Burst-suppression ratio underestimates absolute duration of electroencephalogram suppression compared with visual analysis of intraoperative electroencephalogram.

BACKGROUND: Machine-generated indices based on quantitative electroencephalography (EEG), such as the patient state index (PSI™) and burst-suppression ratio (BSR), are increasingly being used to monitor intraoperative depth of anaesthesia in the endeavour to improve postoperative neurological outcomes, such as postoperative delirium (POD). However, the accuracy of the BSR compared with direct visualization of the EEG trace with regard to the prediction of POD has not been evaluated previously. METHODS: Forty-one consecutive patients undergoing non-cardiac, non-intracranial surgery with general anaesthesia wore a SedLine ® monitor during surgery and were assessed after surgery for the presence of delirium with the Confusion Assessment Method. The intraoperative EEG was scanned for absolute minutes of EEG suppression and correlated with the incidence of POD. The BSR and PSI™ were compared between patients with and without POD. RESULTS: Visual analysis of the EEG by neurologists and the SedLine ® -generated BSR provided a significantly different distribution of estimated minutes of EEG suppression ( P =0.037). The Sedline ® system markedly underestimated the amount of EEG suppression. The number of minutes of suppression assessed by visual analysis of the EEG was significantly associated with POD ( P =0.039), whereas the minutes based on the BSR generated by SedLine ® were not associated with POD ( P =0.275). CONCLUSIONS: Our findings suggest that SedLine ® (machine)-generated indices might underestimate the minutes of EEG suppression, thereby reducing the sensitivity for detecting patients at risk for POD. Thus, the monitoring of machine-generated BSR and PSI™ might benefit from the addition of a visual tracing of the EEG to achieve a more accurate and real-time guidance of anaesthesia depth monitoring and the ultimate goal, to reduce the risk of POD.

Impact of intraoperative hypotension and blood pressure fluctuations on early postoperative delirium after non-cardiac surgery.

INTRODUCTION: Postoperative delirium is common in older patients. Despite its prognostic significance, the pathophysiology is incompletely understood. Although many risk factors have been identified, no reversible factors, particularly ones potentially modifiable by anaesthetic management, have been identified. The goal of this prospective cohort study was to investigate whether intraoperative hypotension was associated with postoperative delirium in older patients undergoing major non-cardiac surgery. METHODS: Study subjects were patients >65 years of age, undergoing major non-cardiac surgery, who were enrolled in an ongoing prospective observational study of the pathophysiology of postoperative delirium. Intraoperative blood pressure was measured and predefined criteria were used to define hypotension. Delirium was measured by the Confusion Assessment Method on the first two postoperative days. Data were analysed using t-tests, two-sample proportion tests and ordered logistic regression multivariable models, including correction for multiple comparisons. RESULTS: Data from 594 patients with a mean age of 73.6 years (sd 6.2) were studied. Of these 178 (30%) developed delirium on day 1 and 176 (30%) on day 2. Patients developing delirium were older, more often female, had lower preoperative cognitive scores, and underwent longer operations. Relative hypotension (decreases by 20, 30, or 40%) or absolute hypotension [mean arterial pressure (MAP)<50 mm Hg] were not significantly associated with postoperative delirium, nor was the duration of hypotension (MAP<50 mm Hg). Conversely, intraoperative blood pressure variance was significantly associated with postoperative delirium. DISCUSSION: These results showed that increased blood pressure fluctuation, not absolute or relative hypotension, was predictive of postoperative delirium.

Factors contributing to racial differences in gait mechanics differ by sex.

BACKGROUND: Racial differences in gait mechanics have been recently reported, but we don't know what factors may drive differences in gait and whether these factors are innate or modifiable. The answers to those questions will inform both basic research and clinical interventions and outcomes. RESEARCH QUESTION: Do anthropometric, strength, and health status measures explain racial differences in gait between African Americans (AA) and white Americans (WA)? METHODS: Venous blood samples, anthropometric measures, lower extremity strength, and an assessment of health status were collected from 92 participants (18-30 years old) as part of an Institutional Review Board-approved study. 3D motion capture and force plate data were recorded during 7 walking trials at set regular (1.35 m/s) and fast (1.6 m/s) speeds. Racial differences in gait were identified at both speeds. Correlations between anthropometric, strength, and health status independent variables and outcome measures were computed after stratifying data by sex. Stepwise linear regression models evaluated whether the inclusion of anthropometric, strength, and health status independent variables explained racial effects. RESULTS: In males, no racial differences in gait were explained by independent variables. Q-angle and ankle dorsiflexion strength accounted for racial differences in self-selected walking speed in females. Racial differences in ankle plantarflexion angle were explained by ankle plantarflexion strength differences. SIGNIFICANCE: Factors that explain racial differences in gait in females were both innate and modifiable. These data make clear that it is important to include racially diverse normative gait databases in research studies. These results also identify potential intervention targets aimed at reducing racial health disparities.

Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride.

OBJECTIVES: To evaluate the cognitive effects of acute challenges with the antispasmodic agent oxybutynin hydrochloride in normal older volunteers and to compare these effects with those attributable to diphenhydramine, another commonly used medication with anticholinergic (muscarinic-blocking) activity. DESIGN: A double-blind, placebo-controlled cross-over study. SETTING: Laboratory evaluations of community subjects. PARTICIPANTS: A convenience sample of 12 volunteers, average age 69.17 years. INTERVENTION: Baseline assessment was followed by randomized administration of a placebo, oxybutynin hydrochloride (5 and 10 mg), and diphenhydramine hydrochloride (50 mg) in test sessions separated by 1 week. MEASUREMENTS: Evaluation of cognitive performance with a 1-hour battery of pencil and paper, interviewer-administered, and computer-administered tests beginning 90 minutes after drug (or placebo) administration. RESULTS: Random regression analyses demonstrated that oxybutynin caused significant cognitive decrements on seven of 15 cognitive measures, and diphenhydramine caused decrements on five measures. The most sensitive measures for detecting the effects of oxybutynin hydrochloride were the Buschke Selective Reminding Test and Reaction Time. CONCLUSIONS: These findings demonstrate that oxybutynin can cause cognitive impairment and suggest that physicians prescribing it should monitor their patients to facilitate the early recognition of those who experience drug-related cognitive deficits. More generally, the findings demonstrate that systematic research with normal volunteers can identify cognitive toxicity not recognized during the process of drug development or postmarketing surveillance.

Effects of exercise training in the elderly on the occurrence and time to onset of cardiovascular diagnoses.

To examine the long-term effects of aerobic exercise on the occurrence and time to onset of cardiovascular diagnoses, 184 initially healthy older subjects were randomized into either a long-term exercise group (Group A, n = 80), a short-term exercise group (Group B, n = 42), or a contract control group (Group C, n = 62). After completion of two years in the study, data on new cardiovascular diagnoses and time to onset of these diagnoses in each of the three groups were compared. The occurrence rates for new onset diagnoses were as follows: Group A, 2.5%; Group B, 2%; and Group C, 13%; the average time to onset was greatest for the long-term exercisers and shortest for the contact control group (P less than or equal to .02). The results suggest that a regular program of exercise may have cardiovascular benefits for those over 60 years of age.

Reduced employment in caregivers of frail elders: impact of ethnicity, patient clinical characteristics, and caregiver characteristics.

BACKGROUND: Without family caregivers, many frail elders who live at home would require nursing home care. However, providing care to frail elders requires a large time commitment that may interfere with the caregiver's ability to work. Our goal was to determine the patient and caregiver characteristics associated with the reduction of employment hours in caregivers of frail elders. METHODS: This was a cross-sectional study of 2806 patients (mean age 78, 73% women, 29% African American, 12% Hispanic, 54% with dementia) with at least one potentially working caregiver (defined as one who is either currently employed or who would have been employed if they had not been providing care) and their 4592 potentially working caregivers. Patients were enrollees at 11 sites of the Program of All-Inclusive Care for the Elderly (PACE). Social workers interviewed patients and caregivers at the time of PACE enrollment. Caregivers were asked if they had reduced the hours they worked or had stopped working to care for the patient. Nurses interviewed patients and caregivers to assess independence in activities of daily living (ADLs) and the presence of behavioral disturbances. Comorbid conditions were assessed by physicians during enrollment examinations. RESULTS: A total of 604 (22%) of the 2806 patients had at least one caregiver who either reduced the number of hours they worked or quit working to care for the patient. Patient characteristics independently associated with a caregiver reducing hours or quitting work were ethnicity, 95% confidence interval [CI] 1.14-1.78 for African American;, 95% CI 1.43-2.52 for Hispanic), ADL function below the median (, 95% CI 1.44-2.15), a diagnosis of dementia (, 95% -2.17 if associated with a behavioral disturbance;, 95% CI 1.06-1.63 if not associated with a behavioral disturbance), or a history of stroke (OR = 1.42, 95% CI 1.16-1.73). After controlling for these patient characteristics, caregiver characteristics associated with reducing work hours included being the daughter or daughter-in-law of the patient (OR = 1.69, 95% CI 1.37-2.08) and living with the patient (OR = 4.66, 95% CI 3.65-5.95 if no other caregiver lived at home, OR = 2.53, 95% CI 2.03-3.14 if another caregiver lived at home). CONCLUSIONS: Many caregivers reduce the number of hours they work to care for frail elderly relatives. The burden of reduced employment is more likely to be incurred by the families of ethnic minorities and of patients with specific clinical characteristics. Daughters and caregivers who live with the patient are more likely to reduce work hours than other caregivers. Future research should examine the impact of lost caregiver employment on patients' families and the ways in which the societal responsibility of caring for frail elders can be equitably shared.

