Search PubMed⌕ Search

Biomedical subjects

Myron F Weiner

Publications and source records attributed to Myron F Weiner.

13 recordsLinked to original sources
PubMed2003

Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease.

BACKGROUND: The statin treatment of dyslipidemia is associated with a reduced risk of development of Alzheimer disease (AD). The effect may be mediated by a reduction in cholesterol biosynthesis in the brain, by lowering levels of apolipoprotein E (apo E)-containing lipoproteins, or by pleitropic effects such as reduction in beta-amyloid production. In the brain, cholesterol from damaged or dying neurons is converted to 24S-hydroxycholesterol by cholesterol 24-hydroxylase (CYP46). The oxysterol is subsequently transferred across the blood-brain barrier, transported to the liver by low-density lipoproteins (LDLs), and excreted as bile acids. Most of plasma 24S-hydroxycholesterol is derived from brain cholesterol; consequently, plasma levels of the oxysterol reflect brain cholesterol catabolism. OBJECTIVE: To examine the effect of 3 statins and a nonstatin hypolipidemic agent on plasma levels of 24S-hydroxycholesterol and apo E in patients with AD. STUDY DESIGN: The study had a sequential parallel design. It was open-labeled and involved lipoprotein and 24S-hydroxycholesterol evaluations at baseline and at 6 weeks of treatment with 40 mg of lovastatin, simvastatin, or pravastatin sodium per day, or 1 g of extended-release niacin per day. Blood samples were drawn after a 12-hour fast for measurement of plasma sterols, oxysterols, lipoprotein cholesterol, and levels of apo E, plasma transaminases, and glucose. Measurements were made at baseline and during treatment. RESULTS: Statin treatment reduced levels of plasma lathosterol by 49.5%, 24S-hydroxycholesterol by 21.4%, LDL cholesterol by 34.9%, and total cholesterol by 25%. The ratios of lathosterol-campesterol and 24S-hydroxycholesterol-LDL cholesterol were reduced significantly, but the ratio of 24S-hydroxycholesterol-total cholesterol was unchanged. Extended-release niacin also significantly reduced levels of 24S-hydroxycholesterol by 10% and LDL cholesterol by 18.1%. None of the agents lowered plasma concentration of apo E. CONCLUSIONS: Statins lowered levels of plasma 24S-hydroxycholesterol without affecting levels of apo E. The LDL lowering was more pronounced than 24S-hydroxycholesterol reductions. The effect of statins on LDL partially explains the reduction of plasma oxysterol level.

Aged↗
PubMed2003

Comorbidity of psychopathological domains in community-dwelling persons with Alzheimer's disease.

In this post hoc analysis of baseline responses to the CERAD Behavior Rating Scale for Dementia in a clinical trial of interventions for agitation in Alzheimer's disease (AD), the authors investigated the distribution of, and relationships between, agitation, depression, and psychosis in 148 individuals with AD. Prevalence of depressive symptoms was highest (78.4%), followed by agitation (77.6%) and psychotic symptoms (69.3%); 51.1% of the sample had symptoms in all 3 domains. Cross-sectionally, psychotic symptoms were most closely associated with Mini-Mental State Examination (MMSE) scores, while agitation was less so. Depressive symptoms were relatively consistently prevalent across MMSE levels. After controlling for the presence of agitated symptoms, psychosis and depression were significantly associated, but neither symptoms of psychosis nor of depression were associated with agitation when depression or psychosis, respectively, was controlled for. Significant psychopathological comorbidity should be considered in the design of clinical trials targeting particular psychopathology in this disease population.

Aged↗
PubMed2003

A double-blind comparison of olanzapine versus risperidone in the acute treatment of dementia-related behavioral disturbances in extended care facilities.

