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BACKGROUND: Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks. METHODS: Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks. RESULTS: In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity. CONCLUSIONS: Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis. REGISTRATION: ClinicalTrials.gov NCT02332291.
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Transtorno Depressivo Maior , Humanos , Idoso , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Escitalopram , Bupropiona/farmacologia , Bupropiona/uso terapêutico , Depressão , Encéfalo/diagnóstico por imagem , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Mapeamento Encefálico , Giro do Cíngulo , Imageamento por Ressonância MagnéticaRESUMO
Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions.
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Depressão , Dopamina , Cognição , RecompensaRESUMO
OBJECTIVE: Late-life depression is associated with substantial heterogeneity in clinical presentation, disability, and response to antidepressant treatment. We examined whether self-report of severity of common symptoms, including anhedonia, apathy, rumination, worry, insomnia, and fatigue were associated with differences in presentation and response to treatment. We also examined whether these symptoms improved during treatment with escitalopram. DESIGN: Eighty-nine older adults completed baseline assessments, neuropsychological testing and providing self-reported symptom and disability scales. They then entered an 8-week, placebo-controlled randomized trial of escitalopram, and self-report scales were repeated at the trial's end. Raw symptom scale scores were combined into three standardized symptom phenotypes and models examined how symptom phenotype severity was associated with baseline measures and depression improvement over the trial. RESULTS: While rumination/worry appeared independent, severity of apathy/anhedonia and fatigue/insomnia were associated with one another and with greater self-reported disability. Greater fatigue/insomnia was also associated with slower processing speed, while rumination/worry was associated with poorer episodic memory. No symptom phenotype severity score predicted a poorer overall response to escitalopram. In secondary analyses, escitalopram did not improve most phenotypic symptoms more than placebo, aside for greater reductions in worry and total rumination severity. CONCLUSION: Deeper symptom phenotype characterization may highlight differences in the clinical presentation of late-life depression. However, when compared to placebo, escitalopram did not improve many of the symptoms assessed. Further work is needed to determine whether symptom phenotypes inform longer-term course of illness, and which treatments may best benefit specific symptoms.
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Depressão , Distúrbios do Início e da Manutenção do Sono , Humanos , Idoso , Depressão/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Escitalopram , Anedonia , Resultado do Tratamento , Cognição , Fadiga/tratamento farmacológico , Citalopram/uso terapêuticoRESUMO
OBJECTIVE: To identify cognitive phenotypes in late-life depression (LLD) and describe relationships with sociodemographic and clinical characteristics. DESIGN: Observational cohort study. SETTING: Baseline data from participants recruited via clinical referrals and community advertisements who enrolled in two separate studies. PARTICIPANTS: Non-demented adults with LLD (n = 120; mean age = 66.73 ± 5.35 years) and non-depressed elders (n = 56; mean age = 67.95 ± 6.34 years). MEASUREMENTS: All completed a neuropsychological battery, and individual cognitive test scores were standardized across the entire sample without correcting for demographics. Five empirically derived cognitive domain composites were created, and cluster analytic approaches (hierarchical, k-means) were independently conducted to classify cognitive patterns in the depressed cohort only. Baseline sociodemographic and clinical characteristics were then compared across groups. RESULTS: A three-cluster solution best reflected the data, including "High Normal" (n = 47), "Reduced Normal" (n = 35), and "Low Executive Function" (n = 37) groups. The "High Normal" group was younger, more educated, predominantly Caucasian, and had fewer vascular risk factors and higher Mini-Mental Status Examination compared to "Low Executive Function" group. No differences were observed on other sociodemographic or clinical characteristics. Exploration of the "High Normal" group found two subgroups that only differed in attention/working memory performance and length of the current depressive episode. CONCLUSIONS: Three cognitive phenotypes in LLD were identified that slightly differed in sociodemographic and disease-specific variables, but not in the quality of specific symptoms reported. Future work on these cognitive phenotypes will examine relationships to treatment response, vulnerability to cognitive decline, and neuroimaging markers to help disentangle the heterogeneity seen in this patient population.
