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Several studies employ multi‐site rs‐fMRI data for major depressive disorder (MDD) identification, with a specific site as the to‐be‐analyzed target domain and other site(s) as the source domain. But they usually suffer from significant inter‐site heterogeneity caused by the use of different scanners and/or scanning protocols and fail to build generalizable models that can well adapt to multiple target domains. In this article, we propose a dual‐expert fMRI harmonization (DFH) framework for automated MDD diagnosis. Our DFH is designed to simultaneously exploit data from a single labeled source domain/site and two unlabeled target domains for mitigating data distribution differences across domains. Specifically, the DFH consists of a domain‐generic student model and two domain‐specific teacher/expert models that are jointly trained to perform knowledge distillation through a deep collaborative learning module. A student model with strong generalizability is finally derived, which can be well adapted to unseen target domains and analysis of other brain diseases. To the best of our knowledge, this is among the first attempts to investigate multi‐target fMRI harmonization for MDD diagnosis. Comprehensive experiments on 836 subjects with rs‐fMRI data from 3 different sites show the superiority of our method. The discriminative brain functional connectivities identified by our method could be regarded as potential biomarkers for fMRI‐related MDD diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders. Cognitive complaints are commonly reported in MDD and cognitive impairment is a criterion item for MDD diagnosis. As cognitive processes are increasingly understood as the consequences of distributed interactions between brain regions, a network-based approach may provide novel information about the neurobiological basis of cognitive deficits in MDD. Methods 51 Depressed (MDD, n = 23) and non-depressed (control, n = 28) adult participants completed neuropsychological testing and resting-state fMRI (rsfMRI). Cognitive domain scores (processing speed, working memory, episodic memory, and executive function) were calculated. Anatomical regions of interests were entered as seeds for functional connectivity analyses in: default mode (DMN), salience, and executive control (ECN) networks. Partial correlations controlling for age and sex were conducted for cognitive domain scores and functional connectivity in clusters with significant differences between groups. Results Significant rsfMRI differences between groups were identified in multiple clusters in the DMN and ECN. Greater positive connectivity within the ECN and between ECN and DMN regions was associated with poorer episodic memory performance in the Non-Depressed group but better performance in the MDD group. Greater connectivity within the DMN was associated with better episodic and working memory performance in the Non-Depressed group but worse performance in the MDD group. Conclusions These results provide evidence that cognitive performance in MDD may be associated with aberrant functional connectivity in cognitive networks and suggest patterns of alternate brain function that may support cognitive processes in MDD. [ABSTRACT FROM AUTHOR]

Background: Cognitive complaints are common in depression, and cognition may be an important treatment target as cognitive problems often remain during remission and may contribute to recurrence risk. Previous studies of cognitive performance in depression have mainly examined late-life depression, with a focus on older adults, or assessed performance in specific cognitive tasks rather than cognitive domains.Methods: This study examined cognitive performance across multiple cognitive domains in antidepressant-free depressed adults with early onset recurrent depression compared to never-depressed controls. Domain scores were calculated for episodic memory, executive function, processing speed, and working memory, and the effect of depression diagnosis, depression severity, and depression duration on each domain score was examined, including interactions with age, sex, and education.Results: Currently depressed adults (n = 91) exhibited poorer performance in the processing speed domain compared with never-depressed adults (n = 105). Additionally, there was an interactive effect of depression duration and age on processing speed and executive function domain performance, such that performance was worse with older age and longer duration of depression. There were no effects of depression severity on performance across the cognitive domains.Conclusions: These findings support that processing speed deficits appear in young adults with early onset depression that may not be related to current mood. Additionally, the effects of cumulative depressive episodes may interact with aging such that cognitive performance deficits worsen with recurrence over the lifespan. [ABSTRACT FROM AUTHOR]

