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Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia.

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) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB) 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 responders in the two treatment groups differed significantly in favor of EGb 761, with p < 0.005 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.

Aged↗

[Patchy changes in white matter in cranial computerized and magnetic resonance tomography--significance for (differential) diagnosis of dementia of the Alzheimer type and vascular dementia].

With the advancement of technical progress, especially with respect to magnetic resonance imaging, patchy cerebral white matter lesions (WML) are being found with increasing frequency. The (differential) diagnosis between the two main dementias of old age, (senile) dementia of the Alzheimer type ([S]DAT) and vascular dementia (VD) is made more frequently in favour of the latter, since the detection of WML leads to support a vascular origin for dementia. The present article reviews the literature concerning X-ray computed tomography (CT) and magnetic resonance imaging (MRI) in these disorders. For comparison purposes some methodological problems must be taken into account including different scoring systems for WML severity, differences in imaging techniques and in the criteria for the selection of patients and controls. A great number of studies demonstrates a strong association of frequency and severity of WML with increasing age and presence of cerebrovascular risk factors such arterial hypertension. Some studies revealed an association with neuropsychiatric deficits including gait disorders, urinary incontinence, affective lability and reduced attention and information processing speed. In CT studies, about 30% of patients with (S)DAT had WML but 36-88% in MR studies. However, only few studies controlled for the presence of cerebrovascular risk factors. More recent studies - with improved techniques - revealed a higher frequency of (slight or moderate) WML in the (S)DAT group compared to controls. The prevalence of WML in VD patients was 75-97% in CT studies and about 100% in MR studies. Therefore, without the presence of WML, the diagnosis of VD is currently in doubt. A number of in vivo investigations proved consistently - and with different methods - that cerebral blood flow was reduced in WML regions. As shown in some studies the neuropathologic correlates of WML have in common that the relative tissue water content is increased: This includes inflammation, gliosis, complete and incomplete infarctions, dilation of the perivascular (Virchow-Robin) spaces with myelin atrophy. Thus the finding of WML in watershed areas can be understood. Three case reports serve to illustrate the problems pointed out. In conclusion, the occurrence of WML is an unspecific finding which is observed in up to 50% of the elderly. Diagnostic classification as "vascular lesions" or signs of "vascular encephalopathy" or VD based on CT or MRI alone, should not be made.

Aged↗

Effects of education in dementia assessment: evidence from standardizing the Korean-Dementia Rating Scale.

This study established norms and examined validity and reliability of the recently developed Korean version of the Dementia Rating Scale (K-DRS; Chey, 1998) for the elderly Korean population. The K-DRS was administered to 148 normal elderly Korean people and 20 patients with dementia of the Alzheimer's type (DAT). Norms were developed a priori for two age groups (55-64 and 65-84 years). Education (p < .0001) and age (p < .05) proved significant factors in the performance of the K-DRS, whereas gender did not. Accordingly, norms were further specified into two educational levels (6 years or fewer, and more than 6 years). Education was recognized as an important factor in evaluating dementia in a population with limited education. These implications are significant for dementia studies done in developing countries where educational opportunities have been limited for elderly people. Evidence supporting the validity and reliability of the scale was also found. K-DRS total scores correlated well with diagnostic status (r(pb) = .63) and mental status exam scores (r = .80). Test-retest reliability was .96, and interrater reliability was .99.

Age Factors↗

The prevalence of dementia in a statewide sample of new nursing home admissions aged 65 and older: diagnosis by expert panel. Epidemiology of Dementia in Nursing Homes Research Group.

This study estimated the prevalence of dementia in 2,285 new admissions age 65+ to a statewide sample of 59 nursing homes in Maryland, 1992-1995. Dementia was ascertained according to DSM-III-R criteria by an expert panel of geriatric psychiatrists, neurologists, and a geriatrician using detailed information collected by trained lay evaluators from residents, family, staff, and medical records. Admissions to Maryland nursing homes are similar to admissions to nursing homes elsewhere in the United States. The prevalence of dementia was 48.2% (CI: 43.6-52.8) with an upper bound estimated at 54.5% (CI: 49.9-59.1). Prevalence is highest in facilities with <50 beds versus 200+ beds (65.5% vs 39.6%) and those in urban versus rural areas (50.0% vs 39.1%). Those who are non-White, married, and with fewer years of education are more likely to be demented. Prevalence is highest among those with 4+ physical impairments versus 0-1 (60.3% vs 27.7%) and lowest in those with 4+ comorbidities versus 0-1 (44.8% vs 52.0%). There was considerable overlap in the comorbid status of demented and nondemented admissions, and both groups contained members with only a few functional limitations. Results suggest that the level of medical supervision provided in nursing homes may not be required for some residents with dementia.