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Disfunção Cognitiva , Depressão , Humanos , Depressão/diagnóstico , Depressão/psicologia , Função Executiva/fisiologia , Disfunção Cognitiva/diagnóstico , Cognição , Testes Neuropsicológicos , FenótipoRESUMO
OBJECTIVE: Greater depressive symptoms are associated with worse cognitive functions in Parkinson's disease (PD); however, it is unclear what underlying factors drive this association. Apathy commonly develops in PD and may be a pathway through which depressive symptoms negatively influence cognition. Prior research examining depressive symptoms, apathy, and cognition in PD is limited by being predominantly cross-sectional. This study examined the role of apathy as a within- and between-person mediator for the longitudinal relationships between depression severity and cognitive functioning in patients with early PD. METHODS: Participants included 487 individuals newly diagnosed with PD followed annually for up to 5 years by the Parkinson's Progression Marker Initiative. At each visit, participants completed depressive symptom measures, apathy ratings, and cognitive tests. Multi-level structural equation models examined both the within- and between-person effects of depressive symptoms on cognition through apathy, controlling for demographics and motor severity. RESULTS: At the within-person level, apathy mediated the association between depressive symptoms and select cognitive functions (global cognition, attention/working memory, visuospatial functions, and immediate verbal memory; indirect effects, bootstrap p's <0.05). Significant between-person direct effects were found for depressive symptoms predicting apathy (boostrap p <0.001) and lower scores on most cognitive tests (bootstrap p's <0.05). However, the indirect effects did not reach significance, suggesting between-person mediation did not occur. CONCLUSION: Findings suggest worsening of depressive symptoms over time in patients with PD may be a risk factor for increased apathy and subsequent decline in specific cognitive functions.
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Apatia , Doença de Parkinson , Cognição , Estudos Transversais , Depressão/psicologia , Humanos , Análise de Mediação , Doença de Parkinson/complicações , Doença de Parkinson/psicologiaRESUMO
OBJECTIVE: Late-life depression (LLD) is characterized by accelerated biological aging. Accelerated brain aging, estimated from structural magnetic resonance imaging (sMRI) data by a machine learning algorithm, is associated with LLD diagnosis, poorer cognitive performance, and disability. We hypothesized that accelerated brain aging moderates the antidepressant response. DESIGN AND INTERVENTIONS: Following MRI, participants entered an 8-week randomized, controlled trial of escitalopram. Nonremitting participants then entered an open-label 8-week trial of bupropion. PARTICIPANTS: Ninety-five individuals with LLD. MEASUREMENTS: A machine learning algorithm estimated each participant's brain age from sMRI data. This was used to calculate the brain-age gap (BAG), or how estimated age differed from chronological age. Secondary sMRI measures of aging pathology included white matter hyperintensity (WMH) volumes and hippocampal volumes. Mixed models examined the relationship between sMRI measures and change in depression severity. Initial analyses tested for a moderating effect of MRI measures on change in depression severity with escitalopram. Subsequent analyses tested for the effect of MRI measures on change in depression severity over time across trials. RESULTS: In the blinded initial phase, BAG was not significantly associated with a differential response to escitalopram over time. BAG was also not associated with a change in depression severity over time across both arms in the blinded phase or in the subsequent open-label bupropion phase. We similarly did not observe effects of WMH volume or hippocampal volume on change in depression severity over time. CONCLUSION: sMRI markers of accelerated brain aging were not associated with treatment response in this sequential antidepressant trial.
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Bupropiona , Depressão , Envelhecimento/psicologia , Antidepressivos/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Depressão/psicologia , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
This study examined individual components of the Geriatric Depression Scale-15 (GDS-15) to determine whether the 3-item Withdrawal-Apathy-Lack of Vigor (WAV) subscale, which has been validated in older adults and advanced Parkinson's disease (PD), was applicable to newly diagnosed patients with PD. Baseline Parkinson's Progression Markers Initiative (PPMI) data (n = 345), including GDS-15 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) depression, apathy, and anxiety scores, were examined. Data reduction techniques (i.e., principal components, confirmatory factor analyses) were used. Model fit was poor for the previously identified GDS-15 factor structures. Via principal components analysis, 5 components were identified, none of which reflected the 3-item WAV subscale previously reported in the literature. Internal consistency of the GDS-15 was acceptable, as was the internal consistency for the largest component (labeled "Dysphoria"). All 5 components significantly correlated with the MDS-UPDRS depression, apathy, and anxiety items. Model fit was fair for the "Dysphoria" factor only. Overall, the 3-item WAV factor reported in previous literature was not supported in this sample of de novo PD patients.
