Shirley S. Kishiyama

Randomized controlled trial of yoga and exercise in multiple sclerosis

Objective: To determine the effect of yoga and of aerobic exercise on cognitive function, fatigue, mood, and quality of life in multiple sclerosis (MS). Methods: Subjects with clinically definite MS and Expanded Disability Status Score less than or equal to 6.0 were randomly assigned to one of three groups lasting 6 months: weekly Iyengar yoga class along with home practice, weekly exercise class using a stationary bicycle along with home exercise, or a waiting-list control group. Outcome assessments performed at baseline and at the end of the 6-month period included a battery of cognitive measures focused on attention, physiologic measures of alertness, Profile of Mood States, State-Trait Anxiety Inventory, Multi-Dimensional Fatigue Inventory (MFI), and Short Form (SF)-36 health-related quality of life. Results: Sixty-nine subjects were recruited and randomized. Twelve subjects did not finish the 6-month intervention. There were no adverse events related to the intervention. There were no effects from either of the active interventions on either of the primary outcome measures of attention or alertness. Both active interventions produced improvement in secondary measures of fatigue compared to the control group: Energy and Fatigue (Vitality) on the SF-36 and general fatigue on the MFI. There were no clear changes in mood related to yoga or exercise. Conclusion: Subjects with MS participating in either a 6-month yoga class or exercise class showed significant improvement in measures of fatigue compared to a waiting-list control group. There was no relative improvement of cognitive function in either of the intervention groups.

Adherence to yoga and exercise interventions in a 6-month clinical trial

BackgroundTo determine factors that predict adherence to a mind-body intervention in a randomized trial.DesignWe analyzed adherence data from a 3-arm trial involving 135 generally healthy seniors 65–85 years of age randomized to a 6-month intervention consisting of: an Iyengar yoga class with home practice, an exercise class with home practice, or a wait-list control group. Outcome measures included cognitive function, mood, fatigue, anxiety, health-related quality of life, and physical measures. Adherence to the intervention was obtained by class attendance and biweekly home practice logs.ResultsThe drop-out rate was 13%. Among the completers of the two active interventions, average yoga class attendance was 77% and home practice occurred 64% of all days. Average exercise class attendance was 69% and home exercise occurred 54% of all days. There were no clear effects of adherence on the significant study outcomes (quality of life and physical measures). Class attendance was significantly correlated with baseline measures of depression, fatigue, and physical components of health-related quality of life. Significant differences in baseline measures were also found between study completers and drop-outs in the active interventions. Adherence was not related to age, gender, or education level.ConclusionHealthy seniors have good attendance at classes with a physically active intervention. Home practice takes place over half of the time. Decreased adherence to a potentially beneficial intervention has the potential to decrease the effect of the intervention in a clinical trial because subjects who might sustain the greatest benefit will receive a lower dose of the intervention and subjects with higher adherence rates may be functioning closer to maximum ability before the intervention. Strategies to maximize adherence among subjects at greater risk for low adherence will be important for future trials, especially complementary treatments requiring greater effort than simple pill-taking.

Pharmacologically induced changes in arousal: effects on behavioral and electrophysiologic measures of alertness and attention

The relationships between the diffuse subcortical neurotransmitter systems and behavioral and physiologic measures of alertness and attention are not well understood. This study was designed to further understand these relationships. In this double-blind experiment, 23 subjects ingested methylphenidate, diphenhydramine or placebo on 3 different days and performed behavioral and cognitive tasks including covert orienting of spatial attention and visual search tasks. Subjective and physiologic measures of alertness included EEG frequency analysis, EEG event-related desynchronization, and amount of sleep and sleep onset time in the unstimulated eyes closed state. Performance on the cognitive tasks improved with MP and worsened with DPHA, but there were no specific attentional effects. The best measures of alertness were based on self-rated scales and on EEG recorded in the unstimulated eyes closed state. These observations suggest that methylphenidate and diphenhydramine primarily affected overall state and that healthy humans were able to partially compensate for the pharmacologically induced alertness changes during cognitive task performance.

Expectancy effect: impact of pill administration on cognitive performance in healthy seniors.

Expectancy or placebo effects on cognitive function have not been well studied. To determine the effect of taking pills on cognitive function, 40 participants were randomly assigned to a pill or no-pill condition. Healthy seniors who took a 2-week supply of methylcellulose pills, which they were told was an experimental cognitive enhancer, were compared to seniors not taking any pills. There were 2 primary outcome measures defined prior to the study—Consortium to Establish a Registry for Alzheimers Disease (CERAD) Word List delayed recall and Stroop color word task time—as well as 7 other cognitive outcome measures. There was a significant effect of pill taking on the 2 primary outcome measures. There was also an effect of pill taking on choice reaction time and Word List immediate recall but not on the other 5 secondary cognitive outcome measures. In an exploratory analysis of potential predictors of the expectancy effect, perceived stress and self-efficacy but not personality traits interacted with the pill-taking effect on cognitive function. Further characterizing and understanding this observed expectancy effect is important to maximize cognitive health and improve clinical trial design.

