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S H Ferris

Publications and source records attributed to S H Ferris.

At least 19 recordsLinked to original sources

Prediction of longitudinal cognitive decline in normal elderly with subjective complaints using electrophysiological imaging.

An extensive literature reports changes in quantitative electroencephalogram (QEEG) with aging and a relationship between magnitude of changes and degree of clinical deterioration in progressive dementia. Longitudinal studies have demonstrated QEEG differences between mild cognitively impaired (MCI) elderly who go on to decline and those who do not. This study focuses on normal elderly with subjective cognitive complaints to assess the utility of QEEG in predicting future decline within 7 years. Forty-four normal elderly received extensive clinical, neurocognitive and QEEG examinations at baseline. All study subjects (N = 44) had only subjective complaints but no objective evidence of cognitive deficit (evaluated using the Global Deterioration Scale [GDS] score, GDS stage = 2) at baseline and were re-evaluated during 7-9 year follow-up. Baseline QEEGs of Decliners differed significantly (p < 0.0001, by MANOVA) from Non-Decliners, characterized by increases in theta power, slowing of mean frequency, and changes in covariance among regions, especially on the right hemisphere. Using logistic regression, an R2 of 0.93 (p < 0.001) was obtained between baseline QEEG features and probability of future decline, with an overall predictive accuracy of 90%. These data indicate high sensitivity and specificity for baseline QEEG as a differential predictor of future cognitive state in normal, subjectively impaired elderly.

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Switching previous therapies for Alzheimer's disease to galantamine.

Acetylcholinesterase inhibitors (AChEIs) are the most frequently prescribed drugs for the treatment of Alzheimer's disease (AD). To date, donepezil is prescribed most often, but newer AChEIs have become available. Rivastigmine entered the pharmaceutics market for AD in 2000, and galantamine was approved for use in the United States in February 2001. Some patients with AD may already be taking a cholinesterase inhibitor, but they or their caregivers may want to change therapies for various reasons, such as lack of efficacy or poor tolerability. Therefore, defined protocols for discontinuing one therapy and initiating another therapy (ie, "switching") while maintaining efficacy and minimizing cholinergic toxicity will be essential. A post-hoc analysis of a clinical trial that enrolled patients with and without previous exposure to AChEIs indicated that the efficacy and tolerability of a second and different cholinesterase treatment were similar in both subpopulations of patients. These findings suggest that discontinuation of prior AChEI treatment is not predictive of future poor response to an effective treatment.

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Addition of a frequency-weighted score to the Behavioral Pathology in Alzheimer's Disease Rating Scale: the BEHAVE-AD-FW: methodology and reliability.

The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) is a well-established instrument, designed to assess potentially remediable behavioral symptoms in Alzheimer's disease (AD) patients as well as to evaluate treatment outcome. It consists of 25 symptoms grouped into seven categories. Each symptom is scored on the basis of severity on a four-point scale. A knowledgeable caregiver is queried and items are scored on the basis of symptoms noted in the preceding two weeks. Reliability, construct validity and criterion validity data for the BEHAVE-AD have previously been published. Because of the significance of psychopathology in dementia, it is necessary to optimally describe and define the nature, magnitude and prevalence of behavioral symptomatology. Accordingly, a frequency component was added to each of the 25 items of the BEHAVE-AD scale. The objective of the present report is to describe this new Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW) and to establish its inter-rater reliability. In this investigation the BEHAVE-AD-FW scale was administered to caregivers of 28 patients with either mildly impaired cognitive function or a dementia diagnosis. Two clinicians separately and independently rated the responses. Analyses determined that the intraclass correlation coefficients (ICCs) for the frequency component varied between 0.86 and 0.97 for each of the seven BEHAVE-AD categories (p(s) < 0.001). ICCs for the frequency-weighted scores (item severity score x item frequency score) ranged from 0.69 to 0.98 for the seven symptom categories (p(s) < 0.001). For the BEHAVE-AD-FW total scores, the ICC was 0.91 (P < 0.001). These results indicate that the frequency-weighted component is a reliable addition to the BEHAVE-AD scale.

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Neuropsychological prediction of decline to dementia in nondemented elderly.

This study examined whether baseline neuropsychological performance in elderly assessed at a research clinic could accurately predict subsequent decline to dementia. Logistic regression analyses were applied to (1) 213 nondemented elderly with a Global Deterioration Scale (GDS) score of 1, 2, or 3, of whom 74 (35%) subsequently declined to any diagnosis of dementia, and (2) a diagnostically more restricted subset of this sample (N = 179), of whom 56 (31%) declined to a diagnosis of probable Alzheimer's disease (AD). The mean follow-up intervals were 3.8 and 3.7 years, respectively. A small set of baseline neuropsychological measures (especially a Paragraph Delayed Recall Test) significantly differentiated decliners from nondecliners to dementia or AD, after accounting for the contribution of age, sex, education, follow-up interval, and the rating of global clinical status. When examined in combination with the other factors or alone, the cognitive tests produced reasonably high specificities (91%-97%) and sensitivities (73%-89%). Using the obtained regression model, a similar level of classification accuracy was replicated on an independent sample of 119 nondemented elderly. A subanalysis of the high-risk GDS 3 subgroup indicated that cut scores from the paragraph test distinguished nondecliners from decliners (overall accuracies 87%-91%), implying that this assessment may accurately predict future cognitive status in elderly with mild cognitive impairment.