Background: Dual-task paradigms, in which an individual performs tasks separately and then concurrently, often demonstrate that people with neurodegenerative disorders experience more dual-task interference, defined as worse performance in the dual-task condition compared to the single-task condition.Objective: To examine how gait-cognition dual-task performance differs between cognitively normal older adults with and without an APOE ɛ4 allele.Methods: Twenty-nine individuals ages 60 to 72 with normal cognition completed a dual-task protocol in which walking and cognitive tasks (executive function, memory) were performed separately and concurrently. Fourteen participants carried APOE ɛ4 alleles (ɛ3/ɛ4 or ɛ2/ɛ4); fifteen had APOE genotypes (ɛ2/ɛ2, ɛ2/ɛ3, or ɛ3/ɛ3) associated with lower risk of Alzheimer's disease (AD).Results: The two risk groups did not differ by age, sex, race, education, or gait or cognitive measures under single-task conditions. Compared to low risk participants, APOE ɛ4 carriers tended to exhibit greater dual-task interference. Both the memory and executive function tasks resulted in dual-task interference on gait, but effect sizes for a group difference were larger when the cognitive task was executive function. In the dual-task protocol that combined walking and the executive function task, effect sizes for group difference in gait interference were larger (0.62- 0.70) than for cognitive interference (0.45- 0.47).Discussion: Dual-task paradigms may reveal subtle changes in brain function in asymptomatic individuals at heightened risk of AD. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the association between physical frailty and neurocognitive performance in late-life depression (LLD).Methods: Cross-sectional design using baseline data from a treatment study of late-life depression was used in this study. Individuals aged 60 years and older were diagnosed with major depressive disorder at time of assessment (N = 173). All participants received clinical assessment of depression and completed neuropsychological testing during a depressive episode. Physical frailty was assessed using an adaptation of the FRAIL scale. Neuropsychological domains were derived from a factor analysis that yielded three factors: (i) speeded executive and fluency, (ii) episodic memory, and (iii) working memory. Associations were examined with bivariate tests and multivariate models.Results: Depressed individuals with a FRAIL score >1 had worse performance than nonfrail depressed across all three factors; however, speeded executive and fluency was the only factor that remained significant after controlling for depression symptom severity and demographic characteristics.Conclusions: Although physical frailty is associated with broad neurocognitive deficits in LLD, it is most robustly associated with deficits in speeded executive functions and verbal fluency. Causal inferences are limited by the cross-sectional design, and future research would benefit from a comparison group of nondepressed older adults with similar levels of frailty. Research is needed to understand the mechanisms underlying associations among depression symptoms, physical frailty, and executive dysfunction and how they are related to the cognitive and symptomatic course of LLD. [ABSTRACT FROM AUTHOR]

Objective: Previous investigations into the relationship between late-life depressive symptoms and cognitive functioning have resulted in mixed findings concerning whether or not depressive symptoms and cognitive functioning are related. The mixed reports may be due in part to differences in clinical and nonclinical samples and to inadequate consideration of the dynamic nature (i.e., fluctuating course) of depressive symptoms and cognitive functioning in older adults. The current study examined the chronic, acute, and longitudinal relationships between depressive symptoms and cognitive functioning in older adults in an ongoing treatment study of major depressive disorder (MDD).Methods: The neurocognitive outcomes of depression in the elderly study operates in a naturalistic treatment milieu using a pharmacological treatment algorithm and regular psychiatric assessment. Four hundred and fifty-three older adults [mean age 70 years, standard deviation (SD) = 7.2] meeting criteria for MDD at study enrollment received annual neuropsychological testing and depressive symptom monitoring for an average of 8.5 years (SD = 4.5).Results: Hierarchical linear modeling revealed that higher age, lower education, and higher average/chronic levels of depressive symptoms were related to lower cognitive functioning. Additionally, results revealed that when an individual's depressive symptoms are higher than is typical for a specific individual, general cognitive function was worse than average. There was no evidence of lagged/longitudinal relationships between depressive symptoms and cognitive functioning in older adults in treatment for MDD.Conclusions: Cognitive functioning and depressive symptoms are concurrently associated in older adults with MDD, highlighting the potential importance for stabilizing mood symptoms as a means to manage cognitive deficits in late-life depression. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to examine the association of appetite loss symptoms to neurocognitive performance in late-life depression (LLD). Methods This study used cross-sectional data from individuals aged 60+ years with major depressive disorder ( N = 322). Participants received clinical assessment of depression and neuropsychological testing. Factor analysis was used to characterize depression symptom factors, and composite scales were developed for episodic memory, psychomotor-executive functions, verbal fluency, and working memory span. Results Factor analysis produced a five-factor solution: (1) anhedonia/sadness; (2) suicidality/guilt; (3) appetite/weight loss; (4) sleep disturbance; and (5) anxiety/tension. In separate multivariate models for each neurocognitive domain and including all five depression factors, higher appetite-loss-related symptoms were associated with lower performance in episodic memory, psychomotor-executive functions, and verbal fluency; results were significant with covariates of age, education, race, sex, age of depression onset, and illness burden. No other depression factors were associated with neurocognitive performance in these models. In an additional set of models, the appetite factor mediated the association between global depression severity and neurocognitive performance. Discussion A factor of appetite and weight loss symptoms in LLD was uniquely associated with neurocognitive performance, in contrast to lack of association among other depression symptom factors. Conclusion Cognitive deficits are a major adverse outcome of LLD, and prominent appetite loss during acute depression may be a marker for these deficits, independent of overall depression severity. Research is needed to understand the mechanisms that may explain this association, and how it is related to the cognitive and symptomatic course of LLD. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Slowed information processing is a prominent deficit in late-life depression (LLD). To better differentiate processing speed components in LLD, we examined characteristics of visual search performance in 32 LLD and 32 control participants. Data showed specific slowing in the comparison stage of visual search in LLD, rather than in encoding/response stages, but also greater overall slowing in LLD during inefficient versus efficient search. We found no group differences on traditional neuropsychological measures of processing speed. Slowed processing speed in LLD may be specific rather than general, which underscores the need to link components of processing speed to underlying neural circuitry. [ABSTRACT FROM PUBLISHER]

