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Biomedical subjects

David S Geldmacher

Publications and source records attributed to David S Geldmacher.

15 recordsLinked to original sources

Conduction aphasia as a function of the dominant posterior perisylvian cortex. Report of two cases.

Assessment of eloquent functions during brain mapping usually relies on testing reading, speech, and comprehension to uncover transient deficits during electrical stimulation. These tests stem from findings predicted by the Geschwind-Wernicke hypothesis of receptive and expressive cortices connected by white matter tracts. Later work, however, has emphasized cortical mechanisms of language function. The authors report two cases that demonstrate that conduction aphasia is cortically mediated and can be inadequately assessed if not specifically evaluated during brain mapping. To determine the distribution of language on the dominant cortex, electrical cortical stimulation was performed in two cases by using implanted subdural electrodes during brain mapping before epilepsy surgery. A transient isolated deficit in repetition of language was reported during stimulation of the posterior portion of the dominant superior temporal gyrus in one patient and during stimulation of the supramarginal gyrus in the other patient. These cases demonstrate a localization of language repetition to the posterior perisylvian cortex. Brain mapping of this region should include assessment of verbal repetition to avoid potential deficits resembling conduction aphasia.

Adult↗

The cost benefit to health plans of pharmacotherapy for Alzheimer's disease.

Treatment of Alzheimer's disease (AD) is a major public health issue, with the potential for significant impact on MCOs. As the number of people affected with AD continues to rise, the importance of this problem will grow as well. This article reviews patient and caregiver outcomes associated with reduced health care costs and their implications for MCOs. Cholinesterase inhibitors (ChEIs) are effective in treating cognitive, functional, and behavioral symptoms for patients with mild to moderate and moderate to severe AD. Treatment with memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to benefit patients with moderate to severe AD. Pharmacoeconomic studies indicate that donepezil and memantine treatment may reduce total costs of care for AD patients and their caregivers, with potential economic benefits to MCOs.

Alzheimer Disease↗

Donepezil (Aricept) for treatment of Alzheimer's disease and other dementing conditions.

Alzheimer's disease is common, incurable and disabling. It is expected to grow dramatically in prevalence over the next 50 years. At current, the standard of care for patients with mild and moderately severe Alzheimer's disease includes the use of acetylcholinesterase inhibitors. Donepezil (Aricept) is a highly selective acetylcholinesterase inhibitors with a pharmacokinetic profile allowing once-daily dosing. There is an extensive knowledge base derived from published clinical trials of donepezil in Alzheimer's disease, revealing consistent efficacy in cognition, global clinical ratings and daily function. Donepezil is also associated with additional meaningful outcomes such as reduced risk for, or delay to, nursing home placement. Despite a sense of limited efficacy of this drug class among prescribers, number needed-to-treat analyses suggest donepezil is highly effective at reducing the long-term adverse outcomes associated with Alzheimer's disease.

Alzheimer Disease↗

Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial.

BACKGROUND AND PURPOSE: Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD. METHODS: Patients (n=603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d (n=198), donepezil 10 mg/d (5 mg/d for first 28 days; n=206), or placebo (n=199). Analyses were based on the intent-to-treat population. RESULTS: At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer's Disease Assessment Scale-cognitive subscale (mean change from baseline score effect size: donepezil 5 mg/d, -1.90; P=0.001; donepezil 10 mg/d, -2.33; P<0.001). Significant improvements in patients' global function were seen versus placebo at week 24 (observed cases), on the Clinician's Interview-Based Impression of Change-Plus version only for patients on donepezil 5 mg/d (P=0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d (P=0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer's Disease Functional Assessment and Change Scale (mean change from baseline score effect size at week 24: donepezil 5 mg/d, -1.31, P=0.02; donepezil 10 mg/d, -1.31, P=0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low (placebo, 11.1%; donepezil 5 mg/d, 11.1%; donepezil 10 mg/d, 21.8%; P=0.005 versus placebo). CONCLUSIONS: These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition.

Activities of Daily Living↗

Visuospatial dysfunction in the neurodegenerative diseases.