BACKGROUND: In addition to demonstrating their superiority to placebo, there is a need to compare the relative efficacy and side effects of atypical neuroleptics for the acute treatment of dementia-related behavioral disturbances in residents of long-term care facilities. METHOD: In a double-blind parallel study allowing dose titration over 14 days, 39 agitated persons with DSM-IV dementia who were residing in long-term care facilities were administered olanzapine (N = 20) or risperidone (N = 19) as acute treatment. Drug was administered once a day at bedtime. The initial dosages were olanzapine, 2.5 mg/day, and risperidone, 0.5 mg/day. Titration was allowed to maximum doses of olanzapine, 10 mg/day, and risperidone, 2.0 mg/day. The primary outcome measures were the Clinical Global Impressions scale (CGI) and the Neuropsychiatric Inventory (NPI). Data were gathered from 2000 to 2002. RESULTS: Both drugs produced significant reductions in CGI and NPI scores (p <.0001), but there was no significant difference between drugs. The mean olanzapine dose was 6.65 mg/day; for risperidone, the dose was 1.47 mg/day. The positive drug effect was not accompanied by decreased mobility, and there was improvement on a quality-of-life measure. The chief adverse events were drowsiness and falls. At baseline, 42% (16/38) of subjects in both groups had extrapyramidal symptoms that increased slightly, but not significantly, by the end of the study. CONCLUSION: Low-dose, once-a-day olanzapine and risperidone appear to be equally safe and equally effective in the treatment of dementia-related behavioral disturbances in residents of extended care facilities.

Aged↗
PubMed2002

Comparison of functional and cognitive donepezil effects in Alzheimer's disease.

Donepezil has been shown to improve aspects of cognitive functioning in persons with Alzheimer's disease (AD), but its impact on instrumental activities of daily living has received little attention. In a within-subject design, 24 community-dwelling persons with AD were treated with open-label donepezil over a 12-month period. To assess functional abilities, a brief, objective measure of instrumental activities of daily living skills was used (Texas Functional Living Scale; TFLS). Global cognitive abilities were assessed with the Mini-Mental State Examination (MMSE). Changes in TFLS and MMSE scores were much the same. Improvements on the TFLS and MMSE were seen over a 3-month period. At 12 months, both TFLS and MMSE scores declined slightly below baseline. These results support an effect of donepezil on cognitive measures and day-to-day function and also suggest that the MMSE reflects well the actual functional ability of persons with moderate AD.

Activities of Daily Living↗
PubMed2002

Prevalence and incidence of major depressive disorder in Alzheimer's disease: findings from two databases.

BACKGROUND: Reports on the frequency of major depression in Alzheimer's disease are conflicting, some suggesting that it is frequent, others suggesting that it is uncommon. METHODS: We examined the prevalence and incidence of symptom clusters meeting criteria for major depressive disorder (MDD) in two large series of cases diagnosed prospectively by NINCDS/ADRDA criteria as probable or possible Alzheimer's disease. Standard DSM-III-R criteria were employed at one site, the CERAD modification of DSM-III-R criteria at the other. Both sites required the presence of depressed mood on direct patient examination at the time of initial evaluation in order to meet criteria for MDD. RESULTS: At the center using standard DSM-III-R criteria (n = 329), there was a 0.9% prevalence of symptom clusters meeting criteria for MDD. At the center using the CERAD modification (n = 586), MDD prevalence was 4.8%. Incidence rates at both centers were below 2% per year over 3 years. CONCLUSIONS: We concluded that DSM-III-R MDD is not common in AD patients.

Adult↗
PubMed2002

Estimating the prevalence of agitation in community-dwelling persons with Alzheimer's disease.

To estimate the prevalence of, and develop norms for, significant agitation in community-dwelling persons with Alzheimer's disease (AD), the authors applied three different criteria to persons with AD (n=235) and normal elderly control subjects (NEC; n=64). The criteria were used to identify the minimum total score on the Cohen-Mansfield Agitation Inventory (CMAI) that represents significant or "excessive" agitation and to estimate its prevalence. The "ultraliberal" criterion resulted in 99.1% of persons with AD and 56.6% of NEC being classified as "excessively" disturbed. The "liberal" and "conservative" criteria classified 66.7% and 68.2% of persons with AD, and no NEC, as "excessively" disturbed. The authors conclude that the best estimate of prevalence of excessive agitation in this population is 67.5%, and that individuals with CMAI scores of 0 to 14 probably should not be considered to have excessive agitation.

Activities of Daily Living↗
PubMed2002

No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients.

