Psychometric task performance measures can be highly sensitive to manipulations that impair functional alertness in young adults; such measures have been shown to be less sensitive to reduced alertness in older adults. The purpose of this study is to determine whether neurophysiologic measures can aid in the detection and characterization of impairments in functional alertness in the elderly.
Double-blind, placebo-controlled, counter-balanced, crossover study.
Twelve healthy older adults (62-75 years of age).
Diphenhydramine, 50 mg.
Behavioral performance and electroencephalogram measures were obtained while participants completed spatial working memory and word recognition episodic memory tasks in a baseline interval before drug ingestion and in 4 hourly test intervals following drug ingestion. Relative to placebo, diphenhydramine had marginal effects on task performance yet was effective in reducing alertness, as evidenced by subjective ratings and objective neurophysiologic (electroencephalogram) markers. Diphenhydramine significantly reduced the amplitude of alertness-sensitive event-related potentials recorded during working memory task performance, including the N160 and P300. It also affected neurophysiologic processes underlying episodic memory, as evidenced by a reduction in the difference in event-related potentials between old and new words in the word recognition task. Discriminant analyses incorporating neurophysiologic measures showed that the time course of the central effects of diphenhydramine in older subjects was similar to that previously observed in young adults.
These results demonstrate that diphenhydramine has adverse neurocognitive effects in elderly individuals and highlights the utility of incorporating direct measures of brain function into assessments of functional alertness.
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[Show abstract][Hide abstract] ABSTRACT: Background: The development of better treatments for brain diseases of the elderly will necessitate more sensitive and efficient means of repeatedly assessing an individual’s neurocognitive status. Aim: To illustrate the development of an assessment combining episodic memory and working memory tasks with simultaneous electroencephalography and evoked potential (EP) brain function measures. Methods: Data from matched groups of elderly subjects with mildly impaired episodic verbal memory on neuropsychological tests and those with no objective signs of impairment were used for scale development. An exploratory multivariate divergence analysis selected task performance and neurophysiological variables that best recognized impairment. Discriminant validity was then initially assessed on separate impaired and unimpaired groups. Results: Decreased response accuracy and parietal late positive component EP amplitude in the episodic memory task best characterized impaired subjects. Sensitivity in recognizing impairment in the validation analysis was 89% with 79% specificity (area under the curve = 0.94). Retest reliability was 0.89 for the unimpaired and 0.74 for the impaired validation groups. Conclusion: These promising initial results suggest that with further refinement and testing, an assessment combining cognitive task performance with simultaneous neurofunctional measures could eventually provide an important benefit for clinicians and researchers.
[Show abstract][Hide abstract] ABSTRACT: To assess the size, time course, and durability of the effects of long-term continuous positive airway pressure (CPAP) therapy on neurocognitive function, mood, sleepiness, and quality of life in patients with obstructive sleep apnea.
Randomized, double-blinded, 2-arm, sham-controlled, multicenter, long-term, intention-to-treat trial of CPAP therapy.
Sleep clinics and laboratories at 5 university medical centers and community-based hospitals. Patients or Participants: Target enrollment is 1100 randomly assigned subjects across 5 clinical centers.
Active versus sham (subtherapeutic) CPAP. Measurements and Results: A battery of conventional and novel tests designed to evaluate neurocognitive function, mood, sleepiness, and quality of life.
The Apnea Positive Pressure Long-term Efficacy Study (APPLES) is designed to study obstructive sleep apnea and test the effects of CPAP through a comprehensive, controlled, and long-term trial in a large sample of subjects with obstructive sleep apnea.
Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 08/2006; 2(3):288-300. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relative effects of levetiracetam (LEV) and carbamazepine (CBZ) on cognitive and neurophysiologic measures are uncertain.
The effects of LEV and CBZ were compared in healthy adults using a randomized, double-blind, two-period crossover design. Outcome measures included 11 standard neuropsychological tests and the score from a cognitive-neurophysiologic test of attention and memory. Evaluations were conducted at screening, baseline pre-drug treatment, end of each maintenance phase (4 weeks), and end of each washout period after drug treatment.
A total of 28 adults (17 women) with mean age of 33 years (range 18 to 51) completed the study. Mean maintenance doses (+/-SD) were CBZ = 564 mg/day (110) and LEV = 2,000 mg/day (0). CBZ was adjusted to mid-range therapeutic level. Mean serum levels (+/-SD) were CBZ = 7.5 mcg/mL (1.5) and LEV = 32.2 mcg/mL (11.2). An overall composite score including all measures revealed worse effects for CBZ compared to LEV (p <or= 0.001) in the primary analysis and for CBZ (p <or= 0.001) and LEV (p <or= 0.05) compared to non-drug in secondary analyses. Across the 34 individual variables, CBZ was worse than LEV on 44% (15/34); none favored CBZ. Compared to the non-drug average, CBZ was worse for 76% (26/34), and LEV was worse for 12% (4 of 34). Sensitivity and specificity of standard neuropsychological tests and the cognitive-neurophysiologic test were determined to direct future studies; detection was most accurate by the cognitive-neurophysiologic test.
Levetiracetam produces fewer untoward neuropsychological and neurophysiologic effects than carbamazepine in monotherapy at the dosages and timeframes employed in this study.