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Journal of palliative medicine 10/2012; · 1.84 Impact Factor
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ABSTRACT: Objectives
Intraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots.Method
Two-hundred and thirty-six pilots (40-69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. RESULTS: Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%-12% of the negative age effect on initial flight performance.DiscussionIIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance.
The Journals of Gerontology Series B Psychological Sciences and Social Sciences 10/2012; · 2.62 Impact Factor
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Jerome A Yesavage,
Lisa M Kinoshita,
Timothy Kimball,
Jamie Zeitzer,
Leah Friedman, Art Noda,
Renaud David,
Beatriz Hernandez,
Tina Lee,
Jauhtai Cheng,
Ruth Oʼhara
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ABSTRACT: : To study the prevalence of sleep-disordered breathing (SDB) in Vietnam- era veterans.
: This was an observational study of Vietnam-era veterans using unattended, overnight polysomnography, cognitive testing, and genetic measures.
: A sample of 105 Vietnam-era veterans with posttraumatic stress disorder: 69% had an Apnea Hypopnea Index >10. Their mean body mass index was 31, "obese" by Centers for Disease Control and Prevention criteria, and body mass index was significantly associated with Apnea Hypopnea Index (Spearman r = 0.41, N = 97, p < 0.0001). No significant effects of sleep-disordered breathing or apolipoprotein status were found on an extensive battery of cognitive tests.
: There is a relatively high prevalence of SDB in these patients which raises the question of to what degree excess cognitive loss in older PTSD patients may be due to a high prevalence of SDB.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 03/2012; 20(3):199-204. · 3.35 Impact Factor
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ABSTRACT: Objective. To find a statistically significant separation point for the QuantiFERON Gold In-Tube (QFT) interferon gamma release assay that could define an optimal "retesting zone" for use in serially tested low-risk populations who have test "reversions" from initially positive to subsequently negative results. Method. Using receiver operating characteristic analysis (ROC) to analyze retrospective data collected from 3 major hospitals, we searched for predictors of reversion until statistically significant separation points were revealed. A confirmatory regression analysis was performed on an additional sample. Results. In 575 initially positive US healthcare workers (HCWs), 300 (52.2%) had reversions, while 275 (47.8%) had two sequential positive tests. The most statistically significant (Kappa = 0.48, chi-square = 131.0, P < 0.001) separation point identified by the ROC for predicting reversion was the tuberculosis antigen minus-nil (TBag-nil) value at 1.11 International Units per milliliter (IU/mL). The second separation point was found at TBag-nil at 0.72 IU/mL (Kappa = 0.16, chi-square = 8.2, P < 0.01). The model was validated by the regression analysis of 287 HCWs. Conclusion. Reversion likelihood increases as the TBag-nil approaches the manufacturer's cut-point of 0.35 IU/mL. The most statistically significant separation point between those who test repeatedly positive and those who revert is 1.11 IU/mL. Clinicians should retest low-risk individuals with initial QFT results < 1.11 IU/mL.
Pulmonary medicine. 01/2012; 2012:291294.
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Lisa M Kinoshita,
Jerome A Yesavage, Art Noda,
Booil Jo,
Beatriz Hernandez,
Joy Taylor,
Jamie M Zeitzer,
Leah Friedman,
J Kaci Fairchild,
Jauhtai Cheng,
Ware Kuschner,
Ruth O'Hara,
Jon-Erik C Holty,
Blake K Scanlon
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ABSTRACT: PURPOSE: The present work aimed to extend models suggesting that obstructive sleep apnea (OSA) is associated with worse cognitive performance in community-dwelling older adults. We hypothesized that in addition to indices of OSA severity, hypertension is associated with worse cognitive performance in such adults. METHODS: The PTSD Apnea Clinical Study recruited 120 community-dwelling, male veterans diagnosed with PTSD, ages 55 and older. The Rey Auditory Verbal Learning Test (RAVLT) and Color-Word Interference Test (CWIT) were measures of auditory verbal memory and executive function, respectively. Apnea-hypopnea index (AHI), minimum and mean pulse oximeter oxygen saturation (min SpO(2), mean SpO(2)) indicators were determined during standard overnight polysomnography. Multivariate linear regression and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: In regression models, AHI (β = -4.099; p < 0.01) and hypertension (β = -4.500; p < 0.05) predicted RAVLT; hypertension alone (β = 9.146; p < 0.01) predicted CWIT. ROC analyses selected min SpO(2) cut-points of 85% for RAVLT (κ = 0.27; χ² = 8.23, p < 0.01) and 80% for CWIT (κ = 0.25; χ² = 12.65, p < 0.01). Min SpO(2) cut-points and hypertension were significant when added simultaneously in a regression model for RAVLT (min SpO(2), β = 4.452; p < 0.05; hypertension, β = -4.332; p < 0.05), and in separate models for CWIT (min SpO(2), β = -8.286; p < 0.05; hypertension, β = -8.993; p < 0.01). CONCLUSIONS: OSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.
