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M Grundman

Publications and source records attributed to M Grundman.

35 records · Page 2Linked to original sources
PubMed1997

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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PubMed1997

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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PubMed1997

An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

We developed a set of informant-based items describing performance of activities of daily living (ADL) by patients with Alzheimer's disease (AD) to identify which ADL are useful for assessment of patients in clinical trials. Evaluation of ADL is an important outcome measure in AD clinical trials. For clinical trial measurement, ADL should have broad applicability, good test-retest reliability, scaling to cover a range of performance, and sensitivity to detect change in disease progression. A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer's Disease Cooperative Study Instrument protocol. Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months. Controls performed virtually all ADL items optimally at baseline and at 12 months. Among subjects with AD, 27 of the 45 ADL were widely applicable, i.e., performed at baseline or premorbidly by > 90% of subjects; showed good test-retest reliability between baseline and 1 and 2 months; correlated with MMSE scores of AD patients cross-sectionally; and showed a decline in performance from baseline to 12 months in at least 20% of AD patients. ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE. The remaining 18 ADL included several that may be useful for trials that target specific populations, e.g., women with AD. Because change on specific items depends on baseline MMSE, ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial.

Activities of Daily Living↗
PubMed1997

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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PubMed1996

Rationale and design of a multicenter study of selegiline and alpha-tocopherol in the treatment of Alzheimer disease using novel clinical outcomes. Alzheimer's Disease Cooperative Study.

This report describes the rationale and design of a clinical trial using selegiline (10 mg/day) and alpha-tocopherol (2,000 IU/day) to slow the progression of dementia in Alzheimer disease (AD). This study was developed by the Alzheimer's Disease Cooperative Study (ADCS), a consortium of clinical research centers actively involved in AD research. The major goal of the consortium is to design and conduct clinical investigations leading to the development of treatments for AD. This study uses a randomized double-blind, placebo-controlled, 2 x 2 factorial, parallel group design to test two drugs for the treatment of AD. The primary outcome of the study is the time to reach any one of the following four endpoints: death, institutionalization, loss of two of three basic activities of daily living, and progression of Clinical Dementia Rating (CDR) stage from 2 to 3. Patients with moderately severe disease (CDR = 2) were enrolled and evaluated 10 times over a period of 2 years to determine if these agents reduce the time to reach any endpoint. A database from the Consortium to Establish a Registry for Alzheimer's Disease indicated adequate power analyses to observe a treatment effect on this clinically meaningful outcome measure. Recruitment and baseline characteristics of the population are provided. The rationale for the choice of a factorial design, the use of a novel, clinically meaningful endpoint, and the selection of a cohort of patients with AD of moderate severity are discussed.

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PubMed1996

The open ring. A new imaging sign in demyelinating disease.

Because demyelinating disease of the brain occasionally presents with large ring-enhancing lesions on computed tomography (CT) scans and magnetic resonance images (MRIs), the authors sought to determine whether the ring pattern differed from that found in other common brain lesions with ring enhancement. Published MRI and CT scans of patients with adrenoleukodystrophy (23), and multiple sclerosis or similar demyelinating disorders (21), as well as a variety of tumors (44) and infections (44) matched to the demyelinating lesions by year of publication, in which ring enhancement was evident, were photographed. Photographs without diagnostic identification were presented randomly to two independent observers. The observers rated the contrast enhancement pattern as (1) open ring, with enhancement in the border of the lesion abutting the white matter; (2) closed ring; or (3) uncertain. For all diagnostically certain cases (n = 112), inter-rater agreement was excellent (kappa = 0.75). As an average of the two reviewers, scans for 11 of 132 cases were read as uncertain; 89% of adrenoleukodystrophy cases, 41% of the multiple sclerosis cases, 3% of tumors, and 9% of infections were classified as having the open-ring pattern. Overall, 66% of demyelinating lesions had an open-ring pattern compared with 7% of the non-demyelinating lesions (chi2 = 41.2, p < 0.0001). An open-ring pattern of enhancement is more likely to be associated with demyelinating lesions than with nondemyelinating lesions.