Activities of Daily Living↗

The neuropsychology of frontal variant frontotemporal dementia and semantic dementia. Introduction to the special topic papers: Part II.

The second part of this review, which accompanies 10 special topic articles dedicated to frontotemporal dementia (FTD), describes some of the advances in understanding frontal variant FTD (fvFTD) and semantic dementia, and the theoretical insights gained into normal cognitive processes from the study of these syndromes. Recent work has clarified the neuropsychiatric features that distinguish fvFTD from Alzheimer's and has begun to spread light on the underlying deficits in social judgement, theory of mind, processing of emotional stimuli and decision making. With regard to central aspects of cognitive processing, such as memory, patients with fvFTD may have a distinctive profile of performance on tests of explicit and implicit memory, and contrary to current views some patients may even have a severe amnesic syndrome. There is also growing evidence that despite relatively well preserved general language skills, patients with fvFTD have particular problems with verb processing. Although there is agreement regarding the key features of semantic dementia, much controversy has surrounded the issue of whether the cognitive findings favour an explanation in terms of progressive breakdown of a central amodal semantic store or differential involvement of verbal and non-verbal systems. Other topics discussed include the impact of semantic breakdown on phonological processes and episodic memory. We also review recent structural and functional neuroimaging findings in semantic dementia.

Dementia↗

Clinical staging of dementia in a population survey: comparison of DSM-III-R and the Washington University Clinical Dementia Rating Scale.

In a population survey in Stockholm, 224 dementia cases were staged using two scales: the Washington University Clinical Dementia Rating Scale and DSM III-R. Both scales had to be modified by adding additional specifications and, in the case of DSM III-R, a new category of questionable dementia. After modification, the comparison of the two scales showed good agreement when all stages were analyzed (kappa = 0.60), but moderate agreement on the questionable and mild stages (kappa = 0.47). These results confirm the staging of mild dementia as the most problematic issue. Finally, the scales both showed moderate agreement with the categorized Mini-Mental State Examination (MMSE) (0-17 for severe and moderate forms; 18-23 for mild cases). Our data suggest new cut-off points for the MMSE when used as a staging scale.

Aged↗

Dementia of depression or depression of dementia in stroke?

This study describes the correlation between changes in mood symptoms assessed by the Hamilton Depression Rating Scale (HDRS) and intellectual impairment assessed by the Brief Cognitive Rating Scale (BCRS) and Mattis Dementia Rating Scale (MDRS) in 166 unselected 1-year survivors after stroke, in whom post-stroke depression (PSD) has previously been described and validated. The course of intellectual impairment associated with PSD was compared with the course of intellectual impairment in non-PSD patients. In general, improvement in mood symptoms was correlated with an improvement in intellectual function. However, in 53 PSD patients improvement in intellectual performance was absent, despite the fact that the patients reported being significantly less distressed by dementia symptoms. Antidepressive medication did not lead to any improvement in MDRS score. No evidence was found to support the hypothesis of 'dementia of depression'. To the contrary, the findings indicate 'depression of dementia'.

Adaptation, Psychological↗

Senile dementia with tangles (tangle predominant form of senile dementia).

Senile dementia with tangles is a sporadic subset of very late onset dementia with preponderance in females over age 80 years. Neuropathology shows diffuse cerebral atrophy with neurofibrillary tangles, often ghost tangles, and neuropil threads almost limited to limbic areas (transentorhinal, entorhinal area, hippocampuS--not exclusively sector CA 1--and amygdala) with only rare and mild involvement of the neocortex, basal ganglia and brainstem (except nucleus basalis and locus ceruleus), absence of neuritic plaques and absence or scarcety of amyloid deposits. This pattern of fibrillary pathology corresponds to Braak stages III and IV or the "limbic" type of Alzheimer disease that is considered the main form in the oldest-old but escapes the current criteria for the morphologic diagnosis of Alzheimer disease. It is distinct from other tau- or tangle-pathology related conditions, e.g. progressive supranuclear palsy, autosomal dominant dementia with tangles, and diffuse tangles with calcification. Very low prevalence of ApoE e4 allele (0.03-0.11%) and higher frequency of ApoE e3 and/or e2 suggest a lack of promoting effect of e4 and a possible protecting effect of e2/3 on amyloidogenesis. Senile dementia with tangles is suggested to be a variant of Alzheimer disease occurring in the oldest-old, but its nosological position within aging disorders of the brain is still controversy.

