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Cholinergic deficiency was postulated to play an important role in the mental decline observed in Alzheimer's (AD), Parkinson's (PD) and multiinfarct (MID) dementia. In the present study, 11 AD, 8 MID and 7 PD patients (DSM III-R diagnostic criteria for dementia) and 9 healthy age-matched controls (CTRL) were given IV 0.5 mg scopolamine (SCO) or placebo (PLA) in random order (double blind) within one week. The Hebrew Short Mental Test (SMT) and Wechsler Memory Scale (WMS) were administered before and after SCO and PLA in each patient. A comparison of SCO vs. PLA utilizing MANCOVA (the covariate being the basal mental performance [BAS] with SMT or WMS) showed that SCO affected all the groups similarly, except for the Wechsler subtest of logic memory which showed larger deterioration in CTRL compared to demented patients. ANOVA and MANCOVA analyses did not distinguish between the three demented groups. SCO administration does not differentiate between demented patients and CTRL and does not enable discrimination between patients with AD, MID and PD. Moreover, some CTRL with still normal cognitive performance, but lower BAS may be more vulnerable to SCO than others. The integrity of the cholinergic system may be responsible for the different sensitivity to SCO challenge.

Peripheral blood mononuclear cells (PBMC) from 40 consecutive patients entering a screening program on cognitive impairment were studied in vitro with respect to their sensitivity to dexamethasone (DEX). Phytohemagglutinin-induced proliferation by PBMC from patients with senile dementia of the Alzheimer type (SDAT) was less sensitive to the inhibitory effect of DEX, compared to PBMC from patients with multi-infarct dementia (MID) and PBMC from patients with miscellaneous causes of cognitive impairment (MISC). An intermediate sensitivity was found with PBMC from patients with clinical signs of both MID and SDAT (= MIXED). These differences could not be explained by differences in the composition of the CD4+ T cell population, interleukin (IL)-2 or IL-4 production, or quantitative differences in the expression of glucocorticoid receptors as measured by flowcytometry. However, the expression of bcl-2 was higher in PBMC from SDAT patients than in cells from MID patients or from MISC patients, whereas the MIXED group showed an intermediate expression; a high bcl-2 expression correlated with a low DEX-sensitivity. These findings suggest that characteristics of PBMC reflect related changes in the central nervous system and indicate that PBMC may be a useful and accessible tool to obtain more insight into the pathogenesis of Alzheimer's disease. Chemicals/CAS: dexamethasone receptor; Dexamethasone, 50-02-2; Immunosuppressive Agents; Interleukin-2; Interleukin-4, 207137-56-2; Phytohemagglutinins; Proto-Oncogene Proteins c-bcl-2; Receptors, Glucocorticoid

It was the aim of the present study to evaluate the validity of the family history method in relatives of a sample of elderly subjects. A total of 201 relatives of patients and 89 relatives of control subjects were interviewed directly using the Composite International Diagnostic Interview and the Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-infarct Dementia and Dementias of other Etiology. At least one relevant other could provide family history information on a respective subject. Family history information for psychiatric disorders including dementia (DSM-III-R) was neither accurate, nor sensitive (10 to 40%), but highly specific (95%). The sensitivity of the family history for dementia and depression increased in relation to the severity of the disorder. Relatives of patients were better informants than relatives of controls (at least for the presence of any psychiatric disorder). The use of several informants only slightly improved the sensitivity of the family history, without reducing the specificity to a significant extent. The combination of different sources of information may serve to reduce information biases. The evaluation of possible biases in future family studies is required to draw adequate conclusions from differences in familial loads.

Abstract “Silent” lacunar stroke, often found in the elderly, has been proposed as a predisposing condition for clinically overt stroke. However, the risk factors related to this condition have not been studied thoroughly. We conducted brain magnetic resonance imaging and measured the levels of fibrinogen, molecular markers of coagulation activation [prothrombin fragment 1+2 (F1+2)] and endothelial cell damage [von Willebrand factor (vWF) and thrombomodulin], and lipid profiles including lipoprotein (a) [Lp(a)] in 178 asymptomatic, high-risk, Japanese subjects aged 44 to 93 years. We also studied 32 symptomatic patients with lacunar stroke (symptomatic lacunar group). The prevalence of silent lacunar stroke increased with age up to 85 years but decreased with age in those 85 years old and older. Of the 160 elderly subjects (≥60 years) 84 (53%) had ≥1 lacunar infarcts (silent lacunar group) and the remaining 76 were considered as the nonlacunar group. Fibrinogen and F1+2 levels in the silent lacunar group were significantly higher than those in the nonlacunar group ( P 30 mg/dL were significantly higher in the symptomatic lacunar group than the nonlacunar group ( P 30 mg/dL more common in the numerous-lacune than in the few-lacune subgroup. We conclude that silent lacunar stroke is often found in asymptomatic, high-risk, elderly Japanese patients and that silent multiple lacunar stroke is associated with hypercoagulability, endothelial cell damage, and high Lp(a) levels.

The cerebral metabolic rate for glucose (CMR glc ) in 18 patients with vascular dementia (VD) and 15 age-matched normal subjects was measured with positron emission tomography (PET) and the 18 F-flurodeoxyglucose technique. Nine of the 18 VD patients manifested abnormal wandering behavior with some psychiatric symptoms: they showed relatively spared CMR glc , which was higher than that of nonwandering patients, especially in the bilateral frontal lobes, left parietal lobe, left temporo-parieto-occipital region, left occipital lobe, and cerebellum. The results suggest that psychiatric wandering behavior of patients with VD could be correlated with partial sparing of CMR glc in the regions listed below.

