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R Doody

Publications and source records attributed to R Doody.

16 recordsLinked to original sources
PubMed2005

Changing patient characteristics and survival experience in an Alzheimer's center patient cohort.

BACKGROUND: Large and diverse dementia patient cohorts can further a variety of research programs aimed at improving diagnosis, treatment, and meaningful survival in AD. METHOD: We recruited 1,502 dementia patients between 1989 and 2002, subclassified using standardized criteria and laboratory procedures, and treated according to established guidelines. Baseline clinical and psychometric measures were repeated annually, in person or by use of a multi-modal telephone follow-up program that included many of the measures obtained at in-person visits. We tracked vital status of all subjects at 6-month intervals and offered autopsies to all participants. We assessed for cohort effects in baseline characteristics by 2-year intervals, examined the characteristics and outcomes for those who remained active compared to those who were eventually lost to follow-up, examined survival times for demographic or diagnostic subgroups, and assessed the accuracy of clinical diagnoses versus neuropathology. RESULTS: The average age at entry, average educational level, and baseline MMSE scores for subjects are increasing over time, and probable AD diagnoses are also increasing. Most (80.6%) subjects have remained active in our Center; those who did not were more likely to have a non-AD diagnosis. Survival averages 5.2 years (CI 4.98--5.37) and is influenced by age and gender, but not by diagnosis of probable versus possible AD. Our diagnostic accuracy is 89.6%, with high sensitivity to the presence of AD (96%). CONCLUSIONS: In a large and representative clinical cohort, the demographics of AD are changing over time. Careful analyses of those who continue and those who drop out from follow-up suggest that atypical diagnosis, rather than severity or demographic issues accounts for most of the attrition. Clinicians are likely to encounter increasingly older patients with milder disease, and these trends have implications for the design of clinical trials. Survival from the onset of first symptoms, similar for probable and possible AD cases, may be increasing over time.

Aged↗
PubMed2004

Specific functional effects of memantine treatment in patients with moderate to severe Alzheimer's disease.

Treatment of Alzheimer's disease (AD) that combats progressive functional deterioration can improve the patient's quality of life and reduce caregiver burden. Memantine, a moderate affinity N-methyl-D-aspartate receptor antagonist, reduces global deterioration in AD patients and provides cognitive and functional benefits relative to placebo. Two previous studies reported statistically significant benefits of memantine for overall functional ability on the Alzheimer Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADL(19)), Functional Assessment Staging, and G2 scale. The present study reports a single-item analysis of the ADL scales from the two trials and shows that patients treated with memantine demonstrated a numerical advantage over placebo on all items assessed. These results help to translate the positive effects of memantine into specific aspects of functional ability, information that is relevant to AD patients and their families as well as to researchers interested in the assessment of functional ability in AD clinical trials.

Activities of Daily Living↗
PubMed2003

Donepezil in vascular dementia: a randomized, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and tolerability of donepezil in patients with vascular dementia (VaD). METHODS: Patients (n = 616; mean age, 75.0 years) with probable or possible VaD, according to National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche en l'Enseignement en Neurosciences criteria, were randomized to receive donepezil 5 mg/day (n = 208), donepezil 10 mg/day (after 5 mg/day for the first 28 days) (n = 215), or placebo (n = 193) for 24 weeks. RESULTS: Seventy-six percent of the patients enrolled had probable VaD. A total of 75.3% of the 10 mg donepezil group and 80.8% of the 5 mg group completed the study compared with 83.4% of the placebo group. Both donepezil-treated groups showed improvements in cognitive function on the Alzheimer's Disease Assessment Scale-cognitive subscale compared with placebo, with a mean endpoint treatment difference, as measured by the change from baseline score, of approximately 2 points (donepezil 5 mg, -1.65 [p = 0.003]; 10 mg, -2.09 [p = 0.0002]). Greater improvements on the Clinician's Interview-Based Impression of Change-plus version were observed with both donepezil groups than with the placebo group (overall donepezil treatment vs placebo p = 0.008); 25% of the placebo group showed improvement compared with 39% (p = 0.004) of the 5 mg group and 32% (p = 0.047) of the 10 mg group. Withdrawal rates due to adverse events were low (placebo, 8.8%; donepezil 5 mg, 10.1%; 10 mg, 16.3%). CONCLUSIONS: Donepezil-treated patients demonstrated significant improvements in cognition and global function compared with placebo-treated patients, and donepezil was well tolerated.

Adult↗
PubMed2002

A videotaped CIBIC for dementia patients: validity and reliability in a simulated clinical trial.