Visuospatial dysfunction is not generally considered a cardinal feature of the common neurodegenerative disorders of late life like Alzheimer's disease (AD), Parkinson's disease (PD), and Dementia with Lewy bodies (DLB). However, a large number of research studies have shown visually related disorders to be surprisingly pervasive among these disease states. Broader recognition of the problems is hindered by a complex literature, which suffers from a lack of uniform definitions of what constitutes "visuospatial" dysfunction and few commonly accepted theoretical models for interpreting results. The interface between visual-spatial function and other variably-defined constructs such as attention and executive function further complicates experimental approaches to this construct. Nonetheless, this review addresses both theoretical and practical issues regarding the presence, importance, and correlates of visual dysfunction associated with neurodegeneration. In addition, the functional impact of the deficits is addressed.

Humans↗

Development of a scale to predict decline in patients with mild Alzheimer's disease.

OBJECTIVES: To develop a scale that can assist in predicting likelihood of decline from mild dementia over 1 year in patients with Alzheimer's disease (AD). DESIGN: Retrospective cohort study. SETTING: University Memory and Aging Center. PARTICIPANTS: Patients with probable or possible AD and Clinical Dementia Rating (CDR) of 1 at baseline, divided into development and validation cohorts (n = 118 each). MEASUREMENTS: The CDR and neurological and neuropsychological assessments were given at baseline and 1 year later. RESULTS: In the development cohort, high education, low Mini-Mental State Examination score, poor insight, psychotic symptoms, and greater activity of daily living impairment predicted decline in CDR from 1 to 2 or 3. Receiver operating characteristics (ROC) curve analysis identified cutoff scores that maximized sensitivity and specificity for each significant predictor of decline. Based on the cutoff, raw scores were recoded to reflect risk for decline, weighted, and summed to create a final scale score. ROC curve analysis established a cutoff to indicate risk for decline on the final scale score. Sensitivity, specificity, and area under the ROC were 0.76, 0.74, and 0.83 in the development cohort and 0.77, 0.69, and 0.80 in the validation cohort, respectively. Positive and negative predictive values were 0.71 and 0.78 in the development cohort and 0.68 and 0.78 in the validation cohort, respectively. CONCLUSIONS: Decline from mild to moderate or severe impairment represents significant clinical change, with implications for patient and caregiver quality of life and treatment options. The clinical scale developed uses data to enhance prediction about change from mild to moderate or severe stages of AD.

Aged↗

Donepezil is associated with delayed nursing home placement in patients with Alzheimer's disease.

OBJECTIVES: To assess the relationship between donepezil treatment and time to nursing home placement (NHP) for patients with Alzheimer's disease (AD). DESIGN: Observational follow-up of patient NHP and vital status. SETTING: Community. PARTICIPANTS: Patients previously enrolled in one of three randomized, double-blind, placebo-controlled clinical trials of donepezil and two subsequent open-label studies (total N = 1,115); 671 patients provided complete data for analysis. MEASUREMENTS: Data were obtained through follow-up interviews with caregivers and chart reviews of patients with AD. Comparison groups were defined by whether patients received an effective dose of donepezil (>/=5 mg/d; >/=80% compliance) for specific numbers of weeks during the double-blind or open-label trial phase, in both phases, or in neither. Cox proportional hazards models were used to estimate risk ratios for NHP and survival curves from which median times to NHP were estimated for first dementia-related placement of longer than 2 weeks and permanent placement. The models were adjusted for age, sex, baseline Mini-Mental State Examination score, whether the caregiver was a spouse, caregiver continuity, and use of other cholinesterase inhibitors after the clinical trials. RESULTS: Use of donepezil of 5 mg/d or more was associated with significant delays in NHP. A cumulative dose-response relationship was observed between longer-term sustained donepezil use and delay of NHP. When donepezil was taken at an effective dose for at least 9 to 12 months, conservative estimates of the time gained before NHP were 21.4 months for first dementia-related NHP and 17.5 months for permanent NHP. CONCLUSION: Use of donepezil by AD patients resulted in significant delays in NHP. Long-term use of donepezil may help AD patients live longer in community settings, with consequent personal, social, and economic benefits.

Aged↗

Alzheimer's disease: current pharmacotherapy in the context of patient and family needs.