The relation between comorbidity and survival was investigated in an 8-year follow-up study of 606 nursing home dementia patients by means of proportional hazards analysis. Two-year survival rates for women (N = 437) and men (N = 169) were 60% and 39%, respectively. Parkinsonism, atrial fibrillation, pulmonary infection, and malignancies were powerful predictors: they more or less doubled the mortality chances. Stroke patients with a pulmonary infection had a particularly poor prognosis. More severely demented patients had more comorbidity than less severely demented patients, but the impact of comorbidity on survival did not depend on severity of dementia. Patients coming from a hospital had more comorbidity and were more severely demented than patients coming from home, but this did not modify the effects of age, gender and comorbidity in a multivariate survival model. It was concluded that comorbidity and severity of dementia independently influence mortality. Thus a better prognostic judgment is obtained from their combination than from each separately.

The efficacy of the Ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT)(1) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB)(2) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responded in the two treatment groups differed significantly in favor of EGb 761, with p0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.

Background and Purpose Vascular dementia (VD) has been an ill-defined term thus far. Recently detailed criteria for the diagnosis of VD have been proposed (Alzheimer’s Disease Diagnostic and Treatment Centers [ADDTC], 1992; Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV], 1994; International Classification of Diseases, 10th revision [ICD-10], 1992, 1993; and National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurosciences [NINDS-AIREN], 1993). Until now the clinical feasibility of these diagnostic guidelines has not been evaluated. Methods This study aimed to compare these criteria in an unselected sample of 167 elderly patients (mean age, 72.0±9.9 years) admitted with probable dementia. Results The number of cases that could be classified as VD differed widely between the various diagnostic guidelines. According to DSM-IV criteria, 45 cases were diagnosed as VD. Twenty-one cases fulfilled the ICD-10 research criteria, but only 12 met the NINDS-AIREN criteria for VD. Twenty-three cases were classified as ischemic VD as defined by the ADDTC criteria. The concordance was very poor since only 5 cases met the criteria for VD of all diagnostic guidelines. Conclusions Our results show that the classification according to different diagnostic guidelines yields rather distinct groups of patients. The reasons responsible for these findings are as follows: (1) different criteria for dementia, (2) limitation to ischemic VD in the ADDTC criteria, (3) no further differentiation of VD into subtypes according to CT or MRI findings (DSM-IV), and (4) the multifactorial etiopathology of VD. Major diagnostic difficulties ensue from the very frequent cases with white matter lesions, since their etiology and classification remain widely unknown.

We report the cases of two patients presenting a peculiar speech disorder, which we have named "echoing approval", in which the patients echo, in replying to questions in a dialogue with short phrases, the positive or negative syntactical construction of a question, or its positive or negative intonation, but without any repetition of whole or part of sentences. When asked about their symptoms, the patients replied 80% of the time with "yes, yes", "that's right", or "exactly" to positive questions and "no, no" or "absolutely not" to negative questions, regardless of their actual symptoms and oblivious to self-contradiction. In addition, when the examining doctor was speaking to a medical colleague in the patient's presence and using medical terminology that the patient did not understand, he/she agreed or disagreed with any sentence and technical word uttered in a way entirely dependent on the syntax or intonation used. To distinguish this speech disorder from echolalia or verbal perseverations, with which it may be superficially confused, we suggest that it be called "echoing approval", as it may be part one of the manifestations of the environment-dependency syndrome. This clinical picture was found to be associated with features of transcortical motor aphasia and frontal lobe signs. One patient had a bilateral callosofrontal malignant glioma and the other a probable multiple system atrophy with global deterioration, pre-eminent frontal release signs, diffuse leukoencephalopathy and multiple lacunes. On the basis of these clinical deficits and neuroimaging features, we are unable to delineate the common, or minimal, lesioned network required for this symptomatology to occur, especially in the absence of a series of patients, and with such a difference in both the location and causes of the lesions. However, bilateral frontosubcortical dysfunction was pre-eminent in the clinical picture in both patients, even though more diffuse brain pathology was seen in one, and it might be speculated that dysfunction of the bilateral orbitofrontal and frontomesial motor frontosubcortical circuits might be involved in the aetiology of this peculiar speech disorder.

Neuropeptide concentrations were determined in the postmortem cerebral cortex from 19 cognitive-impaired schizophrenics, 4 normal elderly subjects, 4 multi-infarct dementia (MID) cases, and 13 Alzheimer's disease (AD) patients. Only AD patients met criteria for AD. The normal elderly and MID cases were combined into one control group. Somatostatin concentrations were reduced in both schizophrenia and AD. Neuropeptide Y concentrations were reduced only in schizophrenia, and corticotropin-releasing hormone concentrations were primarily reduced in AD. Concentrations of vasoactive intestinal polypeptide and cholecystokinin also were reduced in schizophrenia, although not as profoundly as somatostatin or neuropeptide Y. In AD, cholecystokinin and vasoactive intestinal peptide were unchanged. Neuropeptide deficits in schizophrenics were more pronounced in the temporal and frontal lobes than in the occipital lobe. The mechanisms underlying these deficits in schizophrenia and AD are likely distinct. In schizophrenia, a common neural element, perhaps the cerebral cortical gaba-aminobutyric acid (GABA)-containing neuron, may underlie these deficits.

A double-blind, placebo-controlled, parallel-group, multicentre study was conducted to evaluate the efficacy of pentoxifylline (Trental) in patients with multi-infarct dementia (MID) according to DSM-III-R criteria. Men and women aged 45 years or older, with a Hachinski Ischemia Scale scoreor = 7 and a Mini Mental State Examination (MMSE) score of 10-25 at entry, and computed tomographic evidence of vascular disease were enrolled. A total of 289 patients were randomised to receive either oral pentoxifylline 400 mg t.i.d. or placebo for 9 months, and efficacy was assessed every 3 months. The primary outcome variable was the difference in scores between the two treatment groups, as measured on the Gottfries, Bråne, Steen (GBS) scale. Secondary outcome variables included the scores achieved on the Sandoz Clinical Assessment Geriatric (SCAG) scale and MMSE, and a battery of psychological and other tests. The intention-to-treat analysis for patients completing the study (n = 239) showed a statistically significant difference in the total GBS score in favour of pentoxifylline (improvement of 3.5 points, p = 0.028). A significant difference in the total GBS score in favour of pentoxifylline was even almost achieved in the intention-to-treat analysis for all evaluable patients (n = 269, improvement of 2.1 points, p = 0.065). It is concluded that treatment with pentoxifylline is beneficial for patients with MID, the global results of the GBS and SCAG scales being reinforced by significant improvements in those subscales specific for intellectual and cognitive function.