Alleles↗

A neuropsychological instrument adding to the description of patients with suspected cortical dementia: the Milan overall dementia assessment.

A new, short, neuropsychologically oriented test for dementia assessment--the Milan Overall Dementia Assessment (MODA)--is described. Age and education adjusted norms based on 217 healthy controls are given. A validation study on 312 outpatients suspected of dementia (121 with probable Alzheimer's disease) showed that the MODA differentiated patients with cognitive impairment from normal subjects more effectively than did the DSM III-R. The correlation between the MODA and the mini mental state examination was 0.63 in controls and 0.84 in patients with Alzheimer's dementia. The MODA test-retest reliability was 0.83. The test proved to be well suited to longitudinal studies.

Adult↗

Longitudinal EEG findings in dementia related to the parietal brain syndrome and the degree of dementia.

EEG slow-wave activity was correlated with the regional brain syndrome profile in 74 patients with dementia. The EEGs were visually assessed using a semiquantitative rating scale. The intensities of four regional brain syndromes (parietal, frontal, subcortical, global) and the degree of dementia were rated. The patients were examined twice with a 1-year interval. A significant relationship was found between the increase in EEG slow-wave activity and the increase in intensity of the parietal brain syndrome. A somewhat lower significance was found for the relation between increase in slow-wave activity and increase in dementia degree. The results suggest that the EEG deterioration in dementia mainly reflects the gradual decline of parietal brain function.

Aged↗

Epidemiological dementia index: a screening instrument for Alzheimer's disease and other types of dementia suitable for use in populations with low education level.

INTRODUCTION: MMSE and CAMCOG are neuropsychological scales developed for use in everyday clinical practice and epidemiological surveys. MATERIAL AND METHODS: These two instruments were used as part of the assessment during an epidemiological survey in the municipality of Pylaia, Greece. The project was based on the World Health Organization Program for Research on Aging and Age-Associated Dementias (1992). It had two phases. During phase I, nursing students collected demographic data, risk factors, personal and family history data and they applied MMSE, CAMCOG and scales of everyday life functioning. During phase II, 4 physicians examined all subjects that manifested possible cognitive deterioration (MMSE<27), in order to reach a final diagnosis. The final diagnosis was made according to DSM-IV and NINCDS-ADRDA criteria. MMSE and CAMCOG were not taken into consideration in the diagnostic process. Three hundred and eighty subjects were initially screened. All were aged over 70 years. After the exclusion of subjects who were illiterate, blind, etc., the results of 277 subjects were finally analyzed. Subjects with 6 years of education or less accounted for 92.42% of the total study sample. Twelve of them (5.33%) suffered from Alzheimer's disease, 7 from vascular dementia (2.52%) and 1 suffered from secondary dementia (0.36%). RESULTS: MMSE exceeded 90% sensitivity at the level 22/23 and specificity at 14/15. The levels for CAMCOG were 56/57 and 43/44, respectively. This low performance of both tests is to a large extent due to the functional illiteracy of elderly individuals in Greece, to possible coexistence of mood disorders or simply to lack of cooperation. The analysis of data led to the development of an Epidemiological Dementia Index (EDI), with a scale ranging from 0 to 7. Nondemented subjects had a mean EDI of 5.12 (SD = 1.67) and demented patients had a mean EDI of 1.6 (SD = 1. 92). At the level 4/5 sensitivity was 93.33. Specificity was 93.56 at the level 2/3.

Aged↗

Clinical diagnosis of dementia with Lewy bodies in a Japanese dementia registry.