Sleep And Breathing 12/2011; · 1.84 Impact Factor
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ABSTRACT: We tested the hypothesis that single nucleotide polymorphisms (SNPs) in catechol-O-methyltransferase (COMT) are associated with apathy in individuals with Alzheimer's disease (AD). We analyzed a cohort of 105 Caucasian individuals with AD (age = 79.3 ± 7.03 years; MMSE = 20.2 ± 4.4) according to the presence of apathy, as defined either by the Neuropsychiatric Inventory or the Apathy Inventory. Polymorphisms in seventeen SNPs in COMT were examined. A replication cohort consisting of 176 Caucasian AD subjects in the ADNI database was also analyzed. None of the candidate gene SNPs were significantly associated with the presence of apathy in either cohort. We did not find any SNPs in COMT that were consistently associated with apathy in individuals with AD.
Journal of Alzheimer's disease: JAD 07/2011; 27(1):155-61. · 3.74 Impact Factor
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Jerome A Yesavage, Art Noda,
Beatriz Hernandez,
Leah Friedman,
Jauhtai J Cheng,
Jared R Tinklenberg,
Joachim Hallmayer,
Ruth O'hara,
Renaud David,
Philippe Robert,
Elizabeth Landsverk,
Jamie M Zeitzer
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ABSTRACT: One of the hypothesized causes of the breakdown in sleep-wake consolidation often occurring in individuals with Alzheimer disease (AD) is the dysfunction of the circadian clock. The goal of this study is to report indices of sleep-wake function collected from individuals with AD in relation to relevant polymorphisms in circadian clock-related genes.
One week of ad libitum ambulatory sleep data collection.
At-home collection of sleep data and in-laboratory questionnaire.
Two cohorts of AD participants. Cohort 1 (N = 124): individuals with probable AD recruited from the Stanford/Veterans Affairs, National Institute on Aging Alzheimer's Disease Core Center (N = 81), and the Memory Disorders Clinic at the University of Nice School of Medicine (N = 43). Cohort 2 (N = 176): individuals with probable AD derived from the Alzheimer's Disease Neuroimaging Initiative data set.
Determination of sleep-wake state was obtained by wrist actigraphy data for 7 days in Cohort 1 and by the Neuropsychiatric Inventory questionnaire for Cohort 2. Both cohorts were genotyped by using an Illumina Beadstation (Illumina, San Diego, CA), and 122 circadian-related single-nucleotide polymorphisms (SNPs) were examined. In Cohort 1, an additional polymorphism (variable-number tandem repeat in per3) was also determined.
Adjusting for multiple tests, none of the candidate gene SNPs were significantly associated with the amount of wake time after sleep onset (WASO), a marker of sleep consolidation. Although the study was powered sufficiently to identify moderate-sized correlations, we found no relationships likely to be of clinical relevance.
It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 07/2011; 19(7):635-43. · 3.35 Impact Factor
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ABSTRACT: Little is known about how APOE ε4-related differences in cognitive performance translate to real-life performance, where training and experience may help to sustain performance. We investigated the influences of APOE ε4 status, expertise (FAA pilot proficiency ratings), and their interaction on longitudinal flight simulator performance. Over a 2-year period, 139 pilots aged 42-69 years were tested annually. APOE ε4 carriers had lower memory performance than noncarriers (p = .019). APOE interacted with Expertise (p = .036), such that the beneficial influence of expertise (p = .013) on longitudinal flight simulator performance was more pronounced for ε4 carriers. Results suggest that relevant training and activity may help sustain middle-aged and older adults' real-world performance, especially among APOE ε4 carriers.