Attention deficit in Alzheimer's disease is not simulated by an anticholinergic/antihistaminergic drug and is distinct from deficits in healthy aging

Objective.: To evaluate attention deficit in Alzheimers disease (AD) and its relationship to attention deficits associated with aging and with medications altering alertness. Methods.: Ten patients with probable AD, 10 healthy old controls, and 15 young controls performed a covert orienting of spatial attention task. Young controls performed the task an additional time after ingestion of diphenhydramine 1 mg/kg. Reaction times were obtained following valid, neutral, and invalid cues. Results.: In all groups, the reaction times were shortest for the validly cued stimuli and longest for the invalidly cued stimuli. Additionally, the AD patients performed disproportionately worse following the invalid cue than did the control groups. Young controls given diphenhydramine had decreased subjective alertness, performed worse than they did before drug but better than the old controls or AD patients, and had no disproportionate impairment with the invalid cue. Conclusions.: AD patients have disproportionate problems shifting spatial attention compared with age-matched controls. Impaired attentional performance in AD cannot be simulated in young subjects by ingestion of a combined antihistamine/anticholinergic agent at a dose sufficient to produce significant changes in alertness.

Cognition and fatigue in multiple sclerosis: Potential effects of medications with central nervous system activity.

To evaluate the potential effects of medications with central nervous system (CNS) activity on cognitive function and fatigue in multiple sclerosis (MS), we performed a retrospective analysis of medication use among 70 subjects with MS who were participating in a clinical trial for evaluation of the effects of yoga and exercise programs on cognition and fatigue. Among these MS subjects, 74% were taking at least one potentially CNS-active medication. These 70 subjects were divided into two groups: those taking at least one CNS-active medication (n = 52) and those not on any medications with potential CNS activity (n = 18). We compared assessments of cognitive function and fatigue using an analysis of covariance. MS subjects on CNS-active medication had greater impairment on measures of processing speed, sustained attention, and fatigue than those not on these medications. While these findings do not establish a causal relationship between medication use and cognitive impairment and fatigue, the data indicate that researchers need to control for use of CNS-active medications when conducting studies of cognitive impairment and fatigue in MS subjects.

Age-related differences in visual search task performance: relative stability of parallel but not serial search.

The hypothesis that visual search tasks requiring effortful, serial processing are more sensitive to aging than those requiring relatively automatic, parallel processing was tested in 96 healthy adults who performed parallel and serial visual search tasks with fixed presentation times. Reaction times and error rates increased with age in both tasks, but there was no difference between young and old in the effect of increasing numbers of distractors on reaction times. However, the older subjects made significantly more errors with increasing numbers of distractors in the serial search task. Older subjects have disproportionately more difficulty performing serial compared to parallel visual search tasks than do younger subjects. Additionally, this difference is not caused solely by cautious response strategies in the elders.

Endothelium-dependent effects of cigarette smoke components on tone of porcine intrapulmonary arteries in vitro☆

The acute effects of cigarette smoking on the pulmonary vasculature are poorly understood--both vasodilatory and vasoconstrictive effects have been described. To investigate the mechanisms involved, strips of pig intrapulmonary arteries with and without intact endothelium were exposed to an extract of cigarette smoke made by bubbling smoke through phosphate-buffered saline. After contraction with norepinephrine (2.5 X 10(-7) M), smoke extract (concentration range 0.001 to 0.5%) caused a biphasic response in strips with intact endothelium--relaxation at lower concentrations and contraction at higher concentrations. Both relaxation and contraction responses were absent in strips without endothelium. Blockade of muscarinic, beta adrenergic, serotonergic, and histamine type 1 and 2 receptors did not alter the effects. Indomethacin (5 X 10(-6) M) or acetylsalicylic acid (10(-4) M) blocked the relaxation but not contraction effects of smoke extract, suggesting that relaxation was due to cyclooxygenase products of arachidonic acid. Nicotine caused endothelium-dependent contraction of intrapulmonary arteries and the contractile effects of both nicotine and smoke extract were blocked by hexamethonium (10(-6) M). However, the contractile effects of cigarette smoke components are more potent than those of nicotine. These findings help explain previously described acute effects of smoking on the pulmonary vasculature and provide insight into the mechanisms involved.

24 Hour Ambulatory Research System Supporting Multiple Physiologic Sensors

The design and development of a 24-hour ambulatory physiological data collection system is reported. The system was designed specifically to support the needs of investigators studying mind-body interventions but could be used for a variety of research needs. The system is novel in that it supports a wide variety of physiologic sensors with a relatively high sample rate, full data storage, and standalone run-time of greater than 24 hours. Experience with data acquisition and methods for post-acquisition data analysis are also discussed