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B Reisberg

Publications and source records attributed to B Reisberg.

At least 19 recordsLinked to original sources

Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer's disease. Pathophysiologic implications.

Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non-contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD.

Aged

Functional assessment staging (FAST) in Alzheimer's disease: reliability, validity, and ordinality.

Evaluation of changes in functional performance and activities of daily living skills is an essential aspect of the assessment of elderly individuals with chronic illness. Although functional decrement is a central aspect of Alzheimer's disease (AD), many measures currently utilized to assess these changes have limitations. Empirical and systematic examination of the functional changes occurring in patients with AD has resulted in the development of an assessment measure termed Functional Assessment Staging (FAST) that allows for the specific evaluation of these changes throughout the entire course of AD. In this paper the results of three separate investigations regarding the reliability, validity, and progressive ordinality of FAST are described. The results indicate that FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the entire course of the illness. Moreover, the results suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD. Because the elements of functional capacity incorporated in FAST are relatively universal and readily ascertainable, as well as characteristic of the course of AD, FAST can serve as a strong diagnostic and differential diagnostic aid for clinicians. The sensitivity of FAST to the entire course of AD, even in its most severe stages, may be indicative of the potential value of this instrument for further investigation of the temporal longitudinal course of AD, and of the relationships between clinical pathology and neuropathology throughout the entire longitudinal course of AD.

Activities of Daily Living

Management of behavior disturbance in Alzheimer disease: current knowledge and future directions.

Assessment and treatment of behavior problems in patients with Alzheimer disease and related disorders is a seriously neglected area of study. Despite the fact that such problems are integral to the disorder, little is known about effective management. This article summarizes the current thinking on five areas of prime importance to patients, care providers, and health care professionals: agitation, assault/aggression, screaming, wandering, and depression/apathy/withdrawal. Methodological guidelines for studying these disorders are provided. Emphasis is on recognizing that behavior problems are important areas of study in their own right as well as in conjunction with studies of cognition.

Activities of Daily Living

Milacemide: a placebo-controlled study in senile dementia of the Alzheimer type.

OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients.

Acetamides

Pharmacologic treatment of Alzheimer's disease: a methodologic critique based upon current knowledge of symptomatology and relevance for drug trials.

Research on the nature of clinical symptomatology in AD indicates that two fundamentally different types of symptoms are identifiable. Symptoms within each of these two domains have common characteristics. The first symptomatic domain has been termed the "cognitive domain" and the second the "noncognitive behavioral domain." Symptoms and losses in the cognitive domain occur invariably and progressively with the advance of AD over time. Symptoms in the behavioral domain do not invariably occur in AD and do not progress monotonically with the advance in AD over time. However, characteristic behavioral domain symptoms can be described over the course of AD. The two symptomatic domains are likely to differ not only in nature and progression in AD, but also in underlying pathophysiology and in terms of possible treatment modalities. They also pose fundamentally different issues of assessment in AD. These distinct factors necessitate the separate assessment of the two symptomatic domains in AD treatment trials. Judgments of efficacy and utility in remediating either symptomatic domain in AD should take into consideration the effects of treatment on both cognitive domain and behavioral domain symptoms separately and interactively. Appropriate assessment procedures are discussed.

Activities of Daily Living

Cognition-independent neurologic symptoms in normal aging and probable Alzheimer's disease.

Deep tendon reflexes, plantar responses, muscle tone, and release signs were studied as 14 individual clinical variables and as five summary variables in 135 aged subjects, including 27 control subjects, 20 subjects with mild cognitive impairment, and 88 subjects with successive stages of probable Alzheimer's disease. Changes in activity of elicited responses were rated on a seven-point scale. Results were analyzed both as prevalence and mean degree of change in activity. Rating on a variable combining all 14 individual variables was significantly higher in a group with mild cognitive impairment than in a control group. Subjects with an early stage of Alzheimer's disease had both higher prevalence of increased activity and increased mean scores of deep tendon reflexes and muscle tone. They had a higher prevalence of increased activity on a variable combining three release signs. Patients with a late stage of Alzheimer's disease had significantly increased prevalence and mean scores of muscle tone and grasping and sucking reflexes compared with control subjects and patients with the early stage of Alzheimer's disease.

