R. Scott Mackin

Problem-Solving Therapy and Supportive Therapy in Older Adults With Major Depression and Executive Dysfunction

OBJECTIVE The purpose of this study was to determine whether problem-solving therapy is an effective treatment in older patients with depression and executive dysfunction, a population likely to be resistant to antidepressant drugs. METHOD Participants were adults age 60 and older with major depression and executive dysfunction. Problem-solving therapy was modified to be accessible to this population. Participants were randomly assigned to 12 weekly sessions of problem-solving therapy or supportive therapy and assessed at weeks 3, 6, 9, and 12. RESULTS Of the 653 individuals referred for this study, 221 met selection criteria and were enrolled in the study. Reduction of depressive symptom severity was comparable for the two treatment groups during the first 6 weeks of treatment, but at weeks 9 and 12 the problem-solving therapy group had a greater reduction in symptom severity, a greater response rate, and a greater remission rate than the supportive therapy group (response rates at week 9: 47.1% and 29.3%; at week 12:56.7% and 34.0%; remission rates at week 9: 37.9% and 21.7%; at week 12: 45.6% and 27.8%). Problem-solving therapy yielded one additional response or remission over supportive therapy for every 4.4-5.6 patients by the end of the trial. CONCLUSIONS These results suggest that problem-solving therapy is effective in reducing depressive symptoms and leading to treatment response and remission in a considerable number of older patients with major depression and executive dysfunction. The clinical value of this finding is that problem-solving therapy may be a treatment alternative in an older patient population likely to be resistant to pharmacotherapy.

Development and assessment of a composite score for memory in the Alzheimer’s Disease Neuroimaging Initiative (ADNI)

We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer’s Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.

Problem-solving therapy and supportive therapy in older adults with major depression and executive dysfunction: effect on disability.

CONTEXT Older patients with depression and executive dysfunction represent a population with significant disability and a high likelihood of failing pharmacotherapy. OBJECTIVES To examine whether problem-solving therapy (PST) reduces disability more than does supportive therapy (ST) in older patients with depression and executive dysfunction and whether this effect is mediated by improvement in depressive symptoms. DESIGN Randomized controlled trial. SETTING Weill Cornell Medical College and University of California at San Francisco. PARTICIPANTS Adults (aged >59 years) with major depression and executive dysfunction recruited between December 2002 and November 2007 and followed up for 36 weeks. Intervention Twelve sessions of PST modified for older depressed adults with executive impairment or ST. Main Outcome Measure Disability as quantified using the 12-item World Health Organization Disability Assessment Schedule II. RESULTS Of 653 individuals referred to this study, 221 met the inclusion criteria and were randomized to receive PST or ST. Both PST and ST led to comparable improvement in disability in the first 6 weeks of treatment, but a more prominent reduction was noted in PST participants at weeks 9 and 12. The difference between PST and ST was greater in patients with greater cognitive impairment and more previous episodes. Reduction in disability paralleled reduction in depressive symptoms. The therapeutic advantage of PST over ST in reducing depression was, in part, due to greater reduction in disability by PST. Although disability increased during the 24 weeks after the end of treatment, the advantage of PST over ST was retained. CONCLUSIONS These results suggest that PST is more effective than ST in reducing disability in older patients with major depression and executive dysfunction, and its benefits were retained after the end of treatment. The clinical value of this finding is that PST may be a treatment alternative in an older patient population likely to be resistant to pharmacotherapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00052091.

Patterns of Reduced Cortical Thickness in Late-Life Depression and Relationship to Psychotherapeutic Response

OBJECTIVE Cortical atrophy has been associated with late-life depression (LLD) and recent findings suggest that reduced right hemisphere cortical thickness is associated with familial risk for major depressive disorder, but cortical thickness abnormalities in LLD have not been explored. Furthermore, cortical atrophy has been posited as a contributor to poor antidepressant treatment response in LLD, but the impact of cortical thickness on psychotherapy response is unknown. This study was conducted to evaluate patterns of cortical thickness in LLD and in relation to psychotherapy treatment outcomes. METHODS Participants included 22 individuals with LLD and 12 age-matched comparison subjects. LLD participants completed 12 weeks of psychotherapy and treatment response was defined as a 50% reduction in depressive symptoms. All participants underwent magnetic resonance imaging of the brain, and cortical mapping of gray matter tissue thickness was calculated. RESULTS LLD individuals demonstrated thinner cortex than controls prominently in the right frontal, parietal, and temporal brain regions. Eleven participants (50%) exhibited positive psychotherapy response after 12 weeks of treatment. Psychotherapy nonresponders demonstrated thinner cortex in bilateral posterior cingulate and parahippocampal cortices, left paracentral, precuneus, cuneus, and insular cortices, and the right medial orbitofrontal and lateral occipital cortices relative to treatment responders. CONCLUSIONS Our findings suggest more distributed right hemisphere cortical abnormalities in LLD than have been previously reported. In addition, our findings suggest that reduced bilateral cortical thickness may be an important phenotypic marker of individuals at higher risk for poor response to psychotherapy.