BACKGROUND: The global impression of a clinician is an Food and Drug Administration--mandated primary outcome measure for clinical trials in dementia. Reliability and validity of these measures are not well established. METHODS: A videotaped version of the Clinician's Interview Based Impression of Change (CIBIC) was evaluated. Raters were informed that the videotaped interviews were taken at baseline and 6 to 12 months later, when in fact half of the interviews were shown in reverse order. Ratings on "true order" interviews were compared with ratings on "reverse order" interviews. In addition, ratings by neurologists experienced in dementia were compared with those of less experienced raters. RESULTS: Inter-rater reliability of the neurologists was poor when measured by absolute agreement on a 7-point scale (kappa = 0.18). With a less stringent 3-point scale (better, worse, or unchanged), inter-rater reliability was significantly better for the true order videos (kappa = 0.51) than for the reversed order videos (kappa = 0.12). Validity also was reduced in the reverse order group: neurologists rated 90% of subjects correctly in the "true order" group and 63% correctly in the "reversed order" group. The inter-rater reliability of the neurologists was greater than the less experienced raters, but the validity of the neurologists' ratings was only marginally better. CONCLUSIONS: The reliability and validity of the videotape CIBIC are reasonable when patients follow the expected course of gradual decline, but are poor when patients appear to improve. These findings suggest that global assessments should be modified as outcome measures in clinical trials with patients with dementia.

Aged↗
PubMed2001

Current concepts in mild cognitive impairment.

The field of aging and dementia is focusing on the characterization of the earliest stages of cognitive impairment. Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.

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PubMed2000

Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study.

CONTEXT: Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women. OBJECTIVE: To determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD. DESIGN: The Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999. SETTING: Thirty-two study sites in the United States. PARTICIPANTS: A total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy. INTERVENTIONS: Participants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial. MAIN OUTCOME MEASURES: The primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up. RESULTS: The CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01). CONCLUSIONS: Estrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.

Aged↗
PubMed1997

The relationship between extrapyramidal signs and cognitive performance in patients with Alzheimer's disease enrolled in the CERAD Study. Consortium to Establish a Registry for Alzheimer's Disease.

The objective of this study was to determine the relationship between the presence of extrapyramidal signs and the severity of cognitive and functional impairment in patients with Alzheimer's disease (AD). Eleven university medical centers in the United States and France participated in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) study of extrapyramidal signs in AD. Forty-seven patients with probable AD who had extrapyramidal signs were matched by sex, race, education, and age with 132 probable AD patients without extrapyramidal signs. The main outcome measures were the Clinical Dementia Rating, Blessed Dementia Scale, and the CERAD Neuropsychology Battery (verbal fluency, naming, Mini-Mental State Examination, word list learning, word list recall, savings ratio, word list recognition, and constructional praxis). AD patients with extrapyramidal signs performed more poorly than AD patients without parkinsonism on various neuropsychological tests, even after controlling for the Clinical Dementia Rating and reported duration of cognitive impairment. The severity of the extrapyramidal manifestations was related to the degree of cognitive and functional impairment. Muscular rigidity and bradykinesia were the most frequent extrapyramidal signs associated with AD. Patients with AD associated with extrapyramidal signs have greater cognitive and functional impairment than AD patients without clinical evidence of parkinsonism.

Aged↗
PubMed1997

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↗
PubMed1995

SPECT findings on psychosis in Alzheimer's disease.

OBJECTIVE: This study examined whether psychosis in Alzheimer's disease is associated with cerebral perfusion patterns appreciable by single photon emission computed tomography (SPECT) scans. METHOD: All cooperative outpatients enrolled in an Alzheimer's disease research center with the diagnosis of probable Alzheimer's disease and a Clinical Dementia Rating of mild or moderate were interviewed with their primary caregivers. Current and past psychiatric functioning was assessed by using the Hamilton Depression Rating Scale, the Structured Clinical Interview for DSM-III-R, and the Behavioral Pathology in Alzheimer's Disease Rating Scale. Patients without premorbid psychosis received SPECT scans, and the scans of the patients with delusions or hallucinations (N = 30) were compared to the scans of patients without these symptoms (N = 16). RESULTS: The patients with delusions (N = 29) had hypoperfusion of the left frontal lobe in relation to the right frontal lobe. The patients with hallucinations (N = 10) had hypoperfusion in the parietal lobe. CONCLUSIONS: Psychotic patients with Alzheimer's disease had a pattern of cerebral blood flow deficits significantly different from that of nonpsychotic patients. This suggests that patterns of cerebral dysfunction may be expressed symptomatically as psychosis.

Alzheimer Disease↗
PubMed1995

Clinical variables associated with psychosis in Alzheimer's disease.

OBJECTIVE: The authors explored whether personal or family history of major mental illness, negative symptoms, or behavioral measures are associated with positive psychotic symptoms in Alzheimer's disease. METHOD: Fifty-seven patients with Alzheimer's disease were studied prospectively during interviews with the patients and their primary caregivers. RESULTS: Psychotic patients with Alzheimer's disease did not differ in cognitive functioning from nonpsychotic patients with Alzheimer's disease. No association was found between personal or family history of mental illness and psychosis. Asociality was the only negative symptom associated with psychosis. Psychotic patients had more behavioral disturbances. CONCLUSIONS: Positive psychotic symptoms in Alzheimer's disease are not associated with certain aspects of cerebral functioning but are associated with behavioral disturbances.

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PubMed1989

Mental status assessment of insight and judgment.

Although a traditional part of the mental status examination, assessment of insight and judgment has received scant attention from researchers and clinicians. This is unfortunate, because few abilities are more crucial to decisions about whether a patient can continue to live independently or what level of supervision is needed. The authors discuss current and evolving methods for the assessment of insight and judgment, and also address neuroanatomic substrates and theoretical conceptions of these functions.

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