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ABSTRACTBackground:Traditional perspectives conceptualize resilience as a trait and depression as resulting from resilience deficiency. However, research indicates that resilience varies substantially even among adults who are clinically depressed, as well as across the lifespan of an individual. Few studies have investigated resilience in depression, and even fewer have examined resilience in depressed older adults. METHODS:Three hundred thirty-seven adults ≥60 years with major depressive disorder completed the Connor-Davidson Resilience Scale (CD-RISC) and measures of mental health, quality of life (QOL), and medical comorbidity. Exploratory factor analysis was used to explore the factor structure of the CD-RISC. Correlations and general linear models were used to examine associations between resilience and other variables. RESULTS:The rotated component matrix indicated a four-factor model. Sorting of items by highest factor loading revealed constructs associated with (1) grit, (2) active coping self-efficacy, (3) accommodative coping self-efficacy, and (4) spirituality. Resilience was significantly correlated with increased age, lower cognitive functioning, greater cerebrovascular risk, and greater medical comorbidity. Resilience was negatively associated with mental health symptoms (depression, apathy, and anxiety) and positively associated with QOL. The final optimal model identified less depression, less apathy, greater medical comorbidity, higher QOL, and minority (non-White) race as factors that significantly explained variability in resilience. CONCLUSIONS:Resilience was significantly associated with a range of mental health constructs in a sample of older adults with depression. Future clinical trials and dismantling studies may help determine whether interventions targeting grit, active coping, accommodative coping, and spirituality can increase resilience and help prevent and treat depression in older adults.

ObjectivesWith the world population rapidly aging, it is increasingly important to identify sociodemographic, cognitive, and clinical features that predict poor outcome in geriatric depression. Self-report measures of resilience-ie, the ability to adapt and thrive in the face of adversity-may identify those depressed older adults with more favorable prognoses.MethodsWe investigated the utility of baseline variables including 4 factors of resilience (grit, active coping self-efficacy, accommodative coping self-efficacy, and spirituality) for predicting treatment response and remission in a 16-week randomized controlled trial of methylphenidate, citalopram, or their combination in 143 adults over the age of 60 with MDD.ResultsFinal logistic regression models revealed that greater total baseline resilience (Wald χ2  = 3.8, P = 0.05) significantly predicted both treatment response and remission. Specifically, a 20% increase in total resilience predicted nearly 2 times greater likelihood of remission (OR = 1.98, 95% CI = [1.01, 3.91]). Examining the individual factors of resilience, only accommodative coping self-efficacy (Wald χ2  = 3.7, P = 0.05; OR = 1.41 [1.00-2.01]) was significantly associated with remission. We found no relation between baseline sociodemographic factors (age, sex, race, education level) or measures of cognitive performance and posttreatment depressive symptoms.ConclusionsSelf-reported resilience may predict greater responsivity to antidepressant medication in older adults with MDD. Future research should investigate the potential for resilience training-and in particular, interventions designed to increase accommodative coping-to promote sustained remission of geriatric depression.

BACKGROUND:Previous studies suggest that low emotional resilience may correspond with increased or over-active amygdala function. Complementary studies suggest that emotional resilience increases with age; older adults tend to have decreased attentional bias to negative stimuli compared to younger adults. Amygdala nuclei and related brain circuits have been linked to negative affect, and depressed patients have been demonstrated to have abnormal amygdala function. METHODS:In the current study, we correlated psychological resilience measures with amygdala function measured with resting-state arterial spin-labelled (ASL) and blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in older adults with and without depression. Specifically, we targeted the basolateral, centromedial, and superficial nuclei groups of the amygdala, which have different functions and brain connections. RESULTS:High levels of psychological resilience correlated with lower basal levels of amygdala activity measured with ASL fMRI. High resilience also correlated with decreased connectivity between amygdala nuclei and the ventral default-mode network independent of depression status. Instead, lower depression symptoms were associated with higher connectivity between the amygdalae and dorsal frontal networks. LIMITATIONS:Future multi-site studies with larger sample size and improved neuroimaging technologies are needed. Longitudinal studies that target resilience to naturalistic stressors will also be a powerful contribution to the field. CONCLUSIONS:Our results suggest that resilience in older adults is more closely related to function in ventral amygdala networks, while late-life depression is related to reduced connectivity between the amygdala and dorsal frontal regions.