CADASIL is an inherited small vessel disease related to Notch3 gene mutations.To report retinal findings in symptomatic CADASIL patients.Assessment of visual acuity (VA), testing of visual fields (VF), funduscopic examination (FE), and fluorescein angiography (FA) were carried out in 18 symptomatic patients.No visual symptoms were presented by our patients. VA was normal in all. Ophthalmologic abnormalities were found in 8 patients. VF were normal except for a right hemianopia in one subject due to ischemic stroke. FE and FA revealed significant abnormalities in seven other subjects (mean age: 55 years; range: 39-74): nerve fibre loss (n = 4), cotton wool spots (n = 3), sheathed arteries (n = 1), and tortuous arteries (n = 1). Only one patient with both tortuous arteries and nerve fibre loss had multiple vascular risk factors, and another patient with cotton wool spots was a current smoker.FE and FA revealed silent retinal abnormalities in CADASIL patients with nerve fibre loss in 22% and cotton wool spots in 17%. The presence of these abnormal retinal findings does not seem related to the severity of the disorder but may be considered as peripheral markers of this genetic disease.

The aims of the present study were to clarify the findings of magnetic resonance imaging (MRI) in the aging brain, and to relate the MRI findings to higher order cortical function. A total of 118 healthy aged volunteers (41 men, 77 women) underwent cranial MRI electroencephalography (EEG), Benton visual retention test (BVRT) and interview. The subjects had no past history or clinical evidence of cerebrovascular disorder, head trauma or dementia and were living at home without any difficulty. The majority of the subjects have participated in this series of studies since 1982. Using a 1.5 T superconductive MR instrument, T1-weighted, proton density and T2-weighted images were obtained. The MRI data were rated visually by regarding 12 items according to fixed criteria. T2 high signal intensity (T2HSI) lesions were found in 69.5% of subjects, the prevalence of which increased with age. T2HSI lesions were most frequently found in the basal ganglia (61.9%), followed by the thalamus (39.0%), parietal lobe (37.0%), temporal lobe (12.7%) and pons (8.5%). Among these lesions, lacunar infarction showed low signal intensity in T1-weighted images and was found in 24.6% of subjects, the prevalence also increasing with age. These findings, including brain atrophy determined according to similar criteria, were correlated closely with the subjects' age. The results of BVRT showed a close relation with T2HSI, suggesting that T2HSI may influence cognitive function. When the subjects were classified according to the presence of T2HSI, lacunar infarction and EEG abnormalities, brain atrophy was significantly milder in a group of subjects with T2HSI(-), lacunar infarction(-) and normal EEG than in the other groups. This suggests that changes seemingly representing physiological aging may be promoted by another pathological which also exerts influences on higher order cerebral function.

In-person cognitive evaluations can be costly and labor intensive in geographically widespread populations. Reliable telephone instruments that screen for cognitive status would greatly facilitate epidemiologic and other longitudinal studies. We evaluated the reliability of the Blessed Information-Memory-Concentration (IMC) test when administered by telephone. Eighty-four subjects with a wide range of cognitive abilities were administered the Blessed IMC twice over a 3-week interval. Forty-nine of the subjects were administered the test both by telephone and in-person, and 35 of the subjects were tested twice by telephone. Spearman's rank correlation was used to compare scores of the different administrations (.96; P < .001) and to examine test-retest reliability (.96; P < .001). The Blessed Telephone IMC (TIMC) test exhibits excellent reliability both when compared to in-person administration as-well as in test-retest results. The Blessed TIMC appears to be a practical instrument for population and longitudinal studies when in-person assessment is not feasible.

Fifty-seven subjects with moderate to severe dementia (49 with Alzheimer's disease) were rated twice, 8 weeks apart, using the Mini-Mental State Examination (MMSE), the Blessed Information-Memory-Concentration Test (BIMC), and the Stockton Geriatric Rating Scale (SGRC). Only three subjects lived at home; the rest were in long-stay hospital beds or nursing homes. For 29 subjects, the first rating coincided with their referral to a comprehensive geriatric psychiatry service. The main hypothesis, that the level of behavioral disturbance would correlate positively with the level of cognitive impairment, was strongly confirmed. This finding may reflect the severity of dementia in the study sample. The correlations between MMSE and BIMC scores were .87 at entry and .92 at exit, suggesting that the two measures were broadly equivalent, although both had marked floor effects. Test-retest reliability was high for all three measures. Overall, medication was of limited effectiveness in managing severe behavioral disturbance, highlighting the need for introducing effective behavioral programs.

Current understanding of the effects of damage on neural networks is rudimentary, even though such understanding could lead to important insights concerning neurological and psychiatric disorders. Motivated by this consideration, we present a simple analytical framework for estimating the functional damage resulting from focal structural lesions to a neural network model. The effects of focal lesions of varying area, shape, and number on the retrieval capacities of a spatially organized associative memory are quantified, leading to specific scaling laws that may be further examined experimentally. It is predicted that multiple focal lesions will impair performance more than a single lesion of the same size, that slit like lesions are more damaging than rounder lesions, and that the same fraction of damage (relative to the total network size) will result in significantly less performance decrease in larger networks. Our study is clinically motivated by the observation that in multi-infarct dementia, the size of metabolically impaired tissue correlates with the level of cognitive impairment more than the size of structural damage. Our results account for the detrimental effect of the number of infarcts rather than their overall size of structural damage, and for the "multiplicative" interaction between Alzheimer's disease and multi-infarct dementia.