Th determine if teaching caregivers behavior management techniques (BMTs) reduces long-term psychotropic use in Alzheimer's disease (AD) patients, we examined 12-month follow-up data from a 4-month randomized study comparing placebo, BMTs, trazodone, and haloperidol for the treatment of agitated behaviors in persons with AD. After 4 months, treatment was allowed with any agent. Between 42.8% and 51% of AD patients received additional psychotropics between 4 and 12 months. The relative risk of being prescribed any psychotropic drug after the 4-month trial was at or about 1.0 for subjects in each drug arm or placebo arm versus BMTs. We concluded that teaching caregivers BMTs did not diminish long-term prescription of psychotropic drugs.

Aged↗
PubMed2002

Emergent psychopathology in Alzheimer's disease patients over 12 months associated with functional, not cognitive, changes.

In a large, well-characterized population of community-dwelling persons with Alzheimer's disease (AD), we investigated the emergence of behavioral symptomatology and its association with changes in cognitive, global-clinical, and functional status. Behavioral Rating Scale for Dementia (BRSD) item responses from 235 AD patients with varying levels of dementia severity and without significant behavioral disturbance were taken from the baseline and 12-month visits in a study of cognitive and behavioral instruments. Item-level analysis revealed new symptoms at every dementia severity level. The symptoms that emerged in the greatest proportion of patients were change in weight, change in appetite, diurnal confusion, uncooperativeness, restlessness, clingy behavior, loss of initiative, and change in sleeping pattern. Changes in cognitive status over the 12 months were associated with changes in functional status and not with the emergence of behavioral symptomatology; however, change in the latter two domains tended to be associated. The findings support the hypothesis that increasing behavioral disturbance is not strongly associated with decreasing cognitive status and that, except for psychotic symptoms, a previously observed association between dementia severity and behavioral status may have been mediated partly by changes in functional abilities.

Activities of Daily Living↗
PubMedDate not supplied

Brain MRI hippocampal volume and prediction of clinical status in a mild cognitive impairment trial.

Mild Cognitive Impairment (MCI) is considered a transitional stage in the pathogenesis of Alzheimer's disease; however, not all MCI patients progress to clinically defined AD or decline at identical rates. Hippocampal atrophy, as measured by Magnetic Resonance Imaging (MRI), may be a marker for hippocampal pathology in patients with MCI and predict a more rapid deterioration to clinical AD. In this study, we used MRI data from an ongoing MCI clinical trial to determine whether MRI hippocampal volume at baseline was associated with cognitive and functional performance in MCI subjects and whether it predicted those individuals who were more likely to develop AD. We performed correlational analyses between the MRI hippocampal volumes at study entry and the subjects' concurrent performance on neuropsychological measures and clinical ratings. Larger hippocampal volume was associated with better performance on tests of memory, general cognition, and overall clinical ratings. Further analyses suggested that a smaller baseline hippocampal volume may be associated with a higher risk of developing clinical AD. As the trial is still ongoing, these results require confirmation once the trial is completed. In summary, these data suggest that MRI hippocampal volume may be a useful correlate of disease severity in MCI subjects and a prognostic indicator of subsequent AD.

Aged↗
PubMedDate not supplied

Assessing Alzheimer's disease patients with the Cohen-Mansfield Agitation Inventory: scoring and clinical implications.

We explored the applicability of the standard scoring of the Cohen-Mansfield Agitation Inventory (CMAI), a widely used nursing-home derived instrument, to community-dwelling persons with Alzheimer's disease (AD). Item responses to the CMAI were gathered from participants in two large clinical studies, one of which specifically included patients with behavioral disturbances. Confirmatory factor analysis in these two groups of well-characterized AD patients suggested that conventional CMAI subscoring did not adequately describe the responses of these two groups. Exploratory factor analysis indicated that the four CMAI subscores, based on a verbal-physical and aggressive-non-aggressive conceptualization of behavioral disturbance, did not fit community dwelling persons with AD. Based on cross-sectional and longitudinal analyses, there was suggestive evidence for three behavioral clusters, but these clusters did not achieve statistical significance Overall, the CMAI seemed best suited to describe the overall level rather than the specific subtypes of behavioral dyscontrol in community-dwelling persons with AD.

Aged↗