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Adult dementia: history, biopsy, pathology.

The historical events in the evolution of Alzheimer's disease are reviewed, including the initial description by Alois Alzheimer and the subsequent controversy regarding the nosological specificity of this entity. The similarity of senile dementia and Alzheimer's disease is emphasized. The basis for the modern concept of Alzheimer's disease as premature or accelerated aging is included in the review. The pathological correlates of the major categories of adult dementia have been described. The traditional criteria of neurofibrillary tangles and senile plaques have been re-evaluated using the current insight into these changes afforded by electron microscopy and biochemistry. The significance of amyloid has been described because it occurs within the senile plaque and also as the essential component of congophilic angiopathy. The new information regarding neuronal cell counts and the loss of choline acetyltransferase has been evaluated in terms of an indication of a pathogenic mechanism of Alzheimer's disease. The current understanding of normal pressure hydrocephalus, Creutzfeldt-Jakob disease, and multi-infarct dementia has been described. Brain biopsy in dementia has been described as having diagnostic, research, pathogenic, and prognostic value. The precautions involving the performance and handling of the biopsy have been stressed, particularly because these procedures involve conditions of possible slow virus etiology. The polemic for Alzheimer's disease as aging or slow virus infection has been summarized. At this time a consideration seems justified that Alzheimer's disease is an age-related, slow virus disease due to a hitherto unknown immune defect. Aging as an etiological agent must be clarified before Alzheimer's disease, in any form, can be considered to be an inevitable consequence of longevity.

Adult

Longitudinal diagnosis of memory disorders.

Early referral for specialist assessment is becoming more common with memory disorders and dementia: the mean Mini-Mental State Examination (MMSE) score of new patients at our clinic rose from 18.7 to 20.7 between 1986 and 1990. The clinical diagnosis of mild to moderate dementia has been recognized to be difficult, but several studies have reported cross-sectional diagnosis. We examined the number of visits required to establish a clinical diagnosis of dementia in the first 125 patients attending a Memory Disorders Clinic who had at least two visits (six months apart) and the stability of the diagnoses. Just under half of the patients required at least two visits to establish the clinical diagnosis. The MMSE was not a good guide to the number of visits required but the diagnosis at the first visit remained stable in all patients who scored < or = 10/30. Sixteen per cent of patients interchanged between the categories of Alzheimer's, mixed and vascular dementias. Possible age-associated memory impairment progressed to dementia in six of eight cases, and depression to dementia in three cases. The diagnosis of mild to moderate dementia should not be restricted to a cross-sectional approach, but should involve serial clinical, psychological and affective assessments.

Aged

Non-invasive regional study of chronic cerebrovascular disorders using the oxygen-15 inhalation technique.

The regional cerebral metabolism-to-perfusion imbalance has been studied in the three main categories of cerebrovascular disorders in a chronic phase of the disease, using the non-invasive oxygen-15 inhalation technique. In patients presenting with a history of transient ischaemic attacks, regional defects in cerebral perfusion were greater than for the corresponding oxygen uptakes. Areas of relative ischaemia within which there was an enforced increase in the oxygen extraction ratio were highlighted. The reverse pattern was observed frequently in patients with brain infarcts arising from strokes, so indicating areas of relative luxury perfusion as is inferred from the reduction in the oxygen extraction ratio. In the multi-infarct dementia group of patients, there were parallel focal reductions in both flow and metabolism. The oxygen-15 inhalation technique is shown to be a unique tool in investigating cerebrovascular disorders because of its non-invasiveness and its ability to define regional metabolism-to-perfusion imbalance within the brain.

Adult

[Recent therapeutic advances in geriatric neurology].

