Patrick J. Brown

Reaction to a Dementia Diagnosis in Individuals with Alzheimer's Disease and Mild Cognitive Impairment

OBJECTIVES: To examine short‐term changes in depression and anxiety after receiving a dementia diagnosis.

More reasons to be straightforward: Findings and norms for two scales relevant to social anxiety

The validity of both the Social Interaction Anxiety Scale and Brief Fear of Negative Evaluation scale has been well-supported, yet the scales have a small number of reverse-scored items that may detract from the validity of their total scores. The current study investigates two characteristics of participants that may be associated with compromised validity of these items: higher age and lower levels of education. In community and clinical samples, the validity of each scales reverse-scored items was moderated by age, years of education, or both. The straightforward items did not show this pattern. To encourage the use of the straightforward items of these scales, we provide normative data from the same samples as well as two large student samples. We contend that although response bias can be a substantial problem, the reverse-scored questions of these scales do not solve that problem and instead decrease overall validity.

Factorial Validity of the Texas Revised Inventory of Grief-Present Scale among Bereaved Older Adults

The Texas Revised Inventory of Grief-Present scale (TRIG-Present) is one of the most widely used grief measures; however, researchers have only empirically examined the validity and underlying factor structure of TRIG-Present scores in a few studies. Hence, in the present investigation, we sought to examine the factorial validity of the TRIG-Present (those scores that index current grief) among 2 samples of bereaved older adults--a community-dwelling sample of 162 individuals who experienced a diverse set of losses in terms of relationship to the deceased and time since loss, and a recently widowed sample of 212 individuals who were assessed at 2-months and 12-months postloss. Across both samples, we found support for a 3-factor model, composed of clusters of items representing Emotional Response, Thoughts, and Nonacceptance regarding a loss. Additionally, this 3-factor model exhibited significant invariance from 2-months to 12-months postloss in the recently widowed sample. Analyses examining the convergent validity of these 3 factors also suggest that this conceptualization of the TRIG-Present could have practical advantages and potentially influence the way in which clinicians and/or researchers assess grief and evaluate bereavement interventions.

Model stability of the 15-item Geriatric Depression Scale across cognitive impairment and severe depression.

The 15-item Geriatric Depression Scale (GDS) is used in a wide variety of clinical and research settings. The studys purpose was to further establish the validity of the 15-item GDS by exploring the underlying factor structure in a healthy, nondemented sample of older adults and then analyzing whether this factor structure remained stable across a sample of demented individuals and a sample of individuals with a history of depression 6 months after discharge from an inpatient psychiatric setting. A 2-factor model fit the data best in the exploratory analyses. The 2 factors, Life Satisfaction and General Depressive Affect, found in the nondemented sample (r = .39) remained stable across cognitive impairment (r = .12) but merged into a 1-factor model in the psychiatric sample (r = .93). The results indicate that nondepressed older adults with poor life satisfaction may be identified as depressed on screening instruments such as the 15-item GDS.

A Two-Study Comparison of Clinical and MRI Markers of Transition from Mild Cognitive Impairment to Alzheimer’s Disease

A published predictor model in a single-site cohort study (questionable dementia, QD) that contained episodic verbal memory (SRT total recall), informant report of function (FAQ), and MRI measures was tested using logistic regression and ROC analyses with comparable measures in a second multisite cohort study (Alzheimers Disease Neuroimaging Initiative, ADNI). There were 126 patients in QD and 282 patients in ADNI with MCI followed for 3 years. Within each sample, the differences in AUCs between the statistical models were very similar. Adding hippocampal and entorhinal cortex volumes to the model containing AVLT/SRT, FAQ, age and MMSE increased the area under the curve (AUC) in ADNI but not QD, with sensitivity increasing by 2% in ADNI and 2% in QD for a fixed specificity of 80%. Conversely, adding episodic verbal memory (SRT/AVLT) and FAQ to the model containing age, Mini Mental State Exam (MMSE), hippocampal and entorhinal cortex volumes increased the AUC in ADNI and QD, with sensitivity increasing by 17% in ADNI and 10% in QD for 80% specificity. The predictor models showed similar differences from each other in both studies, supporting independent validation. MRI hippocampal and entorhinal cortex volumes showed limited added predictive utility to memory and function measures.

Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical Trials

OBJECTIVE Causes of placebo effects in antidepressant trials have been inferred from observational studies and meta-analyses, but their mechanisms have not been directly established. The goal of this study was to examine in a prospective, randomized controlled trial whether patient expectancy mediates placebo effects in antidepressant studies. METHOD Adult outpatients with major depressive disorder were randomly assigned to open or placebo-controlled citalopram treatment. Following measurement of pre- and postrandomization expectancy, participants were treated with citalopram or placebo for 8 weeks. Independent samples t tests determined whether patient expectancy differed between the open and placebo-controlled groups, and mixed-effects models assessed group effects on Hamilton Depression Rating Scale (HAM-D) scores over time while controlling for treatment assignment. Finally, mediation analyses tested whether between-group differences in patient expectancy mediated the group effect on HAM-D scores. RESULTS Postrandomization expectancy scores were significantly higher in the open group (mean=12.1 [SD=2.1]) compared with the placebo-controlled group (mean=11.0 [SD=2.0]). Mixed-effects modeling revealed a significant week-by-group interaction, indicating that HAM-D scores for citalopram-treated participants declined at a faster rate in the open group compared with the placebo-controlled group. Patient expectations postrandomization partially mediated group effects on week 8 HAM-D. CONCLUSIONS Patient expectancy is a significant mediator of placebo effects in antidepressant trials. Expectancy-related interventions should be investigated as a means of controlling placebo responses in antidepressant clinical trials and improving patient outcome in clinical treatment.