Objective The objective of this study is to examine the association between self-reported functional disability in depressed older adults and two types of executive function processes, attentional set shifting and reversal learning. Methods Participants ( N = 89) were aged 60 or over and enrolled in a naturalistic treatment study of major depressive disorder. Participants provided information on self-reported function in instrumental activities of daily living (IADL) and completed the Intra-Extra Dimensional Set Shift test (IED) from the Cambridge Neuropsychological Testing Automated Battery, which assesses intra-dimensional attentional shifts, extra-dimensional attentional shifts, and reversal learning. Participants were categorized by the presence or absence of IADL difficulties and compared on IED performance using bivariable and multivariable tests. Results Participants who reported IADL difficulties had more errors in extra-dimensional attentional shifting and reversal learning, but intra-dimensional shift errors were not associated with IADLs. Only extra-dimensional shift errors were significant in multivariable models that controlled for age, sex, and depression severity. Conclusions Attentional shifting across categories (i.e., extra-dimensional) was most strongly associated with increased IADL difficulties among depressed older adults, which make interventions to improve flexible problem solving a potential target for reducing instrumental disability in this population. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective The relationship between stress, social support, and cognition in geriatric depression is complex. In this study, we sought to examine whether an increase in stressful life events or a decrease in social support would lead to subsequent cognitive decline among older adults with and without depression. Methods The sample consisted of 112 depressed and 101 non-depressed older adults who enrolled in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study. Participants were assessed clinically, agreed to interviews focusing on stressful life events and social support, and underwent a battery of neuropsychological tests annually. Our global measure of cognition was the Consortium to Establish a Registry in Alzheimer's disease Total Score (CERAD TS). Results We found that a decline in the total number of stressors was associated with a subsequent improvement on CERAD TS. In terms of social support, decreased social interaction, and instrumental social support predicted decline in cognitive performance. These relationships were significant even after controlling for depression status, age, education, and sex. Conclusions These findings extend prior research on the importance of social factors in aging and depression which have largely focused on mood-related outcomes. Future confirmatory studies are needed. In addition, biological and other studies should be conducted to further our understanding of the relationship between stress, social support and cognition in older adults with and without depression. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We can only benefit from raising public awareness about the unique role of clinical neuropsychology in patient care and clinical research. Public awareness of the distinctive skills of our practitioners and researchers and the utility of our products may well be linked to our viability as a field given the current healthcare and funding climates. This article discusses the goals of public awareness efforts for clinical neuropsychology, and outlines current resources that can be utilized toward this end. We review the process of creating new public awareness resources and discuss ideas for how practitioners can become involved public awareness efforts. We consider some of the many issues driving the need for public awareness activities and resources, highlight the need for practitioners and professional organizations to be self-advocates, and hope to inspire our field to the very feasible process of integrating public awareness efforts into professional practice. [ABSTRACT FROM AUTHOR]

