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The clinical differential diagnosis of dementia: concept and methodology.

Dementia is a rather heterogeneous syndrome. This heterogeneity is expressed in the diversity of its clinical characteristics and its evolution and in the underlying etiologic factors. Unfortunately, these divisions do not run in parallel. Therefore, considerable diversity exists in the manifestations of each pathologic entity, thus making a clinical diagnosis of dementia type an educated guess at best. The need for biologic markers of the various entities is stressed in this article.

Alzheimer Disease↗

Leukoaraiosis: correlation of MR and CT findings with blood flow, atrophy, and cognition.

Hypodense periventricular white-matter lesions detected by CT (leukoaraiosis) and high-intensity T2 signals detected by MR imaging were correlated with measurements of local cerebral blood flow (LCBF), cerebral atrophy, and cognitive performance. Subjects studied included elderly volunteers who were neurologically normal (n = 6), patients with chronic cerebral infarctions and intact cognition (n = 2), patients with multiinfarct dementia (n = 14), and patients with Alzheimer dementia (n = 9). Leukoaraiosis correlated with periventricular high-intensity lesions detected by MR, LCBF reductions, cognitive impairments, and cerebral atrophy. Moderate to severe leukoaraiosis was associated with LCBF reductions in the cortex, basal ganglia, and frontal white matter. Periventricular MR lesions correlated with cerebral atrophy but not with cognitive impairments or reductions in LCBF. The exquisite sensitivity of MR revealed small lesions that did not correlate with LCBF reductions and cognitive impairments. Remote subcortical white-matter lesions detected by MR did not correlate with periventricular MR lesions, leukoaraiosis, LCBF, cerebral atrophy, or cognitive performance, indicating little clinical relevance. We concluded that diffuse cerebral hypoperfusion, particularly in combination with the poor collateral circulation of white matter surrounding the lateral ventricles, is responsible for leukoaraiosis.

Aged↗

MR signal abnormalities in memory disorder and dementia.

MR imaging of the brain, performed in 86 normal subjects and 113 patients with objective memory disorder or dementia, demonstrated white- and gray-matter areas of high signal intensity on long TR images (short and long TE). Hyperintensities were analyzed with respect to size (on a scale of 0-3) and location: lesions were periventricular, subcortical, or cortical. The patients with memory disorder and dementia were categorized as having probable/possible Alzheimer disease, a combination of Alzheimer disease and multiinfarct cognitive disorder, or multiinfarct cognitive disorder alone on the basis of clinically determined Hachinski ischemic scores. Significant correlations were found between age and scores for periventricular lesions (r = .40, p less than .0005) and subcortical lesions (r = .39, p less than .0005) in normal subjects. Correlations were also found between the Hachinski ischemic score and scores for periventricular lesions (r = .21, p less than .01), subcortical lesions (r = .27, p less than .0002), and cortical lesions (r = .32, p less than .0005) in subjects with memory disorder/dementia. Comparing multiinfarct cognitive disorder, Alzheimer disease, and normal groups, the mean scores for periventricular lesions were 12.0 +/- 4.6, 7.6 +/- 4.8, and 3.4 +/- 2.6, while mean scores for subcortical lesions were 10.8 +/- 12.2, 4.1 +/- 6.4, and 0.8 +/- 1.2, respectively. Periventricular lesions were present in 99-100% of patients with Alzheimer disease and multiinfarct cognitive disorder. On the other hand, subcortical lesions, which were identified in 100% of patients with multiinfarct cognitive disorder, were present in only about half of the patients with Alzheimer disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regional cerebral blood flow imaging: a quantitative comparison of technetium-99m-HMPAO SPECT with C15O2 PET.

The aim of this study was to compare technetium-99m-hexamethylpropyleneamineoxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) with regional cerebral blood flow (rCBF) imaging using positron emission tomography (PET). As investigation of dementia is likely to be one of the main uses of routine rCBF imaging, 18 demented patients were imaged with both techniques. The PET data were compared quantitatively with three versions of the SPECT data. These were, first, data normalized to the SPECT cerebellar uptake, second, data linearly corrected using the PET cerebellar value and, finally, data Lassen corrected for washout from the high flow areas. Both the linearly-corrected (r = 0.81) and the Lassen-corrected (r = 0.79) HMPAO SPECT data showed good correlation with the PET rCBF data. The relationship between the normalized HMPAO SPECT data and the PET data was nonlinear. It is not yet possible to obtain rCBF values in absolute units from HMPAO SPECT without knowledge of the true rCBF in one reference region for each patient.

