Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin.

BACKGROUND: Antimuscarinic agents used in the treatment of overactive bladder (OAB) differ in their potential to impair cognitive function. It is hypothesised that low brain concentrations and relatively low selectivity for the M(1) muscarinic receptor may reduce the potential for adverse central nervous system (CNS) effects with darifenacin, compared with other antimuscarinics, particularly oxybutynin. METHODS: Cognitive function studies evaluating darifenacin, oxybutynin, tolterodine, solifenacin and/or trospium were identified from publications databases (Medline, Biosis and Embase) and congress abstracts. Preclinical studies and randomised controlled trials in adults were reviewed. RESULTS: Five randomised, double-blind, multiple-dose studies of cognitive function were identified. Oxybutynin was consistently associated with cognitive deficit (four studies), whereas darifenacin did not impair cognition (three studies). These findings were supported by data from sleep/attention and EEG studies. Tolterodine data were limited to one small study with each formulation. For solifenacin and trospium, there were no human studies evaluating memory, the cognitive function most vulnerable to CNS anticholinergics. CONCLUSIONS: There is compelling evidence of cognitive impairment with oxybutynin, whereas darifenacin stands out by demonstrating no impairment of memory or other cognitive functions in three randomised, controlled trials. This may be attributed to the differences in physicochemical properties, efflux mechanisms and relative M(1) muscarinic receptor sparing. The risk of CNS impairment is of particular concern for vulnerable populations such as the elderly (a substantial proportion of the OAB population), and CNS-compromised neurogenic bladder patients such as those with multiple sclerosis or Parkinson's disease.

Initial and steady-state effects of diphenhydramine and loratadine on sedation, cognition, mood, and psychomotor performance.

BACKGROUND: The classic, first-generation histamine1-receptor antagonists used to treat allergic disorders frequently cause sedation. In contrast, sedation is reduced or absent after administration of recommended doses of second-generation histamine1-receptor antagonists. We measured the initial and steady-state effects of diphenhydramine, a first-generation antihistamine, and loratadine, a second-generation antihistamine, by means of a comprehensive battery of psychometric tests that mirror real-world tasks. METHODS: Healthy volunteers (N = 98) were randomly assigned in a double-blind fashion to receive loratadine (n = 33), diphenhydramine (n = 32), or placebo (n = 33). A computerized test battery was administered at baseline, on day 1 after administration of the initial dose, and on days 3 and 5. RESULTS: After the initial dose, subjects taking diphenhydramine demonstrated poorer cognitive performance than subjects taking loratadine or placebo on tasks of divided attention, working memory, speed, and vigilance. Subjects taking diphenhydramine also reported greater fatigue and sleepiness and lower levels of motivation, and rated the quality of their performance as lower than subjects taking loratadine or placebo. On day 3, subjects taking diphenhydramine continued to show more fatigue and lower motivation, and rated the quality of their test performance as poorer than subjects taking loratadine or placebo. There were no differences between loratadine and placebo after the initial dose or steady-state (day 5) dosing for any measure of cognitive or psychomotor test performance, mood, or sedation. CONCLUSIONS: Patients taking diphenhydramine may be at risk of lapses and significant errors that may lead to potential hazards and decreased work productivity.

Neuropsychological consultation in psychiatric practice.

A specialty area with historical roots in behavioral neurology as well as experimental and clinical psychology, clinical neuropsychology offers a unique contribution to psychiatric practice in the form of consultation regarding cognitive, perceptual, and motor functioning. Using quantified, standardized, and repeatable measures, this comprehensive assessment can be helpful in identifying cortical dysfunction, in measuring decline or recovery, and in assessing response to treatment.

Psychological testing and psychological assessment. A review of evidence and issues.

This article summarizes evidence and issues associated with psychological assessment. Data from more than 125 meta-analyses on test validity and 800 samples examining multimethod assessment suggest 4 general conclusions: (a) Psychological test validity is strong and compelling, (b) psychological test validity is comparable to medical test validity, (c) distinct assessment methods provide unique sources of information, and (d) clinicians who rely exclusively on interviews are prone to incomplete understandings. Following principles for optimal nomothetic research, the authors suggest that a multimethod assessment battery provides a structured means for skilled clinicians to maximize the validity of individualized assessments. Future investigations should move beyond an examination of test scales to focus more on the role of psychologists who use tests as helpful tools to furnish patients and referral sources with professional consultation.

Measuring performance decrements in aviation personnel infected with the human immunodeficiency virus.

