Search

Objective: The classification of mild cognitive impairment (MCI) continues to be debated though it has recently been subtyped into late (LMCI) versus early (EMCI) stages. Older adults presenting with both a depressive disorder (DEP) and cognitive impairment (CI) represent a unique, understudied population. Our aim was to examine baseline characteristics of DEP-CI patients in the DOTCODE trial, a randomized controlled trial of open antidepressant treatment for 16 weeks followed by add-on donepezil or placebo for 62 weeks.Methods/design: Key inclusion criteria were diagnosis of major depression or dysthymic disorder with Hamilton Depression Rating Scale (HAM-D) score >14, and cognitive impairment defined by MMSE score ≥21 and impaired performance on the WMS-R Logical Memory II test. Patients were classified as EMCI or LMCI based on the 1.5 SD cutoff on tests of verbal memory, and compared on baseline clinical, neuropsychological, and anatomical characteristics.Results: Seventy-nine DEP-CI patients were recruited of whom 39 met criteria for EMCI and 40 for LMCI. The mean age was 68.9, and mean HAM-D was 23.0. Late mild cognitive impairment patients had significantly worse ADAS-Cog (P < .001), MMSE (P = .004), Block Design (P = .024), Visual Rep II (P = .006), CFL Animal (P = .006), UPSIT (P = .051), as well as smaller right hippocampal volume (P = .037) compared to EMCI patients. MRI indices of cerebrovascular disease did not differ between EMCI and LMCI patients.Conclusions: Cognitive and neuronal loss markers differed between EMCI and LMCI among patients with DEP-CI, with LMCI being more likely to have the clinical and neuronal loss markers known to be associated with Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objective: Depression and cognitive impairment are often comorbid in older adults, but optimal treatment strategies remain unclear. In a two-site study, the efficacy and safety of add-on donepezil versus placebo were compared in depressed patients with cognitive impairment receiving stable antidepressant treatment.Methods: A randomized, double-blind, placebo-controlled trial was conducted in older adults with depression and cognitive impairment (https://clinicaltrials.gov/ct2/show/NCT01658228; NCT01658228). Patients received open-label antidepressant treatment for 16 weeks, initially with citalopram and then with venlafaxine, if needed, followed by random assignment to add-on donepezil 5-10 mg daily or placebo for another 62 weeks. Outcome measures were neuropsychological test performance (Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog] and Selective Reminding Test [SRT] total immediate recall) and instrumental activities of daily living (Functional Activities Questionnaire).Results: Of 81 patients who signed informed consent, 79 patients completed the baseline evaluation. Open antidepressant treatment was associated with improvement in depression in 63.93% responders by week 16. In the randomized trial, there were no treatment group differences between donepezil and placebo on dementia conversion rates, ADAS-Cog, SRT total immediate recall, or FAQ. Neither baseline cognitive impairment severity nor apolipoprotein E e4 genotype influenced donepezil efficacy. Donepezil was associated with more adverse effects than placebo.Conclusion: The results do not support adjunctive off-label cholinesterase inhibitor treatment in patients with depression and cognitive impairment. The findings highlight the need to prioritize discovery of novel treatments for this highly prevalent population with comorbid illnesses. [ABSTRACT FROM AUTHOR]

Objective: To assess potential genetic influences on citalopram treatment efficacy for agitation in individuals with Alzheimer dementia (AD). Six functional genetic variants were studied in the following genes: serotonin receptor 2A (HTR2A-T102C), serotonin receptor 2C (HTR2C-Cys23Ser), serotonin transporter (5HTT-LPR), brain-derived neurotropic factor (BDNF-Val66Met), apolipoprotein E (ε2, ε3, ε4 variants), and cytochrome P450 (CYP2C19). Treatment response by genotype was measured by (1) the agitation domain of the Neurobehavioral Rating Scale, (2) the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change scale (mADCS-CGIC), (3) the agitation domain of the Neuropsychiatric Inventory (NPI), and (4) the Cohen-Mansfield Agitation Inventory.Method: We utilized data from the Citalopram for Agitation in Alzheimer's Disease (CitAD) database. CitAD was a 9-week randomized, double-blind, placebo-controlled multicenter clinical trial showing significant improvement in agitation and caregiver distress in patients treated with citalopram. Proportional odds logistic regression and mixed effects models were used to examine the above-mentioned outcome measures.Results: Significant interactions were noted on the NPI agitation domain for HTR2A (likelihood ratio [LR] = 6.19, df = 2, P = .04) and the mADCS-CGIC for HTR2C (LR = 4.33, df = 2, P = .02) over 9 weeks.Discussion: Treatment outcomes in CitAD showed modest, although statistically significant, influence of genetic variation at HTR2A and HTR2C loci. Future studies should continue to examine the interaction of known genetic variants with antidepressant treatment in patients with AD having agitation. [ABSTRACT FROM AUTHOR]