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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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Assessing patterns of agitation in Alzheimer's disease patients with the Cohen-Mansfield Agitation Inventory. The Alzheimer's Disease Cooperative Study.

As part of the effort of the NIA Alzheimer's disease cooperative study to develop improved instruments for quantifying effects in Alzheimer's disease (AD) clinical trials, patterns of agitated behaviors were evaluated with the Cohen-Mansfield Agitation Inventory (CMAI) in 241 AD patients and 64 healthy elderly controls with valid baseline assessment on the CMAI. The test-retest reliability of the CMAI over 1 month was good (r = 0.74 to 0.92). Physically and verbally nonaggressive behaviors were most often reported, whereas physically aggressive behaviors were rare. Frequency of agitated behaviors increased with dementia severity, especially for patients with a Mini-Mental Status Exam score of 0-4. Agitation tended to increase in the evening with dementia severity for the more impaired patients. Amount of agitation did increase after 12 months in all but controls and mildly demented patients. The CMAI shows promise for evaluating a unique aspect of behavior and may be useful in assessing the effects of cognitive enhancers and other types of psychotropic drugs on behavior in dementia patients.

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A multicenter evaluation of new treatment efficacy instruments for Alzheimer's disease clinical trials: overview and general results. The Alzheimer's Disease Cooperative Study.

Evaluating treatment efficacy in Alzheimer's disease (AD) clinical trials requires optimal assessment methods to determine the extent and clinical meaningfulness of potential therapeutic effects of pharmacologic agents. Development of improved outcome measures for AD clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS Instrument Development Project evaluated the sensitivity, reliability and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. A total of 306 English-speaking subjects were enrolled in the study, including AD patients stratified by disease severity and cognitively normal, age-matched elderly subjects. Half were retested at 1 month and 2 months after baseline, and all received 6- and 12-month follow-up assessments. Spanish versions of these new measures are currently being evaluated. The development of this multisite study, the common methods and procedures, and a detailed description of the cohort are provided in this overview article. This multisite project demonstrates the feasibility of a consortium approach to instrument development. We were able to develop new instruments and efficiently evaluate their reliability and sensitivity to longitudinal change by capitalizing on the experience and patient resources of the participating ADCS research sites.

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Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. The Alzheimer's Disease Cooperative Study.

The cognitive assessment protocol of the Alzheimer's Disease Cooperative Study (ADCS) was designed to evaluate the reliability and validity of cognitive assessment measures that might be valuable additions to the Alzheimer's Disease Assessment Scale (ADAS) or other concise batteries used in antidementia drug trials. As part of an overall ADCS protocol to develop new instruments to be used in trials of treatments for Alzheimer's disease (AD), patients with mild to moderate AD and cognitively normal elderly were administered a battery of five tests at least three times over 1 year. The tests included word list learning with delayed free recall, a recognition memory test for faces, a series of letter and digit cancellation tests to measure concentration, tests of praxis, and a series of maze completion tasks designed to assess planning and executive function. A version of the digit cancellation task was reliable and sensitive to a broad range of dementia severity so that it could provide a useful addition to the present version of the ADAS. Performance on the word learning task with delayed recall and a subset of the mazes task were impaired even in mild AD, so these tasks may be useful in trials involving mild or at-risk subjects. Performances on the facial recognition task and on the praxis tasks were not related to dementia severity, so these tasks would not be useful to evaluate treatments. Therefore, the major outcome of this investigation was the identification of some potential additions to the present ADAS that extend both the cognitive domains and the range of symptom severity covered.

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The severe impairment battery: concurrent validity and the assessment of longitudinal change in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Measurement of cognitive dysfunction in the early stages of Alzheimer's disease (AD) has been well studied and there are many objective tests in use for this purpose. However, with the exception of clinical rating scales, such as the Clinical Dementia Rating Scale, Global Deterioration Scale, and Functional Assessment Staging, there are few objective measures of cognition in the more advanced stages of AD. Given a renewed interest in potential AD therapies, objective measures of mental functioning are needed to adequately assess change in more advanced AD patients. As part of an effort by the NIA-Alzheimer's Disease Cooperative Study to evaluate new measures of efficacy for their utility in treatment studies, the Severe Impairment Battery (SIB) was examined in a 1-year evaluation of change across a wide range of AD severity. The data suggest that the SIB is a reliable and valid measure of progression, particularly in persons with moderate to severe AD. The SIB may therefore be a useful outcome measure in clinical trials that include patients with more advanced stages of AD.