Psychology and Aging 06/2011; 26(2):480-7. · 2.73 Impact Factor
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ABSTRACT: Little is known about how APOE ε4-related differences in cognitive performance translate to real-life performance, where training and experience may help to sustain performance. We investigated the influences of APOE ε4 status, expertise (FAA pilot proficiency ratings), and their interaction on longitudinal flight simulator performance. Over a 2-year period, 139 pilots aged 42–69 years were tested annually. APOE ε4 carriers had lower memory performance than noncarriers (p = .019). APOE interacted with Expertise (p = .036), such that the beneficial influence of expertise (p = .013) on longitudinal flight simulator performance was more pronounced for ε4 carriers. Results suggest that relevant training and activity may help sustain middle-aged and older adults' real-world performance, especially among APOE ε4 carriers. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Psychology and Aging 05/2011; 26(2):480-487. · 2.73 Impact Factor
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Jerome A Yesavage,
Booil Jo,
Maheen M Adamson,
Quinn Kennedy, Art Noda,
Beatriz Hernandez,
Jamie M Zeitzer,
Leah F Friedman,
Kaci Fairchild,
Blake K Scanlon,
Greer M Murphy,
Joy L Taylor
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ABSTRACT: The goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age.
We examined age-related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise. Participants were aircraft pilots (N = 276) aged 40-77.9. Flight simulator performance and cognition were tested yearly; there were an average of 4.3 (± 2.7; range 1-13) data points per participant. Each participant was classified into one of the three levels of aviation expertise based on Federal Aviation Administration pilot proficiency ratings: least, moderate, or high expertise.
Addition of measures of cognitive processing speed and executive function to a model of age-related change in aviation performance significantly improved the model. Processing speed and executive function performance interacted such that the slowest rate of decline in flight simulator performance was found in aviators with the highest scores on tests of these abilities. Expertise was beneficial to pilots across the age range studied; however, expertise did not show evidence of reducing the effect of age.
These data suggest that longitudinal performance on an important real-world activity can be predicted by initial assessment of relevant cognitive abilities.
The Journals of Gerontology Series B Psychological Sciences and Social Sciences 05/2011; 66(4):444-53. · 2.62 Impact Factor
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ABSTRACT: Most airlines enforce no-smoking policies, potentially causing flight performance decrements in pilots who are smokers. We tested the hypotheses that nicotine withdrawal affects aircraft pilot performance within 12 h of smoking cessation and that chewing nicotine gum leads to significant relief of these withdrawal effects.
There were 29 pilots, regular smokers, who were tested in a Frasca 141 flight simulator on two 13-h test days, each including three 75-min flights (0 hr, 6 hr, 12 hr) in a randomized, controlled trial. On the first day (baseline), all pilots smoked one cigarette per hour. On the second day, pilots were randomly assigned to one of four groups: (1) nicotine cigarettes; (2) nicotine gum; (3) placebo gum; (4) no cigarettes/no gum. Flight Summary Scores (FSS) were compared between groups with repeated measures ANOVAs.
No statistically significant differences in overall simulator flight performance were revealed between pilots who smoked cigarettes and pilots who were not allowed to smoke cigarettes or chew nicotine gum, but there was a trend for pilots who were not allowed to smoke to perform worse. However, pilots who chewed placebo gum performed significantly worse during the 6-h (FSS = -0.03) as well as during the 12-h flight (FSS = -0.08) than pilots who chewed nicotine gum (FSS = 0.15 / 0.30, respectively).
Results suggest that nicotine withdrawal effects can impair aircraft pilot performance within 12 h of smoking cessation and that during smoking abstinence chewing one stick of 4-mg nicotine gum per hour may lead to significantly better overall flight performance compared to chewing placebo gum.
Aviation Space and Environmental Medicine 07/2010; 81(7):660-4. · 0.88 Impact Factor
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ABSTRACT: To determine whether bright light can improve sleep in older individuals with insomnia.
Single-blind, placebo-controlled, 12-week, parallel-group randomized design comparing four treatment groups representing a factorial combination of two lighting conditions and two times of light administration.
At-home light treatment; eight office therapy sessions.
Thirty-six women and fifteen men (aged 63.6+/-7.1) meeting primary insomnia criteria recruited from the community.
A 12-week program of sleep hygiene and exposure to bright ( approximately 4,000 lux) or dim light ( approximately 65 lux) scheduled daily in the morning or evening for 45 minutes.
Within-group changes were observed for subjective (sleep logs, questionnaires) and objective (actigraphy, polysomnography) sleep measures after morning or evening bright light.
Within-group changes for subjective sleep measures after morning or evening bright light were not significantly different from those observed after exposure to scheduled dim light. Objective sleep changes (actigraphy, polysomnography) after treatment were not significantly different between the bright and dim light groups. Scheduled light exposure was able to shift the circadian phase predictably but was unrelated to changes in objective or subjective sleep measures. A polymorphism in CLOCK predicted morningness but did not moderate the effects of light on sleep. The phase angle between the circadian system (melatonin midpoint) and sleep (darkness) predicted the magnitude of phase delays, but not phase advances, engendered by bright light.