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Apatia , Doença de Parkinson , Idoso , Transtornos de Ansiedade , Biomarcadores , Estudos de Coortes , Humanos , Testes de Estado Mental e Demência , Doença de Parkinson/complicações , Doença de Parkinson/diagnósticoRESUMO
OBJECTIVES: The associations between subclinical depressive symptoms, as well specific symptom subscales, on brain structure in aging are not completely elucidated. This study investigated the extent to which depressive symptoms were related to brain volumes in fronto-limbic structures in a sample of middle-aged to older adults. METHOD: Eighty participants underwent structural neuroimaging and completed the Beck Depression Inventory, 2nd Edition (BDI-II), which comprises separate affective, cognitive, and somatic subscales. Gray matter volumes were extracted from the caudal and rostral anterior cingulate, posterior cingulate, hippocampus, and amygdala. Hierarchical regression models examined the relationship between brain volumes and (i) total depressive symptoms and (ii) BDI-II subscales were conducted. RESULTS: After adjusting for total intracranial volume, race, and age, higher total depressive symptoms were associated with smaller hippocampal volume (p = 0.005). For the symptom subscales, after controlling for the abovementioned covariates and the influence of the other symptom subscales, more somatic symptoms were related to smaller posterior cingulate (p = 0.025) and hippocampal (p < 0.001) volumes. In contrast, the affective and cognitive subscales were not associated with brain volumes in any regions of interest. CONCLUSION: Our data showed that greater symptomatology was associated with smaller volume in limbic brain regions. These findings provide evidence for preclinical biological markers of major depression and specifically advance knowledge of the relationship between subclinical depressive symptoms and brain volume. Importantly, we observed variations by specific depressive symptom subscales, suggesting a symptom-differential relationship between subclinical depression and brain volume alterations in middle-aged and older individuals.
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Envelhecimento/patologia , Envelhecimento/fisiologia , Córtex Cerebral/patologia , Depressão/fisiopatologia , Sistema Límbico/patologia , Idoso , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Sistema Límbico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Both depression and apathy, alone and in combination, have been shown to negatively affect cognition in patients with Parkinson's disease (PD). However, the influence of specific symptom dimensions of depression and apathy on cognition is not well understood. The current study investigated the relationship between symptom dimensions of depression and apathy, based on factors identified in Kirsch-Darrow et al. (2011), and memory and executive function in PD. METHODS: A sample of 138 non-demented individuals with PD (mean age=64.51±7.43 years) underwent neuropsychological testing and completed the Beck Depression Inventory, 2nd Edition, and Apathy Scale. Separate hierarchical regression models examined the relationship between symptom dimensions of depression and apathy ("pure" depressive symptoms, "pure" apathy, loss of interest/pleasure [anhedonia], and somatic symptoms) and three cognitive domain composites: immediate verbal memory, delayed verbal memory, and executive function. RESULTS: After adjusting for general cognitive status and the influence of the other symptom dimensions, "pure" depressive symptoms were negatively associated with the delayed verbal memory composite (p<.034) and somatic symptoms were positively associated with the executive function composite (p<.026). No symptom dimensions were significantly related to the immediate verbal memory composite. CONCLUSIONS: Findings suggest that specific mood symptoms are associated with delayed verbal memory and executive function performance in non-demented patients with PD. Further research is needed to better understand possible mechanisms through which specific symptom dimensions of depression and apathy are associated with cognition in PD. (JINS, 2018, 24, 269-282).
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Apatia , Cognição , Depressão/etiologia , Doença de Parkinson/psicologia , Idoso , Idoso de 80 Anos ou mais , Depressão/epidemiologia , Depressão/psicologia , Função Executiva , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/complicações , Escalas de Graduação PsiquiátricaRESUMO
OBJECTIVE: Structural neuroimaging studies in older adults have consistently shown volume reductions in both major and subthreshold depression. Cortical thickness, another measure of brain structure, has not been well studied in this population. We examined cortical thickness in older adults across a range of depressive symptom (DS) severity. METHODS: Forty-three community-dwelling older adults (mean age = 68.80 ± 7.00 years) underwent magnetic resonance imaging. Based on a priori hypotheses, we examined cortical thickness in regions of interest in the rostral anterior cingulate, orbitofrontal cortex, middle frontal gyrus, and isthmus cingulate using multiple linear regressions with depression questionnaire scores as the independent variable and age, sex, and mean hemispheric thickness as covariates. We also performed an exploratory vertex-wise analysis. RESULTS: After correction for multiple comparisons, we found an association between increased DSs and greater cortical thickness in the right isthmus cingulate (F(1, 38) = 8.09, false discovery rate corrected p = 0.028; R(2) = 35.78) in the region of interest analysis and in the left precuneus (cluster size = 413, p = 0.00002) in the vertex-wise analysis. CONCLUSIONS: Older adults with higher DSs also have greater cortical thickness in the isthmus cingulate and precuneus, areas important for emotion regulation and self-referential processing. Additional research is needed to elucidate the mechanisms and potential clinical significance underlying this relationship.