Adrenoleukodystrophy↗
PubMed1996

Low body weight in Alzheimer's disease is associated with mesial temporal cortex atrophy.

There are reports of weight loss and low body mass index (BMI) in patients with AD. The mesial temporal cortex (MTC) is involved in feeding behavior and memory and is preferentially involved in AD. We studied 74 subjects, including 58 AD patients and 16 control subjects, to determine whether BMI is associated with atrophy of the MTC or other brain regions. We used MRI morphometric analysis to provide measures of regional brain atrophy. AD patients had significant brain atrophy in all measured brain regions, except the white matter, compared with normal control subjects. The MTC was the only brain region significantly associated with BMI in AD patients (r = 0.39, p = 0.003). Multiple-regression analysis indicated that addition of brain regions other than the MTC to the model did not significantly add to the prediction of BMI. We conclude that low BMI correlates best and specifically with MTC atrophy. This finding supports a connection between limbic system damage and low body weight in AD.

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PubMed1996

Pilot Study of Didanosine in Patients with HIV Dementia.

In a pilot open-labeled study 10 subjects with AIDS dementia complex (ADC) were treated with didanosine. Only half of the subjects were able to complete the trial as a result of side effects. Five subjects exhibited improved performance on neuropsychological testing, but the mean change in performance in this small group was not statistically significant. The study suggests that this drug may have some value in ADC patients unable to tolerate other therapies, but that further study is needed to establish this firmly.

AIDS Dementia Complex↗
PubMed1995

Cerebral infarction in Alzheimer's disease is associated with severe amyloid angiopathy and hypertension.

OBJECTIVE: To determine if severe cerebral amyloid angiopathy (AA) in patients with Alzheimer's disease (AD) is associated with an increased prevalence of cerebral infarction diagnosed at autopsy. Amyloid angiopathy is increasingly recognized as a cause of ischemic infarcts, as well as cerebral hemorrhages. However, the relationship of AA to cerebral infarction in patients with AD is uncertain. DESIGN: Retrospective clinicopathological study of autopsy-confirmed cases of AD. PATIENTS: One hundred forty-five deceased patients with AD confirmed at autopsy. MAIN OUTCOME MEASURES: Semiquantitative scores of AA severity were done in four brain regions: midfrontal, inferior parietal, superior temporal, and hippocampal. The finding of cerebral infarction at autopsy was modeled as a function of AA severity, hypertension, age at death, AD severity, and sex in chi 2 and multiple logistic regression analyses. RESULTS: Severe AA was significantly associated with cerebral infarction at autopsy in patients with AD (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.4 to 8.9). None of the other independent variables in the multiple logistic regression analysis were significant predictors. While hypertension was equally common in the severe and mild AA subgroups, the combination of both severe AA and hypertension interacted to increase the risk of infarction (OR, 14.2; 95% CI, 3.2 to 63.4) beyond that observed with hypertension (OR, 1.1; 95% CI, 0.4 to 3.2) or severe AA (OR, 1.3; 95% CI, 0.3 to 5.3) alone. CONCLUSIONS: Severe AA is associated with an increased frequency of cerebral infarction in patients with AD. This appears to be largely due to an interaction between severe AA and hypertension that may produce multiplicative injuries on the vasculature. Further study with regard as to how AA may cause ischemia and its role in the neuropathologic and clinical progression of AD is needed.

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PubMed1994

Early single-photon emission computed tomography in mild head trauma. A controlled study.

Although computed tomography (CT) and magnetic resonance imaging scans often appear normal after mild head trauma, many patients experience attentional or other cognitive disturbances that are difficult to quantify by neuropsychological testing in the absence of a premorbid profile. Within 2 days of mild head trauma, 14 patients with normal-appearing brain CTs were studied with single-photon emission computed tomography (SPECT). They were compared to 15 normal control subjects and to 12 patients with mild human immunodeficiency virus (HIV) encephalopathy. Ten of 14 head trauma patients were separated from the normal control subjects by both independent readers, blinded to the clinical diagnosis. None of the SPECT results from normal control subjects were "read" as trauma. Trauma could not be differentiated from HIV encephalopathy. The observed percentage agreement between raters was 0.83 (kappa = 0.72). SPECT is more sensitive than CT in detecting brain injury after mild head trauma.

