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

BACKGROUND: To determine factors that predict adherence to a mind-body intervention in a randomized trial. DESIGN: We 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. RESULTS: The 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. CONCLUSION: Healthy 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.

Vigilance, alertness, or sustained attention: physiological basis and measurement.

Vigilance is a term with varied definitions but the most common usage is sustained attention or tonic alertness. This usage of vigilance implies both the degree of arousal on the sleep-wake axis and the level of cognitive performance. There are many interacting neural and neurotransmitter systems that affect vigilance. Most studies of vigilance have relied on states where the sleep-wake state is altered, e.g. drowsiness, sleep-deprivation, and CNS-active drugs, but there are factors ranging from psychophysics to motivation that may impact vigilance. While EEG is the most commonly studied physiologic measure of vigilance, various measures of eye movement and of autonomic nervous system activity have also been used. This review paper discusses the underlying neural basis of vigilance and its assessment using physiologic tools. Since, assessment of vigilance requires assessment of cognitive function this aspect is also discussed.

Cortical excitability and age-related volumetric MRI changes.

OBJECTIVE: Normative data on transcranial magnetic stimulation (TMS)-derived measures of cortical excitability in the elderly is sparse. Nevertheless, elderly subjects are included as controls in studies utilizing TMS to investigate disease states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and white matter hyperintensity (WMH) MRI volumes have uncertain significance in non-demented elderly. Information regarding cortical excitability in neurologically intact elderly would augment our understanding of the pathophysiology of aging and assist in the interpretation of TMS studies involving elderly subjects. METHODS: Twenty-four healthy elderly subjects underwent TMS testing to determine outcomes of resting motor threshold (RMT) cortical silent period (cSP) and central motor conduction time for examination in relation to WMH, vCSF, and CNS volumes. RESULTS: Increased vCSF and WMH volumes were associated with decreased right and left hemisphere RMT. Smaller CNS volumes were associated with decreased right hemisphere RMT and shorted cSP. CONCLUSIONS: Commonly observed age-associated MRI changes are associated with findings consistent with increased cortical excitability. SIGNIFICANCE: Age-related MRI findings likely reflect changes at a cellular level, and may influence cognitive and motor integrity in the elderly. Future TMS studies investigating cortical excitability may wish to consider neuroimaging markers of neurodegeneration prior to enrolling elderly subjects as controls.

Event-related potential correlates of mindfulness meditation competence.

OBJECTIVE: This cross-sectional study evaluated event-related potentials (ERPs) across three groups: naïve, novice, and experienced meditators as potential physiological markers of mindfulness meditation competence. METHODS: Electroencephalographic (EEG) data were collected during a target tone detection task and a Breath Counting task. The Breath Counting task served as the mindfulness meditation condition for the novice and experienced meditator groups. Participants were instructed to respond to target tones with a button press in the first task (Tones), and then ignore the primed tones while Breath Counting. The primary outcomes were ERP responses to target tones, namely the N2 and P3, as markers of stimulus discrimination and attention, respectively. RESULTS: As expected, P3 amplitudes elicited by target tones were attenuated within groups during the Breath Counting task in comparison to the Tones task (p<.001). There was a task by group interaction for P3 (p=.039). Both meditator groups displayed greater change in peak-to-trough P3 amplitudes, with higher amplitudes during the Tones condition and more pronounced reductions in P3 amplitudes during the Breath Counting meditation task in comparison to the naïve group. CONCLUSIONS: Meditators had stronger P3 amplitude responses to target tones when instructed to attend to the tones, and a greater attenuation of P3 amplitudes when instructed to ignore the same tones during the Breath Counting task. This study introduces the idea of identifying ERP markers as a means of measuring mindfulness meditation competence, and results suggest this may be a valid approach. This information has the potential to improve mindfulness meditation interventions by allowing objective assessment of mindfulness meditation quality.

The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease.

