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Biomedical subjects

B Reisberg

Publications and source records attributed to B Reisberg.

At least 37 records · Page 2Linked to original sources

Neuronal and volume loss in CA1 of the hippocampal formation uniquely predicts duration and severity of Alzheimer disease.

In a series of multiple regression models predicting either duration or severity of Alzheimer disease (AD) patients, significant linear correlations were found consistently for the volume of CA1, the subiculum, and the entorhinal cortex. Similarly, the total number of neurons in CA1, CA4, and the subiculum was correlated significantly with both the duration and the severity of AD. A hierarchical multiple regression model was used to examine whether any of these intercorrelated measures had any unique relationship to disease duration or severity. The results showed that only CA1 demonstrated a unique contribution to the explained variance in predicting duration or severity of AD for volume and for neuronal numbers. These results indicate that in the hippocampal formation, volume and neuronal numbers of CA1 appear to show a unique relationship with clinical measures of AD.

Alzheimer Disease↗

Duration of neurofibrillary changes in the hippocampal pyramidal neurons.

The total number of neurons with and without neurofibrillary changes in sectors CA1 to CA4, subiculum, and dentate gyrus of 16 subjects with Alzheimer disease (AD) was estimated. The duration of neurofibrillary changes was calculated on the basis of regressions between the duration of AD and neuronal numbers. In the CA1 and subiculum, it takes 3.4 and 5.4 years, respectively, for an intact neuron affected by neurofibrillary pathology to become a ghost tangle.

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Progression of Alzheimer's disease: variability and consistency: ontogenic models, their applicability and relevance.

Much has been learned about the clinical symptomatology of Alzheimer's disease (AD) and ontogenic reciprocal relationships in the past few decades. It is now possible to describe and verify inexorable symptomatic sequences and corresponding temporal relationships. It is also possible to identify more variable symptoms in AD. Ontogenic models can be useful in providing a clearer understanding of the nature of AD symptomatology in terms of both consistency and variability. These models can also be informative in explicating the management needs of AD patients and the treatment possibilities of AD symptoms as well as the etiology of variability in AD symptoms.

Activities of Daily Living↗

Management of fluoroquinolone resistance in Pseudomonas aeruginosa--outcome of monitored use in a referral hospital.

We evaluated a strategy designed to improve useful activity of ciprofloxacin against Pseudomonas aeruginosa. Following changes in antimicrobial agent use made by the institutional Pharmacy and Therapeutic Drug Committee, monthly drug usage and microbial susceptibility records from June 1992 through October 1995 were reviewed. From July 1992 through October 1992 (Period 1), ciprofloxacin and ofloxacin usage represented 95 and 5% of total quinolone doses; from December 1992 to March 1993 (Period 2), ciprofloxacin represented 19%; from July 1993 to October 1993 (Period 3), ciprofloxacin usage represented 85%; from July 1994 to October 1994 (Period 4), ciprofloxacin represented 95%; and from July 1995 to October 1995 (Period 5), ciprofloxacin and ofloxacin respectively represented 98 and 2% of total quinolone doses. Comparison of the anti-pseudomonal activity of the two fluoroquinolones to ofloxacin use, ciprofloxacin use and total quinolone use during the entire observational period showed the highest (negative) correlation with ofloxacin use versus ofloxacin activity (y = -15.04x + 1367.99, r2 = 0.06, w = 0.126). Increased use of quinolones plus a change to primarily ofloxacin usage appeared to adversely affect the activity of both ofloxacin and ciprofloxacin against P. aeruginosa.

Anti-Infective Agents↗

Reliability of routine clinical instruments for the assessment of Alzheimer's disease administered by telephone.

We investigated the reliability, using a telephone interview procedure, of cognitive, functional, and behavioral scales in an elderly population with normal aging and dementia. Two clinicians performed the assessments: one performed the assessments in a telephone interview format and the other conducted the assessments at the clinic. The telephone interview always preceded the clinic evaluation (2-30 days apart), and both clinicians were blind to any previous evaluations of the patient. The intraclass correlation coefficients between the telephone interview and the ratings obtained by a different clinician on the clinic evaluation varied between 0.92 and 0.98 (P's < or = .001) for comprehensive test scores. These results indicate that a telephone interview format, although not a substitute for a face-to-face diagnostic evaluation, is a reliable procedure for obtaining the assessment modalities studied. These findings are particularly important in aged and dementia research populations where personal contact may not always be feasible.

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Diagnosis of Alzheimer's disease. Report of an International Psychogeriatric Association Special Meeting Work Group under the cosponsorship of Alzheimer's Disease International, the European Federation of Neurological Societies, the World Health Organization, and the World Psychiatric Association.

