Benzodiazepine use and crash risk in older patients.
Explore the source record for details and available documents.
Accidents, Traffic↗
Biomedical subjects
D Deptula
Publications and source records attributed to D Deptula.
Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa. Tolcapone Fluctuator Study Group III.
OBJECTIVE: To assess the efficacy and tolerability of the catechol-O-methyltransferase inhibitor tolcapone in reducing "off/on" fluctuations in levodopa-treated parkinsonian patients. DESIGN: A randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Fifteen Parkinson disease clinics. PATIENTS: Two hundred fifteen referred outpatients with Parkinson disease who showed predictable end-of-dose motor fluctuations that were not controlled by a stable levodopa-carbidopa (Sinemet) regimen of at least 4 weeks' duration. INTERVENTIONS: In addition to their usual levodopa-carbidopa regimen, patients received placebo or tolcapone, 100 or 200 mg, 3 times daily orally for 6 weeks. PRIMARY OUTCOME MEASURE: Change in daily off/on time. RESULTS: Tolcapone, 100 and 200 mg 3 times daily, reduced off time by 2.0 and 2.5 hours per day, respectively, and increased on time by 2.1 and 2.3 hours per day, respectively (P<.001 vs placebo). Investigators' global measures of disease severity indicated that significantly more tolcapone-treated patients had reduced wearing off and symptom severity (P<.001 vs placebo). No significant change in quality-of-life measures occurred. Clinical improvements occurred despite a reduction in total daily levodopa dose of 185.5 mg (23%) in the tolcapone, 100 mg 3 times daily, group and 251.5 mg (29%) in the 200 mg 3 times daily group. Principal adverse events (mainly dyskinesia and nausea) were levodopa related, were not treatment limiting, and were seldom reported as reasons for withdrawal. The frequency of withdrawals because of adverse events was similar in all groups (3% to 7%). CONCLUSIONS: Tolcapone was well tolerated and substantially increased on time and reduced off time in patients with fluctuating Parkinson disease. Additionally, levodopa requirements were significantly decreased.
Aged↗
ApoE-epsilon 4 allele and susceptibility to drug-induced memory impairment in the elderly.
Explore the source record for details and available documents.
Aged↗
Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. Tolcapone Stable Study Group.
In this double-blind, placebo-controlled trial, we investigated the effect of the catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily on activities of daily living and motor function in 298 patients with parkinsonism receiving levodopa but without motor fluctuations. At 6 months, both dosages of tolcapone produced significant reductions in the Unified Parkinson's Disease Rating Scale scores for activities of daily living (Subscale II) and motor function (Subscale III) and in the total score for Subscales I to III. These improvements were maintained up to the 12-month assessment. At 6 months, both tolcapone groups had changes in levodopa dosage that were significantly different from placebo: the tolcapone groups had decreases in mean total daily dose of levodopa, whereas the placebo group had a mean increase. Tolcapone was well tolerated. The principal adverse events were levodopa-related, but these were generally mild or moderate. Diarrhea was the most frequent nondopaminergic adverse event. Tolcapone appears to be beneficial in the treatment of patients with parkinsonism who have not yet developed motor fluctuations.
Aged↗
The acute and chronic performance effects of alprazolam and lorazepam in the elderly: relationship to duration of treatment and self-rated sedation.
We examined the acute performance and sedative effects of single high and low doses of alprazolam and lorazepam, both before and after chronic, 3-week b.i.d. treatment in elderly adults. The effects of chronic treatment also were examined in this parallel, double-blind, placebo-controlled study. Initial acute low doses significantly impaired total recall and increased intrusion errors. High doses also impaired delayed recall and critical flicker fusion threshold (CFF). Only chronic treatment with high-dose alprazolam increased intrusions and self-rated sedation. Single-dose rechallenge after chronic treatment was associated with significantly less impairment than the initial challenge in memory tasks but not in the discriminant reaction time (DRAT) task. For most memory measures, the development of tolerance was only partial; rechallenge still produced significant deficits in relation to placebo. The development of tolerance was task-specific and depended on drug type and dosage. Despite impairments in various memory functions, CFF, and DRAT, volunteers did not report significant drug-induced changes in sedation.
Aged↗
Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. The Tolcapone Stable Study Group.
