Anxiety spectrum disorders are common in patients with orthostatic tremor.

BACKGROUND: Orthostatic Tremor (OT) is a rare movement disorder characterized by a sensation of unsteadiness while standing and associated with high frequency tremors. Patients with OT commonly report a fear of falling and significant limitations in everyday activities. The prevalence of psychiatric comorbidities in OT patients has not been well-studied. METHODS: Subjects were evaluated by trained psychiatry researchers using the Mini International Neuropsychiatric Interview (M.I.N.I.). The M.I.N.I is a validated screening tool for psychiatric disorders. A standardized history covering previous psychiatric symptoms and illnesses was also obtained. RESULTS: 29 OT subjects were evaluated. The mean age was 67.7 years with female preponderance (89.3%). The average disease symptom duration was 18.2 years. 58.6% of the subjects had seen a mental health professional during the course of their OT illness. 24.1% of the subjects had a past history of depression, and 10.3% reported a family history of any psychiatric condition. 37.9% of the subjects screened positive for agoraphobia. Two of 29 subjects (6.9%) were classified as having a current major depressive episode and one subject (3.4%) was at risk for suicide. CONCLUSIONS: Psychiatric comorbidities are highly prevalent in OT patients, especially anxiety-spectrum disorders. Further studies are needed to understand if psychiatric disorders appear as a secondary response to the patient's symptoms, or are a primary non-motor manifestation of OT.

Primary malignant brain tumor incidence and Medicaid enrollment.

BACKGROUND: The relationship between socioeconomic status and health care disparities in the incidence of brain tumors is unclear. OBJECTIVE: To identify the associations between age, sex, and Medicaid enrollment and the incidence of primary malignant brain tumors in Michigan in 1996 and 1997. METHODS: Records were obtained from the Michigan Cancer Surveillance Program on the 1,006 incident cases during this period and cross-checked with Medicaid enrollment files. RESULTS: Persons enrolled in Medicaid were more likely than non-enrolled persons to develop a malignant brain tumor of any type, a glioblastoma multiforme, and an astrocytoma for certain subgroups. In addition, incidence rates for malignant brain tumors in persons enrolled in Medicaid peaked at a younger age. CONCLUSION: Sociodemographic status may be associated with cerebral malignancy and should be considered when targeting treatment and educational interventions at persons at risk.

The incremental direct costs associated with behavioral symptoms in AD.

OBJECTIVE: To determine the incremental costs associated with behavioral symptoms in patients with AD. METHODS: A total of 128 patients with probable AD were enrolled into this study. Cognitive function and extrapyramidal features were assessed in patients with AD. Caregivers were interviewed to determine use of health care services, receipt of unpaid care, severity of behavioral symptoms (Neuropsychiatric Inventory [NPI]), and comorbid medical conditions in patients with AD. Healthcare utilization data were multiplied by unit costs to estimate direct formal costs. Unpaid caregiving hours were multiplied by an hourly wage to estimate direct informal costs. The annual incremental direct costs of additional behavioral symptoms were estimated with multiple regression equations. RESULTS: Annual, direct costs were significantly higher in patients with AD at or above the median score on the NPI (high NPI group), after adjusting for group differences in severity of cognitive impairment and comorbid conditions. Patients in the high NPI group had formal costs between US$3,162 and US$5,919 higher than the low NPI group and total direct costs between US$10,670 and US$16,141 higher, depending on the severity of cognitive impairments. Models for the entire sample estimated that a one-point increase in the NPI score would result in an annual increase of between US$247 and US$409 in total direct costs, depending on the value of unpaid caregiving. CONCLUSIONS: Behavioral symptoms in patients with AD significantly increase direct costs of care.

The costs of caring: medical costs of Alzheimer's disease and the managed care environment.

This review summarizes the medical costs associated with Alzheimer's disease (AD) and related dementias, as well as the payers responsible for these medical costs in the US health care system. It is clear from this review that AD and related dementias are associated with substantial medical costs. The payers responsible for a majority of these costs are families of patients with AD and the US government through the Medicare and Medicaid programs. In an attempt to control expenditures, Medicare and Medicaid have turned to managed care principles and managed care organizations. The increase in "managed" dementia care gives rise to several potential problems for patients with AD, along with many opportunities for systematic improvement in the quality of dementia care. Evidence-based disease management programs provide the greatest opportunities for improving managed dementia care but will require the development of dementia-specific quality of care measures to evaluate and continually improve them.

Cost-utility of three approaches to the diagnosis of sleep apnea: polysomnography, home testing, and empirical therapy.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is usually diagnosed with overnight polysomnography in a sleep laboratory. Home sleep studies can be performed at lower cost, but results are somewhat less reliable. Bedside diagnosis of OSAS without any testing has also been discussed. OBJECTIVE: To model the costs and utility of laboratory polysomnography, home study, and no testing during the 5 years after initial evaluation for OSAS. DESIGN: Cost-utility analysis. DATA SOURCES: Published data. TARGET POPULATION: Hypothetical cohort of persons suspected of having OSAS. TIME HORIZON: The 5 years after initial evaluation for OSAS. PERSPECTIVE: Societal. INTERVENTION: Nasal continuous positive airway pressure when OSAS was diagnosed. MEASUREMENTS: Quality of life, survival and charges (as proxies for costs) for each diagnostic method. RESULTS OF BASE-CASE ANALYSIS: Under almost all modeled conditions, polysomnography provided maximal quality-adjusted life-years in the 5 years after the initial diagnostic evaluation. The incremental charges for polysomnography over home study or no testing were about $13,400 and $9200, respectively, per quality-adjusted life-year gained during this period. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the utility of treatment in the absence of OSAS. CONCLUSIONS: The cost-utility of polysomnography instead of home study or no testing in the diagnosis of OSAS compares favorably with that of other procedures for which society judges the added utility per dollar spent to be worthwhile. More precise determination of certain key variables in this model should be a goal of future research.

