four patients. In the long-term treatment group leukopenia was not observed, and disturbances of liver function appeared to be very infrequent. A second group of seven severely demented psychogeriatric inpatients who were currently being treated with low-dose clozapine underwent a withdrawal study in order to evaluate the therapeutic efficacy of the drug, measured by the NOSIE and the SCAG scales. The results indicate that for patients such as these, with paranoid or socially disturbing behavior who also tend to develop severe neurological side effects with classical neuroleptics, a low-dose administration of clozapine is an acceptable alternative treatment.

Aged

Dissociation of two frontal lobe syndromes by a test of verbal fluency.

Numerous researchers have attempted to localise the behavioural manifestations of frontal pathology to the regions of the frontal lobe. Three prinicpal syndromes have been identified; the disinhibited syndrome associated with damage to the orbital area, the apathetic syndrome associated with damage to the frontal convexity, and the akinetic syndrome associated with damage to medial structures. This study attempted to determine if two of these syndromes could be dissociated from each other on the basis of a test of verbal fluency. This study used some commonly occurring clinical entities as the treatment groups. The orbitally lesioned individuals produced higher levels of disinhibited responding on the test than did non-orbitally lesioned subjects. However, all pathological groups produced lower overall levels of responding than did normals on the fluency component of the test. A number of suggestions are made as to why this may have been the case, and some guidelines for the clinical interpretation of response patterns on the fluency test are suggested.

Adult

Prognosis of transient global amnesia: a long-term follow-up study.

A long-term follow-up study was performed on patients with transient global amnesia (TGA) in order to evaluate the prognosis, the recurrence rate and the occurrence of stroke and dementia. 102 patients (57 women, 45 men; mean age 62.8 +/- 9.4 years) were prospectively included and followed up. The follow-up duration ranged between 12 and 241 months with an average value of 82.2 +/- 51.1 (mean +/- SD). The death rate showed no difference from that of sex- and age-matched subjects. TGA recurred in 19 cases (18.63%). Only 4 patients suffered subsequent stroke, and only 3 showed intellectual deterioration. TGA prognosis was shown to be better than that of RIA and lacunar patients.

Adult

Does the severity of leukoaraiosis contribute to senile dementia? A comparative computerized and positron emission tomographic study.

The present study evaluates the origin, severity and location of leukoaraiosis in senile dementia and in normal ageing. The regional white-matter lucency scores, determined on computed-tomographic scan of the brain, are compared to the regional blood flow, oxygen extraction rate and oxygen consumption, determined by the [15O] steady-state technique with positron emission tomography. Thirty patients, classified according to the presence or absence of leukoaraiosis and their mental status, are examined. The occurrence and severity of dementia appear to be mainly correlated to decreased blood flow and oxygen metabolism in the frontal, temporal and parietal cerebral cortex. Leukoaraiosis in demented and nondemented patients is associated with lowered blood flow in the frontal and parietal white matter. The regional lucency score is increased, and blood flow and oxygen consumption decreased in the frontal white matter of severely demented patients. Frontal leukoaraiosis contributes to dementia and is probably of ischemic origin, while parietal and occipital leukoaraiosis is due to wallerian degeneration.

Aged

Event-related potentials in patients with multiple lacunar infarcts.

We studied event-related potentials (ERPs) occurring in response to attended and unattended stimuli in 31 patients with multiple lacunar infarcts. ERPs were recorded during the performance of visual discrimination tasks using three kinds of stimuli. Each component of P300 response to infrequent nontarget stimuli and P300 response to infrequent target stimuli was defined as non-target P3 or target P3. The non-target P3 latency in patients with multiple lacunar infarcts was significantly longer than in 15 age-equivalent normal subjects, while no significant differences could be found in target P3 latency between patients and normal subjects. From the controlled/automatic standpoint these results suggest that multiple lacunar infarcts are related to impairment of automatic processing reflected by non-target P3, although controlled processing reflected by target P3, is less impaired.

Aged

The noisy elderly patient: prevalence, assessment, and response to the antidepressant doxepin.

To measure the prevalence of noisy behavior as a nursing problem, a survey of head nurses was done in a chronic care hospital to identify patients whose vocalizing was frequently disturbing to other patients, staff, or visitors. We found 17 patients among the total of 154. Subsequently, the medical records of 13 surviving subjects were reviewed more exhaustively, and 11 were described as disruptive, usually when they were left alone. Of these "lonely" patients, eight had a previously documented diagnosis of depression. All were demented. Antipsychotic medication had previously been given to all 11 "lonely" patients, but had failed to control their disruptive behavior. Empirically, six patients were treated with doxepin, and in five, all with a history of previous depression, agitation and noisiness diminished. These observations suggest that the prevalence rate of disturbingly noisy behavior among long-term institutionalized elderly patients is about 11% and that the disturbingly noisy patient is often demonstrating depression in conjunction with dementia.