Current knowledge with respect to the diagnosis of Alzheimer's disease (AD) is reviewed. There is agreement that AD is a characteristic clinicopathologic entity that is amenable to diagnosis. The diagnosis of AD should no longer be considered one of exclusion. Rather, the diagnostic process is one of recognition of the characteristic features of AD and of conditions that can have an impact on presentation or mimic aspects of the clinicopathologic picture. The present availability of improved prognosis, management, and treatment strategies makes the proper, and state-of-the-art, diagnosis of AD a clinical imperative in all medical settings. Concurrently, information regarding the relevance and applicability of current diagnostic procedures in diverse cultural settings must continue to accrue.

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The GDS/FAST staging system.

Staging methodologies are an essential tool in the assessment of disease severity in progressive dementing illness. Several different instruments have been developed for this purpose. One of the most widely used methodologies is the Global Deterioration Scale/Functional Assessment Staging (GDS/FAST) system. This system has been studied extensively and proven to be reliable and valid for staging dementia in Alzheimer's disease (AD) in diverse settings. One of the major advantages of this system is that it spans, demarcates, and describes the entire course of normal aging and progressive AD until the final substages of the disease process. Other advantages include: (a) greatly enhanced ability to track the longitudinal course of AD, (b) improved clinicopathologic observations of AD interrelationships, and (c) enhanced diagnostic, differential diagnostic, and prognostic information. This article presents a brief overview of the GDS/FAST staging system.

Alzheimer Disease↗

Neurologic markers of the progression of Alzheimer's disease.

This article describes the results of studies conducted to determine the usefulness of reflex changes as markers of disease severity in Alzheimer's disease (AD). Standardized and quantified muscle stretch reflexes, cutaneous reflexes, and developmental (primitive) reflexes were studied in normal older adults, in individuals with mild memory impairment, and in patients with AD, in all clinical severity stages as assessed with the Global Deterioration Scale (GDS), the Mini-Mental State Examination (MMSE), and the Functional Assessment Staging (FAST) procedure. Changes in frequency and intensity of these individual reflex variables, as well as of variables consisting of combinations of these individual reflexes, appeared to be sensitive indicators of the progression of AD. These neurological reflex variables showed high Pearson correlations with the GDS (.72), the MMSE (.74), and the FAST (.80). Standardized quantified neurological reflex measures are useful as noncognitive, education-independent, and culture-independent markers of the course of AD.

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Motor/psychomotor dysfunction in normal aging, mild cognitive decline, and early Alzheimer's disease: diagnostic and differential diagnostic features.

To determine the association between cognitive dysfunction and motor behavior in older adults, 41 cognitively normal elderly (NL), 25 nondemented patients exhibiting mild cognitive impairment (MI) and at risk for future decline to dementia, and 25 patients with mild (early) Alzheimer's disease (AD) were examined using a wide array of motor/psychomotor and cognitive assessments. The three groups were recruited from an aging and dementia research center and were composed of well-characterized physically healthy volunteers, with similar ages and gender distributions. The outcome measures included 16 motor/psychomotor tests categorized a priori into gross, fine, and complex, as well as eight cognitive tests of memory and language. Relative to the NL group, MI individuals performed poorly on cognitive, fine, and complex motor measures but not on gross motor tests; AD patients performed worse on cognitive and all motor domains. Differences in complex motor function persisted after adjustment for performance on cognitive and on less complex motor tests. Classification analyses showed similar accuracies in discriminating NL from MI and NL from AD cases for both complex motor (79% and 92% accuracy, respectively) and cognitive tests (80% and 93% accuracy, respectively). Less complex motor tests produced poorer accuracies. Among nondemented subjects, education correlated with several cognitive scores but no motor scores. These results indicate that motor impairment is an important aspect of cognitive decline in older adults. Motor/psychomotor assessments were found to be comparably sensitive to traditional tests of cognitive function in identifying persons affected by the earliest stages of AD pathology and may improve identification of at-risk nondemented elderly, especially among diversely educated individuals.

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Patterns of motor impairement in normal aging, mild cognitive decline, and early Alzheimer's disease.

In order to determine the relationship between cognitive dysfunction and motor behavior in older adults, 41 cognitively normal elderly (NL), 25 cases exhibiting mild cognitive impairment (MI), and 25 patients with mild Alzheimer's disease (AD) were examined using a broad array to motor/psychomotor and cognitive tests. Relative to the NL group, MI individuals (at risk for future decline to AD) performed worse on tasks involving fine and complex motor function (e.g., tracking and manual dexterity). AD patients also exhibited motor dysfunction on tasks assessing relatively more rudimentary motor control. Motor tasks were able to distinguish NL vs MI and NL vs mild AD individuals as effectively as cognitive tests of memory and language. These results indicate that motor impairment is an important aspect of cognitive decline in older adults. Motor/psychomotor assessments may be comparably sensitive to traditional tests of cognitive function in identifying persons affected by the earliest stages of AD pathology.