AIDS Dementia Complex↗
PubMed1991

Extrapyramidal symptoms due to dopamine-blocking agents in patients with AIDS encephalopathy.

OBJECTIVE: The authors attempted to determine whether patients with AIDS are more susceptible to neuroleptic side effects than other patients. METHOD: Retrospective chart review was used to assess the frequency and severity of extrapyramidal symptoms in patients with AIDS and psychotic patients without AIDS who had taken dopamine-blocking agents. The charts of 804 men younger than 50 years were reviewed, and patients were excluded if they had not taken dopamine blockers, had taken them for more than 1 month, had received concomitant antiparkinsonian agents, had focal brain lesions or histories of Parkinson's disease or meningitis, had used cocaine, amphetamines, or opiates within 1 month of admission, or, among the comparison group, had HIV risk factors. For the remaining 31 AIDS and 32 comparison patients, age, duration of dopamine blocker treatment, dose in chlorpromazine equivalents, and nature and severity of parkinsonian complications were recorded. RESULTS: The mean drug dose and body weight were significantly lower in the AIDS group. The likelihood of developing extrapyramidal symptoms was 2.4 times as high among the AIDS patients as among the comparison group. Such symptoms were developed by 50% of the AIDS patients who received less than 4 mg/kg of chlorpromazine equivalents per day and 78% of those who received more than 4 mg/kg per day. CONCLUSIONS: These preliminary results suggest that AIDS patients are more susceptible to extrapyramidal symptoms than psychotic patients without AIDS and that neuroleptics should be used cautiously and in lower doses for patients with AIDS.

AIDS Dementia Complex↗
PubMed1991

Single-photon emission computed tomography in human immunodeficiency virus encephalopathy: a preliminary report.

Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy.

AIDS Dementia Complex↗
PubMed1988

Dementia: characteristics of a referral population and factors associated with progression.

We evaluated in a standard fashion 375 patients presenting with complaints of memory loss. Etiology of memory loss included senile dementia of the Alzheimer type (SDAT)-70%, vascular dementia-5%, mixed dementia (SDAT + vascular)-9%, and other etiologies-16%. Incontinence, transient symptoms, and gait disturbances occurred more frequently in vascular dementia than in SDAT. A history of cardiovascular disease and stroke was more common in vascular dementia than SDAT. Disturbances of gait, bradykinesia, and pyramidal tract findings were commonly seen in vascular dementia. Advanced technology aided diagnosis in only 6% of patients and CT was the most useful of such tests. An earlier age of onset was noted in those with a positive family history of SDAT. Duration of symptoms at presentation for SDAT patients varied inversely with the rate of progression of dementia 15 to 55 months later, suggesting that individuals who progress more slowly require more time to elapse before the family or patient realizes the need for medical attention.

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PubMed1986

Alzheimer's disease: a correlational analysis of the Blessed Information-Memory-Concentration Test and the Mini-Mental State Exam.

We carried out a correlational analysis of the scores on the Blessed Information-Memory-Concentration Test and the Mini-Mental State Exam in 40 subjects with Alzheimer's disease. The average product moment correlation coefficient between the two tests on repeated administration over 6 weeks ranged from -0.73 to -0.83. Both tests demonstrated test-retest reliability coefficients of 0.75 and above. A formula was developed to convert one test score to the other.

Adult↗
PubMed1982

Testosterone affects food intake and body weight of weanling male rats.

The effects of testosterone propionate (TP) on food intake and body weight were investigated using castrated prepubertal male rats. Regardless of dose (1 mg, 0.2 mg or 0.1 mg), daily injections of TP increased body weight gain and food intake during the prepubertal period (from 22 to 40 days to age). Considering previous results, the present observations suggest that in the male rat sensitivity to the effects of gonadal hormones on feeding develops earlier than in females.

Animals↗