Aged

Risk factors in Alzheimer's disease: a clinicopathologic study.

We investigated potential risk factors for Alzheimer's disease (AD) in a clinicopathologic study of 407 patients with definite AD, 100 non-Alzheimer dementia patients, and 50 normal subjects. The AD patients had more first-degree relatives with dementia than the non-AD dementia group (odds ratio of 1.85, 95% confidence interval of 1.07-3.20) or the normal elderly (odds ratio of 3.60, 95% confidence interval of 1.50-8.64) but did not have significantly more head injuries, medical and psychiatric illnesses, or relatives with Down's syndrome. The AD patients with a family history of dementia had their dementia at a later age than those without an affected relative. These findings indicate a familial risk for AD that is greater than for other dementing illnesses and has age-related penetrance. This study does not support other putative risk factors for AD such as head trauma and familial Down's syndrome.

Aged

[A case of delusional melancholia: "a variant of loss of psychological self-activation"?].

A 62 year-old man presented with melancholia with delusions, possibly resulting from lenticular lesion in the left and frontal damages in the right. Atypical signs of our observation led us to consider our patient not as suffering of affective disorder. We suggest that melancholia could be a consequence of a certain type of stereotyped mental activity, and we would compare this stereotyped mental activity to mental compulsive activity described in "loss of psychic self activation" of D. Laplane. In this perspective our observation would be a variant of "Loss of psychic self-activation". Heuristic value of this concept is discussed.

Arousal

[Ischemic stroke in patients under 50 years of age with special reference to its etiology and risk factors].

Eighty-four patients with ischaemic stroke aged 18-50 years were analysed. They had been treated in the years 1985-1989. Forty-five of them were followed up. In a high proportion of cases stroke was a result of thrombosis. Many risk factors were found in this group, mainly hypertension. In most cases stroke was serious, in several cases post-stroke epilepsy and poly-infarction dementia developed.

Adolescent

Functional rating scales and psychometric assessment in Alzheimer's disease: applications in pharmacological trials.

New findings on cognitive aging show that decline in brain functions is not part of a general decline of functioning in old age. We know now that with increasing age there is a differentiation of cognitive functions into two independent dimensions (fluid and crystallized functions). This two-dimensional model allows a more precise description of the cognitive aging process and of pathological changes. While crystallized cognitive abilities can be improved by training till late in life, fluid cognitive functions are subject to a progressive decrease starting as early as age 30, becoming most evident in cases of organic mental disorders. Thus, pathological aging is not necessarily accompanied by global loss of functions. Different abilities undergo changes in different ways, a fact taken into consideration by modern methods of psychometric evaluation. Beyond the aging processes mentioned previously, cognitive and behavioral changes in the elderly may be considered to be early indicators of organic mental disorders. The Nuremberg Self-Evaluation List seems to be a promising approach to diagnosis.

Aged

Global rating, symptoms, behavior, and cognitive performance as indicators of efficacy in clinical studies with nimodipine in elderly patients with cognitive impairment syndromes.

Nimodipine is a calcium antagonist which improves learning and memory in brain-lesioned or aged animals (LeVere & Sandin, 1989; Schuurman & Traber, 1989). It also accelerates the recovery of experimentally damaged sciatic nerves (van der Zee et al., 1987) and reduces age-associated gait abnormalities in aging rats (Schuurman et al., 1987). Selective action on cerebral vessels has also been proven. Vasoconstriction was prevented or reduced with nimodipine under experimental conditions (Toward, 1981) and cerebral blood flow could be increased (Kazda et al., 1982). The drug has been tested in subarachnoid hemorrhage, stroke, severe head injury, cerebral resuscitation after cardiac arrest, impaired brain function in old age, and dementia. Methodological aspects of clinical studies with this agent are examined in this paper.

Aged

[P300 and dementia: diagnostic relevance II].

Recent research on the relationship between ERP-latencies and reduced information process capabilities with demented subjects has yielded divergent results. In the present study P300-latencies and RT are used in an attempt to differentiate between demented and nondemented subjects. Based on the "feature-integration-theory" of Treisman an experiment was designed in order to investigate more complex cognitive processes. The results showed that both P300-latency and RT may be used as additional diagnostic indices for cognitive capability.

Adult

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