OBJECTIVE:Greater psychological resilience may protect against developing depression in a growing geriatric population. Identifying the neural correlates of resilience in geriatric depression could provide neurobiologic targets to inform clinical interventions. However, most prior neuroimaging studies have only considered the presence or absence of resilience and have not addressed the multifactorial nature of resilience. The current study aimed to establish the neural correlates of four factors of resilience in the depressed elderly. METHODS:White matter integrity was assessed using diffusion-weighted magnetic resonance imaging data collected from 70 older adults with major depressive disorder. We used four resilience factors previously derived in an exploratory factor analysis of the Connor-Davidson Resilience Scale in a large sample of depressed older adults: 1, grit; 2, active coping self-efficacy; 3, accommodative coping self-efficacy; and 4, spirituality. RESULTS:The resilience factor "grit" was positively associated with fractional anisotropy in the callosal region connecting prefrontal cortex and fractional anisotropy in cingulum fibers; however, the latter did not survive correction for multiple comparisons. CONCLUSION:Structural integrity of major white matter pathways implicated in cognitive control and emotion regulation (i.e., connecting prefrontal cortex) was positively associated with the resilience factor "grit" in our sample of older adults with depression. Prospective studies are needed to determine the utility of the structural integrity of these pathways as a biomarker in predicting risk for depression and treatment response.

ObjectiveCognitive impairment associated with late-life depression can persist after remission of mood symptoms. Apathy, a common symptom of late-life depression, often leads to worse clinical outcomes. We examined if severity of apathy mediates cognitive difficulties in a cohort of older adults with major depression.MethodsOne hundred thirty-eight older adults with depression (54.4% female; mean [SD] age: 69.7 [7.4] years; mean [SD] education:15.6 [2.7] years) were recruited to participate in a treatment study, and only baseline data were analyzed. All participants received a comprehensive evaluation of depression, apathy, and cognition. We examined whether apathy mediated the relationship between depression and cognition, focusing our attention on memory and cognitive control. We then explored whether the mediation effects differed across women and men.ResultsIncreased apathy was significantly associated with worse depression and lower performance in the cognitive control domain but not in memory. Higher depressive scores were significantly associated with worse cognitive control but not memory. Mediation analyses revealed a significant indirect effect on cognitive control by depression through increased apathy scores with the mediator accounting for 21% of the total effect. Stratifying by sex, we found that women exhibited a significant indirect effect, with the mediator accounting for 47% of the total effect, whereas there was no mediation by apathy in men.ConclusionsThe findings imply that increased apathy mediates the relationship between cognition and depression. The identification of mediating effects may inform future treatment strategies and preventive interventions that can focus on decreasing apathy to improve cognition in late-life depression.

BackgroundNeurotoxicity associated with amyloid and tau protein aggregation could represent a pathophysiological cascade that, along with vascular compromise, may predispose individuals to late-life depression (LLD). In LLD, apathy is common, leads to worsening of functioning, and responds poorly to antidepressant treatment. Better understanding of the pathophysiological mechanisms of apathy in LLD would facilitate development of more effective diagnostic and treatment approaches. In this cross-sectional pilot study, we performed positron emission tomography scans after injection of 2-(1-{6-[(2-[18 F]fluoroethyl)(methyl)-amino]-2-naphthyl}ethylidene) malononitrile ([18 F]FDDNP), an in vivo amyloid and tau neuroimaging study, in patients with LLD to explore neural correlates of apathy.MethodsSixteen depressed elderly volunteers received clinical assessments and [18 F]FDDNP positron emission tomography scans. The cross-sectional relationship of [18 F]FDDNP binding levels with depression (Hamilton Depression Rating Scale) and apathy (Apathy Evaluation Scale) were studied using Spearman's correlation analyses because of the relatively small sample size. Age, sex, and years of education were partialed out. Significance levels were set at P ≤ 0.05.Results[18 F]FDDNP binding in the anterior cingulate cortex was negatively associated with the Apathy Evaluation Scale total (r = -0.62, P = 0.02; where low Apathy Evaluation Scale score equals greater severity of apathy). This suggests that apathy in LLD is associated with higher amyloid and/or tau levels in the anterior cingulate cortex. None of the regional [18 F]FDDNP binding levels was significantly associated with the Hamilton Depression Rating Scale total.ConclusionThis pilot study suggests that increased apathy in subjects with LLD may be associated with greater amyloid and/or tau burden in certain brain regions. Future studies in larger samples would elucidate the generalizability of these results, which eventually could lead to improved diagnostic and treatment methods in LLD.