Cognitive and neuropsychological tests are often employed to help describe the functioning of patients with multi-infarct dementia (MID) or patients with dementia of the Alzheimer's type (DAT). In this study, the Halstead-Reitan Neuropsychological Battery (HRNB), Wechsler Adult Intelligence Scale-Revised (WAIS-R), and Wechsler Memory Scale (WMS) were completed by 20 MID patients and 62 patients with DAT. Total scores on these measures did not differentiate DAT and MID patients. Contrary to clinical observations, cognitive tasks assessing social judgment did not differentiate between the groups. However, MID patients demonstrated greater variability in test scores. Compared with DAT patients, the MID patients demonstrated better preserved memory as shown on the WMS in comparison to the WAIS-R IQ.

Single-photon emission computed tomography (SPECT) imaging has provided the practicing clinician with a method of studying brain function in patients with dementia. A large and growing number of papers report the experiences of a number of laboratories in the use of this technique in the evaluation of demented patients. Studies from several laboratories comparing patients with Alzheimer's disease to control subjects report sensitivity and specificity of SPECT perfusion imaging to be in the 80% vicinity. In addition, a number of studies suggest that the dementias that show the greatest similarities in perfusion patterns to Alzheimer's disease are multi-infarct dementia and dementia associated with Parkinson's disease. Although considerable data exists to guide the physician, a rigorous scientific approach to studying patients in a prospective, unselected clinical sample, with autopsy confirmation of the diagnosis, is needed to define clearly the utility of the technique in diagnosing dementias.

We report three cases of autopsy-proven Binswanger's disease (subcortical arteriosclerotic encephalopathy) with unusual clinical features. Two patients had supranuclear gaze disturbances, early gait dysfunction, and speech disorders suggestive of progressive supranuclear palsy. One of these patients was not demented at the time of death. The third patient had features typical of Parkinson's disease. All three patients were responsive to treatment with levodopa. The clinical spectrum of Binswanger's disease should be expanded to include levodopa-responsive parkinsonism.

The production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (MNC) was assessed in patients with Alzheimer's disease (AD) who were subdivided into two groups--mild and moderately-severe--according to the severity of the disease, probable vascular dementia (VaD) patients and elderly control subjects. No differences in IL-2 secretion were found between mild AD patients and controls. However, there was a significant increase in IL-2 production both in the moderately-severe AD group and in the VaD group. IL-6 levels in AD patients of both groups were similar and significantly higher than those of VaD and controls. Our results suggest that increased levels of IL-2-production correlate with severity of the dementia, whereas increased levels of IL-6 production seem to be related to AD and thus may play a role in AD pathogenesis.

SYNOPSISA series of elderly patients with dementia of Alzheimer type (AD), multi-infarct dementia (MID) and functional (non-organic) psychiatric illness (major depressive disorder) were selected according to DSM-III-R criteria and received: a battery of cognitive tests, EEG and Single Photon Emission Computed Tomography (SPECT) using 99mTc HMPAO. The EEG and SPECT scans were examined independently of the clinical data. The former were divided into two abnormal categories, those showing AD type change and vascular change respectively, and a normal group. The SPECT scans were classified as follows: a SPECT rCBF pattern showing bilateral temporoparietal perfusion deficits (AD type); those showing single focal perfusion deficits or multiple areas of low perfusion in the cerebral cortex suggestive of ischaemic change (vascular type SPECT picture); a mixed AD/MID pattern; and those with normal scan findings. There were significant associations between clinical diagnosis, EEG rating and SPECT rCBF pattern, approximately three-quarters of AD and MID patients having the predicted EEG and scan changes. Normal EEG recordings were more common in the MID patients. The two tests agreed in about two-thirds of cases, with no consistent pattern apparent in the cases with divergent findings. Each test misclassified a minority of dementia patients, but in only one patient were both investigations normal. Almost half of the so called ‘functionally ill’ patients had abnormal rCBF changes, showing mainly vascular changes while one-fifth had abnormal EEGs.

The authors describe the case of a patient referred for evaluation of multiinfarct dementia. Conventional echocardiography revealed an aneurysm of the interatrial septum. A transesophageal echocardiogram demonstrated surimposed thrombus. This rare cause of systemic emboli can be diagnosed only by transesophageal echocardiog raphy and is of major interest to avoid recurrence of ischemic strokes.

We set out to investigate the possible beneficial effects on cognitive function of demented patients with cobalamin deficiency after cobalamin replacement. A total of 181 consecutive, demented (DSM-III or DSM-III-R criteria and score below 24 on the Mini-Mental State Examination [MMSE] outpatients (mean age 77.5 years) were prospectively evaluated and had their vitamin B12 level measured by radioimmunoassay. The frequency of vitamin B12 deficiency (less than 200 pg/mL) was 25% (46 patients). Treatment outcome was obtained in 19 patients (19 of 46). Despite cobalamin replacement, 16 of 19 patients persisted in showing progressive decline during follow-up visits (3 to 24 months). The nonresponse to vitamin B12 replacement in most cases seems to reflect the presence of associated irreversible dementia or a follow-up of shorter duration in a few patients. All of the patients who showed some improvement (MMSE returned to normal values) had mild dementia with a history of less than 2 years. Thus, screening for B12 deficiency should be considered in patients with recent onset of mild mental status changes.