Except for one subjective measure, scheduled morning or evening bright light effects were not different from those of scheduled dim light. Thus, support was not found for bright light treatment of older individuals with primary insomnia.
Journal of the American Geriatrics Society 02/2009; 57(3):441-52. · 3.74 Impact Factor
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ABSTRACT: To determine if donepezil, an acetylcholinesterase (AChE) inhibitor, improved the assimilation of cognitive training by older adults with memory complaints, we gave 168 nondemented, community-dwelling volunteers with memory complaints either 5 mg of donepezil (Aricept) or placebo daily for 6 weeks in a randomized, double-blind, placebo-controlled trial. The dosage rose to 10 mg daily for another 6 weeks before a 2-week course of cognitive training and was maintained for the remainder of a year. Cognitive training improved performance; donepezil was well tolerated. However, there were no significant benefits of donepezil compared with placebo. An additional dose-ranging study with a starting dose of 5 mg a day suggests that the high dose was not the reason. Physiological tolerance may occur with chronic donepezil treatment and may increase AChE levels; this may be why short-term studies have shown the benefit of AChE inhibitor use in nondemented participants whereas chronic use has failed to enhance cognition.
The Journals of Gerontology Series B Psychological Sciences and Social Sciences 10/2008; 63(5):P288-94. · 2.62 Impact Factor
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ABSTRACT: Expert knowledge may compensate for age-related declines in basic cognitive and sensory-motor abilities in some skill domains. We investigated the influence of age and aviation expertise (indexed by Federal Aviation Administration pilot ratings) on longitudinal flight simulator performance.
Over a 3-year period, 118 general aviation pilots aged 40 to 69 years were tested annually, in which their flight performance was scored in terms of 1) executing air-traffic controller communications; 2) traffic avoidance; 3) scanning cockpit instruments; 4) executing an approach to landing; and 5) a flight summary score.
More expert pilots had better flight summary scores at baseline and showed less decline over time. Secondary analyses revealed that expertise effects were most evident in the accuracy of executing aviation communications, the measure on which performance declined most sharply over time. Regarding age, even though older pilots initially performed worse than younger pilots, over time older pilots showed less decline in flight summary scores than younger pilots. Secondary analyses revealed that the oldest pilots did well over time because their traffic avoidance performance improved more vs younger pilots.
These longitudinal findings support previous cross-sectional studies in aviation as well as non-aviation domains, which demonstrated the advantageous effect of prior experience and specialized expertise on older adults' skilled cognitive performances.
Neurology 03/2007; 68(9):648-54. · 8.31 Impact Factor
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ABSTRACT: The objectives of this study were to evaluate the magnitude and sources of site differences in a multisite study of rates of cognitive decline among patients with Alzheimer disease and to seek strategies to reduce the magnitude of site differences in this and future such studies.
A total of 3,280 participants from 15 different sites was analyzed. For each participant, the average rate of change in the Mini-Mental State Examination (MMSE) was calculated. Participants who declined at least three MMSE points per year were classified "rapid decliners." Site differences in sociodemographic distributions and the percentage of rapid decliners were examined, and a signal detection approach was used to identify the main correlates of rapid decline.
The percentage of rapid decliners for the 15 sites initially varied from 8%-40%. Two of the correlates of rapid decline were largely the result of different sampling protocols, namely baseline MMSE and elapsed time between the first and last MMSE. By selecting only those participants at each site with a baseline MMSE between 15 and 23, and limiting the follow-up time to a period of 11-24 months, the authors created greater homogeneity in the protocols across sites and reduced site variability of rapid decliners from 27%-50%.
Results of single-site studies are often nonreproducible, and multisite studies that follow different protocols and do not take site differences into account may be misleading. This study indicates the importance of site differences and how relatively simple efforts to impose common sampling, measurement, and design criteria can reduce, if not totally remove, site differences.
American Journal of Geriatric Psychiatry 12/2006; 14(11):931-8. · 3.64 Impact Factor
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ABSTRACT: Clinical researchers often propose (or review committees demand) pilot studies to determine whether a study is worth performing and to guide power calculations. The most likely outcomes are that (1) studies worth performing are aborted and (2) studies that are not aborted are underpowered. There are many excellent reasons for performing pilot studies. The argument herein is not meant to discourage clinical researchers from performing pilot studies (or review committees from requiring them) but simply to caution against their use for the objective of guiding power calculations.