BackgroundGlobal population aging will result in increasing rates of cognitive decline and dementia. Thus, effective, low-cost, and low side-effect interventions for the treatment and prevention of cognitive decline are urgently needed. Our study is the first to investigate the effects of Kundalini yoga (KY) training on mild cognitive impairment (MCI).MethodsOlder participants (≥55 years of age) with MCI were randomized to either a 12-week KY intervention or memory enhancement training (MET; gold-standard, active control). Cognitive (i.e. memory and executive functioning) and mood (i.e. depression, apathy, and resilience) assessments were administered at baseline, 12 weeks and 24 weeks.ResultsAt baseline, 81 participants had no significant baseline group differences in clinical or demographic characteristics. At 12 weeks and 24 weeks, both KY and MET groups showed significant improvement in memory; however, only KY showed significant improvement in executive functioning. Only the KY group showed significant improvement in depressive symptoms and resilience at week 12.ConclusionKY group showed short- and long-term improvements in executive functioning as compared to MET, and broader effects on depressed mood and resilience. This observation should be confirmed in future clinical trials of yoga intervention for treatment and prevention of cognitive decline (NCT01983930).

ObjectiveThis first pilot study of genome-wide expression as predictor of antidepressant response in late-life depression examined genome-wide transcriptional profiles in a randomized placebo-controlled trial of combined methylphenidate and citalopram.MethodsGenome-wide transcriptional profiles were examined in peripheral blood leukocytes sampled at baseline and 16 weeks from 35 older adults with major depression, who were randomized to methylphenidate + citalopram, citalopram + placebo, or methylphenidate + placebo. Methylphenidate doses ranged between 10 and 40 mg/day, and citalopram doses ranged between 20 and 60 mg/day. Remission was defined as Hamilton Depression Rating Scale score of 6 or below. Early remission was achieved in the first 4 weeks of treatment. We hypothesized that differential gene expression at baseline can predict antidepressant response.ResultsWe analyzed gene expression in 24 remitters and 11 non-remitters. At baseline, we found three genes showing higher expression in all remitters versus non-remitters that satisfied the established level of significance: a fold change of 2 and p-value of 0.05 that included HLA-DRB5, SELENBP1, and LOC388588. Two gene transcripts showed higher expression in early remitters at baseline compared with non-remitters. The first gene was CA1 carbonic anhydrase gene, on chromosome 8 involved in respiratory function (fold change 2.54; p = 0.03). The second gene was the SNCA-α-synuclein gene, implicated, which binds to dopamine transporter (fold change 2.1; p = 0.03).ConclusionsRemission to antidepressants in geriatric depression may be associated with a particular gene expression profile in monoaminergic and metabolic pathways and needs to be replicated in a larger sample.

BackgroundNo study has explored the effect of yoga on cognitive decline and resting-state functional connectivity.ObjectivesThis study explored the relationship between performance on memory tests and resting-state functional connectivity before and after a yoga intervention versus active control for subjects with mild cognitive impairment (MCI).MethodsParticipants ( ≥ 55 y) with MCI were randomized to receive a yoga intervention or active "gold-standard" control (i.e., memory enhancement training (MET)) for 12 weeks. Resting-state functional magnetic resonance imaging was used to map correlations between brain networks and memory performance changes over time. Default mode networks (DMN), language and superior parietal networks were chosen as networks of interest to analyze the association with changes in verbal and visuospatial memory performance.ResultsFourteen yoga and 11 MET participants completed the study. The yoga group demonstrated a statistically significant improvement in depression and visuospatial memory. We observed improved verbal memory performance correlated with increased connectivity between the DMN and frontal medial cortex, pregenual anterior cingulate cortex, right middle frontal cortex, posterior cingulate cortex, and left lateral occipital cortex. Improved verbal memory performance positively correlated with increased connectivity between the language processing network and the left inferior frontal gyrus. Improved visuospatial memory performance correlated inversely with connectivity between the superior parietal network and the medial parietal cortex.ConclusionYoga may be as effective as MET in improving functional connectivity in relation to verbal memory performance. These findings should be confirmed in larger prospective studies.

