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PubMedDate not supplied

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↗

PubMed1990

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.

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PubMed1986

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.

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PubMedDate not supplied

[Cortisol suppression after dexamethasone administration in patients with dementia].

Sixty-four nondepressed, carefully selected senile demented inpatients underwent two 1.0 mg overnight dexamethasone suppression tests (DSTs) separated by 7 days. These patients had been in a clinically stable and drug-free state for at least six months prior to testing. The Modified Ischemic Scale score and ICD-9 criteria for Alzheimer's disease were used to dichotomize subjects into Alzheimer's and multi-infarct types of dementia. Patients with vascular dementias were significantly more likely to evidence DST nonsuppression, furthermore, DSTs in this group were less reproducible from week to week than DSTs in Alzheimer's patients.

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PubMed1985

Involutional dementias: new perspectives.

13 patients with psycho-organic syndrome (POS) and 10 patients with dementia (senile, Alzheimer, multi-infarct) were treated with drugs considered to influence the neuronal turnover of acetylcholine (Phosphatidylcholine, piracetam, S-adenosylmethionine) for 30 days and compared in respect of CSF ACh levels, reaction times to simple visual stimuli (TRS-V) and to simple hearing stimuli (TRS-H) and scores on the Sandoz Clinical Assessment Geriatric (SCAG) rating scale. The POS patients presented higher CSF ACh levels, shorter TRS-V and TRS-H times and lower SCAG scores than the demented patients before treatment. During treatment the CSF ACh values fell in the POS but not in the demented patients. All the other values improved in both groups but more markedly in the POS group. The CSF ACh variations in the latter appear to correlate with the variations in TRS-V and TRS-H times and SCAG scores. The monitoring of CSF ACh would seem to be useful in assessing both the degree of decline in dementia and the possibilities of treatment in individual patients.

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PubMed1986

Suppression of cortisol following dexamethasone in demented patients.

Sixty-four nondepressed, carefully selected senile demented inpatients underwent two 1-mg overnight dexamethasone suppression tests (DSTs) separated by 7 days. These patients were in a clinically stable and drug-free state for at least 6 months before testing. The Modified Ischemic Score and ICD-9 criteria for Alzheimer's disease were used to dichotomize subjects into Alzheimer's and multi-infarct types of dementia. Patients with vascular dementias were significantly more likely to evidence DST nonsuppression. Furthermore, DSTs in this group were less reproducible from week to week than DSTs in Alzheimer's patients.

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PubMed1986

Clinical and neuropsychological rating scales for differential diagnosis of dementias.

Clinical and neuropsychological rating scales were used in two studies of patients. The first one included 20 patients with progressive dementia and was divided into two groups according to their ischemic score evaluation and ancillary examinations (EEG, cerebral evoked potentials, CT scan, Doppler, xenon-133 clearance). The first group consisted of 10 patients with primary degenerative dementia of the Alzheimer type (SDAT) (n = 10). The second group included 10 patients with dementia caused by multi-infarction (MID). The second study included 18 patients with a confusional state, examined repeatedly for 1-6 months afterwards. The clinical and neuropsychological procedure consisted of a multi-dimensional assessment including 8 rating scales. A significant difference was found in the overall clinical and neuropsychological profile of patients with SDAT and MID. Cognitive functions were homogeneously impaired in the group of SDAT patients and heterogeneously in the group of MID patients. In chronic confusional states the overall profile was similar to that of the group of MID patients. Further reassessment showed a normalization in 9 patients, a vascular MID profile in 6 cases, an SDAT profile in 3 cases, and an undifferentiated one in 2 cases. Reversibility of the confusional state might be predicted at the onset of the cognitive disorder by history-taking and evaluation of the ischemic score.

Aged↗

PubMed1979

[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.

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PubMed1988

White matter changes in dementia of Alzheimer's type. Biochemical and neuropathological correlates.

A correlative neuropathological-biochemical study was undertaken in order to characterize the selective incomplete white matter infarctions (SIWI) frequently found in dementia of Alzheimer's type. The brain tissue analysed represented white matter with incomplete infarction, complete infarcts and with histologically normal tissue, in cases with dementia, mainly of Alzheimer and multi-infarct type, in nondemented subjects with cerebral infarcts and in age-matched control cases. The biochemical results verify the existence of the white matter changes and agree on their regional distribution as they appear in the morphological analyses. The increasing severity of SIWI as assessed histologically was reflected in a proportional reduction of several biochemically quantified white matter components. The histological difference between incomplete and complete infarction was also expressed biochemically. Incomplete white matter infarction with and without associated complete infarcts were biochemically similar. The aetiological significance of the loss of different white matter components is discussed. The biochemical data support the concept of SIWI as being an independent white matter disorder of cerebrovascular, hypoperfusional/hypoxic origin.

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PubMed1988

The reversible dementias: do they reverse?