Marked advances in the treatment of neurological disorders which affect the elderly have been established in recent years. Cerebrovascular disorders including stroke and vascular dementia are still among the most frequent diseases in the Japanese elderly. For treatment of hypertensive patients with or without a history of stroke, slight decrease of blood pressure (BP) is recommended since recent PET studies have revealed that an excessive drop of BP markedly decreases cerebral blood flow. Furthermore, 24-hour-monitoring of BP revealed that physiological fluctuation of BP consisting of high daytime BP and low nocturnal BP disappears in hypertensive patients with vascular dementia and those with non-symptomatic vascular lesions on MRI. Recommendable BP levels for the hypertensive elderly must be established. The efficacy of both aspirin and ticlopidine for prevention of stroke has been established. Recent multi-centric trials have revealed that ticlopidine is more effective in preventing stroke but has more dangerous adverse effects than aspirin. Aspirin is reported to improve both the intellectual scale and cerebral blood flow in vascular dementia. In Parkinson's disease (PD), L-DOPA therapy, usually in combination with a dopa decarboxylase inhibitor, is common. Other dopaminergic drugs including bromocriptine, lisuride and pergolide are used clinically or are being studied. Recently selective monoamine oxidase (MAO) B inhibitors have been used in order to slow clinical progression of the disease, in addition to an attempt to increase the potential of dopamine through inhibition of MAO. Neural transplants to the striatum of PD were first applied using autografts of the adrenal medulla in 1985, but resulted in transient or only slight improvements.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Cerebrospinal fluid gamma-aminobutyric acid in neurologic disease.

Cerebrospinal fluid gamma-aminobutyric acid (CSF GABA) was analyzed in 151 patients who underwent evaluation for central nervous system disease. CSF GABA was not detected in 19 of these patients, who had no evidence of neurologic disease and who served as controls. GABA was most frequently detected in patients with cerebrovascular disease, and was detected only in Parkinson's syndrome of atherosclerotic origin and dementia of multi-infarct type. CSF GABA was not detected in Alzheimer's disease or Huntington's disease. Patients with grand mal seizures exhibited CSF GABA elevation within 24 hours of the ictus. In patients with multiple sclerosis GABA detection was related to the presence or exacerbation of spinal cord lesions. Further study is necessary to evaluate the significance of elevated CSF GABA in central nervous system disease.

Aminobutyrates

EEG mapping and psychopharmacological studies with denbufylline in SDAT and MID.

Computed tomography (CT), electroencephalograms (EEG), clinical and psychometric data were obtained in 96 mildly to moderately demented patients (72 women, 24 men), aged 61-96 years (mean 82), diagnosed according to DSM-III criteria. Patients were off drugs for at least 2 weeks and subdiagnosed according to the modified Marshall-Hachinski ischemic score and CT in 45 senile dementia of the Alzheimer type (SDAT) and 51 multiinfarct dementia (MID) patients. Evaluations were carried out before and 12 weeks after treatment with either 100 mg denbufylline BID or placebo and included EEG mapping, the Sandoz Clinical Assessment Geriatric (SCAG) score/factors, the Clinical Global Impression (CGI), the Digit Symbol Substitution Test (DSST), the Trail-Making Test (TMT) and the Digit Span Test (DS). Descriptive data analysis including confirmatory statements found delta/theta activity enhanced, alpha and beta activity reduced, total power augmented, and the centroid slowed down over various brain regions in patients as compared with controls. The two subtypes of dementia could be differentiated in some conventional EEG variables but mostly by means of power asymmetry indices. Denbufylline induced a statistically significant and clinically relevant improvement in both SDAT and MID patients, whereas after placebo this was not the case in CGI, the TMT, and the DS, with interdrug differences being significant in all primary target variables such as the CGI, MMS, SCAG, and DSST. Thus, both the degenerative and vascular type of dementia exhibited a therapeutic benefit that could be objectified at the neurophysiological level by EEG mapping in an improvement of vigilance.

Aged

Is the tyramine test for depressive illness useful in elderly patients?

There were no significant differences in tyramine sulphate excretion following tyramine ingestion between elderly depressed, demented or control patient groups, in contrast with younger subjects where this test is a trait marker for unipolar endogenous depression. There are inherent problems in urine collection studies in the elderly and the results may have been influenced by the medication that elderly patients have to take for other disorders. This study suggests that the tyramine test is unlikely to be of clinical usefulness in the over 65 age group.

Aged

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

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

[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

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