Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Treatment-resistant major depression is common and potentially life-threatening in elderly people, in whom little is known about the benefits and risks of augmentation pharmacotherapy. We aimed to assess whether aripiprazole is associated with a higher probability of remission than is placebo. METHODS: We did a randomised, double-blind, placebo-controlled trial at three centres in the USA and Canada to test the efficacy and safety of aripiprazole augmentation for adults aged older than 60 years with treatment-resistant depression (Montgomery Asberg Depression Rating Scale [MADRS] score of ≥15). Patients who did not achieve remission during a pre-trial with venlafaxine extended-release (150-300 mg/day) were randomly assigned (1:1) to the addition of aripiprazole (target dose 10 mg [maximum 15 mg] daily) daily or placebo for 12 weeks. The computer-generated randomisation was done in blocks and stratified by site. Only the database administrator and research pharmacists had knowledge of treatment assignment. The primary endpoint was remission, defined as an MADRS score of 10 or less (and at least 2 points below the score at the start of the randomised phase) at both of the final two consecutive visits, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00892047. FINDINGS: From July 20, 2009, to Dec 30, 2013, we recruited 468 eligible participants, 181 (39%) of whom did not remit and were randomly assigned to aripiprazole (n=91) or placebo (n=90). A greater proportion of participants in the aripiprazole group achieved remission than did those in the placebo group (40 [44%] vs 26 [29%] participants; odds ratio [OR] 2·0 [95% CI 1·1-3·7], p=0·03; number needed to treat [NNT] 6·6 [95% CI 3·5-81·8]). Akathisia was the most common adverse effect of aripiprazole (reported in 24 [26%] of 91 participants on aripiprazole vs 11 [12%] of 90 on placebo). Compared with placebo, aripiprazole was also associated with more Parkinsonism (15 [17%] of 86 vs two [2%] of 81 participants), but not with treatment-emergent suicidal ideation (13 [21%] of 61 vs 19 [29%] of 65 participants) or other measured safety variables. INTERPRETATION: In adults aged 60 years or older who do not achieve remission from depression with a first-line antidepressant, the addition of aripiprazole is effective in achieving and sustaining remission. Tolerability concerns include the potential for akathisia and Parkinsonism. FUNDING: National Institute of Mental Health, UPMC Endowment in Geriatric Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, National Center for Advancing Translational Sciences, and the Campbell Family Mental Health Research Institute.

Design and Recruitment for a Randomized Controlled Trial of Problem-Solving Therapy to Prevent Depression among Older Adults with Need for Supportive Services.

OBJECTIVE: Addressing subthreshold depression (indicated prevention) and vulnerabilities that increase the risk of major depression or anxiety disorders (selective prevention) is important for protecting mental health in old age. The Depression-Agency Based Collaborative (Dep-ABC) is a prevention trial involving older adults recruited from aging services sites (home care agencies, senior housing, senior centers) who meet criteria for subthreshold depression and disability. Therefore, the authors examine the effectiveness of partnerships with aging services sites for recruiting at-risk older adults, the quality of recruitment and acceptability of the Dep-ABC assessment and intervention, and the baseline status of participants. METHODS: Dep-ABC is a single-blind randomized controlled prevention trial set in aging services settings but with centralized screening, randomization, in-home assessments, and follow-up. Its intervention arm involves six to eight sessions of problem-solving therapy, in which older adults aged 60+ learn to break down problems that affect well-being and develop strategies to address them. We examined participation rates to assess quality of recruitment across sites and level of disability according to service use. RESULTS: Dep-ABC randomized 104 participants, 68.4% of eligible older adults. Screening using self-reported disability successfully netted a sample in which 74% received home care agency services, with remaining participants similarly impaired in structured self-reports of impairment and on observed performance tests. CONCLUSION: Direct outreach to aging services providers is an effective way to identify older adults with service needs at high risk of major depression. Problem-solving therapy is acceptable to this population and can be added to current services.

Insomnia is associated with suicide attempt in middle-aged and older adults with depression.