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Córtex Cerebral/patologia , Transtorno Depressivo/patologia , Idoso , Idoso de 80 Anos ou mais , Transtorno Depressivo/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Escalas de Graduação Psiquiátrica , Análise de Regressão , Índice de Gravidade de DoençaRESUMO
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has grown in popularity over the past two decades as an alternative treatment option for various neuropsychiatric disorders. tDCS modulates cortical excitability through the application of a weak direct current to the scalp via electrodes placed over cortical regions of interest. It has been shown to be a promising and relatively safe treatment tool with few adverse events. In this article, we will briefly review the efficacy of tDCS in depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder. We will also discuss biomarkers of tDCS efficacy in depression, as it is the most studied neuropsychiatric disorder using tDCS application. We will then offer suggestions for future directions. Although efficacy results show promise, more studies with larger samples and longer treatment periods are needed to better understand the benefits of using tDCS as an alternative treatment option for neuropsychiatric disorders.
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BACKGROUND: Late-life depression (LLD) is characterized by a poor response to antidepressant medications and diminished cognitive performance, particularly in executive functioning. There is currently no accepted pharmacotherapy for LLD that effectively treats both mood and cognitive symptoms. This study investigated whether transdermal nicotine augmentation of standard antidepressant medications benefitted mood and cognitive symptoms in LLD. METHODS: Nonsmoking participants aged 60 years or older with unremitted LLD on stable SSRI or SNRI medications (N = 29) received transdermal nicotine patches up to a 21 mg daily dose over 12 weeks. Clinical measures assessed depression severity, secondary affective symptoms, and cognitive performance. Nicotine metabolite concentrations were obtained from blood samples. RESULTS: Depression severity significantly decreased over the trial, with a 76 % response rate and 59 % remission rate. Change in depression severity was positively associated with nicotine exposure. Participants also exhibited improvement in self-reported affective symptoms (apathy, insomnia, rumination, and generalized anxiety symptoms), negativity bias, and disability. Executive function test performance significantly improved, specifically in measures of cognitive control, as did subjective cognitive performance. Adverse events were generally mild, with 75 % of the sample tolerating the maximum dose. CONCLUSION: The current study extends our previous pilot open-label trial in LLD, supporting feasibility and tolerability of transdermal nicotine patches as antidepressant augmentation. Although preliminary, this open-label study supports the potential benefit of transdermal nicotine patches for both mood and cognitive symptoms of LLD. Further research, including definitive randomized, blinded trials, is warranted to confirm these findings and explore long-term risk and benefit. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT04433767).
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Afeto , Antidepressivos , Função Executiva , Nicotina , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração Cutânea , Afeto/efeitos dos fármacos , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Quimioterapia Combinada , Função Executiva/efeitos dos fármacos , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Nicotina/uso terapêutico , Dispositivos para o Abandono do Uso de Tabaco , Resultado do TratamentoRESUMO
Background: Late-life depression is characterized by disability, cognitive impairment and decline, and a high risk of recurrence following remission. Aside from past psychiatric history, prognostic neurobiological and clinical factors influencing recurrence risk are unclear. Moreover, it is unclear if cognitive impairment predisposes to recurrence, or whether recurrent episodes may accelerate brain aging and cognitive decline. The purpose of the REMBRANDT study (Recurrence markers, cognitive burden, and neurobiological homeostasis in late-life depression) is to better elucidate these relationships and identify phenotypic, cognitive, environmental, and neurobiological factors contributing to and predictive of depression recurrence. Methods: Across three sites, REMBRANDT will enroll 300 depressed elders who will receive antidepressant treatment. The goal is to enroll 210 remitted depressed participants and 75 participants with no mental health history into a two-year longitudinal phase focusing on depression recurrence. Participants are evaluated every 2 months with deeper assessments occurring every 8 months, including structural and functional neuroimaging, environmental stress assessments, deep symptom phenotyping, and two weeks of 'burst' ecological momentary assessments to elucidate variability in symptoms and cognitive performance. A broad neuropsychological test battery is completed at the beginning and end of the longitudinal study. Significance: REMBRANDT will improve our understanding of how alterations in neural circuits and cognition that persist during remission contribute to depression recurrence vulnerability. It will also elucidate how these processes may contribute to cognitive impairment and decline. This project will obtain deep phenotypic data that will help identify vulnerability and resilience factors that can help stratify individual clinical risk.
