Art Noda

Categorical versus dimensional approaches to diagnosis: methodological challenges.

The arguments pitting categorical versus dimensional approaches to psychiatric diagnosis have been long ongoing with little sign of imminent resolution. We argue that categorical and dimensional approaches are fundamentally equivalent, but that one or other approach is more appropriate depending on the clinical circumstances and research questions being addressed. This paper aims to demonstrate (a) how these two approaches necessarily interdigitate, (b) to clarify the conditions under which one should utilize one approach over the other, and (c) to alert psychiatric clinicians and researchers to issues in the methodology literature that might facilitate their considerations. Using an example from the Infant Health and Development Program (IHDP), we illustrate the importance of using dimensional approaches for hypothesis testing, identify the problems with power and with interpretation that arise from employing a categorical approach, and underscore the importance of identifying the appropriate cutpoints when a categorical approach is necessitated. We argue that failure to utilize the correct approach under the appropriate circumstances can result in impaired clinical and research decision-making.

An Actigraphic Comparison of Sleep Restriction and Sleep Hygiene Treatments for Insomnia in Older Adults

We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG. (J Geriatr Psychiatry Neurol 2000; 13:17-27).

Modeling the prevalence and incidence of Alzheimer's disease and mild cognitive impairment

A number of systems have been proposed for classifying older adults who suffer from cognitive impairment or decline but do not yet meet criteria for Alzheimers disease (AD). The classification, Mild Cognitive Impairment (MCI), has attracted much attention. It uses relatively specific diagnostic criteria and individuals who meet these criteria appear to be at substantial risk for the development of AD. However, little data is available to define the prevalence of MCI in any age group. We propose a simple mathematical model for the progression of patients from Non-Affected (NA) to MCI to AD. This first-order Markov model defines the likely prevalence of MCI at specific ages. Primary assumptions of the model include an AD prevalence of 1% at age 60 increasing to 25% at age 85 and a conversion rate from MCI to AD of 10% constant across all ages considered. We used the best available information for our model and found (1) that the MCI prevalence increased from 1% at age 60 to 42% at age 85 and (2) that the conversion rate from NA to MCI increased from 1% per year at age 60 to 11% at age 85. In conclusion, this model allows estimation of prevalence of MCI and conversion from NA to MCI based upon known prevalences of AD, conversion rates of MCI to AD, and death rates. Due to its substantial prevalence, MCI may be an important target for screening and possible intervention.

Scheduled bright light for treatment of insomnia in older adults.

OBJECTIVES: To determine whether bright light can improve sleep in older individuals with insomnia.

Sleep/Wake Disruption in Alzheimer’s Disease: APOE Status and Longitudinal Course

Disturbed sleep is a major clinical problem in Alzheimer’s disease (AD). Apolipoprotein •4 (APOE •4) carrier status may increase risk of AD, yet there are no data on relations between APOE status and progression of sleep disturbance in AD. The objective of this study was to determine if sleep parameters in AD patients change over time as a function of APOE carrier status. Forty-four community-dwelling AD patients with diagnosis of probable AD were followed from early stages of disease. Their sleep/wake parameters were compared according to APOE status. For APOE •4 carriers, only wake after sleep onset (WASO) increased in association with lower cognitive function as indicated by the Mini-Mental State Examination (MMSE); for non-•4 subjects, increases in WASO and declines in total sleep time, sleep efficiency, and the amplitude of the rest/activity circadian rhythm over time were associated with lower performance on the MMSE. In these data, APOE status was associated with the progression of sleep/wake disturbances in AD. Overall, there was greater deterioration on sleep parameters in patients negative for the •4 allele.

Delineating a Retesting Zone Using Receiver Operating Characteristic Analysis on Serial QuantiFERON Tuberculosis Test Results in US Healthcare Workers.

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 manufacturers 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.

Relationship of age and simulated flight performance.

OBJECTIVE: To determine the relationship between age and aviator performance on a flight simulator.

APOE-epsilon4 and aging of medial temporal lobe gray matter in healthy adults older than 50 years.

Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimers disease (AD). APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers. To examine APOE ε4 effects in relation to aging, we performed a longitudinal magnetic resonance imaging study involving cognitively normal adults (25 APOE ε4 carriers and 31 ε3 homozygotes), initially aged 51-75 years. We used growth curve analyses, which can provide information about APOE ε4-related differences initially and later in life. Hippocampal volume was the primary outcome; nearby medial temporal regions were secondary outcomes. Brain-derived neurotrophic factor, val66met was a secondary covariate. APOE ε4 carriers had significantly smaller initial hippocampal volumes than ε3 homozygotes. Rate of hippocampal atrophy was not greater in the APOE ε4 group, although age-related atrophy was detected in the overall sample. The findings add to the growing evidence that effects of APOE ε4 on hippocampal size begin early in life, underscoring the importance of early interventions to increase reserve.

Circadian Clock Gene Polymorphisms and Sleep–Wake Disturbance in Alzheimer Disease

OBJECTIVES 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. DESIGN One week of ad libitum ambulatory sleep data collection. SETTING At-home collection of sleep data and in-laboratory questionnaire. PARTICIPANTS Two cohorts of AD participants. Cohort 1 (N = 124): individuals with probable AD recruited from the Stanford/Veterans Affairs, National Institute on Aging Alzheimers 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 Alzheimers Disease Neuroimaging Initiative data set. MEASUREMENTS 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. RESULTS 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. CONCLUSIONS It is unlikely that a relationship with a clinically meaningful correlation exists between the circadian rhythm-associated SNPs and WASO in individuals with AD.

Modeling the effects of obstructive sleep apnea and hypertension in Vietnam veterans with PTSD

PurposeThe 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.MethodsThe 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 SpO2, mean SpO2) indicators were determined during standard overnight polysomnography. Multivariate linear regression and receiver operating characteristic (ROC) curve analyses were performed.ResultsIn 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 SpO2 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 SpO2 cut-points and hypertension were significant when added simultaneously in a regression model for RAVLT (min SpO2, β = 4.452; p < 0.05; hypertension, β = −4.332; p < 0.05), and in separate models for CWIT (min SpO2, β = −8.286; p < 0.05; hypertension, β = −8.993; p < 0.01).ConclusionsOSA severity and presence of self-reported hypertension are associated with poor auditory verbal memory and executive function in older adults.