There is controversy over whether cognitive impairment occurs in early human immunodeficiency virus (HIV) disease. When impairment is reported, findings are typically subclinical, affect only a minority, and their relationship to occupational functioning has not been established. Despite such findings, it has been recommended that HIV-seropositive pilots be disqualified from flying. This paper reviews research relevant to measuring performance decrements in HIV-infected aviators. Based upon current data, we conclude that although subtle neurobehavioral dysfunction may occur in some asymptomatic HIV-seropositive individuals, there is no research which has demonstrated associated decrements in aviation-related skills. Thus, it may be premature to recommend medical disqualification of all HIV-seropositive aviators. We propose, instead, that sensitive neurocognitive measures, incorporated into a comprehensive neurodiagnostic evaluation, could be used to evaluate asymptomatic HIV-seropositive aviators. Only those who are impaired on evaluation would be disqualified from flying. Concurrently, research investigating the relationship between abnormalities and aviation abilities would be conducted.

Assessing boundary violations in psychotherapy: survey results with the Exploitation Index.

The usefulness of the Exploitation Index (Epstein & Simon, 1990) was evaluated in a survey of psychiatrists. Forty-three percent of the respondents indicated that at least one item alerted them to behavior they thought could have been counterproductive to treatment. Twenty-nine percent found that they were stimulated to make specific changes in future treatment practice. On average, female respondents endorsed fewer boundary violations than males.

The effects of antihistamines on cognition and performance.

Allergic diseases are responsible for substantially more disability than is generally realized. Allergic rhinitis alone results in 3.5 million lost workdays and 2 million missed school days in the United States each year. Comorbid conditions such as asthma and sinusitis can be disabling as well, resulting each year in more than 10 million missed school days and more than 73 million days of restricted activity, respectively. Antihistamines continue to be the mainstay of treatment for allergic disorders. In the case of the first-generation antihistamines, however, the treatment may well be worse than the disease. Although these agents are effective H(1)-receptor antagonists, they are also highly lipophilic and readily cross the blood-brain barrier, causing considerable sedation. The second-generation agents are more lipophobic and possess different ionic charges than the first-generation antihistamines. As a result, they are far less likely to cross the blood-brain barrier and, for that reason, cause little if any sedation. In a recent comparative trial, subjects who were treated with the first-generation agent diphenhydramine were found to have significant performance deficits on tests of divided attention, working memory, vigilance, and speed. By contrast, subjects who were treated with the second-generation antihistamine loratadine performed as well as subjects who were treated with placebo. The sedative effects of the first-generation agents persist well into the next day and thus can potentially interfere with daytime performance and safety even when taken the night before. It is therefore recommended that patients whose occupations require vigilance, divided attention, or concentration receive only second-generation antihistamines.

Loratadine: a non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation.

Although equally potent at blocking the H1 receptor, first- and second-generation antihistamines can be distinguished with respect to their different effects on the central nervous system (CNS). First-generation antihistamines readily cross the blood-brain barrier leading to significant drowsiness, altered mood, reduced wakefulness, and impaired cognitive and psychomotor performance. This paper reviews of studies CNS functioning conducted with loratadine, a second-generation H1-receptor antagonist, at its therapeutic dose of 10 mg per day. Studies employing self-report measures, such as diary cards, visual analogue scales, rating scales, and mood inventories have shown that the effect of loratadine on somnolence, fatigue, and mood was comparable to those found with placebo. In studies exploring physiological indices of CNS functioning, such as EEG-evoked potentials, and sleep latency tests, loratadine has been shown to be free of CNS effects. In addition, studies have investigated the effects of loratadine on actual driving performance, and on tests of cognitive and psychomotor functioning. On all of these performance measures, loratadine has been shown to have effects comparable to placebo. In contrast, diphenhydramine, a common first-generation antihistamine, usually available without a doctor's prescription, has significant adverse effects on vigilance, divided attention, working memory and psychomotor performance. Impairment has been shown to occur even in the absence of self-reported sleepiness.

Computerized assessment in neuropsychology: a review of tests and test batteries.

This article contains detailed reviews of 13 computerized neuropsychological and performance test batteries and six stand-alone computer tests. Tasks found on these instruments are described and tables illustrate which batteries employ which measures. In addition to issues of reliability and validity, special considerations apply to computerized assessment. These issues are discussed and readers are provided information to help them assess computerized tests in relation to their particular clinical and research needs. Since many computerized tests were developed as performance assessment tools, the relationship between performance and neuropsychological assessment is examined.

Impact of sedating antihistamines on safety and productivity.