Cognitive, behavioral, and motor effects of the NMDA antagonist ketamine in Huntington's disease.

BACKGROUND: Excitotoxicity may contribute to neuronal degeneration in Huntington's disease (HD). N-methyl-D-aspartate (NMDA) receptor antagonists can prevent neuronal degeneration caused by excitotoxicity, but their effects in HD patients are not known. METHODS: We investigated the acute cognitive, behavioral, and motor effects of the NMDA-receptor antagonist ketamine in HD patients. Double-blind infusions of 0.10, 0.40, and 0.60 mg/kg/hr ketamine were given to 10 HD patients on one test day and compared with placebo infusions on a second, identical testing day. Linear mixed-effects models and randomization tests were used to identify whether, and at which dose, a significant change from baseline occurred in outcome variables. RESULTS: We demonstrated that ketamine is well tolerated at low and intermediate subanesthetic doses. Intermediate ketamine doses produced specific decline in memory and verbal fluency. Higher subanesthetic doses caused a significant increase in psychiatric symptoms and impairment of eye movements. CONCLUSIONS: These results describe the spectrum of clinical effects produced by increasing NMDA receptor blockade in HD patients. The clinical effects appearing with higher levels of NMDA receptor blockade can identify the range of doses used in clinical trials of NMDA receptor antagonists.

Apolipoprotein E and Alzheimer's disease: strength of association is related to age at onset.

Apolipoprotein E (apoE) epsilon 4 allele frequency among Alzheimer's disease (AD) patients is increased compared to control subjects and is influenced by the presence of other genetic factors and age at symptom onset. We examined the relationship between age at AD symptom onset and apoE by comparing the apoE epsilon 4 allele frequency of normal, elderly control subjects (n = 107) to that in AD patients (n = 123), divided into four age-at-onset periods. Additionally, the distribution of symptom onset ages of AD patients with and without apoE epsilon 4 alleles was determined. We observed increased apoE epsilon 4 allele frequencies between the AD onset ages of 55 and 75 years, but not at the extremes of onset ages (i.e. onset between 45 and 54 years of age and after age 75). Our data suggests that having an apoE epsilon 4 allele increases the likelihood that AD patients will develop symptoms in the middle range of onset ages. At the extremes of AD onset ages, non-apoE factors, including other genetic factors and age, are more important determinants of risk of developing AD.

Novel amyloid precursor protein gene mutation (codon 665Asp) in a patient with late-onset Alzheimer's disease.

Amyloid plaques in Alzheimer's disease contain beta-amyloid, encoded by portions of exons 16 and 17 of the amyloid precursor protein. The specific association of rare amyloid precursor protein mutations with some kindreds with early-onset familial Alzheimer's disease suggests that specific abnormalities in amyloid precursor protein may contribute to the pathogenesis of Alzheimer's disease. Until now, there has been no evidence suggesting that amyloid precursor protein mutations could be involved in late-onset or sporadic Alzheimer's disease. We used reverse transcription-polymerase chain reaction, denaturing gradient gel electrophoresis, and direct DNA sequencing to analyze amyloid precursor protein exons 16 and 17 from postmortem cerebellar samples from patients with histologically confirmed Alzheimer's disease and control subjects. We found a novel point mutation, substitution of cytosine for guanine, at nucleotide 2119 (amyloid precursor protein 770 messenger RNA transcript) in a patient with late-onset Alzheimer's disease. This substitution deletes a BglII site and substitutes aspartate for glutamine at codon 665. Denaturing gradient gel electrophoresis analysis showed that this mutation was absent in 40 control subjects and 127 dementia patients. Whether this mutation is a rare but normal variant or contributes to the development of Alzheimer's disease is not known. The BglII restriction fragment length polymorphism enables investigators to determine the frequency of this polymorphism in normal subjects and Alzheimer's disease patients.

Neuroimaging of epilepsy, movement disorders, and degenerative diseases.

Neuroimaging has improved the understanding, diagnosis, and management of several neurologic diseases and syndromes. Recent advances in the neuroimaging of epilepsy, movement disorders, and degenerative diseases of the nervous system are reviewed. Current research confirms that structural and functional neuroimages each provide unique, clinically useful information in these disorders. Quantification of images improves their diagnostic sensitivity and specificity. Presymptomatic or early neurochemical changes have been identified and followed longitudinally in several neurodegenerative diseases, providing a method for monitoring response to therapeutic intervention and pathophysiologic hypothesis testing. Functional activation studies and receptor-specific radioligands continue to advance our understanding of these disorders. Future methods will take increasing advantage of both the ability to measure neuropharmacological and neurochemical changes in vivo, and the ability to combine images and information obtained with distinct structural and functional neuroimaging modalities.