Age and anxiety and depressive symptoms: the effect on domains of quality of life.

The present study investigated whether anxiety and depressive symptomatology moderates the relationship between age and quality of life.

A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in Late-Life Depression

OBJECTIVE Depressed older adults with executive dysfunction (ED) may respond poorly to antidepressant treatment. ED is a multifaceted construct and different studies have measured different aspects of ED, making it unclear which aspects predict poor response. Meta-analytic methods were used to determine whether ED predicts poor antidepressant treatment response in late-life depression and to determine which domains of executive functioning are responsible for this relationship. METHODS A Medline search was conducted to identify regimented treatment trials contrasting executive functioning between elderly responders and nonresponders; only regimented treatment trials for depressed outpatients aged 50 and older were included. Following the most recent PRISMA guidelines, 25 measures of executive functioning were extracted from eight studies. Six domains were identified: cognitive flexibility, planning and organization, response inhibition, selective attention, verbal fluency, and the Dementia Rating Scale Initiation/Perseveration composite score (DRS I/P). Hedges g was calculated for each measure of executive functioning. A three-level Bayesian hierarchical linear model (HLM) was used to estimate effect sizes for each domain of executive functioning. RESULTS The effect of planning and organization was significantly different from zero (Bayesian HLM estimate of domain effect size: 0.91; 95% CI: 0.32-1.58), whereas cognitive flexibility, response inhibition, selective attention, verbal fluency, and the DRS I/P composite score were not. CONCLUSION The domain of planning and organization is meaningfully associated with poor antidepressant treatment response in late-life depression. These findings suggest that therapies that focus on planning and organization may provide effective augmentation strategies for antidepressant nonresponders with late-life depression.

Predictive Utility of Type and Duration of Symptoms at Initial Presentation in Patients with Mild Cognitive Impairment

Background/Aims: To assess (1) the duration and symptoms present in participants with mild cognitive impairment (MCI) and (2) the impact of these variables on predicting conversion to Alzheimer’s disease (AD). Methods: Participants with MCI (n = 148) were assessed and followed systematically. Results: Decline in memory was reported as the first symptom in 118 of the cases. Converters had more symptoms (e.g. language decline, depression), and the combination of decline in memory and in performance of high-order social/cognitive activities as well as disorientation more often than nonconverters (p = 0.036). In an age-stratified Cox model, predictors of conversion to AD were shorter time since onset of memory decline and lower baseline MMSE score. Conclusions: Recent onset of memory decline with older age, decreased MMSE score, change in performance and disorientation indicate a greater likelihood of short-term conversion to AD.

Inflammation, Depression, and Slow Gait: A High Mortality Phenotype in Later Life

BACKGROUND Inflammation, slow gait, and depression individually are associated with mortality, yet little is known about the trajectories of these measures, their interrelationships, or their collective impact on mortality. METHODS Longitudinal latent class analysis was used to evaluate trajectories of depression (Center for Epidemiologic Studies Depression ≥ 10), slow gait (<1.0 m/s), and elevated inflammation (interleukin 6 > 3.2 pg/mL) using data from the Health Aging and Body Composition Study. Logistic regression was used to identify their associations with mortality. RESULTS For each outcome, low-probability (n inflammation = 1,656, n slow gait = 1,471, n depression = 1,458), increasing-probability (n inflammation = 847, n slow gait = 880, n depression = 1,062), and consistently high-probability (n inflammation = 572, n slow gait = 724, n depression = 555) trajectories were identified, with 22% of all participants classified as having increasing or consistently high-probability trajectories on inflammation, slow gait, and depression (meaning probability of impairment on each outcome increased from low to moderate/high or remained high over 10 years). Trajectories of slow gait were associated with inflammation (r = .40, p < .001) and depression (r = .49, p < .001). Although worsening trajectories of inflammation were independently associated with mortality (p < .001), the association between worsening trajectories of slow gait and mortality was only present in participants with worsening depression trajectories (p < .01). Participants with increasing/consistently high trajectories of depression and consistently high trajectories of inflammation and slow gait (n = 247) have an adjusted-morality rate of 85.2%, greater than all other classification permutations. CONCLUSIONS Comprehensive assessment of older adults is warranted for the development of treatment strategies targeting a high-mortality risk phenotype consisting of inflammation, depression, and slow gait speed.