Behavioral interventions are becoming increasingly popular approaches to ameliorate age-related cognitive decline, but their underlying neurobiological mechanisms and clinical efficiency have not been fully elucidated. The present study explored brain plasticity associated with two behavioral interventions, memory enhancement training (MET) and a mind-body practice (yogic meditation), in healthy seniors with mild cognitive impairment (MCI) using structural magnetic resonance imaging (s-MRI) and proton magnetic resonance spectroscopy (1H-MRS). Senior participants (age ≥55 years) with MCI were randomized to the MET or yogic meditation interventions. For both interventions, participants completed either MET training or Kundalini Yoga (KY) for 60-min sessions over 12 weeks, with 12-min daily homework assignments. Gray matter volume and metabolite concentrations in the dorsal anterior cingulate cortex (dACC) and bilateral hippocampus were measured by structural MRI and 1H-MRS at baseline and after 12 weeks of training. Metabolites measured included glutamate-glutamine (Glx), choline-containing compounds (Cho, including glycerophosphocholine and phosphocholine), gamma-aminobutyric acid (GABA), and N-acetyl aspartate and N-acetylaspartyl-glutamate (NAA-NAAG). In total, 11 participants completed MET and 14 completed yogic meditation for this study. Structural MRI analysis showed an interaction between time and group in dACC, indicating a trend towards increased gray matter volume after the MET intervention. 1H-MRS analysis showed an interaction between time and group in choline-containing compounds in bilateral hippocampus, induced by significant decreases after the MET intervention. Though preliminary, our results suggest that memory training induces structural and neurochemical plasticity in seniors with MCI. Further research is needed to determine whether mind-body interventions like yoga yield similar neuroplastic changes.

OBJECTIVE: The authors evaluated the potential of methylphenidate to improve antidepressant response to citalopram, as assessed by clinical and cognitive outcomes, in elderly depressed patients. METHOD: The authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups: methylphenidate plus placebo (N=48), citalopram plus placebo (N=48), and citalopram plus methylphenidate (N=47). The primary outcome measure was change in depression severity. Remission was defined as a score of 6 or less on the Hamilton Depression Rating Scale. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition. RESULTS: Daily doses ranged from 20 mg to 60 mg for citalopram (mean=32 mg) and from 5 mg to 40 mg for methylphenidate (mean=16 mg). All groups showed significant improvement in depression severity and in cognitive performance. However, the improvement in depression severity and the Clinical Global Impressions improvement score was more prominent in the citalopram plus methylphenidate group compared with the other two groups. Additionally, the rate of improvement in the citalopram plus methylphenidate group was significantly higher than that in the citalopram plus placebo group in the first 4 weeks of the trial. The groups did not differ in cognitive improvement or number of side effects. CONCLUSIONS: Combined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in mood and well-being, as well as a higher rate of remission, compared with either drug alone. All treatments led to an improvement in cognitive functioning, although augmentation with methylphenidate did not offer additional benefits.

ObjectiveThe authors evaluated the potential of methylphenidate to improve antidepressant response to citalopram, as assessed by clinical and cognitive outcomes, in elderly depressed patients.MethodThe authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups: methylphenidate plus placebo (N=48), citalopram plus placebo (N=48), and citalopram plus methylphenidate (N=47). The primary outcome measure was change in depression severity. Remission was defined as a score of 6 or less on the Hamilton Depression Rating Scale. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition.ResultsDaily doses ranged from 20 mg to 60 mg for citalopram (mean=32 mg) and from 5 mg to 40 mg for methylphenidate (mean=16 mg). All groups showed significant improvement in depression severity and in cognitive performance. However, the improvement in depression severity and the Clinical Global Impressions improvement score was more prominent in the citalopram plus methylphenidate group compared with the other two groups. Additionally, the rate of improvement in the citalopram plus methylphenidate group was significantly higher than that in the citalopram plus placebo group in the first 4 weeks of the trial. The groups did not differ in cognitive improvement or number of side effects.ConclusionsCombined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in mood and well-being, as well as a higher rate of remission, compared with either drug alone. All treatments led to an improvement in cognitive functioning, although augmentation with methylphenidate did not offer additional benefits.