Activities of Daily Living

Mild cognitive impairment in the elderly: predictors of dementia.

We conducted full diagnostic evaluations, including a comprehensive cognitive assessment battery, of a group of 32 elderly subjects with a clinically identified mild cognitive impairment and a group of 32 age-matched and education-matched normal subjects. The mildly impaired subjects performed significantly more poorly than the controls on tests of recent memory, remote memory, language function, concept formation, and visuospatial praxis. Follow-up evaluations of cognitive status 2 years later revealed clinically detectable cognitive decline relative baseline in 23 (72%) of the mildly impaired subjects. Several of the objective psychological tests accurately discriminated at baseline between the decliners and nondecliners in the mildly impaired group. Among the 20 mildly impaired subjects with no complicating conditions, 16 exhibited cognitive deterioration between baseline and follow-up. These results suggest that most elderly subjects with mild cognitive deficits, as determined by clinical evaluation and objective psychological testing, will manifest the progressive mental deterioration characteristic of dementia and that psychometric predictors can be used to distinguish between benign and more significant underlying disorders in mildly impaired elderly subjects.

Aged

Application of Piagetian measures of cognition in severe Alzheimer's disease.

Conventional psychometric measures uniformly yield zero or near zero scores (i.e., "bottom-out") as patients with Alzheimer's disease (AD) progress to the more severe stages of the illness. Consequently, there are no psychometric measures which objectively assess the mental abilities of AD patients with very severe cognitive impairment. We explored the hypothesis that mental function in AD patients with very severe cognitive impairment can be effectively assessed using test measures developed to assess the earliest stage of cognitive development as proposed by Piaget. We also investigated the relationship between decline on these experimental cognitive measures and progressive functional disability in patients with severe cognitive impairment. The results indicate that modified instruments derived from measures developed to assess Piaget's sensorimotor stage of cognitive development provide useful information about the cognitive abilities of very severely impaired AD patients. These modified instruments provide a measure of cognition in these extremely impaired patients that has acceptable validity and demonstrable reliability.

Aged

The effects of mood changes and antidepressants on the cognitive capacity of elderly depressed patients.

Seventy-eight nondemented elderly depressed patients underwent an extensive battery of cognitive tests both before and after seven weeks of treatment with nortriptyline, phenelzine, or placebo. Clinical and cognitive evaluations of the patients were under double-blind conditions. Response to treatment did not appear to significantly affect cognitive capacity; neither did treatment with an active substance as compared to placebo. In addition, the baseline level of cognitive functioning did not appear related to whether a patient responded to treatment. The authors conclude that under optimal conditions neither antidepressant produces measurable changes in the cognitive capacity of nondemented elderly patients.

Affect

Alzheimer's disease: longitudinal CT studies of ventricular change.

A 3-year longitudinal study was conducted with 50 Alzheimer's disease patients and 45 elderly control subjects. All study participants received an extensive evaluation that included brain CT at baseline and follow-up. Quantitation of ventricular size, using both linear and volume methods, revealed highly significant cross-sectional and longitudinal differences between the Alzheimer patients and control subjects. Specifically, the annual rate of change in ventricular volume was approximately 9% in the Alzheimer patients and approximately 2% in the controls. The presence of age-related white matter lesions had no effect on the clinical course of the patients or on the changes in ventricular size. Among the Alzheimer patients, the rate of clinical decline was strongly related to the rate of change in ventricular size. Baseline ventricular measurements were of no value in predicting the subsequent rate of clinical deterioration or ventricular enlargement. The results suggest that changes in ventricular size closely reflect the clinical changes in Alzheimer patients.

Aged

The stage specific temporal course of Alzheimer's disease: functional and behavioral concomitants based upon cross-sectional and longitudinal observation.

A series of studies published over the past 6 years now permit a relatively precise description of the temporal course of Alzheimer's disease (AD). Initially, 7 global stages of CNS aging and AD were described. Subsequently, data on the stage specific relationship between these stages and widely employed mental status, psychometric, and other assessment measures were collected. Longitudinal studies helped to clarify the borders between normal CNS aging and AD using these measures. Other studies described functioning and self-care correlates of the 7 global stages. These were ultimately divisible into 16 clearly defined, ordinal functional stages. Empirical longitudinal observations permitted the description of the mean temporal course of each of the 16 functional stages of aging and AD. The cross-sectional stage specific data on mental status and other measures can now be applied to the mean temporal course observations and the validity of the temporal estimates forwarded can be investigated in detail. Etiologic hypotheses based upon the observed phenomenologic and temporal course of AD are discussed.