BACKGROUND: Insomnia increases in prevalence with age, is strongly associated with depression, and has been identified as a risk factor for suicide in several studies. The aim of this study was to determine whether insomnia severity varies between those who have attempted suicide (n = 72), those who only contemplate suicide (n = 28), and those who are depressed but have no suicidal ideation or attempt history (n = 35). METHODS: Participants were middle-aged and older adults (age 44-87, M = 66 years) with depression. Insomnia severity was measured as the sum of the early, middle, and late insomnia items from the Hamilton Rating Scale for Depression. General linear models examined relations between group status as the independent variable and insomnia severity as the dependent variable. RESULTS: The suicide attempt group suffered from more severe insomnia than the suicidal ideation and non-suicidal depressed groups (p < 0.05). Differences remained after adjusting for potential confounders including demographics, cognitive ability, alcohol dependence in the past month, severity of depressed mood, anxiety, and physical health burden. Moreover, greater insomnia severity in the suicide attempt group could not be explained by interpersonal difficulties, executive functioning, benzodiazepine use, or by the presence of post-traumatic stress disorder. CONCLUSIONS: Our results suggest that insomnia may be more strongly associated with suicidal behavior than with the presence of suicidal thoughts alone. Accordingly, insomnia is a potential treatment target for reducing suicide risk in middle-aged and older adults.

Improving health-related quality of life in older African American and non-Latino White patients.

OBJECTIVE: To compare the effect of problem-solving therapy against a health-promotion intervention (dietary practices) on health-related quality of life (HRQOL) and examine if there is a differential effect on non-Latino white patients and African American patients between the two interventions. This paper also explores participant characteristics (problem-solving style and physical functioning) as potential predictors of HRQOL. METHODS: Secondary analysis of data from a randomized depression prevention trial involving 247 older adults (154 non-Latino white, 90 African American, 3 Asian). Participants were randomly assigned to receive either problem solving therapy for primary care (PST-PC) or coaching in healthy dietary practices (DIET). RESULTS: Both PST-PC and DIET improved HRQOL over two years and did not differ significantly from each other. African American patients in both conditions had greater improvements in mental health-related quality of life (MHRQOL) compared with non-Latino white patients. In addition, higher social problem-solving and physical functioning were predictive of improved MHRQOL. CONCLUSION: PST-PC and DIET have the potential to improve health-related quality of life in a culturally relevant manner. Both hold promise as effective and potentially scalable interventions that could be generalized to highly disadvantaged populations in which little attention to HRQOL has been paid.

Advancing the screening of fibromyalgia in late-life depression: practical implications for psychiatric settings.

BACKGROUND: Fibromyalgia (FM) is common in older adults suffering from mood disorders. However, clinical diagnosis of FM is challenging, particularly in psychiatric settings. We examined the prevalence of FM and the sensitivity of three simple screeners for FM. METHODS: Using cross-sectional data, we evaluated three tests against the American College of Rheumatology (ACR) 1990 Criteria for the Classification of FM: a "Do you often feel like you hurt all over?" question, a pain map score, and the Pope and Hudson (PH) interview for FM. Participants were 185 community-dwelling adults ≥ 60 years old with comorbid depression and chronic low back pain evaluated at a late-life mental health clinic. RESULTS: Fifty three of 185 participants (29%) met the ACR 1990 FM criteria. Compared to those without FM, the FM group had more "yes" answers to the "hurt all over?" question and higher pain map scores. To reach a sensitivity of at least 0.90, the cut-off score for the pain map was 8. The sensitivity of the pain map, "hurt all over?" question, and PH criteria were 0.92 [95%CI 0.82-0.98], 0.91 [95%CI 0.79-0.97], and 0.94 [95%CI 0.843-0.99] respectively. CONCLUSIONS: Nearly one in three older adults suffering from depression and chronic low back pain met ACR 1990 FM criteria. Three short screening tests showed high sensitivity when compared to the ACR 1990 FM criteria. Implementation of one of the simple screeners for FM in geriatric psychiatry settings may guide the need for further diagnostic evaluation.

Neuroprogressive effects of lifetime illness duration in older adults with bipolar disorder.