ObjectivesDepressed older adults are at risk for the development of mild cognitive impairment (MCI), but few studies have characterized MCI subtypes in geriatric depression. The objective of this study was to identify the clinical patterns of MCI in late-life depression.DesignBaseline demographic, clinical, and neuropsychological test data collected as part of a randomized antidepressant trial for geriatric depression.SettingUCLA-based outpatient clinic.ParticipantsOne hundred thirty-eight older adults with major depression.MeasurementsA neuropsychological test battery and comprehensive evaluations of depression, apathy, quality of life, medical burden, and vascular risk factors.ResultsSeventy-one participants (51%) had MCI and 67 (49%) were cognitively normal. Of subjects with MCI, 14 (20%) had amnestic MCI and 57 (80%) had non-amnestic MCI. Overall, patients with MCI had greater depression severity, poorer quality of life, and worse performance on the Mini-Mental State Exam than patients without MCI. Patients with non-amnestic MCI had significantly greater depression severity than patients without MCI. Across all subjects, depression severity correlated with impaired performance in language and visuospatial functioning.ConclusionOur findings suggest that MCI is associated with greater severity of depression, poorer quality of life, and worse global cognitive function. Overall, subtypes of MCI in geriatric depression differ in the patterns of functional impairment, which may require different therapeutic approaches.

Background Neurotoxicity associated with amyloid and tau protein aggregation could represent a pathophysiological cascade that, along with vascular compromise, may predispose individuals to late-life depression (LLD). In LLD, apathy is common, leads to worsening of functioning, and responds poorly to antidepressant treatment. Better understanding of the pathophysiological mechanisms of apathy in LLD would facilitate development of more effective diagnostic and treatment approaches. In this cross-sectional pilot study, we performed positron emission tomography scans after injection of 2-(1-{6-[(2-[18 F]fluoroethyl)(methyl)-amino]-2-naphthyl}ethylidene) malononitrile ([18 F]FDDNP), an in vivo amyloid and tau neuroimaging study, in patients with LLD to explore neural correlates of apathy. Methods Sixteen depressed elderly volunteers received clinical assessments and [18 F]FDDNP positron emission tomography scans. The cross-sectional relationship of [18F]FDDNP binding levels with depression (Hamilton Depression Rating Scale) and apathy (Apathy Evaluation Scale) were studied using Spearman's correlation analyses because of the relatively small sample size. Age, sex, and years of education were partialed out. Significance levels were set at P ≤ 0.05. Results [18 F]FDDNP binding in the anterior cingulate cortex was negatively associated with the Apathy Evaluation Scale total ( r = −0.62, P = 0.02; where low Apathy Evaluation Scale score equals greater severity of apathy). This suggests that apathy in LLD is associated with higher amyloid and/or tau levels in the anterior cingulate cortex. None of the regional [18 F]FDDNP binding levels was significantly associated with the Hamilton Depression Rating Scale total. Conclusion This pilot study suggests that increased apathy in subjects with LLD may be associated with greater amyloid and/or tau burden in certain brain regions. Future studies in larger samples would elucidate the generalizability of these results, which eventually could lead to improved diagnostic and treatment methods in LLD. [ABSTRACT FROM AUTHOR]

Behavioral interventions are becoming increasingly popular approaches to ameliorate age-related cognitive decline, but their underlying neurobiological mechanisms and clinical efficiency have not been fully elucidated. The present study explored brain plasticity associated with two behavioral interventions, memory enhancement training (MET) and a mind-body practice (yogic meditation), in healthy seniors with mild cognitive impairment (MCI) using structural magnetic resonance imaging (s-MRI) and proton magnetic resonance spectroscopy (¹H-MRS). Senior participants (age ≥55 years) with MCI were randomized to the MET or yogic meditation interventions. For both interventions, participants completed either MET training or Kundalini Yoga (KY) for 60-min sessions over 12 weeks, with 12-min daily homework assignments. Gray matter volume and metabolite concentrations in the dorsal anterior cingulate cortex (dACC) and bilateral hippocampus were measured by structural MRI and ¹H-MRS at baseline and after 12 weeks of training. Metabolites measured included glutamateglutamine (Glx), choline-containing compounds (Cho, including glycerophosphocholine and phosphocholine), gamma-aminobutyric acid (GABA), and N-acetyl aspartate and N-acetylaspartyl-glutamate (NAA-NAAG). In total, 11 participants completed MET and 14 completed yogic meditation for this study. Structural MRI analysis showed an interaction between time and group in dACC, indicating a trend towards increased gray matter volume after the MET intervention. ¹H-MRS analysis showed an interaction between time and group in choline-containing compounds in bilateral hippocampus, induced by significant decreases after the MET intervention. Though preliminary, our results suggest that memory training induces structural and neurochemical plasticity in seniors with MCI. Further research is needed to determine whether mind-body interventions like yoga yield similar neuroplastic changes. [ABSTRACT FROM AUTHOR]