Aging

Beta-amyloid protein probe hybridized to chromosome 9 in 3 Alzheimer disease individuals.

We have reported recently the sublocalization of an Alzheimer Disease-associated gene that encodes for cerebrovascular beta-amyloid protein (BAP). Its locus appears to be at or proximal to band 21q2105 through band 21q11.1. We have also observed hybridization to chromosome 20 in normal and Down syndrome individuals using the single-stranded form of the probe. Further, we have found that BAP hybridizes to chromosome 9 in lymphoblastoid cells from three individuals from two families with familial Alzheimer Disease (AD). We have now obtained additional data which shows significant hybridization to chromosomes 9,20 and 21 for two normal control individuals, a Down syndrome (DS) individual and three AD individuals. When the normal and Down Syndrome individuals were compared to the group of individuals with AD, significant hybridization to chromosome 9 occurred in the Alzheimer group only (p less than .05). Almost half of the silver grains on chromosome 9 in the three AD individuals were localized to the distal area of the long arm. Whether these observations demonstrate an apparent genetic marker in these three individuals with familial AD, or whether our observations have identified a marker for both familial and sporadic AD will be determined by further studies.

Alzheimer Disease

Clinical features of a neuropathologically verified familial Alzheimer's cohort with onset in the fourth decade: comparison with senile onset Alzheimer's disease and etiopathogenic implications.

Clinical and pathologic features of a family with early onset, autosomal dominant, familial Alzheimer's disease (AD) are compared and contrasted with senile onset dementia of the Alzheimer type. Late onset AD has previously been observed to have a characteristic progression and clinical course. A previously unreported pedigree, with two siblings and their father affected, of early clinical onset is presented. Molecular genetic study of this family using in situ chromosome hybridization showed an apparent marker on chromosome 9. This early onset form of AD is observed to be clinically consistent with the common late onset form of AD, but follows a more rapid course. An etiopathogenic model explaining the early onset, and other forms of AD is presented.

Adult

Equivalent spatial-rotation deficits in normal aging and Alzheimer's disease.

Two tests of spatial-rotation ability were administered to 17 young normals, 23 aged normals, and 51 patients with diagnoses of Alzheimer's disease (AD). The AD patients consisted of 28 early dementia patients and 23 advanced dementia patients. On a computerized version of the Boston Naming Test, 40 objects were presented for naming, 20 of which were rotated 180 degrees. The subjects' capacity for mental rotation was assessed on the basis of their accuracy of naming of rotated vs. unrotated objects. On Money's Standardized Road Map Test, in which the subject is asked whether turns on a map are to the left or to the right, spatial-rotation ability was assessed on the basis of the subject's left-right orientation on turns with movement away from the subject (requiring no rotation) vs. turns with movement toward the subject (requiring rotation). Performance on both tasks was progressively worse in the young normal, aged normal, early dementia, and advanced dementia groups. Both tasks demonstrated a clear spatial-rotation deficit in the elderly. Although the spatial-rotation effect was superimposed upon deficits in naming and left-right orientation in the demented subjects, the magnitude of the rotation effect did not significantly differ in the aged normal vs. the early dementia group on either task, suggesting that early AD produces no further impairment of spatial-rotation abilities than is produced by normal aging.

Adolescent

A curriculum for education in geriatric psychiatry.

The authors present recommendations for educating medical students and psychiatric residents in geropsychiatry. They are primarily concerned with the objectives and methods rather than the content of training. Proposals are structured in terms of training objectives and educational settings in which such training takes place. The proposals are intended to be specific enough to be truly useful and at the same time sufficiently generalizable to adapt to geropsychiatric training in a variety of institutions. Priority is given to integrating knowledge of normal and abnormal aging with the clinical skills and empathy necessary to approach patients with competence and understanding.

Aged