In this double-blind, placebo-controlled trial, we investigated the effect of the catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily on activities of daily living and motor function in 298 patients with parkinsonism receiving levodopa but without motor fluctuations. At 6 months, both dosages of tolcapone produced significant reductions in the Unified Parkinson's Disease Rating Scale scores for activities of daily living (Subscale II) and motor function (Subscale III) and in the total score for Subscales I to III. These improvements were maintained up to the 12-month assessment. At 6 months, both tolcapone groups had changes in levodopa dosage that were significantly different from placebo: the tolcapone groups had decreases in mean total daily dose of levodopa, whereas the placebo group had a mean increase. Tolcapone was well tolerated. The principal adverse events were levodopa-related, but these were generally mild or moderate. Diarrhea was the most frequent nondopaminergic adverse event. Tolcapone appears to be beneficial in the treatment of patients with parkinsonism who have not yet developed motor fluctuations.
Activities of Daily Living↗
Aging, emotional states, and memory.
OBJECTIVE: This study compared the relation between negative mood states and memory in young and elderly subjects. METHOD: Forty-five normal, healthy young volunteers (ages 19-35 years) and 45 normal, healthy elderly volunteers (ages 60-78 years) were administered a verbal list-learning task and self-rated scales of affective states. RESULTS: The elderly group, but not the young group, consistently exhibited significant correlations between their performance on verbal recall measures and their ratings of their anxiety, depression, and withdrawal; i.e., within the elderly group, higher levels of negative affective states were associated with poorer memory. CONCLUSIONS: These findings indicate that aging modulates the relation between emotional state and memory functions, and they are consistent with the hypothesis that the elderly are more vulnerable than the young to the adverse effects of negative emotional states on memory. Therefore, even in normal elderly individuals without diagnosable psychopathology, negative affective states (such as anxiety and depression) may interfere with memory functioning.
Adult↗
Increased CSF HVA response to arecoline challenge in Alzheimer's disease.
The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p < .01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease.
Aged↗
Glutamate and other CSF amino acids in Alzheimer's disease.
The authors compared CSF amino acid levels of 10 patients with mild to moderate dementia and probable Alzheimer's disease who had never received antidepressant or neuroleptic medication with those of 10 normal subjects of similar age. The Alzheimer's patients had significantly higher levels of CSF glutamate. This finding was not related to age, sex, or severity of dementia. Elevated CSF glutamate may reflect greater glutamatergic activity early in the course of Alzheimer's disease. The authors speculate that the excitotoxic effects of glutamate may contribute to progressive neuronal loss in Alzheimer's disease.
Age Factors↗
Asymmetry of recall in depression.
We compared the verbal (auditory/semantic) and nonverbal (visual/configurational) recall of carefully defined depressed patients with a demographically matched control group of normal volunteers. Whereas controls were split as to whether their nonverbal recall exceeded or was inferior to their verbal recall, 89% of depressed patients demonstrated an asymmetry characterized by poorer nonverbal than verbal recall. Depressive subgroups (determined by clinical and psychoendocrine criteria) differed from controls, but not from each other, in demonstrating this asymmetry of recall. In contrast, depressed patients did not individually demonstrate an asymmetry between verbal and nonverbal recognition that differed from controls.
Adult↗
Pretreatment postural blood pressure drop as a possible predictor of response to the cholinesterase inhibitor velnacrine (HP 029) in Alzheimer's disease.
The failure of cholinesterase inhibitors to produce noticeable improvement in about half of patients with Alzheimer's disease (AD) may result from heterogeneity of neurotransmitter abnormalities in this disorder. This study examined whether pretreatment postural blood pressure (BP) drop, which presumably reflects sympathetic response, differed in patients who were responders or nonresponders to the cholinesterase inhibitor, HP 029. Twenty-three AD patients completed a double-blind dose-finding phase of a clinical trial in which four doses of HP 029 and placebo were administered. Evaluation for efficacy occurred after 7 days of treatment at each dose. Of the 23 patients, 12 were classified as responders in the dose-ranging phase of the study. Nonresponders demonstrated significantly greater decreases in pretreatment systolic postural BPs when going from a supine to sitting position than did responders. The greater postural BP drop in nonresponders may identify a subgroup of AD patients that responds poorly to cholinesterase inhibitors.
