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D A Drachman

Publications and source records attributed to D A Drachman.

At least 19 recordsLinked to original sources
PubMed1992

A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group.

BACKGROUND: In Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease. METHODS: Of 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living. RESULTS: At the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P < 0.001). There were no differences between the groups in their global-rating scores. The tacrine group had a significantly smaller decline in the activities of daily living. The results of the Mini-Mental State Examination favored tacrine, but the differences were small and not statistically significant (a score of 16.0 with tacrine vs. 15.3 with placebo; P = 0.08). Gastrointestinal symptoms, elevation of aminotransferase levels, and headache were the most frequent side effects; all could be reversed by reducing the dose or discontinuing treatment. CONCLUSIONS: In this short-term study in patients with Alzheimer's disease who were selected for apparent responsiveness to tacrine, treatment with tacrine resulted in a statistically significant reduction in the decline of cognitive function, although this reduction was not large enough to be detected by the study physicians' global assessments of the patients.

Activities of Daily Living↗
PubMed1992

Neuropsychological features of familial Alzheimer's disease.

It has been proposed that early-onset familial Alzheimer's disease (FAD) and sporadic Alzheimer's disease (AD) have different causes, with FAD due to a single dominant gene with disease onset before the sixth decade, whereas sporadic AD has a later onset and is not associated with a dominant pattern of inheritance. Given these differences, we questioned whether these etiologically distinct forms of AD also differ neuropsychologically. In this study we performed neuropsychological evaluations on patients from two well-documented families with FAD and a group of patients with sporadic AD. The groups were matched on global disease severity at entry. Two groups of education- and age-matched normal controls were recruited for comparison. The groups were analyzed for psychometric findings and pattern of deficits. Both patients with FAD and patients with sporadic AD showed a similar pattern of neuropsychological impairment relative to age-matched controls, i.e., mildly to moderately impaired verbal performance and concentration, severely slowed psychomotor speed, and severely impaired delayed recall of verbal material. There were no differences in pattern suggestive of disproportionately severe anomia, amnesia, agnosia, or apraxia in the early onset FAD group, as has been reported previously.

Adult↗
PubMed1992

Active and passive P3 latency and psychometric performance: influence of age and individual differences.

The relationship of P3 latency of the event-related potential (ERP) to psychometric performance was investigated in 41 subjects who ranged in age from 20 to 88 years. P3 responses were recorded from subjects using an auditory oddball paradigm with and without task-demands. Subjects also received psychometric tests of verbal performance, visuospatial performance, concentration, and immediate, recent and remote memory. Factor analysis was used to reduce the set of psychometric measures to four factors (Verbal learning, general intelligence, narrative recall/fluency, and concentration). Both passive and active P3 latency showed a linear increase with age. Age was inversely correlated with verbal learning performance. After accounting for the influence of age, passive P3 latency correlated with the psychometric factor associated with narrative recall and verbal fluency. Active P3 latency was correlated with factors reflecting general intelligence and concentration. These findings suggest that cognitive processing speed contributes to psychometric performance in adults. The psychological or biological basis for this relationship remains to be identified.

Adult↗
PubMed1992

The Caretaker Obstreperous-Behavior Rating Assessment (COBRA) Scale.

OBJECTIVE: To evaluate the usefulness and reliability of the Caretaker Obstreperous-Behavior Rating Assessment (COBRA), a new test instrument for caretaker assessment of types and severity of "obstreperous behaviors" (OBs) in demented patients. DESIGN: COBRA was completed by caretakers of 31 outpatients and 36 nursing home inpatients with dementia. Test-retest reliability was determined when 25 of the outpatient caretakers re-evaluated their demented relative 1 week later; inter-rater reliability was determined on nursing home inpatients by comparing the reports of two nurse's aids with equivalent knowledge of seven of the patients. SETTING: (1) University medical center Alzheimer's Disease and Related Disorders Clinic; (2) community nursing home. PATIENTS: Thirty-one sequentially-seen outpatients with dementia; 36 nursing home patients with dementia. INTERVENTION: Following instruction in the use of the COBRA Scale, caretakers provided scores for their demented patient. The instrument has three unique features: (1) it divides OBs into four categories for ease of comprehension: Aggressive/Assaultive; Mechanical/Motor; Ideational/Personality; and Vegetative; (2) a companion videotape shown to caretakers in advance illustrates each behavior to improve reliability of reporting; (3) the significance of each OB is estimated with severity and frequency measures. MAIN OUTCOME MEASUREMENTS: Frequency and severity of OBs are epitomized in 12 summary scores. Test-retest correlations (for outpatients) and inter-rater correlations (for inpatients) were analyzed with Pearson Product Moment and Spearman Rank Order correlations. RESULTS: Prevalence of OBs and severity was reported for the experimental groups. Summary scores revealed test-retest correlations of .95 to .73 for 11 of 12 scores (outpatients), and inter-rater correlations of .99 to .73 for 8 of 12 scores (inpatients). Age, gender, and disease etiology were not significantly related to OBs; clinical severity correlated with type and severity of OBs. CONCLUSIONS: The COBRA scale provides a convenient, comprehensive, and reliable means for caretakers to identify the types and measure the severity of OBs in demented outpatients and nursing home inpatients. If additional studies confirm these observations, COBRA will be a useful instrument for assessing the effects of interventions on OBs in patients with dementia.