OBJECTIVE: The aim of the present study was to examine the long-term effects of bipolar disorder (BD) on brain structure (gray matter volumes). METHODS: Fifty-four adults with BD [mean (standard deviation) age = 64.4 (5.4) years] underwent brain MR imaging along with comprehensive clinical assessment. Total gray matter, hippocampal, and amygdala volumes were extracted using methods developed through the Geriatric Neuroimaging Laboratory at the University of Pittsburgh (Pittsburgh, PA, USA). RESULTS: Lower total gray matter volumes were related to longer duration of BD, even when controlling for current age and cerebrovascular accident (CVA) risk/burden. Additionally, longer exposure to antipsychotic medication was related to lower gray matter volumes. Lower hippocampal volumes were related to total years of antipsychotic agent exposure and CVA risk/burden scores. Older age was related to lower total gray matter, hippocampal, and amgydala volumes. CONCLUSIONS: Our study of older adults with BD supports the understanding that BD is a neuroprogressive disorder with a longer duration of illness and more antipsychotic agent exposure related to lower gray matter volume.

Dynamic prediction of treatment response in late-life depression.

OBJECTIVE: To identify actionable predictors of remission to antidepressant pharmacotherapy in depressed older adults and to use signal detection theory to develop decision trees to guide clinical decision making. METHOD: We treated 277 participants with current major depression using open-label venlafaxine XR (up to 300 mg/day) for 12 weeks, in an NIMH-sponsored randomized, placebo-controlled augmentation trial of adjunctive aripiprazole. Multiple logistic regression and signal detection approaches identified predictors of remission in both completer and intent-to-treat samples. RESULTS: Higher baseline depressive symptom severity (odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.80-0.93; p <0.001), smaller symptom improvement during the first two weeks of treatment (OR: 0.96, 95% CI: 0.94-0.97; p <0.001), male sex (OR: 0.41 95% CI: 0.18-0.93; p = 0.03), duration of current episode ≥2 years (OR: 0.26, 95% CI: 0.12-0.57; p <0.001) and adequate past depression treatment (ATHF ≥3) (OR: 0.34, 95% CI: 0.16-0.74; p = 0.006) predicted lower probability of remission in the completer sample. Subjects with Montgomery Asberg (MADRS) decreasing by greater than 27% in the first 2 weeks and with baseline MADRS scores of less than 27 (percentile rank = 51) had the best chance of remission (89%). Subjects with small symptom decrease in the first 2 weeks with adequate prior treatment and younger than 75 years old had the lowest chance of remission (16%). CONCLUSION: Our results suggest the clinical utility of measuring pre-treatment illness severity and change during the first 2 weeks of treatment in predicting remission of late-life major depression.

Neuroimaging and neurocognitive abnormalities associated with bipolar disorder in old age.

OBJECTIVES: Cognitive dysfunction is prevalent in older adults with bipolar disorder (BD). High white matter hyperintensity (WMH) burden, a marker of white matter disease, detected on T2/fluid-attenuated inversion recovery brain magnetic resonance imaging (MRI) has been consistently reported in BD across all age ranges, including older adults. Yet, whether high WMH burden is related to the excess cognitive impairment present in older adults with BD is unknown. Therefore, we examine whether higher WMH burden is related to worse cognitive function in older adults with BD. METHODS: This is a cross-sectional study of 27 non-demented BD patients aged ≥50 years and 12 similarly aged mentally healthy comparators (controls). Subjects underwent both brain MRI and comprehensive neurocognitive assessment. We employed correlational analyses to evaluate the burden of WMH and the relationship between WMH and cognitive function. RESULTS: Although BD subjects had worse performance in all cognitive domains, BD subjects had less total WMH burden (t[13.4] = -3.57, p = 0.003). In control subjects, higher WMH was related to lower global cognitive function (ρ = -0.57, n = 12, p = 0.05). However, WMH did not correlate with neuropsychological performance in BD subjects. Further, BD and control subjects did not differ with respect to total gray and hippocampal volumes. CONCLUSIONS: Cognitive dysfunction in late-life BD does not appear to be due primarily to processes related to increased WMH or reduced gray matter volume. Future longitudinal studies should examine other potential neuroprogressive pathways such as inflammation, mitochondrial dysfunction, serum anticholinergic burden, and altered neurogenesis.

Additive effect of age on disability for individuals with spinal cord injuries.