This study examined some aspects of psychogeriatric care in Münster, Germany. The diagnostic and therapeutic attitudes of 94 general practitioners/internists and neurologists/psychiatrists toward demented patients were investigated by questionnaire. This figure represents a return rate of approximately 55% on the questionnaires. As is typical in Germany, no physicians were specializing in geriatric patients, and fewer general practitioners/internists than neurologists/psychiatrists had undergone supplementary psychogeriatric training. A higher percentage of the latter group estimated more than 10% of their elderly patients were demented. Both estimated Alzheimer's disease as less frequent than multi-infarct dementia. Physicians with training in psychogeriatrics claimed to treat more elderly patients than physicians with out it. With regard to therapeutic procedure, physicians with psychogeriatric training prescribed nootropics more guardedly. The data from this pilot study suggest that there are no eminent discrepancies between the different medical groups with regard to psychogeriatric care, but there is a great need for supplementary training.

(3H)Hemicholinium-3 ((3H)HCh-3), a potent, selective, and competitive inhibitor of the high-affinity choline uptake process was used for the detection of high-affinity choline carriers in the hippocampus (gyrus parahippocampalis), neocortex (gyrus frontalis medius), and cerebellum (lobulus semilunaris inferior) in autopsy samples of people with Alzheimer's disease, multi-infarct dementia and from other psychiatric and nonpsychiatric patients. The effect of postmortem delay was eliminated by means of the cerebellum used as an individual standard. The density of (3H)HCh-3 binding sites was decreased in the hippocampus and neocortex from individuals with multi-infarct dementia and unchanged in the brain tissue from people with Alzheimer's disease in comparison with control patients. No changes in dissociation constants were found. In Alzheimer's disease, high-affinity choline transport appears to be reduced by a dysfunction of cholinergic neuronal membrane rather than by a significant decrease in the number of presynaptic cholinergic nerve terminals. Results provide evidence of a decrease in the number of nerve endings in people with multi-infarct dementia and suggest different vulnerability of particular brain areas to vascular disorders.

The present study was designed to assess performance of Alzheimer's (AD) and Multi-infarct (MID) demented patients on the explicit and implicit versions of two memory tasks, namely Word-Stem Completion and Word-Pair Learning. Consistently with previous studies, the AD patients were deficient on the explicit and implicit versions of both tasks. In MID patients, a dissociation emerged between normal implicit and deficient explicit Word-Stem Completion. Two multiple regression analyses were performed to evaluate patients' ability on measures of lexical-semantic competence, explicit memory, and global intellective efficiency in predicting level of repetition priming. The results demonstrate a close association between explicit and implicit memory performance in AD patients but no relation between repetition priming level and measures of lexical-semantic competence or general intelligence. Overall, the results of the present study do not support previous conceptualizations suggesting that a breakdown in the structure of semantic memory is at the root of deficient priming in demented patients. Alternative interpretations of the deficient repetition priming effect in dementia, based on a common mechanism underlying conscious and unconscious retrieval deficits, are discussed.

High levels of plasma fibrinogen in cerebrovascular disease cause deterioration in the hemorheologic pattern, microcirculation and cerebral perfusion. We compared the value of hepa-rin-induced extracorporeal LDL precipitation (HELP) which is a method that safely and effectively reduces plasma fibrinogen and lipoproteins and so improves the hemorheologic pattern and blood flow properties. Regional cerebral blood flow (rCBF) was measured by the 133Xe SPECT clearance method. After first measuring rCBF, 15 patients suffering from cerebral multi-infarct disease underwent a single HELP application. One hour later a second measurement of rCBF was performed. Fifteen other patients with similar clinical symptoms and findings on CAT scans who were not subjected to HELP served as controls. The HELP treatment produced an immediate and statistically significant reduction of all parameters relevant to hemorheology, such as plasma fibrinogen, whole blood viscosity at both high and low shear rate, plasma viscosity, and red cell transit time. Total cholesterol, low density lipo-protein, and triglycerides were also reduced. The treated group showed 9.7-19.9% increased rCBF in different vascular regions examined relative to the untreated controls. The results obtained indicate that HELP has a potent effect in a situation demanding rapid and significant improvement of the blood flow.

The exact cause of Alzheimer's disease and the part played in it by aluminum is still speculative. We have studied serum aluminum in 356 healthy people, and we have observed that serum aluminum concentration is increased in aging people in relation to age. We suggest that this could be associated with an enhanced gastric permeability or by an increase in metal accumulation proportional to age. We have measured serum aluminum levels in patients with probable Alzheimer's disease, patients with other senile dementias, and age-matched group. Patients with probable Alzheimer's disease have statistically significant higher serum aluminum levels than patients with other types of senile dementias (alcoholic, vascular, multi-infart) and an age-matched control group. When we compare serum aluminum of patients with senile dementias from other causes with the age-matched control group, we do not find significant differences.

The following points should be considered in dealing with dementia occurring in patients with lacunar infarctions. Lacune is a pathological term and its definition rests on its size (from 2 to 15 mm in diameter). However, terms such as lacunar syndromes and lacunar infarctions are currently used in clinical parlance and recent papers. Patients with lacunar infarctions differ from patients with large infarctions, being more often hypertensive, showing a characteristic but not specific clinical syndrome, and disclosing a significantly lower recurrence rate for new episodes and a significantly higher survival rate. Patients with lacunar infarctions develop a state of dementia 5 times as often as the general population and 25 times as often as in the age group of our patients (65-69 years). Leukoaraiosis, significantly related to arterial hypertension, to lacunar infarction, to an extra risk of future stroke, may be considered an increased risk of cerebral vascular lesions possibly leading to dementia. The relationship between vascular lesions and dementia includes: the strategic location of the lesion (thalamus, corticothalamic areas, bilateral lesions); the whole cerebral hypoperfusion apart from the infarcted area, as shown by PET and SPET; remote effects of cerebral infarctions (diaschisis phenomenon); the so-called incomplete infarction; cerebral atrophy and, particularly, the enlargement of cerebral ventricles, significantly higher in patients with lacunes and dementia as compared with patients with lacunes without dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

We have shown that the response to flash stimulation of the occipital electroencephalogram (EEG) in Alzheimer disease (AD) patients is smaller than in normal subjects. To ascertain whether this is a specific feature of AD or a nonspecific effect of dementia, we investigated in AD and multi-infarct dementia (MID) patients the relationship between cognitive function, measured as Mini-Mental State Examination score, and EEG power response, measured as the difference in spectral power between flash-stimulated EEG and resting EEG. Both variables were positively correlated and the regression equations of AD and MID patients were not significantly different, showing nonspecificity. The coupling between cognitive function and power response is discussed in relation to the dynamic binding hypothesis of cognition.