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Objective: Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder. About 40%-50% of PD patients experience depression, making it one of the most common neuropsychiatric disturbances in PD. Cognitive deficits (e.g., difficulties with memory, attention) are an additional common complication in PD. Past studies among healthy aging individuals suggest that depression is a risk factor for cognitive decline, and the risk increases with older age. This study aims to examine the association between depressive symptoms on cognitive decline as a function of age among patients with PD. It is hypothesized that older PD patients with more severe depressive symptoms will be at greater risk of cognitive decline than their younger or less depressed counterparts. Methods: Four hundred and eighty-seven newly diagnosed patients with PD, were assessed for depression and cognition over a five-year period. Participants completed neuropsychological tests that assessed memory, learning, attention, visuospatial functioning, processing speed, and verbal fluency. Multilevel-modeling was used to examine the longitudinal association between cognition, age, and depressive symptoms. Results: Our results indicated a significant three-way interaction (age X occasion X depressive symptoms) predicting language and working memory/attention performance. More specifically, detrimental associations of depressive symptoms on cognitive decline in these domains were more pronounced among older adults. Conclusions: Our findings support that older PD patients with comorbid depressive symptoms experience greater cognitive decline compared to their younger counterparts. Findings suggest that older individuals with PD may be more vulnerable to neurotoxic effects of depression (e.g., neuroinflammation, HPA axis disruption), and better management of depression could potentially reduce cognitive decline and dementia risk.
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Late-life depression occurring in older adults is common, recurrent, and malignant. It is characterized by affective symptoms, but also cognitive decline, medical comorbidity, and physical disability. This behavioral and cognitive presentation results from altered function of discrete functional brain networks and circuits. A wide range of factors across the lifespan contributes to fragility and vulnerability of those networks to dysfunction. In many cases, these factors occur earlier in life and contribute to adolescent or earlier adulthood depressive episodes, where the onset was related to adverse childhood events, maladaptive personality traits, reproductive events, or other factors. Other individuals exhibit a later-life onset characterized by medical comorbidity, pro-inflammatory processes, cerebrovascular disease, or developing neurodegenerative processes. These later-life processes may not only lead to vulnerability to the affective symptoms, but also contribute to the comorbid cognitive and physical symptoms. Importantly, repeated depressive episodes themselves may accelerate the aging process by shifting allostatic processes to dysfunctional states and increasing allostatic load through the hypothalamic-pituitary-adrenal axis and inflammatory processes. Over time, this may accelerate the path of biological aging, leading to greater brain atrophy, cognitive decline, and the development of physical decline and frailty. It is unclear whether successful treatment of depression and avoidance of recurrent episodes would shift biological aging processes back towards a more normative trajectory. However, current antidepressant treatments exhibit good efficacy for older adults, including pharmacotherapy, neuromodulation, and psychotherapy, with recent work in these areas providing new guidance on optimal treatment approaches. Moreover, there is a host of nonpharmacological treatment approaches being examined that take advantage of resiliency factors and decrease vulnerability to depression. Thus, while late-life depression is a recurrent yet highly heterogeneous disorder, better phenotypic characterization provides opportunities to better utilize a range of nonspecific and targeted interventions that can promote recovery, resilience, and maintenance of remission.
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Fatores Biológicos , Depressão , Adolescente , Humanos , Idoso , Adulto , Criança , Depressão/terapia , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , EnvelhecimentoRESUMO
Purpose: Chemotherapy-related cognitive impairment (CRCI) is a distressing and increasingly recognized long-term sequela reported by breast cancer patients following cancer treatment. There is an urgent but unmet clinical need for treatments that improve CRCI. In this context, we proposed the use of a novel cognitive enhancement strategy called Neuroflex to target CRCI experienced by breast cancer survivors. Methods: The primary aim of this pilot study was to evaluate the feasibility and acceptability of Neuroflex, a novel digital cognitive enhancement strategy, in breast and gynecologic cancer survivors with CRCI. Secondary analyses focused on whether improvements in performance on Neuroflex were associated with improvement in subjective cognitive complaints and objective cognitive performance measures. Results: Participants (N = 21) completed an average of 7.42 hours of Neuroflex training per week, an average of 44.5 (±1.01) hours total, and had a 100% completion rate. Participants exhibited significant improvement in self-reported cognitive function as well as significant improvement on tasks of verbal learning and memory and auditory working memory. Participants also exhibited improvement in mood, as well as improvement on a disability assessment. Conclusions: Results demonstrate feasibility and that breast cancer survivors are capable of completing a lengthy and challenging cognitive training program. Secondly, Neuroflex may confer specific cognitive benefits to both self-reported and objective performance. Results strongly support further investigation of Neuroflex in a larger controlled trial to establish efficacy for CRCI symptoms. Further studies may also result in optimization of this digital intervention for women with CRCI.