We found 15 patients with dementia with Lewy bodies (DLB) and 232 patients with Alzheimer's disease (AD) among 327 consecutive patients with mild to moderate dementia in a Japanese dementia registry, using the clinical criteria of the Consortium on DLB International Workshop. The percentage of females was significantly lower in DLB than in AD (p < 0.01), while age at examination, Mini-Mental State Examination score and duration of cognitive symptoms were comparable between the two diseases. Eight of the 15 DLB patients (53%) had spontaneous parkinsonism, which was observed in 6 of the 232 AD patients (2.6%). Visual hallucinations were reported by 11 of the 15 DLB patients (73%) and 8 of the 232 AD patients (3.4%). Cognitive fluctuation was positive in 13 of the 15 DLB patients (87%). We found two types of episodic cognitive deterioration: one was characterized by pronounced disturbances of attention and alertness (inattention type), and the other was characterized by marked and bizarre disturbances of orientation in time and places, and misidentification of persons (disorientation type). Systematized delusion was observed in 8 DLB patients, and 5 patients showed neuroleptic sensitivity. Patients with DLB have a unique dementia syndrome even in the stage of mild to moderate cognitive impairments. Further studies are recommended to establish diagnosis, treatment and management.

Aged↗

Impact of applying NINDS-AIREN criteria of probable vascular dementia to clinical and radiological characteristics of a stroke cohort with dementia.

BACKGROUND: There are no data concerning the relative representation of clinical vascular risk factors and radiological lesions in cases that have been ruled in and ruled out for probable vascular dementia (VaD) according to NINDS-AIREN criteria. METHODS: Three months after their index stroke, a psychiatrist interviewed patients and made a diagnosis of VaD according to both DSM-IV and NINDS-AIREN criteria for probable VaD. Patients who fulfilled the DSM-IV criteria for VaD were divided into two groups: those who were ruled in and ruled out according to NINDS-AIREN criteria as probable VaD. Demographic characteristics, vascular risk factors, clinical features of the index stroke and radiological findings were then compared between the two groups. RESULTS: Of the 297 patients screened, 56 (18.8%) had a DSM-IV diagnosis of dementia. Among these demented patients, 55 (98.2%) and 22 (39.3%) fulfilled DSM-IV and NINDS-AIREN diagnosis of VaD, respectively. The concordance and level of agreement (kappa statistic) between DSM-IV and NINDS-AIREN diagnoses were 40% and 0.02, respectively. Reasons of failure to meet NINDS-AIREN criteria included the lack of temporal relationship between dementia and stroke (n = 20), the absence of focal neurological signs and/or radiological evidence of stroke (n = 6) and both of the above (n = 7). There was no significant difference between the above two groups in terms of demographic data, features of index stroke, vascular risk factors and CT scan findings, except that leukoaraiosis (p = 0.021) and bilateral lesions (p = 0.015) were more frequent in subjects diagnosed according to NINDS-AIREN criteria of probable VaD. The difference between these two groups with respect to the number of lesions was borderline for significance (p = 0.052). CONCLUSIONS: The use of NINDS-AIREN criteria for VaD for case selection in poststroke dementia research may exclude a number of subjects with VaD.

Acute Disease↗

Creativity with dementia patients. Can creativity and art stimulate dementia patients positively?

BACKGROUND: Creative activities could be stimulating for dementia patients. This article gives a review of practical forms of treating dementia patients with art therapeutic indications. It is also a ground for long-term research objective: in brief, I take exception to such a view, contrary to the common belief in the society and some professionals in the healthcare of dementia patients, on the ground that the patients do not have the capacity to improve their own creativity. METHODS: The theory of cognition tells us about the principle of being creative as a basis for human life. This specific principle is effective for the aged as well. In the long-term, the creative potential of old patients will be unblocked in individual and group therapy sessions. RESULTS: Creative activity has been shown to reduce depression and isolation, offering the power of choice and decisions. Towards the end of life, art and creativity offer a path of opening up the windows to people's emotional interiors. CONCLUSIONS: Creative- and art therapy provides possibilities that are mostly indicated to sharpen the capacity of the senses and the patients' propensity to act themselves. Nonverbal therapy methods, such as painting, music, etc., are able to influence the well-being of the patients positively, within the modern healthcare system in nursing homes. The elderly and some of the dementia patients take the initiative to combine creativity and arts and to define his/her feeling for aesthetical matters. Furthermore, group therapy sessions help against isolation and lack of life perspective and hope.

Aged↗

Changing relative prevalence of Alzheimer disease versus non-Alzheimer disease dementias: have we underestimated the looming dementia epidemic?

The relative prevalence of neurodegenerative dementias in our Veterans' Affairs dementia clinic has shifted from predominantly Alzheimer disease (AD) to predominantly non-AD diagnoses. Because our clinic was the only Veterans' Affairs clinic in Oklahoma that could initiate cholinesterase inhibitors, we had a captured patient referral source. If future epidemiologic studies establish that non-AD dementias are as, or more, prevalent than AD, then the looming dementia epidemic in the United States will be greater in magnitude than currently predicted.