We examined whether late-life depression, including depressive symptoms and antidepressant use, was associated with smaller total brain volume, smaller hippocampal volume, and larger white matter hyperintensity (WMH) volume in a large community-based cohort of old persons without dementia. Within the Washington/Hamilton Height-Inwood Columbia Aging Project (WHICAP), a community-based cohort study in northern Manhattan, 630 persons without dementia (mean age 80 years, SD = 5) had volumetric measures of the total brain, hippocampus, and WMH at 1.5 Tesla MRI and data on current depression, defined as a score of 4 or higher on the 10-item Center for Epidemiologic Studies-Depression (CES-D) scale, or use of antidepressants. Multiple linear regression analyses adjusted for age, gender, ethnicity, education, cardiovascular disease history, and MRI parameters showed that subjects with current depression had smaller relative total brain volume (B = -0.86%; 95% CI -1.68 to -0.05%; p < 0.05), smaller relative hippocampal volume (B = -0.07 ml; 95% CI -0.14 to 0.00 ml; p = 0.05), and larger relative WMH volume (natural logtransformed B = 0.19 ml; 95% CI 0.02 to 0.35 ml; p < 0.05). When examined separately, antidepressant use was significantly associated with smaller total brain, smaller hippocampal, and larger WMH volume, while high CES-D scores were not significantly associated with any of the brain measures, although the direction of association was similar as for antidepressant use. With the caveat that analyses were cross-sectional and we had no formal diagnosis of depression, our findings suggest that in this community-based sample of old persons without dementia, late-life depression is associated with more brain atrophy and more white matter lesions, which was mainly driven by antidepressant use. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the efficacy of antidepressants in people with depression and dementia. DESIGN: A systematic review and meta-analysis based on a literature search of Medline and Cochrane Trials Registry for acute-phase, double-blind, placebo-controlled, parallel-design, random-assignment trials of antidepressants marketed in the United States. SETTING: Outpatient clinics, inpatient units, residential settings. PARTICIPANTS: People with criterion-based diagnoses of dementia and depression. MEASUREMENTS: Numbers of participants randomized; baseline and end point depression scale scores; and response, remission, and discontinuation rates were extracted. Random-effects meta-analyses were performed for response and remission rates, change scores using standardized mean differences, and discontinuation rates. Sensitivity analyses were planned to examine effects of depression diagnosis, severity, and trial duration. RESULTS: Seven trials with 330 participants met selection criteria. The odds ratio (OR) for six trials reporting response rates with antidepressant and placebo was 2.12 (95% confidence interval (CI)=0.95-4.70; Z=1.84, P=.07). The OR for five trials reporting remission rates was 1.97 (95% CI=0.85-4.55; Z=1.59, P=.11). Both analyses demonstrated heterogeneity. The standardized mean difference in trials was 0.29 (95% CI=0.02-0.60, Z=1.86, P=.06). This analysis did not demonstrate significant heterogeneity. Adverse event discontinuation rates (9.0%) were not significantly higher with drug than placebo (6.0%), and were low. CONCLUSION: The evidence for antidepressant treatment of people with depression and dementia, although suggestive, does not confirm efficacy. All of the trials were significantly underpowered to detect differences, resulting in inconclusive findings. Variable trial methods, comorbid conditions, and differences in antidepressants employed further confounded findings. [ABSTRACT FROM AUTHOR]

Objective: Depression is common, frequently resistant to antidepressant treatment, and associated with impairments in cognition and everyday functioning. Computerized cognitive training (CCT) paradigms offer potential to improve cognition, mood and everyday functioning, but their effectiveness is not well established. The goal of this article was to conduct a systematic review and meta-analysis to determine the efficacy of CCT in depressive disorders.Method: A search was conducted to identify high quality randomized controlled CCT trials per PRISMA guidelines using PsycINFO and MEDLINE with the keywords "Cognitive training" or "Cognitive remediation" or "Cognitive rehabilitation" and "Depression". 9 randomized trials for depressed adults met inclusion criteria. Effect sizes (Hedge's g) were calculated for key outcome measures of mood symptom severity, daily functioning, and cognition. A 3-level Bayesian hierarchical linear model was used to estimate effect sizes for each domain and study. Publication bias was assessed using Classic Fail Safe N's and homogeneity was evaluated using Q and I(2) indexes.Results: Significant small-moderate effects for Symptom Severity (0.43) and Daily Functioning (0.72), and moderate-large effects for Attention (0.67), Working Memory (0.72), and Global Functioning (1.05) were found. No significant effects were found for Executive Functioning or Verbal Memory. Moderator variable analysis revealed decreased effect of CCT with age. Gender and concurrent medication treatment did not affect the results.Limitations: Small sample size, short duration, pseudo-specificity, and high heterogeneity for Verbal Memory measures.Conclusions: CCT is associated with improvement in depressive symptoms and everyday functioning, though produces inconsistent effects on cognition. [ABSTRACT FROM AUTHOR]