OBJECTIVE: To determine the effect of treatment with Ginkgo biloba extract on objective measures of cognitive function in patients with Alzheimer disease (AD) based on formal review of the current literature. METHODS: An attempt was made to identify all English and non-English-language articles in which G. biloba extract was given to subjects with dementia or cognitive impairment. Inclusion criteria for the meta-analysis were (1) sufficiently characterized patients such that it was clearly stated there was a diagnosis of AD by either Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, or National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, or there was enough clinical detail to determine this by our review; (2) clearly stated study exclusion criteria, ie, those studies that did not have stated exclusions for depression, other neurologic disease, and central nervous system-active medications were excluded; (3) use of standardized ginkgo extract in any stated dose; (4) randomized, placebo-controlled and double-blind study design; (5) at least 1 outcome measure was an objective assessment of cognitive function; and (6) sufficient statistical information to allow for meta-analysis. RESULTS: Of more than 50 articles identified, the overwhelming majority did not meet inclusion criteria, primarily because of lack of clear diagnoses of dementia and AD. Only 4 studies met all inclusion criteria. In total there were 212 subjects in each of the placebo and ginkgo treatment groups. Overall there was a significant effect size of 0.40 (P<.0001). This modest effect size translated into a 3% difference in the Alzheimer Disease Assessment Scale-cognitive subtest. CONCLUSIONS: Based on a quantitative analysis of the literature there is a small but significant effect of 3- to 6-month treatment with 120 to 240 mg of G. biloba extract on objective measures of cognitive function in AD. The drug has not had significant adverse effects in formal clinical trials but there are 2 case reports of bleeding complications. In AD, there are limited and inconsistent data that preclude determining if there are effects on noncognitive behavioral and functional measures as well as on clinician's global rating scales. Further research in the area will need to determine if there are functional improvements and to determine the best dosage. Additional research will be needed to define which ingredients in the ginkgo extract are producing its effect in individuals with AD.

Neurologic evaluation of the optimally healthy oldest old.

OBJECTIVE: Individuals aged 85 years or older (the "oldest old") are the fastest-growing age group in the United States. Because there is little information characterizing expected neurologic function in this group, our goal was to determine clinical neurologic traits characteristic of the optimally healthy oldest old. DESIGN: Standardized neurologic evaluation findings of optimally healthy persons older than 84 years compared with those of equally healthy control subjects aged 65 to 74 years. SETTING: Community-based, longitudinal aging study. PARTICIPANTS: Community-residing, consecutively recruited volunteers who were screened for the absence of chronic disease or medication use. MAIN OUTCOME MEASURE: Standardized neurologic examination coded into ordinal or interval variables. RESULTS: Significant between-group differences were greatest for tests of mental status, sensory function (ie, smell, hearing, vibratory discrimination, and stereognosis), oculomotor function, distal movement speed, and balance. Discriminant function analysis suggests that of these changes, membership in the oldest group is best predicted by poor performance on clinical tests of balance (heel-toe walking and one-leg balancing with eyes closed), smell, and visual pursuit. CONCLUSIONS: Many neurologic signs appear with aging that cannot be attributed to disease, even in the very old. Deficits in balance, olfaction, and visual pursuit discriminate best between the aging changes of the healthy very old and changes seen in younger elderly persons.

Electrophysiologic function in the healthy, extremely old.

We analyzed conventional EEG, computerized EEG frequency analysis (CEEGFA), and long-latency auditory evoked potentials in 22 extremely healthy subjects over age 84 (range, 84 to 98) and compared them with 11 younger elderly subjects as well as subjects under age 65 years. Intermittent temporal slowing in the conventional EEG was present in 50% of the elderly. Its presence was related to the presence of white matter hyperintensities on MRI but not to blood pressure or cognitive function. The posterior peak frequency determined by CEEGFA was maintained above 8 Hz in all subjects under age 84, but was between 7 and 8 Hz in five of 22 subjects over age 84 years. Three other CEEGFA variables studied (relative theta, relative alpha, and median-power frequency in the posterior channels) all demonstrated a significant change with age, most marked above age 80 years. Well-defined P3s were not present in five of 22 subjects over age 84 and in only one of 38 subjects under age 84 years. The P3 latency increased by 0.8 msec per year throughout the adult age range, while the P3 amplitude was relatively stable until the eighties. This study highlights the effects of healthy aging on clinical electrophysiologic tests of cerebral function.

Computerized EEG frequency analysis: sensitivity and specificity in patients with focal lesions.

We performed computerized EEG frequency analysis (C-EEGFA) in 69 controls and 20 patients with focal brain lesions and focally abnormal conventional EEGs. Individual channel EEG frequency analysis variables that were helpful in differentiating the 2 groups were absolute delta and theta band power, relative delta, theta, and alpha band powers, and median-power frequency. High-frequency beta band power (20 to 32 Hz) was not useful. Changes in EEG with age were seen only after age 50 and generally consisted of an increase in anterior alpha power, with no significant increase in slowing. Correlations of C-EEGFA variables with posterior alpha power were more significant than correlations with age. Calculating normative C-EEGFA data for 5 subsets of controls, each with a different amount of posterior alpha power, increased the sensitivity of the EEG frequency analysis test without altering the specificity. Even with this correction 2 of 20 patients with focal lesions and focally abnormal conventional EEGs had normal C-EEGFA studies. If these obvious focal lesions produced normal results, more subtle diseases might not be detected. A significant clinical utility of C-EEGFA remains to be proven.