Aged↗
PubMed1991

Expression of heat shock proteins in Alzheimer's disease.

In an investigation of heat shock proteins (HSPs) in the brains of Alzheimer's disease (AD) patients and cognitively intact control subjects, we found that 2 HSPs, termed "HSP72" and "GRP78," underwent major changes in expression in AD. HSP72, which was present at very low levels in control brains, increased dramatically in AD patients, and was localized exclusively in neuritic plaques and neurofibrillary tangles. We hypothesize that HSP72 is induced as an early response to the formation of abnormal proteins, perhaps targeting them for proteolysis. In contrast, GRP78 increased in AD only in neurons that remained cytologically normal, especially in the CA3 subfield of the hippocampus and the deep layers of the entorhinal cortex. The increased expression of GRP78 within successfully surviving neurons suggests that this protein may protect such cells from AD-specific damage.

Aged↗
PubMed1991

Primary progressive aphasia with focal neuronal achromasia.

We describe the clinical, radiologic, neuropsychological, and neuropathologic features of a 69-year-old man with a 3-year history of progressive transcortical expressive aphasia. Neuropsychological testing showed progressive dysfunction of expressive language. Neuropathologic examination demonstrated focal cortical degeneration involving the left superior frontal gyrus, with swollen achromasic neurons and no evidence of Alzheimer's disease, Pick's disease, Creutzfeldt-Jakob disease, Lewybody disease, or other dementing disorders. This case adds to the known heterogeneity of the underlying pathology of patients with primary progressive aphasia.

Aged↗
PubMed1990

The prognosis in Alzheimer's disease. 'How far' rather than 'how fast' best predicts the course.

Clinical features at the initial examination of 42 patients with probable Alzheimer's disease were tested for prognostic value at subsequent follow-up of 54 +/- 25 months. These potential prognostic features were of three types: degree of severity features (eg, IQ scores); variable clinical features (eg, extrapyramidal signs); and individual distinguishing features (eg, gender, education, and age). The power of these potential prognostic features to predict prognosis was assessed using the Kaplan-Meier life-tables method and the Cox proportional hazards model. Three clinical end points were considered: total dependence in activities of daily living; incontinence; and institutionalization at follow-up. Degree of severity features (subtests of the Wechsler Adult Intelligence Scale-Revised and the Wechsler Memory Scale, and the Clinical Severity Score) predicted subsequent dependence in activities of daily living, incontinence, and institutionalization. Historical disease duration, age, gender, family history of dementia, retrospective rate of progression, anxiety, psychosis, depression, and extrapyramidal signs did not influence prognosis. These results suggest that initial degree of severity ("how far") rather than variation in the rate of progression ("how fast") best predicts prognosis in the early to intermediate stages of Alzheimer's disease. The relationship of disease severity to prognosis should be taken into account before concluding that there are subtypes of Alzheimer's disease that have different rates of progression.

Activities of Daily Living↗
PubMed1989

Tumor-associated aphasia in left hemisphere primary brain tumors: the importance of age and tumor grade.

Although one-quarter of patients with primary brain tumors have language disturbances at the time of initial presentation, the factors contributing to their aphasia are not clear. A group of 32 patients with primary tumors of the left hemisphere was collected retrospectively and the relationship between clinical, radiographic, and pathologic factors and tumor-associated aphasia was examined. We assessed language function before beginning any treatment including steroids. The factor that best predicted language disturbance was greater patient age; the only other significant factor was tumor grade. Tumor size made a nearly significant impact, but tumor location within the left hemisphere did not correlate with aphasia.

Adult↗
PubMed1989

Thalamic dementia and motor neuron disease.

A 46-year-old woman developed a progressive neurologic disorder over the course of 30 months which was characterized by profound dementia complicated by a motor neuron disorder that became evident 10 months prior to death. Postmortem examination of the nervous system disclosed extensive neuronal loss and gliosis of the thalamus, predominantly involving the dorsomedial nuclei, as well as severe degeneration of the corticospinal tracts, spinal anterior horns, and hypoglossal nuclei. The disease could not be transmitted to experimental animals by intracerebral inoculation of the patient's brain tissue. This case represents a unique dementing disorder, possibly familial, with associated motor neuron disease.

Brain↗
PubMed1989

Synaptic loss in Alzheimer's disease and other dementias.