Psychological stress perturbs epidermal permeability barrier homeostasis: implications for the pathogenesis of stress-associated skin disorders.

BACKGROUND: A large number of skin diseases, including atopic dermatitis and psoriasis, appear to be precipitated or exacerbated by psychological stress. Nevertheless, the specific pathogenic role of psychological stress remains unknown. In 3 different murine models of psychological stress, it was recently shown that psychological stress negatively impacts cutaneous permeability barrier function and that coadministration of tranquilizers blocks this stress-induced deterioration in barrier function. OBJECTIVES AND METHODS: The relationship between psychological stress and epidermal permeability barrier function was investigated in 27 medical, dental, and pharmacy students without coexistent skin disease. Their psychological state was assessed with 2 well-validated measures: the Perceived Stress Scale and the Profile of Mood States. Barrier function was assessed simultaneously with the stress measures at periods of presumed higher stress (during final examinations) and at 2 assumed, lower stress occasions (after return from winter vacation [approximately 4 weeks before final examinations] and during spring vacation [approximately 4 weeks after final examinations]). RESULTS: The subjects as a group demonstrated a decline in permeability barrier recovery kinetics after barrier disruption by cellophane tape stripping, in parallel with an increase in perceived psychological stress during the higher vs the initial lower stress occasions. During the follow-up, presumed lower stress period, the subjects again displayed lower perceived psychological stress scores and improved permeability barrier recovery kinetics, comparable to those during the initial lower stress period. Moreover, the greatest deterioration in barrier function occurred in those subjects who demonstrated the largest increases in perceived psychological stress. CONCLUSION: These studies provide the first link between psychological status and cutaneous function in humans and suggest a new pathophysiological paradigm, ie, stress-induced derangements in epidermal function as precipitators of inflammatory dermatoses.

Change and stability in adult intellectual functioning assessed by Wechsler item responses.

Change in adult intellectual performance was assessed with longitudinal data from the Intergenerational Studies at the Institute of Human Development. Wechsler Intelligence data from two age cohorts spanning ages 18 to 61 were analyzed at the subtest and item level. Hotelling T2 analyses on sets of equivalent items from Wechsler subtests were studied to determine if change in response occurred between pairwise combinations of occasions of test administrations. We used Bowker's test to analyze data at the item level to determine the direction of change in performance. Consistent improvement in performance occurred between the ages of 18-40 and 18-54. Between the ages of 40 and 61, results showed mostly improved performance on the Information, Comprehension, and Vocabulary subtests, mixed change on the Picture Completion subtest, and decline on the Digit Symbol and Block Design subtests. The pattern of mixed change on the Picture Completion subtest indicated improvement on the easy items and decline on the difficult items. Decline in performance on the Block Design test occurred only for the most difficult items.

Clock drawing as an assessment tool for dementia.