Age Factors↗

Validity and reliability of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. The Alzheimer's Disease Cooperative Study.

This article reports the development and psychometric properties of the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC). At present, a number of unvalidated CGIC scales are used in clinical trials, with various methods for making ratings. The ADCS-CGIC was designed on the basis of a survey of ADCS clinicians and by adapting existing instruments. It includes an organized but unstructured format, with which a clinician can address clinically relevant change. The instrument's reliability and validity were assessed in a prospective trial of Alzheimer's disease (AD) and healthy subjects over a 12-month period. It showed good short-term reliability at 1 and 2 months, with 90 and 94% of AD subjects, respectively, rated as having changed not at all or only minimally. The ADCS-CGIC's face validity was demonstrated by untreated. AD subjects rated as having worsened over time at both 6 months (56% rated as having worsened) and 12 months (81% rated as having worsened), whereas only 2% of control subjects showed minimal worsening. As a measure of predictive validity, ADCS-CGIC ratings at 12 months were significantly associated with change on four severity scales. As with other measures, change ratings were sensitive to dementia severity. Moderately impaired subjects showed greater worsening than other subjects. ADCS-CGIC ratings of greater worsening were made after the informant interview, regardless of whether informants or subjects were interviewed first. The ADCS-CGIC is a valid and reliable instrument for use in clinical trials.

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Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease.

The total numbers of neurons with and without neurofibrillary changes in the hippocampal subdivisions were estimated in 16 subjects with Alzheimer disease (AD) and in 5 normal elderly controls. On the basis of clinical symptoms, AD patients were subdivided into relatively less (AD-1. Functional Assessment Staging [FAST] stages 7a to 7c) and more severely affected (AD-2, FAST stages 7e to 7f) patient groups. In the AD-1 group relative to controls, the total number of neurons was reduced only in CA1 and in the subiculum. In the AD-2 group, neuronal losses were found in all sectors of the cornu Ammonis and in the subiculum and ranged from 53% in CA3 to 86% in CA1. The dentate gyrus was the only hippocampal subdivision without significant neuronal loss. Within the combined AD patient groups, significant correlations were noted between both clinical stage and duration of AD and both the total number of neurons and the percentage of neurons with neurofibrillary changes in CA1, CA4, and the subiculum. Regression analyses predicted neuronal losses over the maximal observed duration of 22 years of 87% in CA1, 63% in CA4, and 77% in the subiculum. Our data suggest that over the course of AD, continuous neurofibrillary tangle formation and continuous neuronal loss occur in the hippocampal subdivisions. The rate of neuronal loss appears to be similar for CA1, CA4, and the subiculum.

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Utility of developmental reflexes in the differential diagnosis and prognosis of incontinence in Alzheimer's disease.

Four developmental reflexes, the tactile suck reflex, the palmar and plantar grasp reflexes, and the plantar extensor reflex, were examined in 784 individuals, including healthy elderly, cognitively and functionally mildly impaired individuals, and patients with Alzheimer's disease (AD) in all stages of clinical severity. The study population was classified into six categories of increasingly impaired functional performance, and prevalence of the four individual reflexes and of a summary reflex measure, consisting of a combination of these four reflexes, was determined for each category. Prevalence of all five reflex measures was more than six times higher for those categories that comprised only permanently doubly incontinent patients as compared to those categories that comprised only continent individuals (P < .001). Frequency of developmental reflexes rose sharply with the onset of progressive incontinence. Since the return of these reflexes in AD is associated with severe cortical dysfunction, it is concluded that these developmental reflexes are useful in differentiating incontinence of cortical origin from incontinence resulting from potentially reversible causes.

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Neuromotor changes in Alzheimer's disease: implications for patient care.

As a result of the neuropathologic process of Alzheimer's disease (AD), significant changes occur in neuromotor function (e.g., paratonia and compulsive grasping). These changes become manifest in the moderately severe stage of AD, when patients begin to require ongoing assistance with activities of daily life (ADL), and they are prominent in the severe stage of AD, when patients are continuously dependent on a caregiver. Patients in these stages often display behavioral disturbances during care activities. These disturbing behaviors result not only from cognitive impairment, but also from a patient's physical inability to cooperate with the caregiver. When care management strategies take into account the characteristic physical restrictions resulting from the neuromotor changes that accompany advanced AD, the caregiving process may be significantly facilitated.

Activities of Daily Living↗

Clinical global measures of dementia. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines.