The extent and location of neuronal losses necessary or sufficient to produce dementia in patients with Alzheimer's Disease (AD) is unknown. To approach this question, we studied synaptic terminals in postmortem brain tissue utilizing immunohistochemical techniques. We used antibodies against two proteins found in synaptic terminals--synapsin I and synaptophysin--as synaptic markers in the hippocampal complexes of eight patients with autopsy-proven AD and eight nondemented control subjects. Quantitative microscopy measured the regional density of synaptic staining. All AD patients showed a striking decrease in synaptic staining in the outer half of the molecular layer of the dentate gyrus compared with control brains, where the density of synaptic terminals was uniform throughout. In an additional patient with progressive degenerative dementia but without plaques or tangles on neuropathologic examination, similar depletion of synaptic staining was seen in the dentate gyrus. Quantitative densitometric analyses confirmed the focal decrease in synaptic staining in the outer half of the molecular layer in demented patients. We also found a slight increase in synaptic staining in the inner half of this layer.

Adolescent↗
PubMed1988

Measuring dementia: assessment of multiple deficit domains.

A fundamental problem in the assessment of dementia is the brief, but adequate measurement of intellectual impairment. We evaluated 82 demented patients of heterogeneous etiology with 21 neuropsychological tests. Factor analysis identified five deficit domains among the tests: verbal ability, visuospatial ability, verbal memory, orientation, and concentration. One test was selected from each domain to form a Brief Battery for Dementia (BBD), which was used to explore the relationship between deficit patterns and disease characteristics. The pattern of deficits among the five tests altered with increasing disease severity: Logical Memory (a test of verbal memory) was severely impaired in the earliest stages, while tests of verbal concept formation, perceptual organization, and orientation declined more slowly. This battery discriminated between demented and normal subjects, with a sensitivity of 91% and specificity of 97%. Disease severity appeared to be a primary determinant of degree, number, and pattern of deficits in dementing disorders and may be an important factor that modulates the apparent discriminating power of intellectual tests.

Aged↗
PubMed1988

Troublesome and disruptive behaviors in dementia. Relationships to diagnosis and disease severity.

Patients with dementia often manifest troublesome and disruptive behaviors in addition to intellectual impairments. This study evaluated behavioral disturbances in 126 demented patients examined sequentially, using questionnaires administered to primary caregivers to quantify the types and severity of behavioral disturbances. Eighty-three percent of the patients exhibited one or more of the targeted behaviors. The most common troublesome and disruptive behaviors clustered into three categories: aggressive, ideational, and vegetative. The prevalence and severity of the behaviors increased with global severity of dementia, but did not differ in either frequency or type when patients with three diagnoses were compared: Alzheimer's disease (AD), multi-infarct dementia (MID), and mixed AD and MID (MIX). The occurrence and severity of the target behaviors correlated modestly with the severity of dementia. Impairments of mental status correlated weakly with only a single troublesome and disruptive behavior--assaultiveness. These results suggest that troublesome and disruptive behaviors are a very frequent component of dementing disorders, are related to disease severity, and parallel (but are probably not determined by) intellectual deficit.

Adult↗
PubMed1987

Vacuolar change in Alzheimer's disease.

A retrospective neuropathologic study of brains from 66 patients with Alzheimer's disease (AD) demonstrated the presence of a vacuolar change (VC) in 50 cases that was virtually indistinguishable histologically from the spongiform change characteristic of Creutzfeldt-Jakob disease (CJD). Indeed, in several instances, there was initial diagnostic confusion with CJD. Unlike the spongiform change in CJD, however, VC was almost entirely restricted to the medial temporal cortex and amygdala. Furthermore, the severity of VC was usually less intense than the spongiform change observed in cases of CJD with severe neurologic impairment. The VC could be readily distinguished from the fine microvacuolation of the upper layers of the isocortex reported in a number of different conditions, including AD. It also differed from the status spongiosus of the cerebral cortex that occurs in advanced AD and CJD as well as in other degenerative diseases. The artifactual rarefaction that occurs in improperly processed paraffin-embedded brain tissue was excluded as a contributory factor to the VC. Since VC does not invariably occur in AD, it conceivably could represent a subtype of this disorder or may represent a variant of the pathologic changes that can occur. Its relationship to CJD or other slow virus disorders is to date unknown but unlikely.

Aged↗
PubMed1987

Motor neuron disease and paraproteinemia.

We studied two patients with motor neuron disease and paraproteinemia. One had amyotrophic lateral sclerosis (ALS) and IgG lambda monoclonal gammopathy. The second had slowly progressive muscular atrophy and an IgM kappa paraprotein, followed by a biclonal gammopathy when an IgA kappa paraprotein appeared. Treatment with immunosuppressive agents and plasmapheresis lowered the serum concentration of the paraproteins. The ALS syndrome progressed despite therapy. The other patient improved, was stable for several years, but then deteriorated despite continued therapy.

Aged↗