Thirty-two studies (2889 subjects) that investigated the prevalence of the causes of dementia were critically reviewed. Particular attention was paid to potential and actual reversibility. Although dementia manifests itself primarily in old age (particularly age 75 and older), the mean age of patients for the studies that reported age data (56%) was 72.3 years. Twenty-five studies originated from secondary or tertiary centers, and four were community-based. Dementias consisted of Alzheimer disease, 56.8%; multi-infarct, 13.3%; depression, 4.5%; alcoholic, 4.2%; and drugs, 1.5%. No single other cause contributed more than 1.6% of the cases. Potentially reversible causes made up 13.2% of all cases. However, the more important question of whether patients with potentially reversible causes were followed and reversal actually seen was not always examined. In 11 studies (34%) that provided follow-up, 11% of dementias resolved, either partially (8%) or fully (3%). The commonest reversible causes were drugs, 28.2%; depression, 26.2%; and metabolic, 15.5%. Due to the presence of various biases (selection, lack of "blinded" investigators, and others) in the surveyed works, it is probable that the true incidence of reversible dementias in the community is even lower than that reported. Research implications as well as a conservative approach to the workup of a new case of dementia are offered.

Age Factors↗

PubMed1992

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.

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PubMed1991

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↗

PubMed1990

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↗

PubMed1991

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↗

PubMed1988

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↗

PubMed1990

Arteriolosclerotic leucoencephalopathy in the elderly and its relation to white matter lesions in Binswanger's disease, multi-infarct encephalopathy and Alzheimer's disease.

Arteriolosclerotic leucoencephalopathy in the elderly (ALE) is characterized by white matter lesions associated with atherosclerosis and arteriolosclerosis. Mild lesions are focal and probably represent early status cribosus or incomplete lacunar infarcts. Moderate and severe lesions are diffuse areas of demyelination in the centrum semiovale in which lacunar infarcts are seldom observed. The incidence of ALE in a consecutive necropsy series of 50 cases (mean age 62.6 +/- 13.1 years) was 52%, it was rare in the fourth and fifth decades but increased thereafter to reach a prevalence of 100% at the age of 80 years. Mild lesions occurred in 19 patients and lesions were moderate or severe in 7 (14%). The mean age was higher in this group (74.7 +/- 7.6 years) than in patients with white matter changes as a whole. Dementia occurred only in 3 patients with moderate or severe ALE. These data suggest that (a) ALE is common in old age and is probably the cause of leuko-araiosis in most CT scans in the elderly; (b) ALE may be asymptomatic; (c) the severity of white matter changes may be not related to the severity of neurological deficits; and (d) multiple lacunar infarcts or associated degenerative diseases (i.e., Alzheimer's disease) may be the main cause of dementia in patients with ALE. White matter lesions in ALE, Binswanger's disease, transition areas in multi-infarct encephalopathy (MIE) and Alzheimer's disease (AD) are similar in morphology and are probably the result of a subacute hypoperfusion/hypoxic process. Increased arterial blood pressure is a frequent risk factor in ALE, Binswanger's disease and MIE, whereas congophilic angiopathy of the meningeal and cortical vessels, in addition to mild or moderate arteriolar hyalinosis in the white matter, may play a role in the pathogenesis of incomplete infarctation of the white matter in patients with AD.

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PubMed1982

A post-mortem study of the cholinergic and GABA systems in senile dementia.

Choline acetyltransferase (ChAT) activity and gamma-aminobutyric acid (GABA) concentration were measured in 19 cerebral cortical areas and 22 subcortical areas of brains from 26 control and 25 histologically proven cases of Alzheimer's disease. Reduced ChAt activity was observed in all the cortical areas examined in the Alzheimer cases dying before the median age of 79 years. In the Alzheimer cases aged greater than 79 years at death, 7 out of the 9 frontal cortical areas had a normal ChAT activity when compared with controls. Significant reductions in GABA concentrations in the Alzheimer cases were confined to the temporal cortex. Significant reductions in ChAT activity in subcortical areas were confined to 8 of the 22 regions examined. Notably these included the septal nuclei and substantia innominata, the proposed origins of the cholinergic projections to the hippocampus and neocortex, respectively. There were no reductions in GABA concentrations outside the cerebral cortex. Four multi-infarct cases and 6 cases with normal histology were found to have a small reduction in ChAT activity confined to only a few areas. The data are consistent with a predominant loss in Alzheimer's disease of the diffuse cholinergic projection from the brainstem and basal forebrain.

Aged↗

PubMedDate not supplied

A histoquantitative study of the striate cortex and lateral geniculate body in normal, blind and demented subjects.

The amount of myelin in the outer band of Baillarger in the human visual cortex stained by Luxol Fast Blue MBS, has been measured in normal individuals of wide age range, in a group of blind and severely visually impaired but otherwise normal individuals and in a series of demented patients of the Alzheimer and multi-infarct type who were apparently visually normal. The amount of myelin is found to be significantly reduced in the blind and demented groups. Examination of the lateral geniculate body in the blind cases demonstrated slight reduction in neuron numbers and marked reduction in mean neuron diameter. Neuronal cytoplasmic ribonucleic acid, nucleolar volume and numbers of tetraploid glial nuclei in the blind or visually impaired cases were significantly reduced when compared with controls, indicating reduced function in these neurons. Similar results were obtained on examining this nucleus in Alzheimer and multi-infarct cases, suggesting that the visual pathways may be involved in these conditions. It is concluded that loss of myelin from the outer band of Baillarger occurs in association with reduced function of neurons in the lateral geniculate body.

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