Clock drawing has recently been shown to lie useful in differentiating Alzieimer's disease patients from normal controls. Our procedure for clock drawing differed from other published reports in that a copy condition was employed and patients were asked to set clock hands to read "ten after eleven". We found both clock drawing procedures to be correlated with tests related to executive and visuospatial functioning. In both conditions, nondemented controls performed significantly better than demented patients. In the command condition there was no difference between Alzheimer patients and patients with cerebrovascular dementia. In the copy condition, patients with cerebrovascular dementia performed significantly worse than Alzheimer patients. The inclusion of a copy condition appears to greatly expand the utility of this test. Although our scoring system did not differentiate between various dementing disorders in the command condition, if clock drawing is used as a screening instrument, lack of improvement in the copy condition in comparison to the command condition may be a sign of a vascular involvement.

Further analyses of clock drawings among demented and nondemented older subjects.

In a previous article we described a 10-point scoring system (i.e., scale 1) to grade clock drawings to command and copy with hands set for "ten after 11" among demented patients. Alzheimer's subjects (AD) improved from the command to copy conditions, whereas subjects with ischaemic vascular dementia (IVD) did not. To investigate the underlying cognitive deficits responsible for this profile, an additional scale was developed (scale 2) that tallied errors in graphomotor functioning, hand/number placement, and executive control. On an independent sample of subjects, AD subjects, again, made significant improvement on scale 1 from the command to copy condition, whereas no such improvement occurred among the IVD subjects. On scale 2, IVD subjects made more graphomotor errors in the command condition, and more executive control and more total errors in the copy conditions than AD subjects. A number of positive correlations were noted between tests of language and memory on scale 1. By contrast, scores on tests of executive control declined as scale 2 errors increased. In addition, a principal component analysis indicated that scale 2 test performance loaded on a factor with other tests related to executive control. These results suggest that impairment in frontal systems functioning may explain why IVD subjects do not improve from the command to copy conditions on scale 1. Such a pattern of performance in clock drawing may also be helpful in making a differential diagnosis between AD and IVD.

Nitrous oxide does not change the incidence of postoperative delirium or cognitive decline in elderly surgical patients.

BACKGROUND: Postoperative delirium and cognitive decline are common in elderly surgical patients after non-cardiac surgery. Despite this prevalence and clinical importance, no specific aetiological factor has been identified for postoperative delirium and cognitive decline. In experimental setting in a rat model, nitrous oxide (N(2)O) produces neurotoxic effect at high concentrations and in an age-dependent manner. Whether this neurotoxic response may be observed clinically has not been previously determined. We hypothesized that in the elderly patients undergoing non-cardiac surgery, exposure to N(2)O resulted in an increased incidence of postoperative delirium than would be expected for patients not receiving N(2)O. METHODS: Patients who were >or=65 yr of age, undergoing non-cardiac surgery and requiring general anaesthesia were randomized to receive an inhalational agent and either N(2)O with oxygen or oxygen alone. A structured interview was conducted before operation and for the first two postoperative days to determine the presence of delirium using the Confusion Assessment Method. RESULTS: A total of 228 patients were studied with a mean (range) age of 73.9 (65-95) yr. After operation, 43.8% of patients developed delirium. By multivariate logistic regression, age [odds ratio (OR) 1.07; 95% confidence interval (CI) 1.02-1.26], dependence on performing one or more independent activities of daily living (OR 1.54; 95% CI 1.01-2.35), use of patient-controlled analgesia for postoperative pain control (OR 3.75; 95% CI 1.27-11.01) and postoperative use of benzodiazepine (OR 2.29; 95% CI 1.21-4.36) were independently associated with an increased risk for postoperative delirium. In contrast, the use of N(2)O had no association with postoperative delirium. CONCLUSIONS: Exposure to N(2)O resulted in an equal incidence of postoperative delirium when compared with no exposure to N(2)O.

Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients.

In this randomized pilot clinical trial, the authors tested the hypothesis that using gabapentin as an add-on agent in the treatment of postoperative pain reduces the occurrence of postoperative delirium. Postoperative delirium occurred in 5/12 patients (42%) who received placebo vs 0/9 patients who received gabapentin, p = 0.045. The reduction in delirium appears to be secondary to the opioid-sparing effect of gabapentin.

Blood pressure and intellectual functioning in late midlife.