Aged↗
Effects of antidepressants on human performance: a review.
Despite widespread use of antidepressants, major gaps remain in our knowledge of the effects of antidepressants on human performance. While most single-dose studies with normal subjects have suggested that the more sedating tricyclic antidepressants tend to produce impairment, the effects of antidepressant treatment in clinical populations have been less thoroughly examined, with both drug-induced impairment and improvement reported. This review suggests that factors such as age, diagnosis, drug plasma concentration, and length of treatment need to be explored to establish the effects of antidepressants on performance in clinical populations.
Age Factors↗
Equivalence of five forms of the Selective Reminding Test in young and elderly subjects.
This study evaluated the equivalence of five forms of the Selective Reminding Test, a widely used measure of verbal learning, 45 normal young and 45 normal elderly subjects were randomly administered three of the five test forms on three separate sessions. The five forms generally correlated well with one another and were of comparable difficulty, suggesting adequate test equivalence. Four of the five forms were particularly well matched.
Adolescent↗
CSF corticotropin-releasing factor (CRF) in Alzheimer's disease: its relationship to severity of dementia and monoamine metabolites.
The concentration of corticotropin-releasing factor-like immunoreactivity (CRF-LI) in the cerebrospinal fluid (CSF) of 15 probable Alzheimer's disease (AD) patients with mild to moderate dementia and 10 neurologically normal age-matched controls was examined. There were no significant alterations in the mean CSF CRF-LI concentration in AD compared to controls. However, in the AD group, CSF CRF-LI correlated significantly with the global neuropsychological impairment ratings, suggesting that greater cognitive impairment was associated with lower CSF CRF-LI concentrations. There was a significant reduction in the CSF concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the AD patients, and there was a positive correlation between the concentration of CRF-LI and 5-HIAA in CSF. This latter finding suggests that serotoninergic neuronal systems may interact with CRF-containing neurons.
Aged↗
CSF GABA in caregiver spouses of Alzheimer patients.
The authors studied CSF gamma-aminobutyric acid (GABA) in 14 Alzheimer patients and nine age-matched normal subjects. The five normal subjects who were wives of the demented patients had higher CSF GABA concentrations than the four normal subjects without demented spouses.
Alzheimer Disease↗
Possible muscarinic supersensitivity in Alzheimer's disease.
In contrast to the well established presynaptic cholinergic deficits which are associated with Alzheimer's Disease (AD), the functional status of the remaining muscarinic receptors has not received adequate attention. This paper examined the possibility that the presynaptic cholinergic deficits in AD may be accompanied by muscarinic supersensitivity. While the majority of QNB binding studies have failed to find an upregulation of muscarinic receptors in AD patients, most of those studies did not differentiate between presynaptic and postsynaptic receptors. In addition, receptor density and functional response are not necessarily correlated. To determine whether AD is accompanied by alterations in the functional status of central muscarinic receptors, we studied the biological responses to a muscarinic agonist in AD patients and controls. In this pilot study, AD patients demonstrated an increased arecoline-induced HVA response in the CSF. This finding is consistent with the hypothesis that AD is accompanied by muscarinic supersensitivity.
Alzheimer Disease↗
Effects of diazepam on recall memory: relationship to aging, dose, and duration of treatment.
Explore the source record for details and available documents.
Adult↗
Loss of the cortisol response to naltrexone in Alzheimer's disease.
The administration of a single dose of the opiate antagonist naltrexone (NT) was accompanied by significant elevations in plasma cortisol in normal elderly subjects; in contrast, the cortisol response to NT was absent in individuals of comparable age with Alzheimer's disease (AD). The differential effect of AD on the cortisol response was not accompanied by a significant group difference in plasma prolactin in response to NT administration. Furthermore, this differential cortisol response to NT was not associated with any evident differences in age, sex ratio, plasma levels of naltrexone or its major metabolite beta-naltrexol, or with differences in measures of nonspecific stress, such as plasma free MHPG, pulse, or blood pressure, between the two groups. The absence of the well-characterized cortisol response to NT in AD, together with other reports of abnormal responses to other pharmacological challenges, suggests that neuroendocrine abnormalities might be an important concomitant and possibly a central contributor to the pathophysiology of Alzheimer's disease.
Aged↗