Circumstantial evidence suggests that vascular dementia (VaD) may be associated with cholinergic denervation. The specificity of this association has been difficult to assess because many of the patients are elderly and have the additional cholinergic lesions of aging and AD. A patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) who died at age 36 showed that pure white matter infarcts, similar to those seen in VaD, can cause cortical cholinergic denervation, but in patterns that vary from those seen in AD.

OBJECTIVE To study the effect of Sailuotong capsule (Sailuotong) on learning and memory functions of multi-infarct dementia (MID) rats and its mechanism. METHOD All SD rats were divided into five groups, namely the sham operation group, the model group, the positive group, the low dosage Sailuotong-treated group and the high dosage Sailuotong-treated group. The multi-infarct dementia model was established by injecting the micro-sphere vascular occlusive agent. On the 10th day after the successful operation, the rats were administered intragastrically with distilled water, memantine hydrochloride (20 mg x kg(-1)) and Sailuotong (16.5 mg x kg(-1) and 33.0 mg x kg(-1)) once a day for 60 days respectively, in order to detect the effect of Sailuotong in different doses on the latent period and route length in Morris water maze and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissues. RESULT Compared with the sham operation rats, it had been observed that the latent period and route length of MID rats in Morris water maze were significantly increased (P < 0.05 or P < 0.01), and the activity of ChAT in brain tissues was significantly decreased (P < 0.05). After the intervention with Sailuotong for sixty days, the latent period and route length of MID rats in Morris water maze significantly shrank (P < 0.05 or P < 0.01). Additionally, Sailuotong decreased AchE activity, while increasing ChAT activity in brain tissues of MID rats (P < 0.05 or P < 0.01). CONCLUSION Sailuotong capsule can improve cognitive dysfunction of MID rats to some extent. Its mechanism may be related to its different regulation of activities of ChAT and AchE in brain tissues.

Neurological deficits associated with cerebrovascular disease such as aphasia, dementia, anosognosia and aprosodia may impair the ability to express or experience depressive symptoms. Identification of depression in the absence of verbal report on subjective mood state is a difficult task. The value of various diagnostic methods including depressive rating scales, standard psychiatric interviews and biological variables in the diagnosis of depression in cerebrovascular disease is considered. This review concludes by focusing on the deficiencies of existing approaches in the diagnostic assessment of depression in patients with severe communication and comprehension deficits and emphasizes the importance of devising a standard diagnostic method with less reliance on verbal responses.

Periventricular white matter hyperintensities (PVHs) seen on T2 weighted MRI studies are common in elderly people and often represent demyelination of fibres. Damage to these fibres could lead to functional disconnection between brain regions. Electroencephalographic coherence, a measure of shared electrical activity between regions, was examined to determine if there was evidence for such disconnection. Twenty two subjects with clinically diagnosed dementia of the Alzheimer's type, 16 with multi-infarct dementia, and 18 normal controls were studied. It was hypothesised that coherence between areas presumably linked by fibres that traverse the periventricular region would be decreased in subjects with PVHs, and that PVHs would have a stronger association with decreased coherence than clinical diagnosis. It was also hypothesised that coherence between areas presumably connected by long corticocortical tracts that are neuroanatomically separated from the ventricles would be low in patients with Alzheimer's disease because of pyramidal cell death in this group, but would not be affected by the presence of PVHs. Patients with PVHs in fact had lower coherence than those without PVHs in the pre-Rolandic and post-Rolandic areas, where connecting fibres traverse the periventricular region. There was no effect of PVHs, however, on coherence between areas separated by the Rolandic fissure that were connected by long corticocortical tracts; this coherence was lowest among the patients with Alzheimer's disease. These patterns of association suggest that coherence may detect different types of neurophysiological "disconnection," and may be sensitive to selective damage to different fibre pathways.

This study tested predictions specifying the influence of caregiver personality traits on negative outcomes of caregiving, health complaints and burden. Two-hundred and thirteen caregivers, who were caring for family members with dementia, were interviewed and their relatives were assessed on cognitive status and aggression. At follow-up conducted twenty-four months later, forty-five caregivers were still continuing to provide home care for their dependents. Caregivers who scored higher on a measure of neuroticism experienced higher levels of burden and health complaints both at initial and follow-up assessment. Caregiver extraversion-introversion did not influence the experience of caregiving. At both initial and final assessment, the ability to enjoy some aspects of caregiving, recreational activities, and satisfaction with social support from family and friends mitigated negative outcomes of caregiving, while appraising the dependent as more troublesome increased negative outcomes. Caring for more cognitively impaired and more aggressive dependents and being female increased negative outcomes initially. Personality traits and most other study variables demonstrated significant continuity across time for caregivers continuing home care.