The use of sedating antihistamines by allergy sufferers remains common, and physicians continue to prescribe these older antihistamines with great frequency. Precautionary statements warning of possible drowsiness and the need for caution when driving or operating machinery, which are required for sedating antihistamines, don't appear to be having much impact. Sedating antihistamines are frequently found to be a causal factor in fatal traffic accidents and are the leading medication found on autopsy of pilots who have crashed their aircraft. Patients taking sedating antihistamines frequently don't feel sleepy, yet they have difficulty staying awake and their brain functioning is impaired. The impact on safety is found in the increased risk of traumatic work-related injuries, driving accidents, and aviation fatalities. The cognitive and psychomotor deficits translate into losses in worker productivity and student learning.

[Stabilized NADH (ENADA) improves jet lag-induced cognitive performance deficit]. / Stabilisiertes NADH (ENADA) verbessert die durch Jetlag reduzierte Hirnleistung.

Current remedies for jet lag (phototherapy, melatonin, stimulant, and sedative medications) are limited in efficacy and practicality. The efficacy of a stabilized, sublingual form of reduced nicotinamide adenine dinucleotide (NADH, ENADAlert, Menuco Corp.) as a countermeasure for jet lag was examined. Because NADH increases cellular production of ATP and facilitates dopamine synthesis, it may counteract the effects of jet lag on cognitive functioning and sleepiness. Thirty-five healthy, employed subjects participated in this double-blind, placebo-controlled study. Training and baseline testing were conducted on the West Coast before subjects flew overnight to the East Coast, where they would experience a 3-hour time difference. Upon arrival, individuals were randomly assigned to received either 20 mg of sublingual stabilized NADH (n = 18) or identical placebo tablets (n = 17). All participants completed computer-administered tests (including Cog Screen) to assess changes in cognitive functioning, mood, and sleepiness in the morning and afternoon. Jet lag resulted in increased sleepiness for over half the participants and deterioration of cognitive functioning for approximately one third. The morning following the flight, subjects experienced lapses of attention in addition to disruptions in working memory, divided attention, and visual perceptual speed. Individuals who received NADH performed significantly better on 4 cognitive test measures (P < or = .05) and reported less sleepiness compared with those who received placebo. No adverse effects were observed with NADH treatment. Stabilized NADH significantly reduced jet lag-induced negative cognitive effects and sleepiness, was easily administered, and was found to have no side effects.

Relating cognitive function to military aviator performance in early HIV infection.

There has been controversy about whether cognitive changes occur in early human immunodeficiency virus (HIV) disease. In those studies reporting cognitive changes, these are typically subclinical, and their relationship to daily and/or occupational functioning has not been addressed. The potential effects of changes may vary as a function of occupational demands. This is germane to military performance, where occupational demands cover a wide spectrum of complexity. In particular, such effects are important to consider in the many cognitively demanding specialties associated with military aviation. This paper will explore ways in which possible HIV-related military performance decrements in aviators may be measured empirically. First, studies from Walter Reed Army Medical Center (WRAMC), which have shown cognitive changes in early HIV disease, will be described. This will be followed by a summary of presentations and discussions at a conference in November 1990, entitled 'HIV and Military Performance: Assessment Methodologies' held at WRAMC. The third section of the paper will describe a programme of research, which is developing measures to detect cognitive difficulties in civilian aviators. The application of measures from this research to research on HIV will be discussed. Finally, a research programme being developed to examine the possible impact of HIV-related cognitive changes on military aviator performance will be described.

Discriminability of the Wisconsin Card Sorting Test using the standardization sample.

The four neurological patient groups and the normals from the Wisconsin Card Sorting Test (WCST) standardization sample were used to examine the discriminability of the WCST's indices. Results reveal consistent differentiation of normals from the patient groups on all WCST variables, with classification rates averaging 71% accuracy. However, patient groups with frontal, diffuse, and nonfrontal lesions were not consistently discriminable from each other. The results suggest that the WCST is most usefully conceptualized as a measure of executive abilities that involves the frontal lobes, but should not be considered solely as a marker of isolated frontal lobe pathology.

Effect of cerebral lesions on continuous performance test responses of school age children born prematurely.

Examined attention skills, as measured by the Continuous Performance Test (CPT), in a group of 64 children born premature and 40 full-term children, ages 6 to 8 years. Premature children were classified by neonatal cerebral lesions into no lesion, mild lesion, and severe lesion groups. It was predicted that severity of lesion would be associated with CPT performance. While mean differences among the groups of prematures did not reach significance, children with severe lesions made significantly more errors of omission and commission than the full-term comparison group. Children with mild lesions were poorer than full terms in errors of commission. Children with no lesions also made more errors of omission and commission than full terms, suggesting attention deficits secondary to prematurity even in the absence of identified brain lesion. With increasing severity of lesion, increasing percentages of each group were found to perform more than 2 SD below the mean in errors of commission. Results suggest that premature children, with and without identified lesions, are at risk for attention deficits.