To determine how much change in cognitive performance can be attributed to blood pressure status, 103 adults were assessed on two occasions approximately 11 years apart. Subjects' ages ranged from 49 to 63 years on the second occasion. Regression analyses were performed to determine how much variance in change in performance on the Digit Span, Block Design, Object Assembly, and Digit Symbol tests was accounted for by blood pressure status. Time 1 and Time 2 diastolic blood pressure, and change in hypertension medication significantly predicted Time 2 performance on the Digit Span Forward test even after Time 1 test performance, age, education, and gender were accounted for. The results further confirm the importance of assessing health functioning when studying age-related changes in cognitive performance.

Effects of sensory and motor functioning on adult intellectual performance.

This study examined longitudinal health and intelligence data to determine whether sensory or motor deficits account for some of the age-related intellectual changes that are commonly seen from midlife onward. Although sensory and motor functioning did not account for the age-related decrements in performance on speeded, visual perceptual tasks found for this sample in previous work, we did find that hearing deficits added error variance to performance estimates on two verbal subtests of the Wechsler scales.

Self-restriction of medications due to cost in seniors without prescription coverage.

OBJECTIVE: Little is known about patients who skip doses or otherwise avoid using their medications because of cost. We sought to identify which elderly patients are at highest risk of restricting their medications because of cost, and how prescription coverage modifies this risk. DESIGN AND PARTICIPANTS: Cross-sectional study from the 1995-1996 wave of the Survey of Asset and Health Dynamics Among the Oldest Old, a population-based survey of Americans age 70 years and older. MEASUREMENTS: Subjects were asked the extent of their prescription coverage, and whether they had taken less medicine than prescribed for them because of cost over the prior 2 years. We used bivariate and multivariate analyses to identify risk factors for medication restriction in subjects who lacked prescription coverage. Among these high-risk groups, we then examined the effect of prescription coverage on rates of medication restriction. MAIN RESULTS: Of 4,896 seniors who regularly used prescription medications, medication restriction because of cost was reported by 8% of subjects with no prescription coverage, 3% with partial coverage, and 2% with full coverage (P <.01 for trend). Among subjects with no prescription coverage, the strongest independent predictors of medication restriction were minority ethnicity (odds ratio [OR], 2.9 compared with white ethnicity; 95% confidence interval [95% CI], 2.0 to 4.2), annual income <$10,000 (OR, 3.8 compared with income > or =$20,000; 95% CI, 2.4 to 6.1), and out-of-pocket prescription drug costs >$100 per month (OR, 3.3 compared to costs < or =$20; 95% CI, 1.5 to 7.2). The prevalence of medication restriction in members of these 3 risk groups was 21%, 16%, and 13%, respectively. Almost half (43%) of subjects with all 3 risk factors and no prescription coverage reported restricting their use of medications. After multivariable adjustment, high-risk subjects with no coverage had 3 to 15 times higher odds of medication restriction than subjects with partial or full coverage (P <.01). CONCLUSIONS: Medication restriction is common in seniors who lack prescription coverage, particularly among certain vulnerable groups. Seniors in these high-risk groups who have prescription coverage are much less likely to restrict their use of medications.

Monitoring Alzheimer's patients for acute changes in cognitive functioning.

To develop and evaluate the use of cognitive monitoring for detecting episodes of acute, excess cognitive decline in individual Alzheimer's disease (AD) patients, the authors conducted six repeated cognitive assessments over 11 weeks on 41 otherwise healthy people with mild-to-moderate AD. Patients demonstrated stable cognitive performance over 11 weeks on seven standard neuropsychological tests. Prediction intervals quantitatively defined the expected limits of cognitive decline. They indicated with 90% certainty that over the 11-week period, healthy mild-to-moderate AD patients should not decline more than 4 points on the Word List Recall test, 3 points on the Digit Span test, or 8 items on the Digit Symbol or Verbal Fluency tests. The cognitive stability of healthy AD patients indicates that it is possible to monitor them for acute, excess cognitive decline.

Assessing individual patients for cognitive benefits from acetylcholinesterase inhibitors.