Motor slowing precedes cognitive impairment in the oldest old.

Eighty-five healthy elderly subjects were prospectively evaluated for 3 years to determine motor differences between those who remain cognitively intact and those who developed cognitive impairment during prospective follow-up. The 18 subjects who developed cognitive impairment had slower finger tapping and took longer to walk 30 feet before or at the time of cognitive impairment. Coordination was more impaired and steps, but not balance, deteriorated more rapidly, independent of other variables.

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 Alzheimer's 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.

Neurologic function in the optimally healthy oldest old. Neuropsychological evaluation.

We examined cognition on a wide range of standardized neuropsychological tests in two groups of optimally healthy, elderly volunteers. One was composed of community-dwelling, functionally independent individuals aged 84 years and older, and the other group was nearly 20 years younger. The effect of aging was greatest on visual perceptual and constructional tasks rather than on memory tasks. Many cognitive functions were relatively well preserved in the optimally healthy oldest old.

Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia.

OBJECTIVE: To determine initial locus and rate of degeneration of temporal lobe structures (total lobe, hippocampus and parahippocampus) in preclinical dementia. BACKGROUND: Postmortem studies suggest that the earliest changes in Alzheimer's disease are neurofibrillary tangle formation in hippocampus and adjacent cortex. MRI volume analysis of temporal lobe structures over time in subjects prior to developing dementia may allow the identification of when these processes begin, the rate they develop, and which areas are key to symptom development. METHODS: 30 nondemented (NoD), healthy, elderly individuals enrolled in a prospective study of healthy aging evaluated annually over a mean of 42 months. Twelve subjects with subsequent cognitive decline were assigned to the preclinical dementia group (PreD). All 120 annual MRI studies analyzed by volumetric techniques assessed group differences in temporal lobe volumes and rates of brain loss. RESULTS: NoD as well as PreD subjects had significant, time-dependent decreases in hippocampal and parahippocampal volume. Rates of volume loss between the groups did not significantly differ. PreD cases had significantly smaller hippocampi when asymptomatic. Parahippocampal volume did not differ between PreD and NoD cases. Significant time-dependent temporal lobe atrophy was present only in PreD. CONCLUSIONS: Hippocampal and parahippocampal atrophy occurs at a similar rate regardless of diagnostic group. Those who develop dementia may have smaller hippocampi to begin with, but become symptomatic because of accelerated loss of temporal lobe volume. Temporal lobe volume loss may mark the beginning of the disease process within six years prior to dementia onset.

Alertness and attention: basic science and electrophysiologic correlates.

There has been much research in the electrophysiologic correlates of alertness and attention, but it is fragmented into many subfields. This article integrates current knowledge across multiple disciplines and methodologies to provide a broad overview of alertness and attention. First, terms that are related to alertness and attention are clarified. Then, there is a discussion of basic neuroscience, human neurophysiology, and clinical fields that impact on alertness and attention. Areas discussed include thalamic and neurotransmitter-specific ascending pathways. EEG, event-related potentials, and both physiologic and pathologic states of decreased alertness or attention.

Localizing acute stroke-related EEG changes: assessing the effects of spatial undersampling.

Because of its sensitivity to metabolic and ionic disturbances related to ischemia, the EEG can be a potentially useful tool for acute stroke detection and for monitoring affected tissue. However, the clinical use of the EEG in detecting stroke is determined in part by how accurately the spatial information is characterized. The purpose of the current study was to determine the effects of spatial undersampling on the distribution and interpretation of the stroke-related topographic EEG. Using a 128-channel sensor montage, EEG was recorded from six stroke patients acutely (between 8 and 36 hours) after symptom onset. The EEG was submitted to a spectral analysis and was compared with patient symptoms and MRI and computed tomographic findings. To determine loss of spatial and clinical information resulting from spatial undersampling, the average-referenced data from the original 128-channel recording montage were subsampled into 64-, 32-, and 19-channel arrays. Furthermore, the analytical findings were compared with a board-certified electroencephalographer's review of the raw EEG using a conventional clinical montage. As predicted, the results showed that accurate description of stroke-related topographic EEG changes is dependent on adequate spatial sampling density. Accurate description of the spatial distribution of the stroke-related EEG was achieved only with the 64- and 128-channel EEG. As the recording density decreases to 32 channels, the distribution of the scalp EEG spectra is distorted, potentially resulting in mislocalization of the affected region. Results of the clinical review by an expert electroencephalographer corroborated the quantitative analyses, and the results also demonstrated the shortcomings of the conventional 10-20 recording density for capturing focal EEG abnormalities in several cases. The EEG provides useful information about the localization of acute cerebral ischemia, but recording densities of 64 channels or higher are required for accurate spatial characterization of focal stroke-related EEG changes.

