摘要:

This study evaluated the efficacy and safety of donepezil in patients with mild to moderately severe Alzheimer''s disease, and examined the relationships between plasma donepezil concentration, red blood cell acetylcholinesterase (AChE) activity and clinical response. The trial was of a multicenter, double-blind, parallel-group design and patients were randomised to once-daily treatment with either donepezil (1, 3 or 5 mg) or placebo. The 12-week double-blind phase was followed by a 2-week single-blind placebo washout. 161 patients (55-85 years of age) entered the study and 141 completed treatment. Patients treated with donepezil showed dose-related improvements in the Alzheimer''s Disease Assessment Scale - cognitive subscale score (ADAS-cog) and in MMSE scores. The improvements in ADAS-cog were statistically significantly greater with donepezil 5 mg/day than with placebo. There was a 50% reduction in the percentage of patients showing clinical decline with donepezil at 5 mg/day (11%) relative to placebo (20%). In addition, a statistically significant correlation between plasma concentrations of donepezil and AChE inhibition was demonstrated. A plateau of inhibition (76-84%) was reached at plasma donepezil concentrations >50 ng/ml. The correlation between plasma drug concentrations and ADAS-cog (p = 0.014), MMSE (p = 0.023) and patient quality of life scores, assessed by the patient (p = 0.037) were also statistically significant, as was the correlation between AChE inhibition and change in ADAS-cog (p = 0.008). The incidence of treatment-emergent adverse events with all three dosages of donepezil (64-68%) was comparable to that observed with placebo (65%). Donepezil had no clinically significant effect on vital signs, haematology or clinical biochemistry tests. Importantly, donepezil was not associated with any hepatotoxicity, as observed with acridine-based cholinesterase inhibitors.

ISSN:1420-8008    

DOI:10.1159/000106895

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

This study measured brain atrophy in patients with idiopathic Parkinson''s disease and diffuse Lewy body disease, all of whom had equivalent loss of midbrain dopaminergic neurons and absence of Alzheimer''s disease. Characteristic patterns of volume loss were found throughout the brain, depending on the age of onset and clinical signs. An equivalent loss of medial temporal lobe structures occurred in all parkinsonian patients. This atrophy was similar in magnitude to that seen in Alzheimer''s disease and is likely to be the anatomical substrate for the memory deficits found in each of these patient groups. Frontal lobe atrophy was a feature of both late-onset Parkinson''s disease (mild atrophy) and diffuse Lewy body disease (significant atrophy) groups, with all cases analyzed having dementia. Atrophy of frontal lobes correlated with the duration of motor symptoms in these patients and may suggest an association between dopaminergic deafferentation, frontal atrophy and dementia.

ISSN:1420-8008    

DOI:10.1159/000106896

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In this study the best combination of quantitative electroencephalographic variables (qEEG) for the discrimination of groups with mild to moderate Alzheimer''s disease (AD), mild cognitive impairment and healthy subjects was defined and related to neuropsychological performance. The study population included 18 patients with mild to moderate probable AD, 19 subjects with objective memory disturbances, 17 subjects with subjective memory complaints who did not have clinical evidence of memory disturbance, and 16 healthy controls. AD patients had significantly increased theta and decreased alpha relative power, mean frequency, and temporoparietal coherence. There was no significant difference in the mean frequency in the left temporal region between AD patients and subjects with objective memory disturbances. Temporoparietal coherence appeared as a discriminant variable together with alpha and theta relative power only between AD patients and controls, giving 77.8% sensitivity and 100% specificity. Significant correlations between regional changes in qEEG variables and cognitive functions were found.

ISSN:1420-8008    

DOI:10.1159/000106897

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The careful definition of cases is fundamental to diagnosis and to any study of cognitive, behavioural and functional problems in dementia. This paper presents an algorithmic approach which mimics a crucial component of diagnostic decision-making; symptoms and signs do not occur independently, but are conditioned on each other. First, we examine whether the conditioned items can be assembled to yield a differential diagnosis of dementia which corresponds to clinical diagnoses, and second, we explore whether subjects whose algorithmic profiles do not fit the clinical diagnoses form new discernable patterns. Such a technique offers two advantages: it allows for the development of validation protocols which are crucial to epidemiological studies, and it allows for the analysis of new patterns of signs and symptoms for emerging criteria of dementia subtypes. This approach has the potential to refine and enhance criteria for the differential diagnosis of dementia and to have an impact on case identification and assessment, particularly in large epidemiologic studies.

ISSN:1420-8008    

DOI:10.1159/000106898

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

This paper addresses the synergy and antagonism between symptoms and signs among 2,914 elderly Canadians diagnosed in 15 categories, including no cognitive impairment, cognitive impairment but no dementia, mild, moderate and severe forms of Alzheimer''s disease and vascular dementia, 4 subtypes of possible Alzheimer''s disease, Parkinson''s dementia, unspecified other dementias and unclassified dementias. Attention is paid to the relationships between symptoms and signs rather than conventional analyses which assume independent signs. We demonstrate that dementia progression and specific aetiologies have characteristic patterns of decline and destruction from the strong synergy that exists between symptoms and signs among the population with no cognitive impairment. These findings have potential implications for the incorporation of new diagnostic criteria into existing databases.

ISSN:1420-8008    

DOI:10.1159/000106899

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Neuropsychological screening tests such as the Mini Mental State Examination (MMSE) are commonly used for case finding in community studies on dementia or Alzheimer''s disease (AD). However, the high proportion of false-positives is an important limitation to the feasibility of such studies. The aim of this study was to evaluate whether adding apolipoprotein E (apoE) genotyping to the MMSE is followed by a significant reduction of the false-positive rate. Subjects were 70 AD patients (MMSE 13-28) and 70 normal controls (MMSE 25-30). Multivariable discriminant analysis was used to classify subjects on the basis of age, gender, MMSE score and the presence of the ε4 allele of apoE. When sensitivity was set at 99%, the model including age, gender and MMSE had a false-positive rate of 13.5%, while adding ε4 to the previous variables decreased this figure to 6.7%. In a hypothetical community study screening for AD in a population of 1,000,000, this would turn in a decrease of false-positives from about 19,000 to about 9,500. We conclude that the use of apoE genotyping in community case-finding studies is promising and should deserve further consideration.

ISSN:1420-8008    

DOI:10.1159/000106900

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Experimental data suggest an involvement of immune cellular components in the development of Alzheimer''s disease (AD). Against this background, the spontaneous natural killer (NK) cell activity and the NK-induced cytotoxicity after interleukin-2 (IL-2) were studied in healthy elderly subjects and in patients with dementia of Alzheimer type (SDAT) and multi-infarct type (MID). Higher NK cytotoxicity (expressed as total lysis and percent increase) at different IL-2 concentrations (50 and 100 IU/ml/cells) was demonstrated in patients with SDAT than in healthy elderly subjects (p < 0.001) and MID patients (p < 0.001). NK cell activity of MID patients was similar to that of healthy elderly and healthy young subjects. A negative correlation between the percent increase in NK cytotoxicity after IL-2 and the Mini Mental State Examination Score was also found in SDAT patients (p < 0.01). Alterations of IL-2-mediated NK cytotoxicity may therefore support the neuroimmune hypothesis of AD.

ISSN:1420-8008    

DOI:10.1159/000106901

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1420-8008    

DOI:10.1159/000106902

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1420-8008    

DOI:10.1159/000106903

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1420-8008    

DOI:10.1159/000106904

出版商:S. Karger AG    

年代:1996

数据来源: Karger