To evaluate an objective method for individually assessing Alzheimer patients for cognitive benefits from acetylcholinesterase inhibitors, we conducted a secondary analysis of data from 234 subjects enrolled in a 30-week efficacy trial of tacrine hydrochloride. We determined which patients showed treatment-related improvement on the Alzheimer Disease Assessment Scale--Cognitive subscale (ADAS-Cog) and the MiniMental State Examination (MMSE). Four weeks after administration of the maximum dose, 14% showed significant improvement from baseline in their ADAS-Cog scores, and 30.6% showed significant improvement in their MMSE scores. Examination of response patterns over time revealed that 65% of patients showed no improvement in MMSE scores during the 120-160-mg phases of the trial, whereas 18% showed consistent improvement in MMSE scores during that time. Three percent of patients showed improvement in their MMSE scores only for the 160-mg assessment. How the methodology from this study can be generalized to other Alzheimer patients is discussed. We calculated prediction intervals to document the magnitude of fluctuation in performance that is normal for Alzheimer patients similar to those in this study. Patients who change more than the limit specified by the prediction interval have statistically significantly improved performance. We determined that an improvement on the MMSE of three or more points across a time period of 6 weeks marks statistically significant change for an individual. For intervals between 6 and 16 weeks, improvement of four or more points on the MMSE is statistically significant. The results indicate that monitoring individual patients for statistically significant improvements in cognitive functioning is feasible, sensitive to drug-related changes in performance, and could facilitate drug monitoring in patients.

Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases.

BACKGROUND: An accurate, sensitive, but brief quality-of-life outcomes measure is needed for studies of dermatologic care. OBJECTIVE: To construct a single-page version of Skindex (a dermatologic quality-of-life instrument) that would have two new features compared with the current 29-item version: (1) fewer items to which a majority of patients choose the same response, and (2) measurement of bother rather than frequency of patient experiences. METHODS: Random samples of patients waiting for dermatology appointments in clinics of Veterans Affairs hospitals and in private dermatology practices completed questionnaires; 692 patients responded to the parent instrument and 541 additional patients responded to the brief version. Reproducibility, internal consistency reliability, validity, and responsiveness of the brief version of Skindex were determined. RESULTS: For 16 items of the current 29-item version (55%), more than 50% of patients responded "Never." After an explicit process of item analysis and elimination, a single-page 16-item version was composed that asks patients about bother from their experiences; responses are reported as three scales, Symptoms, Emotions, and Functioning. For 6 items of the 16-item version (38%), more than 50% of patients responded "Never." Scale scores were reproducible after 72 hours (r = 0.88-0.90) and were internally reliable (Cronbach's alpha = 0.86-0.93). The instrument demonstrated both content and construct validity: Most patients' responses to an open-ended question about their skin disease was addressed by the items; patients with inflammatory dermatoses had higher scores than those with isolated lesions; and in an exploratory principal axes factor analysis with an oblique rotation, 74% of the common variance was explained by three factors that correlated with the a priori scales. Mean scale scores stayed the same or changed in the expected direction in patients who reported that their skin was the same or had improved. CONCLUSION: This brief single-page version of Skindex accurately and sensitively measures how much patients are bothered by their skin conditions.

Bedside clinical and electrophysiological assessment: assessment of change in vulnerable patients.

Current approaches to the diagnosis of delirium are based upon the recognition of symptoms that emerge in the pathological state. As an alternative, we propose an approach to case identification for research purposes based on the recognition of significant changes in the cognitive or cerebral state of the individual patient. Categorical change can be defined using prediction intervals calculated from repeated measures on a population of medically stable subjects. Data from subjects enrolled in a prospective study of delirium in a long-term care population were utilized to calculate prediction intervals for the Mini-Mental Status Examination and for measures of the electroencephalographic background frequency as obtained with a two-channel microprocessor-based EEG device. Preliminary findings support the validity of this quantitative approach for defining changes in brain state. Future research should evaluate both cognitive and electrophysiological techniques for monitoring vulnerable patients.

Examination of the cognitive effects of cimetidine in normal elderly volunteers.

The authors evaluated the cognitive effects of acute challenges with the H2 receptor-antagonist cimetidine in normal older volunteers. The study was a double-blind, placebo-controlled, crossover study of 12 volunteers, average age 71.25 years. Baseline assessment was followed by randomized administration of a placebo or ascending doses of cimetidine (400 mg, 800 mg, or 1,600 mg) in test sessions separated by 1 week. Cognitive performance was evaluated with a 1-hour battery of tests beginning 90 minutes after administration of a single dose of drug (or placebo). There were no significant cognitive decrements associated with cimetidine. Despite numerous case reports of cognitive toxicity, this study found no observable decrements in cognitive performance in a group of healthy elderly subjects; therefore, case reports in the literature may be reporting effects for patients with specific impairments or sensitivities.