Following is the report of the committee working on clinical global measures for antidementia drug guidelines. The concepts involved in global scales, the distinctions between change and severity scales, advantages and disadvantages of structured interviews, and anchoring of change scores are discussed, and selected existing clinical global scales are described. In addition, the committee assessed the utility of global scales in clinical trials for antidementia drugs. There was a consensus among the members of the working group on the following: (1) Clinical global scales are interview based; in most cases, they include information obtained from caregivers as well as directly from patients, but they can rely on information from the subject only. (2) Clinicians' global ratings are intended to assess clinically meaningful change based on multidimensional clinical assessment and take into account the clinical heterogeneity of dementia by assessing at least cognition, behavior, and functioning. (3) There are two distinct types of clinical global measures: (a) clinicians' interview-based global severity scales, which generally incorporate classification by stage or severity of illness and (b) clinicians' interview-based global change scales, which incorporate global assessment ratings of clinical change. The committee could not reach a consensus on whether global scales should be required in phase II and phase III clinical trials, or whether other specific assessments such as well-designed activities of daily living, cognition, and behavior measures could, when used in appropriate combinations, replace the global as assessments of clinical meaningfulness.

Activities of Daily Living↗

Informant-rated activities-of-daily-living (ADL) assessments: results of a study of 141 items in the U.S.A., Germany, Russia, and Greece from the International ADL Scale Development Project.

The analyses of an international pilot study presented in this article focused on the development of a cross-nationally valid activities-of-daily-living (ADL) scale sensitive to therapeutic effects in patients with mild memory impairment and mild to moderately severe dementia. The present report, which is part of an ongoing international research project, describes field testing results for 141 informant-rated items. The comparability of samples investigated in research centers in the U.S.A., Germany, Russia, and Greece concerning cognitive decline was evaluated globally as well as psychometrically using the Global Deterioration Scale, the Short Cognitive Performance Test, and the Mini-Mental State Examination. In the participating countries, a composite ADL score discriminated well between different stages of cognitive impairment because of dementia. However, international differences between the applied measures were observed. A practical ADL scale showing therapeutic sensitivity and international utility, will be constructed from the 141 informant-rated items under investigation in this pilot work.

Activities of Daily Living↗

Overview of methodologic issues for pharmacologic trials in mild, moderate, and severe Alzheimer's disease.

To address the issue of mild, moderate, and severe Alzheimer's disease (AD), it is necessary to initially establish some agreement on terminology. In recent decades, these terms have frequently been defined using screening instrument scores with measures such as the Mini-Mental State Examination (MMSE). There are many problems with this approach, perhaps the most salient of which is that it has contributed to the total and tragic neglect of patients with severe AD. An alternative approach to the classification of AD severity is staging. This approach has advanced to the point where moderately severe and severe AD can be described in detail. Procedures for describing this previously neglected latter portion of AD have recently been extensively validated. Staging is also uniquely useful at the other end of the severity spectrum, in differentiating early aging brain/behavior changes, incipient AD, and mild AD. Temporally, with staging procedures, it is possible to track the course of AD approximately three times more accurately than with the MMSE. The net result of the advances in AD delineation is that issues such as prophylaxis, modification of course, treatment of behavioral disturbances, loss of ambulation, progressive rigidity, and the development of contractures in AD patients can now be addressed in a scientifically meaningful way that will hopefully bestow much benefit in AD patients and those who care for them.

Activities of Daily Living↗

Reliability of the Modified Ordinal Scales of Psychological Development: a cognitive assessment battery for severe dementia.

Two reliability studies were performed on a recently developed cognitive assessment battery for severe dementia. The method, the Modified Ordinal Scales of Psychological Development (M-OSPD), is based on the Piagetian developmental model of sensorimotor functions. Procedures have been adapted from this test battery, which was originally applied to infants and small children, for the assessment of remaining cognitive capacity in severe dementia. Two independent interrater reliability studies were conducted. In these studies, two different raters simultaneously evaluated patients with severe dementia. One interrater reliability study was performed in a nursing home setting (Study 1), and the other reliability study consisted of a sample of community-residing patients (Study 2). The Global Deterioration Scale and the Mini-Mental State Examination were used to assess dementia severity. Study 1 (N = 22) resulted in an intraclass correlation coefficient (ICC) of .99 (p < .01) for the M-OSPD total score. Study 2 (N = 19) resulted in an ICC of .96 (p < .01) for the M-OSPD total score. The M-OSPD proved to be a reliable instrument in these studies. This cognitive assessment measure can provide meaningful information regarding the cognitive abilities of late-stage dementia patients. Until recently, these late-stage dementia patients had been considered untestable in studies that utilized conventional psychometric and mental status evaluation measures.

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