The objective of this paper is to review current evidence and treatment patterns for pharmacotherapy in Alzheimer's disease (AD), with an emphasis on outcomes considered important to patients and families. The sources for the information are the peer-reviewed literature, Food and Drug Administration-approved package labeling for acetylcholinesterase inhibitors (AChEIs), expert opinions expressed at the First Annual Dementia Congress, and clinical experience. Three AChEI agents are in routine use in the United States. They are considered part of the standard of care for patients with mild-to-moderate AD. There are differences in metabolism, pharmacokinetics, side effects, and ease of use that may influence the prescriber's choice of agent and dosage. The three approved agents have similar outcomes in cognition and global clinician ratings of effectiveness in double-blind placebo controlled trials. Persistent therapy with effective doses of AChEIs is associated with reduced risk for, or delayed, nursing home placement, which is a stated priority of AD caregivers. Agents from this class of drugs have also been shown to be associated with statistically significant preservation of daily function and benefits in treatment of adverse behaviors in AD. Numerous additional choices are available to the clinician for pharmacotherapy of adverse behaviors. Community-based psychoeducational support is also of value to caregivers.

Alzheimer Disease↗

Optimizing coding and reimbursement to improve management of Alzheimer's disease and related dementias.

The objectives of this study were to review the diagnostic, International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM), diagnosis related groups (DRGs), and common procedural terminology (CPT) coding and reimbursement issues (including Medicare Part B reimbursement for physicians) encountered in caring for patients with Alzheimer's disease and related dementias (ADRD); to review the implications of these policies for the long-term clinical management of the patient with ADRD; and to provide recommendations for promoting appropriate recognition and reimbursement for clinical services provided to ADRD patients. Relevant English-language articles identified from MEDLINE about ADRD prevalence estimates; disease morbidity and mortality; diagnostic coding practices for ADRD; and Medicare, Medicaid, and managed care organization data on diagnostic coding and reimbursement were reviewed. Alzheimer's disease (AD) is grossly undercoded. Few AD cases are recognized at an early stage. Only 13% of a group of patients receiving the AD therapy donepezil had AD as the primary diagnosis, and AD is rarely included as a primary or secondary DRG diagnosis when the condition precipitating admission to the hospital is caused by AD. In addition, AD is often not mentioned on death certificates, although it may be the proximate cause of death. There is only one ICD-9-CM code for AD-331.0-and no clinical modification codes, despite numerous complications that can be directly attributed to AD. Medicare carriers consider ICD-9 codes for senile dementia (290 series) to be mental health codes and pay them at a lower rate than medical codes. DRG coding is biased against recognition of ADRD as an acute, admitting diagnosis. The CPT code system is an impediment to quality of care for ADRD patients because the complex, time-intensive services ADRD patients require are not adequately, if at all, reimbursed. Also, physicians treating significant numbers of AD patients are at greater risk of audit if they submit a high frequency of complex codes. AD is grossly undercoded in acute hospital and outpatient care settings because of failure to diagnose, limitations of the coding system, and reimbursement issues. Such undercoding leads to a lack of recognition of the effect of AD and its complications on clinical care and impedes the development of better care management. We recommend continuing physician education on the importance of early diagnosis and care management of AD and its documentation through appropriate coding, expansion of the current ICD-9-CM codes for AD, more appropriate use of DRG coding for ADRD, recognition of the need for time-intensive services by ADRD patients that result in a higher frequency of use of complex CPT codes, and reimbursement for CPT codes that cover ADRD care management services.

Aged↗

Cost-effective recognition and diagnosis of dementia.

Alzheimer's disease (AD) has the potential to become the most overwhelming public health concern of this century due to increasing life expectancy and growth in the aging population. As a result, primary care physicians and neurologists will be seeing a greater number of elderly patients in their practice and will subsequently be expected to both identify and initiate treatment in those individuals who may display signs of dementia and related neurologic conditions. There is good evidence that AD is underrecognized or undercoded in primary care settings. Underrecognition is an important problem in this population because early treatment and counseling have been shown to provide benefits to both patients and caregivers. As their patient population ages, physicians need to learn to recognize the early symptoms of AD and make a diagnosis in order to provide cost-effective therapies.

Aged↗