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The Spanish Instrument Protocol: design and implementation of a study to evaluate treatment efficacy Instruments for Spanish-speaking patients with Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Development of improved outcome measures for Alzheimer's disease (AD) clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS is committed to recruiting and following minority patients in clinical trials. At present, a serious impediment to recruiting non-English-speaking minorities is the lack of instruments with adequate translation. Because Spanish is the second most commonly spoken language in the United States and because persons of Hispanic origin represent approximately 10% of the population, we conducted an instrument development protocol for Spanish-speaking patients. Evaluating treatment efficacy in Spanish-speaking AD patients requires the development of assessments that are comparable to those used for English-speaking participants in clinical trials. The ADCS Instrument Development Project evaluated the sensitivity, reliability, and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. These new treatment efficacy instruments were translated for Spanish speakers and a Spanish Instrument Study was conducted in parallel with the English version of the study. This report describes instrument translation, entry criteria, and recruitment procedures. In addition, the demographic and clinical characteristics of the cohort at baseline are presented and compared to the English-speaking cohort. Implications for the development of comparably sensitive Spanish language instruments are discussed.

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Multicenter evaluation of new instruments for Alzheimer's disease clinical trials: summary of results. The Alzheimer's Disease Cooperative Study.

The Instrument Development Project of the Alzheimer's Disease Cooperative Study (ADCS) evaluated new assessments in five domains: (a) cognitive function; (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms, and (e) cognition in severely impaired patients. These new instruments demonstrate excellent discrimination between normal controls and patient groups and show adequate validity and reliability. Stability of measurement and sensitivity to longitudinal change were also demonstrated in each of these areas. Examination of several domain-specific questions also contributed new information on the measurement of cognitive function with different subtasks across AD severity levels, the stability of clinical ratings of global change, and the applicability of behavioral assessment across severity levels. The success of this project enhances the state of the art in the measurement of efficacy in AD clinical trials and also provides a basis for future research on improving AD outcome measures.

Activities of Daily Living↗

Behavioral outcomes in clinical trials for Alzheimer disease.

The use of behavioral scales is an important component in determining efficacy of new drugs in clinical trials for Alzheimer disease (AD). Behavioral assessment in clinical trials must be sensitive to disease heterogeneity, disease progression, and drug modification of behavior. Three such scales, the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Behavior Rating Scale for Dementia (C-BRSD), and the Cohen-Mansfield Agitation Inventory (CMAI), are useful in clinical trials. The BEHAVE-AD reliably assesses the severity of a range of AD symptoms (7 areas with 25 items) and rates behavioral impact on caregivers. The C-BRSD enables reliable assessment of the frequency of behaviors (8 areas with 48 items) in AD and monitors relevant behaviors throughout the course of the disease. However, it does not assess the impact of behaviors on caregivers. The CMAI focuses on assessment of agitation and aggression and is compatible with C-BRSD but does not assess the impact of agitation on caregivers. A recent trial evaluated the C-BRSD and the CMAI in more than 300 AD and normal elderly individuals. Both of these scales discriminated between AD and non-AD patients, were sensitive across disease severity, and could track behavioral changes over 12 months of AD progression. The BEHAVE-AD, C-BRSD, and CMAI scales are valid, reliable, rapid to administer, cover relevant behaviors occurring during the course of the disease, and are appropriate for use in AD clinical trials.

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Measurement choices in multi-site studies of outcomes in dementia.

This paper summarizes the measurement choices made by selected current or recently completed multi-site projects with a common emphasis on measuring outcomes in dementia. Information on number of items and scoring, reason(s) for selecting the measure, and reliability and validity of the measure (either citations providing this information or a report of pertinent unpublished findings) is presented for eight domains: cognition, behavioral symptoms, physical health status, physical functioning and self-care abilities, quality of life, family/staff caregiver outcomes, service use, and cost. We found considerable reliance on the published literature as a guide to measurement choice, motivated largely by measures' superior psychometric properties, their ubiquity in the literature, and/or their brevity or ease of use. There is still evidence of "starting from scratch" in some domains, however. To the extent that these projects reflect the state of the art in dementia-relevant outcomes research, we conclude that comparison of outcomes across studies will continue to be problematic. However, as long as dissemination of methodological as well as substantive findings continues to characterize outcome studies in dementia, there is hope that a more congruent view of how to assess key outcomes in dementia will emerge.

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Assessing cognition in Alzheimer disease research.

Because cognitive impairment is the central, defining symptom of Alzheimer disease, cognitive assessments commonly are used as primary or secondary measures of outcome in Alzheimer disease research. The authors review the cognitive functions that decline in this neurodegenerative disease and summarize the necessary features of appropriate cognitive performance tests. The characteristics, strengths, and weaknesses of the major cognitive batteries employed as outcome measures in Alzheimer disease research are reviewed. Finally, the recent contributions to the development of cognitive measures by the Alzheimer's Disease Cooperative Study are presented briefly, followed by discussion of some critical issues for future test development.

Alzheimer Disease↗