OBJECTIVE: To examine the additive effect of age on disability for adults with spinal cord injury (SCI). DESIGN: Prospective cohort study. SETTING: SCI Model Systems. PARTICIPANTS: Individuals with SCI (median age at injury, 32 y; range, 6-88 y) with a discharge motor FIM score and at least 1 follow-up motor FIM score who also provided measures of other covariates (N=1660). Of the total sample, 79% were men, 72% were white, 16% had incomplete paraplegia, 33% had complete paraplegia, 30% had incomplete tetraplegia, and 21% had complete tetraplegia. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary study outcome was the motor subscale of the FIM. A mixed-models approach was used to examine the additive effect of age on disability for individuals with SCI. RESULTS: When controlling for motor FIM at discharge from rehabilitation, level and severity of injury, age at injury, sex, race, and the age × time interaction were not significant (P=.07). Age at the time of SCI was significantly associated with motor FIM (F1,238=22.49, P<.001). Two sensitivity analyses found significant interactions for both age × time (P=.03, P=.02) and age × time-square (P=.01, P=.006) models. Trajectory of motor FIM scores is moderated slightly by age at the time of injury. The older participants were at the time of injury, the greater the curvature and the more rapid decline were found in later years. CONCLUSIONS: These findings indicate that age moderately influences disability for some individuals with SCI: the older the age at the time of injury, the greater the influence age has on disability. The findings serve as an important empirical foundation for the evaluation and development of interventions designed to augment accelerated aging experienced by individuals with SCI.

Quantitative electroencephalography during rapid eye movement (REM) and non-REM sleep in combat-exposed veterans with and without post-traumatic stress disorder.

Sleep disturbances are a hallmark feature of post-traumatic stress disorder (PTSD), and associated with poor clinical outcomes. Few studies have examined sleep quantitative electroencephalography (qEEG), a technique able to detect subtle differences that polysomnography does not capture. We hypothesized that greater high-frequency qEEG would reflect 'hyperarousal' in combat veterans with PTSD (n = 16) compared to veterans without PTSD (n = 13). EEG power in traditional EEG frequency bands was computed for artifact-free sleep epochs across an entire night. Correlations were performed between qEEG and ratings of PTSD symptoms and combat exposure. The groups did not differ significantly in whole-night qEEG measures for either rapid eye movement (REM) or non-REM (NREM) sleep. Non-significant medium effect sizes suggest less REM beta (opposite to our hypothesis), less REM and NREM sigma and more NREM gamma in combat veterans with PTSD. Positive correlations were found between combat exposure and NREM beta (PTSD group only), and REM and NREM sigma (non-PTSD group only). Results did not support global hyperarousal in PTSD as indexed by increased beta qEEG activity. The correlation of sigma activity with combat exposure in those without PTSD and the non-significant trend towards less sigma activity during both REM and NREM sleep in combat veterans with PTSD suggests that differential information processing during sleep may characterize combat-exposed military veterans with and without PTSD.

Shiftworkers report worse sleep than day workers, even in retirement.

The aim of this study was to explore how the level of shiftwork exposure during an individual's working life might be related to subjectively reported sleep quality and timing during retirement. Telephone interviews regarding past employment and sleep timing and quality (among other variables) were conducted using a pseudo-random age-targeted sampling process. Subjective sleep quality was assessed using a telephone version of the Pittsburgh Sleep Quality Index. Timing of reported habitual bedtimes and rise-times were assessed using the Sleep Timing Questionnaire. Questions measuring morningness and subjective health were also given. Retired seniors (aged >65 years, n = 1113) were studied. Analysis was by analysis of variance, with shiftwork exposure in three bins [0 (n = 387), 1-15 (n = 371) and >15 years (n = 355)], gender (n = 634 male, 479 female) and former occupation [in two broad categories, 'managerial' (n = 437) versus 'other' (n = 676)] as factors. In retired shiftworkers, relative to retired day workers, past exposure to shiftwork was associated with higher (worse) PSQI scores by 1.0 units (1-15 years) and 0.6 units (>15 years) (main effect P = 0.005). There were also main effects of gender and former occupation (males and managerials reporting better sleep), but neither variable interacted with shiftwork exposure. The timing of current mean habitual bedtimes and rise-times (and also the variance around them) were very similar for the three shiftwork exposure groups. The shiftwork exposure effect did not appear to be mediated by either morningness or current health. Prior exposure to shiftwork would appear to be related to currently reported sleep problems during retirement.