A modified receiver operating characteristic (ROC) analysis technique was applied to a sample of 161 consecutive volunteers seen in a dementia clinic. Clinical, imaging, neuro- psychological, and laboratory evaluation guided experienced clinicians in clinical diagnosis, taken as the "gold standard." Two symptom inventories, the Hachinski Ischemic Score and the Dementia of the Alzheimer's Type Inventory, were obtained by clinicians who were blind to final clinical diagnosis; scores on these inventories correlate with the likelihoods of multi- infarct dementia and Alzheimer's disease, respectively. A disjunctive sequential testing strat egy was analyzed such that subthreshold scores on the first test identified patients for whom the second test was considered. Both tests were analyzed at all possible cutoff-point com binations and in both possible testing sequences. Diagnoses based on these tests were compared with the clinical "gold standard" diagnoses to determine the accuracy of the testing procedures. The best strategy correctly classified 154/161 (95.6%) of the dementia patients and required cutoff points (5 for the HIS and 10 for the Dementia of the Alzheimer's Type Inventory) that were lower than those usually recommended for either test used alone (i.e., 7 and 14, respectively). The Hachinski Ischemic Score-then Dementia of the Alzheimer's Type Inventory testing sequence was superior to the reverse strategy. A sensitivity analysis (varying prevalences of Alzheimer's disease, multi-infarct dementia, and other dementias) revealed similar test performances across a wide range of prevalences. These data suggest that simple clinical tests that take approximately 30 minutes to administer can produce diagnostic classifications of dementia that are similar to those of clinicians experienced in dementia diagnosis. Key words: dementia; multi-infarct; Alzheimer's disease; diagnostic tests; ROC analysis. (Med Decis Making 1994;14:393-402)

Estimates of the prevalence rates for dementia vary significantly among countries. Such variation may be explained, at least in part, by methodologic differences in studies. The disparities in prevalence rates of dementia subtypes, particularly Alzheimer's disease and multi-infarct dementia, are especially apparent in studies conducted in Eastern and Western countries. In Japan and China, the prevalence of multi-infarct dementia exceeds that of Alzheimer's disease, whereas in the West, Alzheimer's disease predominates in the vast majority of studies. Clearly, cross-cultural studies of incidence using standard methods are needed to investigate whether a true difference in risk exists, and which risk factors differentially contribute to this variation. Migrant studies of genetically homogeneous populations offer a unique opportunity to answer these questions. This article explores the value of migrant studies, their application to etiologic questions of dementia and its subtypes, and recommendations concerning how to conduct such studies.

Endothelin-1, a potent endothelium-derived vasoconstrictive peptide, is also known to exist in the central nervous system. We determined endothelin-1-like immunoreactivity in cerebrospinal fluid by a radioimmunoassay in 32 normotensive or hypertensive elderly subjects (79 +/- 8 years old) with or without multi-infarction dementia. The mean value of endothelin-1-like immunoreactivity in cerebrospinal fluid was significantly (P < .05) elevated in subjects with essential hypertension (> or = 160/95 mm Hg, n = 5, 79 +/- 9 years old) compared with those with borderline hypertension (140-159/90-94 mm Hg, n = 4, 78 +/- 5 years old) and normotensive subjects (< 140/90 mm Hg, n = 23, 79 +/- 8 years old). The value of endothelin-1-like immunoreactivity in cerebrospinal fluid was significantly (P < .05) positively correlated with both systolic (r = .38) and diastolic (r = .42) blood pressures in all subjects. On the other hand, mean values of endothelin-1-like immunoreactivity in cerebrospinal fluid were also significantly (P < .05) elevated in the groups of patients with multi-infarction dementia that had profoundly decreased Mini-Mental State scores (< or = 10, n = 6) and moderately decreased Mini-Mental State scores (11 to 20, n = 14) compared with those values in subjects with normal cognitive function (score for Mini-Mental State > or = 21, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

Recent work from our laboratory demonstrated that quantitative electroencephalographic (EEG) coherence between brain areas linked by long cortico-cortical fibers (termed “fascicle” coherence) was differentially reduced in subjects with Alzheimer's disease, whereas coherence between brain areas linked by short cortico-cortical and cortico-subcortical fibers in postcentral areas (termed “visual” coherence) was differentially reduced in subjects with multi-infarct dementia. In this study, we investigated whether these differences in coherence represent “trait” or “state” markers for dementia. Visual coherence demonstrated high stability in both demented groups as assessed by both one-year test-retest reliabilities and analysis of group mean change. Fascicle coherence demonstrated good stability in multi-infarct dementia and control subjects, but some variability was observed in Alzheimer's subjects, suggesting both state and trait factors may be involved. These findings complement neuropathologic studies, and suggest that decreases in coherence may serve as a diagnostic trait markers for these two types of dementia. The role of state factors in Alzheimer's disease requires further investigation.

The age-specific prevalence of dementia, its sex difference, and the relative prevalence of important types of dementia were studied in the elderly people in a Korean rural community. A two-stage approach was employed, involving screening and clinical assessment. The prevalence among individuals aged 65 and over was found to be 10.8%, with rates of 7.2% in men and 14.5% in women. The dementia was of the Alzheimer type in 60.0% of cases, multi-infarct dementia in 12.0%, mixed dementia of Alzheimer type and multi-infarct in 10.7%, alcoholic dementia in 8.0%, and others and unclassifiable in 9.3%. The prevalence of dementia of the Alzheimer type was significantly higher in women and rapidly increased with age in both sexes. The prevalence of multi-infarct dementia was not related to sex or age. Alcoholic dementia was identified only in men. These findings indicate that the prevalence of dementia in rural Korea is similar to that reported in Western countries and that the prevalence of dementia of the Alzheimer type in rural Korea is greater than that of multi-infarct dementia.

A report on a cerebro-vascular disease with autosomal dominant inheritance, characterised by stroke-like episodes beginning in early adulthood and progressive dementia, afflicting one family living in Sweden was presented in 1977. Another afflicted member showing gait and coordination disturbances and impaired cognitive functions is now introduced. Magnetic resonance imaging revealed multiple brain lesions indicating ischaemic injuries. Previous autopsy studies of other cases revealed white matter atrophy, multiple infarcts and lacunes. In one patient who had died from a cerebral haemorrhage, obliteration of intracerebral arteries, occasionally with organised thrombi was present. Autopsy material has now been reinvestigated with special attention to changes of intracerebral arterioles. Cases with long duration of the disease presented pronounced fibrous thickening of the wall of numerous intracerebral arterioles, degeneration of smooth muscle cells of the media and obliteration of the lumen. Immunohistochemistry showed marked expression of fibrillary collagen types I, III and V and of the basal lamina components collagen type IV and laminin. These depositions are probably induced by some primary dysfunction of smooth muscle cells or endothelial cells. Perivascular reactive astrocytes with endothelin-1-like immunoreactivity were present in some brain regions. Endothelin-1 is the most powerful vasoconstrictor peptide known to date. Structural remodelling of intracerebral arterial vessels, actions of different vasoactive factors and rheological disturbances may all interfere with local blood flow in this disease and cause the parenchymal changes of the brain.