Archives of General Psychiatry 06/2006; 63(5):484-9. · 12.02 Impact Factor
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ABSTRACT: It is largely unknown why some patients with Alzheimer's disease (AD) decline cognitively more rapidly than others. Genetic differences among patients could influence rate of decline. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in the survival neurons and in memory function. BDNF levels are reduced in the brain in AD. The Val66Met polymorphism in the BDNF gene modifies neuronal BDNF secretion, and affects hippocampal function and memory performance. We tested the hypothesis that the BDNF Val66Met polymorphism influences rate of cognitive decline in AD. In a sample of 149 AD patients followed for an average of 3.9 years, we found no effect of BDNF Val66Met genotype on rate of change in the Mini Mental State Examination. Results were similar when we excluded patients taking an acetylcholinesterase inhibitor, those placed in a nursing home during the study, or those with a neuropathological diagnosis that included AD plus an entity other than AD. We also found no evidence that the effects of the BDNF Val66Met genotype depend on APOE genotype, which itself had no effect on rate of cognitive change. These findings suggest that the functional BDNF Val66Met variant is not a major determinant of rate of cognitive decline in AD.
Journal of Alzheimer's disease: JAD 04/2006; 9(1):43-9. · 3.74 Impact Factor
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Jennifer Hoblyn, Art Noda,
Jerome A Yesavage,
John O Brooks,
Javaid Sheikh,
Tina Lee,
Jared R Tinklenberg,
Bret Schneider,
Ruth O'Hara,
Douglas L Leslie,
Robert A Rosenheck,
Helena C Kraemer
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ABSTRACT: Off-label prescribing of medications, polypharmacy, and other questionable prescribing practices have led investigators to examine a large VA pharmacy database to determine if physician prescribing decisions appear reasonable.
The current study addresses the question of physician prescribing of atypical antipsychotics in 34,925 veterans with schizophrenia, using a series of signal detection analyses.
These results suggest that only three factors (hospital size, age, and secondary diagnosis) allow classification of patients prescribed atypicals into three groups with frequencies of use of atypicals ranging from 43% to 79%, and that these results are consistent with reasonable clinical practice.
Results of two-stage signal detection analyses are readily interpretable by clinicians and administrators who are faced with the task of evaluating how physicians prescribe medications in clinical practice. Physicians' decisions to prescribe atypical antipsychotics are based on both patient and fiscal considerations. This likely reflects a combination of clinical judgment and institutional guidelines.
Journal of Psychiatric Research 04/2006; 40(2):160-6. · 4.66 Impact Factor
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ABSTRACT: Patients often experience ‘preparatory-grief’ as they cope with the dying process. Some may be depressed. The Terminally Ill Grief or Depression Scale (TIGDS), comprising grief and depression sub-scales, is a new self-report measure designed to differentiate between preparatory-grief and depression in adult inpatients.The initial 100-item inventory was assembled based on literature review, interviews with clinicians and dying patients and then shortened to 42 items based on consensus expert opinion. Validity and reliability were tested in a sample of 55 terminally ill adults. The consensus clinical opinion was used as the gold standard to differentiate between preparatory grief and depression. The intra-class correlation coefficient was high (it was calculated to estimate the test-retest reliability for the 47 patients who had completed the TIGDS twice – retest was administered 2 to 7 days after the initial test), ranging from 0.86 (grief) to 0.97 (depression). The validity of TIGDS was assessed using a receiver operating characteristic curve analysis, comparing the first test with the clinical criterion. The first and only variable and cut-point was the depression score (chi-square = 18.4,p < 0.001, cut point = 3). The sensitivity of the TIGDS was 0.727 and specificity was 0.886 for the depression = 3 cutoff score. The construct validity of the TIGDS was tested by comparing with the Hospital Anxiety and Depression Scale (HADS). The TIGDS depression subscale showed strong convergent validity and the TIGDS grief subscale showed strong discriminant validity with the HADS total score. Copyright © 2005 John Wiley & Sons, Ltd.
International Journal of Methods in Psychiatric Research. 03/2006; 14(4):203 - 212.
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ABSTRACT: This descriptive study examined reports of behavioral problems among older patients hospitalized in acute care medical settings. Greater numbers of behavioral problems were reported by nursing staff on the Neuropsychiatric Inventory-Questionnaire than were documented in medical charts over the same time period. Such underreporting may have clinical and administrative implications.
The Gerontologist 09/2005; 45(4):535-8. · 2.48 Impact Factor