Comparison of five actigraphy scoring methods with bipolar disorder.

The goal of this study was to compare 5 actigraphy scoring methods in a sample of 18 remitted patients with bipolar disorder. Actigraphy records were processed using five different scoring methods relying on the sleep diary; the event-marker; the software-provided automatic algorithm; the automatic algorithm supplemented by the event-marker; visual inspection (VI) only. The algorithm and the VI methods differed from the other methods for many actigraphy parameters of interest. Particularly, the algorithm method yielded longer sleep duration, and the VI method yielded shorter sleep latency compared to the other methods. The present findings provide guidance for the selection of signal processing method based on sleep parameters of interest, time-cue sources and availability, and related scoring time costs for the study.

Cognition in older adults with bipolar disorder versus major depressive disorder.

OBJECTIVES: Bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive dysfunction in older age during both acute mood episodes and remitted states. The purpose of this study was to investigate for the first time the similarities and differences in the cognitive function of older adults with BD and MDD that may shed light on mechanisms of cognitive decline. METHODS: A total of 165 subjects with BD (n = 43) or MDD (n = 122), ages ≥ 65 years [mean (SD) 74.2 (6.2)], were assessed when euthymic, using comprehensive measures of cognitive function and cognitive-instrumental activities of daily living (C-IADLs). Test results were standardized using a group of mentally healthy individuals (n = 92) of comparable age and education level. RESULTS: Subjects with BD and MDD were impaired across all cognitive domains compared with controls, most prominently in Information Processing Speed/Executive Function. Despite the protective effects of having higher education and lower vascular burden, BD subjects were more impaired across all cognitive domains compared with MDD subjects. Subjects with BD and MDD did not differ significantly in C-IADLs. CONCLUSION: In older age, patients with BD have worse overall cognitive function than patients with MDD. Our findings suggest that factors intrinsic to BD appear to be related to cognitive deterioration and support the understanding that BD is associated with cognitive decline.

Memantine for late-life depression and apathy after a disabling medical event: a 12-week, double-blind placebo-controlled pilot study.

OBJECTIVE: Preclinical data suggests that memantine, a noncompetitive glutamate N-methyl- D-aspartate-receptor blocker used for the treatment of moderate to severe Alzheimer's disease, could reduce depressive and amotivated behavior occurring in the context of psychosocial stress. Therefore, we examined whether memantine could reduce depressive symptoms and amotivation manifesting in older adults after a disabling medical event, thereby improving their functional recovery. METHOD: We recruited subjects aged 60 years and older who had recently suffered a disabling medical event and were admitted to a skilled nursing facility for rehabilitation. Participants with significant depressive symptoms, defined as a Hamilton Rating Scale for Depression score of 10 or greater, and/or significant apathy symptoms, defined as an Apathy Evaluation Scale score of 40 or greater, were randomized to memantine (10 mg/d for 1 week, then 10 mg twice daily) or placebo, for 12 weeks. We also recruited participants without depressive or apathy symptoms for naturalistic follow-up as a non-depressed comparison group. Depressive and apathy symptoms were main outcomes; functional recovery, and self-report rating of helplessness, and onset of new depressive disorders were secondary outcomes. RESULTS: Thirty-five older adults with significant depressive and/or apathy symptoms were randomized, of whom 27 (77.1%) completed the 12 week randomized controlled trial. Both groups showed reduction in depressive symptoms (but no significant reduction in apathy symptoms) and improved function. However, there were no group differences between the memantine-randomized and placebo randomized participants on any outcome. CONCLUSION: Memantine was not associated with superior affective or functional outcome compared with placebo in medically rehabilitating older adults with depressive and apathy symptoms.

Sleep variability, health-related practices, and inflammatory markers in a community dwelling sample of older adults.