Objective: To determine the usefulness or otherwise of the awake electroencephalogram (EEG) in the diagnosis of Alzheimer's disease (AD). Design: Prospective collection of one or more awake EEGs in patients diagnosed as having AD or mixed AD and multi-infarct dementia according to current systematic criteria with analysis of those cases confirmed by postmortem examination. Systematized blind interpretation of EEGs. Setting: Tertiary care practice with both ambulatory and hospitalized patients, ie, neurological department in general hospital and psychogeriatric unit in psychiatric hospital. Patients: A series of 86 subjects with AD and 17 with mixed AD and multi-infarct dementia being those members of a consecutive series on whom postmortem information was available. Awake EEGs in 56 age- and sex-matched control subjects. Results: Seventy-five patients with AD (87.2%) and 13 of the mixed group (76.5%) had abnormal EEGs on first testing, giving a sensitivity of 87.2% for uncomplicated AD. Ultimately, 79 (92%) of 86 patients with AD had abnormal EEGs. Twenty (35%) of 56 EEGs for matching control subjects were abnormal. Moderately abnormal or severely abnormal EEGs were found in 10 (50%) of 20 of the patients with AD of less than 4 years' duration compared with two (4.1%) of 49 of the control subjects, giving a specificity of 95.9% for EEGs with this degree of abnormality. The normal EEG had a negative predictive value of 0.825 with respect to the diagnosis of AD in these populations. Conclusions: Widespread availability, low cost, and high sensitivity support the use of the awake EEG in the diagnosis of AD.

The incidence of stroke increases dramatically with advancing age. Progressive carotid atherosclerosis, cardiac arrhythmia and emboli, and vascular changes all contribute to this increasing incidence of stroke in the elderly. Treatment of hypertension and other risk factors have resulted in a decline in stroke over the last 50 years. The decline has been most prominent in the elderly. In recent years, this decline has slowed down or may even be reversing. Early and effective control of risk factors together with comprehensive management of acute stroke in a specialized unit is needed to further improve prognosis. Such an approach is especially important in the elderly, who may suffer from multiple problems. Treatment of hypertension and other risk factors have resulted in a decrease in an overall decline in the incidence of stroke over the last 50 years. This decline has been most apparent in the elderly. In recent years, however, there has been a slowing or possibly a reversal of this trend. Early and effective management of risk factors, aggressive therapy of patients with transient ischemic attacks and comprehensive management of acute stroke patients in specialized units may be required to further improve prognosis.

The question was addressed whether the three vascular dementia (VAD) subtypes, multi-infarct dementia (MID), strategic-infarct dementia (SID), and subcortical white matter dementia (SWMD) fulfil the basic criteria for a disease: does a distinct pattern of clinical features match a distinct pathological picture for the various VAD subtypes? No obvious correspondence between structural pathological changes and symptoms or signs was found in the MID and SID subtypes. Therefore, the disease status of these VAD subtypes can be questioned. The VAD subtype SWMD, however, appeared to fulfil the basic criteria for a disease, as the subcortical white matter changes corresponded to the subcortical symptom pattern, with mental slowness, extrapyramidal and bilateral pyramidal deficits.

The inhibition of alpha-chymotrypsin induced by cerebrospinal fluid from patients with senile dementia of Alzheimer's type, vascular dementia, and nondemented controls was investigated. We optimized the sensitivity of the assay so that the inhibition of alpha-chymotrypsin could be measured in all samples. The competitive inhibition was proportional to the amount of cerebrospinal fluid (CSF) added to the reaction mixture. After correction for protein concentration, the inhibition was higher with CSF from patients with senile dementia of Alzheimer's type than with those from patients with vascular dementia or controls. Inhibitory activity appeared to be specific for alpha-chymotrypsin because no inhibition for papain was found. Moreover, the depletion of alpha 1-antichymotrypsin from CSF by immunoadsorption revealed that this serpin was responsible for the disappearance of the inhibitory activity. Our findings suggested that the increased alpha-chymotrypsin inhibitory activity might represent an in vivo functional index of an abnormal protease metabolism in patients with Alzheimer's disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can mimic multiple sclerosis (MS), leading to diagnostic confusion. We report a family with CADASIL in which the index case and the daughter of the index case were initially erroneously diagnosed with MS. Relatively specific magnetic resonance imaging (MRI) markers of CADASIL include involvement of the anterior temporal lobes and external capsules and, as illustrated in this report, these MRI findings may aid in the differentiation of the two conditions.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the notch3 epidermal growth factor–like repeats. A Colombian kindred carries a novel C455R mutation located in the predicted ligand-binding domain. Stroke occurred in the patients at an unusually early age (median age: 31 years) in comparison to the more frequent onset in the fourth decade of life in other CADASIL populations, including a second Colombian kindred with an R1031C mutation.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a vascular dementia arising from abnormal arteriolar vascular smooth muscle cells. CADASIL results from mutations in Notch3 that alter the number of cysteine residues in the extracellular epidermal growth factor–like repeats, important for ligand binding. It is not known whether CADASIL mutations lead to loss or gain of Notch3 receptor function. To examine the functional consequences of CADASIL mutations, we engineered 4 CADASIL-like mutations into rat Notch3 and have shown that the presence of an unpaired cysteine does not impair cell-surface expression or ligand binding.