Early noncognitive change in Alzheimer's disease and healthy aging.

Recent studies in Alzheimer's disease have focused on behavioral disturbances in the more advanced stages of the illness rather than behavioral and personality changes occurring early in the disease course. We present a new instrument, the Oregon Noncognitive Inventory for Dementia (ONID), that was developed specifically for patients in the early stages of dementia, to identify subtle behavioral alterations that may precede the more severe cognitive changes of Alzheimer's disease. Mildly demented Alzheimer's patients were compared with age-matched healthy subjects on the ONID. Caregivers of these patients reported significantly more of the behaviors addressed by the ONID than did relatives of the healthy elderly. The results indicate that changes in behavior and personality can be reliably reported by family caregivers of patients with mild dementia. Future clinical applications of the ONID might include measuring change in drug trials, longitudinal studies of the progression of change, and differentiating Alzheimer's disease from other dementias based on a characteristics pattern of change.

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.

Verbal fluency task affects gait in Parkinson's disease with motor freezing.

We examined the effects of a simultaneous verbal fluency task on walking in Parkinson's disease (PD) patients with freezing of gait (PD-F) compared to nonfreezing patients (PD-NF) or control subjects (C). Effects of antiparkinsonian medications on gait in PD-F were examined. PD-F patients exhibited a greater increase in the number of steps to complete the walk with verbal fluency, even when the effect of medication was taken into account (mean increase +/- SD): PD-F = 4.2 +/- 4.6, n = 10; PD-NF = 0.1 +/- 1.6, n = 9; C = 1.5 +/- 1.5, n = 19; P = .007. Medications improved walking in PD-F patients by decreasing the number of steps, the time to walk, and freezing. PD-F patients may be more dependent on attention for walking.

Age-related differences in global-local processing: stability of laterality differences but disproportionate impairment in global processing.

Visual processing of global and local features differentially engages the right and left hemispheres and requires different allocations of spatial attention. To further understand the decline in visual cognition and visual attention with age, we studied the performance of healthy young subjects and healthy elders on a global-local figures task. The results showed that elders processed global images more quickly when presented in the left visual field and local images in the right visual field, similarly to the young controls. However, we did observe a significant impairment in the elders' ability to process global figures compared with local figures, despite there being no overall difference between global and local processing speed among the young. It is thought that this age-related decline in global processing is related to the narrowed attentional field that can be demonstrated in other age-related visual processing declines such as visual search and useful field of view.

Methylphenidate increases the motor effects of L-Dopa in Parkinson's disease: a pilot study.

We determined whether methylphenidate, a dopamine transporter blocker, modifies motor, cognitive, or affective responses to L-Dopa in Parkinson's disease (PD). Five patients who reported benefit from L-Dopa/carbidopa and motor fluctuations were admitted and withdrawn from their usual antiparkinsonian medications. On 3 consecutive days in a randomized double-blinded fashion, they took 0.2 mg/kg oral methylphenidate or placebo followed 30 minutes later by a 1-hour intravenous L-Dopa (2 mg/kg per h) or placebo infusion. Vital signs, tapping, walking, dyskinesias, mood, anxiety, concentration, and arousal were monitored every 30 minutes. Cognitive testing was performed before and following the infusion. Methylphenidate combined with L-Dopa led to greater peak right-hand tapping speed than either alone. Dyskinesia severity increased most when methylphenidate and L-Dopa were co-administered. There were no differences between conditions on the Stroop test, digit ordering, simple reaction time, or covert orienting of attention validity effect. Methylphenidate alone led to improvement in choice reaction time. Change in self-assessed analogue ratings of mood, anxiety, arousal, or concentration did not differ between conditions. Methylphenidate increased the motor effects of L-Dopa with minimal effects on cognitive or affective functions, suggesting a physiologic role for the dopamine transporter in patients with PD with motor fluctuations.