OBJECTIVE: To explore relationships between wake- and sleep-related health behaviors and circulating concentrations of inflammatory markers (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) in a cohort of community dwelling older adults. Low-grade chronic inflammation is an important risk factor for age-related morbidity. Health behaviors, including average aggregate measures of sleep, have been linked to increased inflammation in older adults. Variability in sleep timing may also be associated with increased inflammation. METHOD: Participants were community dwelling older adults ≥ 60 years (n = 222: 39 bereaved, 55 caregivers, 52 with insomnia, and 76 good sleepers). Mean values and intraindividual variability in sleep, as well as caffeine and alcohol use, exercise, and daytime napping, were assessed by sleep diaries. Blood samples were obtained in the morning. RESULTS: Several interactions were noted between sleep behaviors, inflammatory markers, and participant group. Greater variability in wake time and time in bed was associated with higher IL-6 among good sleepers relative to caregivers and older adults with insomnia. Good sleepers who consumed moderate amounts of alcohol had the lowest concentrations of IL-6 compared with the other three groups who consumed alcohol. Insomnia subjects, but not good sleepers, showed increased concentrations of IL-6 associated with caffeine use. Caregivers showed increased concentrations of TNF-α with alcohol use relative to good sleepers. Greater variability in bedtime, later wake times, and longer time in bed was associated with higher TNF-α regardless of group. CONCLUSIONS: Moderation and regularity in the practice of certain health behaviors, including sleep practices, were associated with lower plasma levels of inflammatory markers in older adults. Life circumstances and specific sleep disorders may modify these associations.

Changes in neuropsychological functioning following treatment for late-life generalised anxiety disorder.

BACKGROUND: Generalised anxiety disorder (GAD) in older adults is associated with neuropsychological impairment. Aims We examined neuropsychological functioning in older adults with GAD in comparison with psychiatrically healthy older adults at baseline, and we examined changes following a 12-week placebo-controlled trial of escitalopram. METHOD: A total of 160 participants without dementia aged ≥60 with current GAD and 37 individuals in a comparison group without psychiatric history underwent neuropsychological assessment. Of these, 129 participants with GAD were reassessed post-treatment (trial registration: NCT00105586). RESULTS: The participants with GAD performed worse than the comparison group in information processing speed, working memory, inhibition, problem-solving (including concept formation and mental flexibility) and immediate and delayed memory. Neuropsychological functioning was correlated with everyday functioning. After treatment, those with low cognitive scores experienced working memory, delayed memory and visuospatial ability improvement and those who reported clinical improvement in anxiety exhibited improvement in the ability to engage inhibition and episodic recall. These improvements were modest and of similar magnitude in both treatment conditions. CONCLUSIONS: Generalised anxiety disorder in older adults is associated with neuropsychological impairments, which are associated with functional impairment. Those with GAD who either have a low cognitive performance or report clinical improvement in anxiety post-treatment, show improvement in multiple cognitive domains. These findings underscore the importance of treatments that aid cognition as well as anxiety symptoms.

Duloxetine and care management treatment of older adults with comorbid major depressive disorder and chronic low back pain: results of an open-label pilot study.

OBJECTIVE: In older adults, major depressive disorder (MDD) and chronic low back pain (CLBP) are common and mutually exacerbating. We predicted that duloxetine pharmacotherapy and Depression and Pain Care Management (DPCM) would result in (1) significant improvement in MDD and CLBP and (2) significant improvements in health-related quality of life, anxiety, disability, self-efficacy, and sleep quality. DESIGN AND INTERVENTION: Twelve week open-label study using duloxetine up to 120 mg/day + DPCM. SETTING: Outpatient late-life depression research clinic. PATIENTS: Thirty community-dwelling adults >60 years old. OUTCOME MEASURES: Montgomery Asberg Depression Rating Scale (MADRS) and McGill Pain Questionnaire-Short Form (MPQ-SF). RESULTS: 46.7% (n = 14) of the sample had a depression remission. All subjects who met criteria for the depression remission also had a pain response. 93.3% (n = 28) had a significant pain response. Of the subjects who met criteria for a low back pain response, 50% (n = 14) also met criteria for the depression remission. The mean time to depression remission was 7.6 (SE = 0.6) weeks. The mean time to pain response was 2.8 (SE = 0.5) weeks. There were significant improvements in mental health-related quality of life, anxiety, sleep quality, somatic complaints, and both self-efficacy for pain management and for coping with symptoms. Physical health-related quality of life, back pain-related disability, and self-efficacy for physical functioning did not improve. CONCLUSIONS: Serotonin and norepinephrine reuptake inhibitors like duloxetine delivered with DPCM may be a good choice to treat these linked conditions in older adults. Treatments that target low self-efficacy for physical function and improving disability may further increase response rates.

