摘要:

Summary:Pathological correlations were sought between cerebral amyloid angiopathy (CAA) and other classical neurodegenerative changes in 101 consecutive cases of autopsy- confirmed Alzheimer disease (AD). Some degree of CAA was found in at least one area of the brain in 81% of the cases; severe CAA was found in at least one brain region in 29% of the cases. In a subset of 42 cases for which genomic DNA was available, greater severity of CAA was associated more with cases that were homozygous for apolipoprotein e4 than in cases with only one or no e4 alleles (Fisher's exact test,p= 0.005). In all brain regions, severity of CAA was inversely correlated with numbers of neurons. This correlation was statistically significant in the temporal lobe (r=-0.29,p= 0.004) and the frontal lobe (r=— 0.22,p= 0.02). Our findings suggest that two factors may modify the severity of AD pathology: Apolipoprotein E4 may accentuate the vascular deposition of β-amyloid, and severe CAA may accelerate neuronal loss.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:As known from inflammatory diseases, oligoclonal bands in the cerebrospinal fluid (CSF-OCB) may indicate a humoral immune response within the central nervous system. Previous studies on the CSF IgG content in Alzheimer disease (AD) have been controversial about the relationship of OCB and elevated IgG indices. To explore this problem, we combined qualitative (isoelectric focusing) and quantitative methods (IgG index) to detect intrathecal IgG production and related these findings to the presence of blood-cerebrospinal-fluid barrier (BCB) dysfunction. Fifty-one AD patients were compared with patients with vascular dementia (VD), major depression (MD), multiple sclerosis (MS), and age-matched control subjects. CSF-OCB could be traced in 20% of AD patients. An elevated IgG index was found in 6% and a BCB dysfunction in 16% of all AD patients. Either intrathecal IgG synthesis or BCB dysfunction were detected in a subgroup of 36% of all AD cases and in 40% of patients with late-onset AD. Intrathecal IgG synthesis and BCB dysfunction may suggest underlying immunological or inflammatory changes in an as-yet undefined subgroup of AD patients and support the notion of a heterogeneous nature of AD.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:The purpose of the present study was to evaluate methanesulfonyl fluoride (MSF), a very long-acting CNS-selective acetylcholinesterase (AChE) inhibitor, as a palliative treatment for senile dementia of the Alzheimer type (SDAT). In experiment I, MSF (0.03-0.18 mg/ kg) was administered orally to 10 normal volunteers to measure toxicity and establish dose/ response function in erythrocyte AChE. MSF produced a dose-response function of % inhibition=(40)(Logl0[MSF mg/ kg] + 51.7) with no toxicity at these doses. Experiment II was a 16-week double-blind, placebo-controlled study of the safety and efficacy of MSF in doses of up to 0.18 mg/Kg given three times per week in 5 men and 10 women (60-82 years), with Mini-Mental State Examination (MMSE) scores of 9-24, who had SDAT. MSF produced a mean of 89.5% inhibition of erythrocyte AChE in patients and improved cognitive performance as measured by the MMSE, Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-COG), Global Deterioration Scale, and the Clinical Interview Based Impression of Change (CIBIC). Most of the improvement on the ADAS-COG was maintained 8 weeks after ending MSF. No patients left the study because of drug-related adverse events and there were no toxic effects. MSF may be a safe and effective palliative treatment for SDAT and further clinical trials in larger groups of patients are warranted.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:To evaluate an objective method for individually assessing Alzheimer patients for cognitive benefits from acetylcholinesterase inhibitors, we conducted a secondary analysis of data from 234 subjects enrolled in a 30-week efficacy trial of tacrine hydrochloride. We determined which patients showed treatment-related improvement on the Alzheimer Disease Assessment Scale—Cognitive subscale (ADAS-Cog) and the Mini- Mental State Examination (MMSE). Four weeks after administration of the maximum dose, 14% showed significant improvement from baseline in their ADAS-Cog scores, and 30.6% showed significant improvement in their MMSE scores. Examination of response patterns over time revealed that 65% of patients showed no improvement in MMSE scores during the 120-160-mg phases of the trial, whereas 18% showed consistent improvement in MMSE scores during that time. Three percent of patients showed improvement in their MMSE scores only for the 160-mg assessment. How the methodology from this study can be generalized to other Alzheimer patients is discussed. We calculated prediction intervals to document the magnitude of fluctuation in performance that is normal for Alzheimer patients similar to those in this study. Patients who change more than the limit specified by the prediction interval have statistically significantly improved performance. We determined that an improvement on the MMSE of three or more points across a time period of 6 weeks marks statistically significant change for an individual. For intervals between 6 and 16 weeks, improvement of four or more points on the MMSE is statistically significant. The results indicate that monitoring individual patients for statistically significant improvements in cognitive functioning is feasible, sensitive to drug-related changes in performance, and could facilitate drug monitoring in patients.