Aged↗

Neuropsychological results of long-term therapy with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia in comparison with a control group.

The cognitive and behavioral effects of oxiracetam therapy during long-term treatment in patients with dementia of Alzheimer type (DAT) and multi-infarct dementia (MID) were studied in comparison with a historical control group. Twenty DAT/MID outpatients, aged 54-86 years, received oxiracetam (800 mg twice a day) for a period of 6 months. Another 20 DAT/MID outpatients, aged 67-85 years, were selected from our clinical records in order to obtain a control group of patients matched for age, sex, diagnosis, baseline Mini Mental State Examination (MMSE) score and follow-up duration. All the patients were diagnosed as having mild to moderate degrees of dementia as defined by a baseline MMSE score between 14 and 24. The patients of both groups underwent, both at baseline and after 6 months, the following neuropsychological tests: MMSE, Idiopathic Cerebral Dysfunction Scale, Babcock Test, Gibson Spiral, Toulouse-Pieron Test. Statistical analysis of experimental data demonstrated that at baseline the two groups were comparable. At the end of the study period the oxiracetam group scored significantly better on the majority of the tests evaluating memory, attention, orientation, concentration and psychomotricity than the control group, in which a worsening trend was seen on the whole. No side effects were seen during oxiracetam treatment. The present study, showing positive clinical findings after long-term oxiracetam therapy in controlled conditions, confirms that this drug can be a useful pharmacological treatment for mild to moderate degrees of dementia.

Aged↗

Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID).

This trial was performed to investigate the efficacy of pyritinol in the treatment of senile dementia. Initially, a total of 183 inpatients were screened for eligibility. Of 164 patients who met the inclusion criteria, 156 completed the trial. Allocation of the patients to the Senile Dementia of the Alzheimer Type group or the Multi-Infarct Dementia group was based on the Hachinski Ischemic Score, computed tomography scans and electroencephalographic (EEG) findings. In a 12-week double-blind treatment phase either 200 mg pyritinol dihydrochloride-monohydrate or placebo was given 3 times daily. Confirmatory statistics included item 2 of the Clinical Global Impression, the total score of the Short Cognitive Performance Test (Syndrom Kurz Test) and the factor 'cognitive disturbances' of the Sandoz Clinical Assessment Geriatric scale. In addition, data on tolerance, of EEG brain mapping and of a responder analysis were evaluated based on descriptive statistics. The therapeutic efficacy of pyritinol was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all 3 target variables. The clinical relevance of the outcome was underlined by the analysis of the descriptive variables and by the convergence found at the different observation levels. The EEG mapping demonstrated significant differences between placebo and pyritinol, with the latter decreasing slow and increasing fast alpha and beta activity, which reflects improvement of vigilance. Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative and vascular etiology.

Aged↗

Brain neurotransmitters in aging and dementia: similar changes across diagnostic dementia groups.

Reductions of the levels of transmitter substances and of the activities of enzymes involved in their synthesis have been demonstrated in the aging brain. The sensitivity to the aging process varies for different transmitters and brain regions. Dopamine neurons are more age-sensitive than most other neurons investigated. The metabolism of monoaminergic neurotransmitters is enhanced in the aging brain, as evidenced by increased metabolite/neurotransmitter ratios, perhaps to compensate for the loss of transmitter. In various types of dementia, including Alzheimer's disease (AD) and senile dementia of Alzheimer type (SDAT), several neurotransmitter indices are reduced, as compared to age-matched controls. Moreover, a decrease in neurotransmitter metabolites suggests that compensatory mechanisms are insufficient. No correlation could be found between the neurotransmitter changes and the histological changes characteristic of AD (senile plaques and neurofibrillary tangles). Neither could any relationship between multiple infarctions and neurotransmitter indices be detected. Recently observed changes in the lipid composition of the white matter, indicating demyelinization, in the brains of patients with AD/SDAT, emphasize the multifactorial aspects of dementia. Taken together, the data underline the difficulties in drawing clear demarcation lines between normal and pathological aging and between different subgroups of dementia. Despite the obvious difficulties, future therapeutic efforts should aim at substitution for the neurotransmitter deficiencies. Preventive measures have to await the clarification of the mechanisms underlying neural degeneration. Studies of the toxicity of oxygen and of autoxidation products are among the areas of research that may help to shed light on this problem.

Aging↗