Disability in late-life major depression: patterns of self-reported task abilities, task habits, and observed task performance.

This article describes patterns of concordance/discordance between self-reported abilities ("can do") and habits ("does do") and observed task performance of daily living tasks in three groups of older adults: late life depression with mild cognitive impairment (n=53), late life depression without mild cognitive impairment (n=64), and non-depressed, cognitively normal controls (n=31). Self-reported data were gathered by interview in participants' homes, followed by observation of task performance. Significant differences in the patterns of response were found between controls and respondents with both late life depression and mild cognitive impairment for the cognitive instrumental activities, and between the two depressed groups and controls for the physical instrumental activities. For both sets of activities, controls exhibited the greatest overestimation of task performance. No differences were found among the groups for the less complex functional mobility and personal care tasks. However, for the more complex instrumental activities, concordance was close to, or less than, chance. The findings led us to conclude that when performance testing is not feasible, self-reports of functional status that focus on habits may be more accurate than those that focus on abilities.

The longitudinal course of cognition in older adults with bipolar disorder.

OBJECTIVES: Epidemiological studies suggest that elders with bipolar disorder (BD) may be at increased risk for dementia compared to the general population. We sought to investigate whether older adults with BD would present with more cognitive dysfunction than expected for their age and education, and whether they would experience a more rapid cognitive decline over three-year prospective follow-up. METHODS: Thirty-three subjects age > or = 50, mean (SD) age 69.7 (7.9) years, with BD I (n = 28) and II (n = 5) had neuropsychological examination at baseline and longitudinally over three years. All subjects were administered the Dementia Rating Scale (DRS) when euthymic. Thirty-six mentally healthy comparators ('controls'), equated on age and education, were selected from ongoing studies in our research center examining the longitudinal relationship between late-life mood disorders and cognitive function. RESULTS: Compared to mentally healthy comparators, subjects with BD performed significantly worse on the DRS at baseline [mean (SD) 135.2 (4.7); n = 33 versus 139.5 (3.3); n = 36], and over follow-up [131.9 (7.7); n = 14 versus 139.1 (3.4); n = 22]. There was a group-by-time interaction between the subjects with BD and the controls [group x time: F(1,64) = 5.07, p = 0.028]. CONCLUSIONS: In our study, older adults with BD had more cognitive dysfunction and more rapid cognitive decline than expected given their age and education. Cognitive dysfunction and accelerated cognitive decline may lead to decreased independence, with increased reliance on family and community supports, and potential placement in assisted-living facilities.

High worry severity is associated with poorer acute and maintenance efficacy of antidepressants in late-life depression.

BACKGROUND: Co-morbid anxiety symptoms are common in late-life depression (LLD) and predict poorer treatment outcomes. No research has delineated the impact of different dimensions of anxiety (such as worry/anxious apprehension and panic/anxious arousal) on treatment response in LLD. We explored the impact of the dimensions of worry and panic on acute and maintenance treatment outcomes in LLD. METHODS: We measured anxiety symptoms in 170 LLD subjects receiving protocolized treatment. Exploratory principal component analysis was used to delineate dimensions of anxiety symptoms. We defined sub-groups based on factor scores. We used survival analysis to test the association of pretreatment anxiety dimensions with time to response and time to recurrence of LLD. RESULTS: The principal component analysis found two factors: "worry" and "panic." Three sub-groups were defined: low panic-low worry, low panic-high worry, and high panic-high worry. The low panic-high worry and high panic-high worry sub-groups had longer time to response than the low panic-low worry sub-group. Time to recurrence was longer in low panic-low worry subjects randomized to drug. Among subjects with high worry, there was no difference between those with low versus high panic regarding both time to response and time to recurrence of LLD. CONCLUSION: High levels of worry were associated with longer time to response and earlier recurrence with pharmacotherapy for LLD. There was no additional effect of panic symptoms on treatment outcomes when accounting for the effects of excessive worry. These results suggest that worry symptoms should be a focus of strategies to improve acute and maintenance treatment response in LLD.