Daniel P. Zajdel

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.

Sensitivity to Mental Effort and Test-Retest Reliability of Heart Rate Variability Measures in Healthy Seniors

OBJECTIVES To determine (1) whether heart rate variability (HRV) was a sensitive and reliable measure in mental effort tasks carried out by healthy seniors and (2) whether non-linear approaches to HRV analysis, in addition to traditional time and frequency domain approaches were useful to study such effects. METHODS Forty healthy seniors performed two visual working memory tasks requiring different levels of mental effort, while ECG was recorded. They underwent the same tasks and recordings 2 weeks later. Traditional and 13 non-linear indices of HRV including Poincaré, entropy and detrended fluctuation analysis (DFA) were determined. RESULTS Time domain, especially mean R-R interval (RRI), frequency domain and, among non-linear parameters - Poincaré and DFA were the most reliable indices. Mean RRI, time domain and Poincaré were also the most sensitive to different mental effort task loads and had the largest effect size. CONCLUSIONS Overall, linear measures were the most sensitive and reliable indices to mental effort. In non-linear measures, Poincaré was the most reliable and sensitive, suggesting possible usefulness as an independent marker in cognitive function tasks in healthy seniors. SIGNIFICANCE A large number of HRV parameters was both reliable as well as sensitive indices of mental effort, although the simple linear methods were the most sensitive.

Nicotine effects on alertness and spatial attention in non-smokers

Nicotine reportedly improves covert orienting of spatial attention, but enhanced alertness may also play a role. The present study explored nicotine effects on measures of spatial attention and alertness in non-smokers. Nicotine was delivered to 17 non-smokers (data from 12 subjects were analyzed) by a 7-mg transdermal patch (one patch in a low-nicotine condition; two patches in a high-nicotine condition). We examined nicotines effects on spatial attention using a covert orienting task with central, predictive cue stimuli. Nicotine effects on alertness were examined with EEG and subjective questionnaires. Blood was drawn and serum levels of nicotine are reported. Nicotine decreased overall reaction times in the covert orienting task. There was no change in the validity effect, the reaction time difference between validly and invalidly cued targets. However, nicotine significantly improved both EEG and self-rated measures of alertness. We conclude that nicotine increases alertness in non-smokers, but we found no improvement in spatial attention using a covert orienting task.

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.

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.

Assessing Sleep Architecture in Dementia Caregivers at Home Using an Ambulatory Polysomnographic System

Findings from previous research assessing sleep quality in caregivers are inconsistent due to differences in sleep assessment methods. This study evaluated sleep in dementia caregivers using a comprehensive sleep assessment utilizing an ambulatory polysomnography (PSG) device. A total of 20 caregivers and 20 noncaregivers rated their perceived sleep quality, stress, and depressive symptoms; provided samples of cortisol and inflammatory biomarkers; and completed an objective sleep assessment using a portable PSG device. Caregivers reported greater perceived stress than noncaregivers. Next, the groups had different sleep architecture: caregivers spent less proportion of their sleep in restorative sleep stages compared to noncaregivers. Further, levels of C-reactive protein and awakening salivary cortisol were greater in caregivers than in noncaregivers, and these measures were related to sleep quality. Our findings indicate that sleep disruption is a significant concomitant of caregiving and may affect caregiver’s health. Sleep quality of caregivers might be a useful target for a clinical intervention.

Heart rate variability analysis of effect of nicotine using periodograms

Heart rate variability (HRV) is frequently used to measure autonomic nervous system (ANS) activity. However, little is known about the mechanism underlying pharmacologically induced changes in HRV. Previous research has shown that nicotine exposure stimulates the ANS, mediating a wide spectrum of physiological and behavioral effects, including altered respiratory sinus arrhythmia and enhanced arousal and attention. Using Lomb-Welch periodograms, the effect of nicotine on the ANS in 14 nicotine-naive human subjects are studied. Results showed an increase in the low frequency (LF) to high frequency (HF) ratio with little change in mean heart rate. Results suggest that nicotine affects both sympathetic and parasympathetic reactivities and that the LF/HF best characterizes early ANS activated nicotine changes in HRV. The Lomb-Welch periodogram of the HRV is also compared to the conventional interpolated Welch periodogram. The attenuation of the high frequency components due to interpolation of the non-uniform R-R intervals is found to be a function of the power of the high frequency components, increasing with increasing power. Thus analyses using Welch periodograms that make use of the high frequency components may yield erroneous results.

Second generation complementary and alternative medicine physiologic data collection and monitoring research platform

Progress on our second generation portable system specifically designed to collect 24 hour ambulatory physiologic data from human subjects is reported. The upgraded system has more sensor flexibility and better performance and is smaller, lighter, and simpler to use than our previous version. The new system continues to support a wide variety of sensors found useful for complementary and alternative medicine (CAM) research and has been designed using a modular approach for future expansion of capabilities. The system has improved data storage and supports popular physiologic data formats. Support for wireless control and real-time data monitoring has been added which demonstrates capabilities to be used for physiologic feedback control. The system was designed specifically to support the needs of investigators studying CAM mind-body interventions but could be used for a variety of research needs.

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