Cognitive functioning in individuals with severe compulsive hoarding behaviors and late life depression

The cognitive characteristics of individuals with severe compulsive hoarding behaviors (SCH) are not well understood and existing studies have largely focused on individuals with SCH and concurrent anxiety disorders. The present study was conducted to evaluate the frequency with which SCH co‐occurs with LLD and to compare the cognitive characteristics of individuals with late life depression and concurrent SCH (LLD + SCH) to that of LLD individuals without SCH (LLD).

Patterns of Alcohol and Drug Use Among Depressed Older Adults Seeking Outpatient Psychiatric Services

OBJECTIVE Alcohol and drug use and related problems may compromise depression treatment, and older adults may be especially at risk for poor outcomes. However, alcohol and drug use among older adults have not been studied in settings in which depression treatment is provided. This study examined the prevalence and clinical and demographic correlates of alcohol and drug use and misuse of prescription drugs among adults with depression seeking outpatient psychiatric care (excluding chemical dependency treatment). METHODS The sample included 154 older adults (age 60 years and older who scored ≥10 on the Beck Depression Inventory-II [BDI-II] at intake). Participants also completed alcohol and drug use questions and the Short Michigan Alcohol Screening Test. RESULTS Recent alcohol and drug use, heavy episodic drinking, and history of alcohol-related problems were common. Alcohol use in the prior 30 days was reported by 53% of men and 50% of women. Cannabis use in the prior 30 days was reported by 12% of men and 4% of women; and misuse of sedatives in the prior 30 days was reported by 16% of men and 9% of women. In exact logistic regression, higher BDI-II score was associated with cannabis use (odds ratio = 15.8, 95% confidence interval = 2.0-734.0, exactp = 0.003). CONCLUSIONS Older adults with depression are likely to present for treatment with a range of concurrent alcohol and drug use patterns, including cannabis use and misuse of prescription medication. Clinicians should evaluate depressed patients for substance use and related problems and consider appropriate interventions.

Neuroimaging abnormalities in adults with sickle cell anemia Associations with cognition

Objective: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). Methods: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). Results: After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = −2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = −3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. Conclusions: Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA.

The transitional association between β-amyloid pathology and regional brain atrophy

Alzheimers disease (AD) is characterized by the accumulation of β‐amyloid (Aβ) associated with brain atrophy and cognitive decline. The functional form to model the association between Aβ and regional brain atrophy has not been well defined. To determine the relationship between Aβ and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Aβ to identify subjects as Aβ+ and Aβ− with a trilinear spline model of CSF Aβ.

The Sensitivity and Specificity of Cognitive Screening Instruments to Detect Cognitive Impairment in Older Adults With Severe Psychiatric Illness

Background: Older adults with severe psychiatric illness are often treated at community mental health centers (CMHCs) and these individuals commonly have numerous risk factors for cognitive impairment (CI). Brief cognitive screening instruments are frequently used to evaluate cognitive functioning in CMHCs, but the validity of these measures for detecting CI has not been adequately evaluated in this patient population. Objectives: To determine the sensitivity and specificity of 2 cognitive screening measures (the Mini-Mental Status Examination [MMSE] and the Stroop Color and Word Test [SCWT]) for detecting CI in a sample of older adults with severe psychiatric illness. Methods: Data were collected from 52 older adults receiving services at a CMHC. Diagnosis of CI was made by a neuropsychologist. Sensitivity and specificity coefficients for 2 cutoff scores for the MMSE and the SCWT were calculated. Results: A cutoff score of 25 on the MMSE yielded a sensitivity of 43.3% and a specificity of 90.4% for detecting CI, whereas a cutoff score of 21 yielded sensitivity of 13.1% and 100% specificity. Using an age- and education-corrected scaled score (SS) on the SCWT falling at or below 7 as the criterion the SCWT had 88.8% sensitivity and 36.8% specificity, whereas a cutoff score of 5 or below yielded sensitivity of 59.2% and specificity of 57.8%. Conclusions: Overall, the MMSE was found to be the more clinically useful cognitive screening tool for use in CMHC. Yet, because of the poor sensitivity of the MMSE for detecting CI in this patient population, alternative screening methods should be explored.

Impaired financial capacity in late life depression is associated with cognitive performance on measures of executive functioning and attention

Few studies have evaluated the prevalence of impairments of financial capacity among individuals with psychiatric disorders. Late life depression (LLD) is a common psychiatric disorder associated with significant disability and cognitive impairment. The purpose of this investigation was to determine the prevalence and cognitive correlates of impairments of financial capacity among individuals with LLD. Participants included 65 LLD individuals and 32 comparison subjects. Assessments included measures of financial capacity, cognitive functioning, and depression symptom severity. Individuals with LLD exhibited a significantly higher rate of impaired financial capacity (22%) than the comparison group (6%). Results of a multiple regression analysis indicated that performance on measures of executive functioning and attention, but not depression severity, were most strongly associated with financial capacity performance in LLD. Our results suggest impairments of financial capacity in LLD are largely explained by cognitive functioning in these domains.