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:The staging of dementia is ideally based on both an examination of the patient and a history taken from an informant. However, in some circumstances, only an informant history is possible. The aim of this study was to assess the validity of the Clinical Dementia Rating (CDR) when the rating is based solely on informant data. The CDR was used in a study of 360 persons aged 78 or older who were participants in a community survey, the Sydney Older Persons Study. The CDR was completed in two ways: (1) a social scientist made the ratings based on an informant interview; and (2) a physician made the ratings after an examination of the subject. All CDRs were scored in the conventional way, as well as by the revised method proposed by Gelb and St. Laurent [Alzheimer Dis Assoc Disord1993;4:202-l 1). The informant CDR showed moderate agreement with the clinician CDR, showing that it would be a valid substitute in situations in which the subject could not be examined. The revised scoring method was slightly easier to implement than the conventional method.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:Alzheimer disease (AD) is characterized by episodic memory impairment. This study was aimed at assessing various aspects of episodic memory, and particularly sensitivity to semantic cuing, in patients with various degrees of cognitive deterioration, compared with normal elderly subjects. One hundred thirty-one patients, subdivided into four subgroups as a function of their Mini-Mental State Examination score, were included. All subjects, including 20 normal elderly subjects, were given an episodic memory test with controlled encoding and selective reminding. The subgroups of patients were homogeneous in terms of free recall and recognition, but differed in terms of responsiveness to cuing by semantic categories corresponding to the to-be-remembered items. The data confirmed that a severe amnesic syndrome occurs very early in AD, even in a subgroup of patients who did not meet the criteria for dementia. The data indicated that free recall performance, characterized in all subgroups by a floor effect, is not likely to be an appropriate index in pharmacological trials. By contrast, sensitivity to semantic cuing seemed relatively preserved in the early stages, and decreased with the progression of the disease. This index would be the most sensitive index of episodic memory in AD.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:Although case-control studies have found elevated risk for Alzheimer disease (AD) associated with a prior psychiatric history, most of the previous research had inadequate controls for familial risk factors. Putative psychiatric risk factors were evaluated for a registry-based sample of 65 twin pairs discordant for AD. Risk ratios were calculated for psychiatric illness at any time and for episodes more than 10 years before dementia onset. Prior psychiatric illness was significantly associated with elevated risk. Most of these cases represented depressive episodes. When analyses were restricted to individuals whose mental illness commenced more than 10 years before dementia onset, the magnitude of the odds ratio decreased markedly. These findings suggest that a history of psychiatric illness, especially depression, may be associated with an elevated risk for AD. In particular, these results are consistent with an interpretation that symptoms of depression and similar complaints represent prodromal phases of dementia.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:There is no brief patient-derived rating scale for staging and following profoundly demented Alzheimer disease (AD) patients. We developed the Baylor Profound Mental Status Examination (BPMSE) modeled after the Mini-Mental State Examination (MMSE) to meet this need. The BPMSE consists of 25 cognitive questions that assess orientation, language, attention, and motor functioning; 10 examiner ratings of presence or absence of problem behaviors; and 2 qualitative observations of language and social interaction. Two hundred eight probable or possible AD patients (MMSE scores of 20 or less) received the BPMSE. Some were also rated on the clinical dementia rating (CDR) and Lawton activities of daily living (ADL). A ceiling effect occurred at MMSE scores above 11. BPMSE cognitive scores and MMSE scores correlated significantly (r= 0.76,p< 0.0001). Subareas of the BPMSE also intercorrelated significantly. The BPMSE correlated with both CDR and ADL scores (p< 0.001). Internal consistency, interrater reliability, and test-retest stability were excellent. There was no floor effect, and BPMSE scores continued to decline after the MMSE reached 0. The BPMSE is a quick and easy staging tool with excellent validity and test-retest stability that measures cognitive function successfully in patients with MMSE scores below 12. The scale is sensitive to longitudinal change and continues to assess decline when performance has reached the lowest levels on conventional measures.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:We investigated types of inappropriate sexual behavior (ISB) and patient characteristics in geriatric patients with dementia. The study group consisted of 133 consecutive geropsychiatric demented patients admitted to our ward. All patients underwent standardized diagnostic procedures for dementia, and ISB was assessed by a questionnaire completed by patients' caregivers and records during hospitalization. Patients were then subdivided on the basis of the presence or absence of ISB. Of the 133 demented patients, 20 (15.0%) were reported to demonstrate ISB at home or during hospitalization. Patients with ISB had various types of dementia. There were no significant differences in patients with and without ISB in regard to age, age of onset, gender, educational level, or Mini-Mental State Examination scores. ISB is not unusual in dementia patients and can be found in different types of dementia. Medical care providers need to be trained to discuss sexual issues with caregivers and offer ideas and training to help cope with patients with ISB.

ISSN:0893-0341    

出版商:OVID    

年代:1999

数据来源: OVID