Aged↗

[Vascular-induced disorders of cerebral performance in the elderly. Long-term therapy with pentoxifylline and psychological mental training].

In a six-week placebo-controlled, randomized, in part double-blind, study, the effectiveness and tolerance of pentoxifylline was investigated in 120 elderly patients with incipient cerebrovascular disorders (OPS). In addition to group I (placebo) and group II (2 X 600 mg pentoxifylline/d), a third group of patients (III) was treated with pentoxifylline plus psychological training. In the two pentoxifylline groups, the mental performance increased to a greater extent than in the placebo group. Despite a tendential superiority of the pentoxifylline plus training group, there was no statistically significant difference between groups II and III. With respect to "state of health and behavior" (summed score of the SCAG), the placebo group revealed a deterioration as compared with improvements in II and III, the improvement being more pronounced in the latter. Such an evaluation was also obtained when the changes in all the variables were considered. It has thus been shown that pentoxifylline is suitable for the symptomatic treatment of organic brain syndrome, and that its positive therapeutic effect can be improved by a simultaneous mental training program.

Aged↗

[Catecholamine metabolism in extrapyramidal disorders in patients with chronic hypertensive encephalopathy].

Total and cerebral metabolism of catecholamines (CA) was examined in patients with associated chronic hypertonic encephalopathy and extrapyramidal disorders. It was discovered for the first time that there was an increase in noradrenaline in the blood and cerebrospinal fluid together with a lowering of the content of dopamine and major metabolite thereof along the pathway of oxidative deamination of homovanillic acid. CA metabolism was shown to correlate with the patients' age, duration and gravity of extrapyramidal disorders. It is suggested that the revealed metabolic disorders of CA--neurotransmitters which are likely to underlie the development of neurological deficiency and characteristic mental disorders occur as a result of the diverse complex of biochemical alterations and are related both to the complex mechanisms of the pathogenesis of essential hypertension and ischemic injury to the brain as well as to the localization in the brain of lacunar infarctions. The complexity of the pathogenic treatment of the disease is emphasized. The main approaches to the pharmacological correction of the revealed disorders are outlined.

Adult↗

[One and a half syndrome and MRI--a case report and functional neuroanatomy of the syndrome].

This is a case report of 63 year old men who presented one and a half syndrome with ipsilateral peripheral type facial palsy due to lacunar infarct. MRI taken one week after the onset (TR 2000, TE 38) demonstrated small high intensity lesion, 4 mm in diameter, located at the dorsal portion of pontine tegmentum, contacting with the floor of 4th ventricle. This MRI coincides with the lesion limited to the abducens nucleus and genu of facial nerve. Traditionally, projections from the PPRF to the ipsilateral abducens nucleus and opposite MLF was postulated. Recently, however, experiment on monkey and autopsy cases showed projection from abducens nucleus, instead of PPRF, to the opposite MLF has been proposed. MRI findings in this case support the latter hypothesis. It is expected that, with the advent of MRI, more meticulous functional neuroanatomy will be developed.

Dementia, Multi-Infarct↗

[Anastomosis of the superficial temporal artery to the middle cerebral artery for occlusive disease of the bilateral internal carotid arteries with dementia].

Two cases are reported of occlusive disease of the bilateral internal carotid arteries with dementia in which the anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA bypass) resulted in marked improvement in clinical aspects. One patient was a 29-year-old male who complained of transient weakness of the extremities and memory impairment. Computerized tomography (CT) scans showed multiple small infarctions, while cerebral angiography demonstrated findings of Moya-like disease. The cognitive function tests were subnormal and the study of cerebral blood flow (CBF study) showed diffuse low flow in both hemispheres. Based on his clinical symptoms and CBF study, the STA-MCA bypass was performed on both sides in two stages without complications. Postoperatively, his clinical symptoms and cognitive function improved gradually, in accordance with increased CBF in both hemispheres. Six months after the operation, cognitive function tests were within normal limits. Another patient was a 61-year-old hypertensive male who complained of motor weakness, impairment of memory and urinary incontinence. CT scans showed multiple small infarctions, while cerebral angiography revealed occlusion of both internal carotid arteries at the cervical portion. The cognitive function was at the pre-dementia level, and CBF study revealed diffuse low flow in both hemispheres. Based on the clinical symptoms and CBF study, the STA-MCA bypass was performed on both sides in two stages. Postoperatively, clinical symptoms and cognitive function markedly improved. From our results, the diagnosis of vascular dementia, and indications for the use of STA-MCA bypass in this category of patients are discussed.

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↗

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 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↗