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Evidence suggests different depressive symptoms are related to specific aspects of cognition, especially in older adults. The current study extended this literature by examining depressive symptom severity, symptom clusters, and cognitive functioning in young-to-middle aged adults. A sample of 2,560 men (mean age = 38.12 ± 2.41 years) withvalid Minnesota Multiphasic Personality Inventories (MMPI) and completed cognitive measures was drawn from a Vietnam veterans study. Bootstrapped regressions examined relationships between cognitive performance, MMPI Depression scores, and Harris-Lingoes depression subscales after covariate adjustments. Follow-up analyses investigated non-elevated and elevated depressive symptom groups. We found inverse relationships between specific subscales (Subjective Depression and Mental Dullness) and attentional control. No significant relationships were evident for total depressive symptoms or for the group analyses. Findings suggest weak associations between depressive symptoms and cognition in young to middle-aged men without clinical depression, which adds to the literature on inconsistent findings in depressive symptom-cognition relationships.
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Transtorno Depressivo Maior , Veteranos , Idoso , Atenção , Cognição , Depressão , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hepatic encephalopathy (HE) is a consequence of liver disease and often diagnosed via psychometric testing. With inpatients, the Montreal Cognitive Assessment (MoCA) may be used as part of cognitive screening for transplant candidacy. However, the MoCA was developed to detect mild cognitive impairment in aging populations and its psychometric properties in inpatients with liver disease have not been determined. Retrospective chart review identified inpatient liver transplant candidates who were administered a MoCA as part of their neuropsychological screening and had either no cognitive dysfunction or a diagnosis of HE made by a neuropsychologist (n = 57, mean age = 48.8 ± 12.6 years). Psychometric analyses were conducted and regression analysis was performed to determine the predictive value of different variables on total MoCA scores. Internal consistency of MoCA domain scores was good (α = 0.80). Significant inverse relationships were found with Trail Making Test, Parts A and B (r's = -0.43 and -0.71, respectively). A cutoff score of 24 or below had the best sensitivity (0.72) and specificity (0.77) for identifying those with a diagnosis of HE. Increasing age and the presence of altered mental status were the strongest predictors of lower MoCA scores (both p's < 0.05, ηp2 = 0.10-0.14). The MoCA is appropriate to use with inpatient liver transplant candidates, with a cutoff of 24 or below to detect abnormal cognition. In addition to the clinical interview and other neuropsychological tests (including, but not limited to, the Trail Making Test, Parts A and B), low MoCA scores can help determine the presence of HE.
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INTRODUCTION: Nonmotor symptoms, including depression, anxiety, apathy, and cognitive dysfunction, are common in Parkinson's disease (PD). Although a link between mood symptoms and cognitive impairment in PD has been theorized vis-à-vis striatal dopamine depletion, studies have been inconsistent regarding the relationship between mood symptoms and cognitive function. Inconsistencies may reflect the cross-sectional nature of previous studies. The current study examined the bidirectional longitudinal relationship between mood and cognition. METHOD: Data were obtained from 310 individuals newly diagnosed with PD, who were followed up to 4 years (baseline, 1st, 2nd, 3rd, and 4th annual follow-ups). Apathy, anxiety, depressive symptoms, motor severity, and neurocognitive functioning were assessed at each annual assessment. The longitudinal relationship between apathy, anxiety, depressive symptoms, and cognition was analyzed with multilevel models. RESULTS: Over the 4-year period, more severe depressive symptoms were related to worse performance on tasks of processing speed, verbal learning, and verbal delayed recall. Additionally, there was a significant Depression × Time interaction, suggesting that individuals with more severe depressive symptoms experience more rapid declines in global cognitive functioning and verbal learning. Apathy and anxiety were not significantly related to performance in any cognitive test. Lagged models revealed that changes in depression precede declines in working memory, verbal learning, delayed verbal recall, and global cognition. CONCLUSION: Findings suggest depressive symptoms may be a harbinger for future cognitive decline among individuals with PD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).