Objective Depression is often associated with decreased cognitive performance among older adults. The current study focused on the association of neuropsychological functioning and personality traits in depressed and non-depressed older adults. Methods Data from 75 depressed and 103 non-depressed adults over the age of 60 were analyzed. All participants underwent standardized clinical assessment for depression prior to participation and completed the NEO-PI-R and a series of neuropsychological assessments. Results A series of multiple linear regressions were conducted to examine the relationships between personality and neuropsychological performance among depressed and non-depressed older adults. Results indicated that higher Openness to Experience was related to better performance on Parts A and B of the Trail Making Test among depressed older adults, and to better Digit Span Backward performance among all participants. Higher levels of neuroticism were related to poorer performance on Digit Span Backward, but only among depressed older adults. Depressed participants performed more poorly on the Symbol Digit Modalities Test and the Controlled Oral Word Association Test. Conclusions Personality characteristics, particularly Openness to Experience, modified the relationship between depression and neuropsychological functioning among older adults. Results indicate that interventions aimed at increasing one's Openness to Experience could potentially attenuate some of the neuropsychological impairments that are associated with depression. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents an assessment of cognitive impairment in geriatric depression. It provides a list of elements that are important to a comprehensive evaluation of geriatric depression. It focuses on interviewing and screening for depression, the influence of medical comorbidities on cognitive impairment and depression, and the differentiation of cognitive impairment secondary to depression from comorbid depression and Alzheimer disease.

Poor task persistence is often observed among depressed individuals, and may be associated with some of the same frontal regions that are involved in depression. The current study explored the association between white-matter lesion volume in prefrontal cortex and noncompletion rates on a complex neurocognitive task among older adults in a treatment study for depression. Older adults in treatment for depression (n=83) and nondepressed (n=47) elders were administered the Stockings of Cambridge subtest (SoC) of the Cambridge Automated Neuropsychological Testing Battery (CANTAB) and completed a brain magnetic resonance imaging scan as part of an ongoing research study. Noncompletion of the SoC occurred in approximately 19% of depressed participants (16/83) and only 2% of nondepressed participants (1/47), which was statistically significant. In multivariate models, failure to complete the SoC was consistently and significantly associated with greater volume of white matter lesions in the anterior-most region of prefrontal cortex, particularly in the left hemisphere, and with greater age. Although SoC completion was not significantly associated with depression severity, noncompletion rates were significantly higher among unremitted individuals and those with comorbid anxiety at study entry. The inability to initiate behavior sufficient to sustain a complex neurocognitive task is a characteristic of geriatric depression which may be associated with integrity of left-prefrontal regions. Future research should investigate whether task impersistence is a construct that generalizes to other neurocognitive tasks, and if it is associated with other adverse outcomes in geriatric depression related to cerebrovascular pathology, such as poor treatment response.Neuropsychopharmacology (2007) 32, 2135–2142; doi:10.1038/sj.npp.1301339; published online 14 February 2007 [ABSTRACT FROM AUTHOR]

Objective To explore the association of executive functions to the everyday memory complaints of healthy older adults. Methods Ninety-nine community-dwelling women aged 60 and above were administered a battery that included neuropsychological tests of executive functions and memory, along with self-report measures of everyday memory complaints, depression, and anxiety. Results Multivariate regression analyses revealed that a measure of response inhibition (Stroop Color-Word) accounted for unique variance in predicting memory complaints above and beyond measures of episodic memory, depression, and anxiety. Depression, however, accounted for the largest variance in memory complaints. Conclusions Higher frequency of everyday memory complaints among older adults was associated with decreased response inhibition independent of episodic memory and affective state. Further research is needed to understand the interrelationships among these and other predictors of everyday memory complaints. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Recent studies suggest that neuropsychological measures involving the prefrontal cortex are associated with treatment remission in late- life depression. To further explore this issue, we studied the neuropsychological performance of 110 depressed individuals aged 60 years and over who are participating in an ongoing pharmacologic treatment study. Participants were clinically depressed at entry to the study as rated by the Montgomery-Asberg Depression Rating Scale (MADRS ≥ 15), at which time they also completed a neuropsychological assessment that included measures of prefrontal/executive functions. A geriatric psychiatrist treating the participant using a standardized pharmacologic treatment algorithm evaluated the participant at baseline and 3-month follow-up, completing a MADRS at both visits. Using logistic discriminative procedures to predict depression remission at 3 months while controlling for age, gender, education, ethnicity, and baseline MADRS severity, we found that perseverative responses during verbal initiation tasks significantly predicted remission status (MADRS <7). This finding is consistent with previous single-agent treatment studies suggesting a relationship between prefrontal neuropsychological function and treatment response in ate-life depression. The current results, however, appear to differentiate verbal perseveration from verbal initiation as the cognitive process that is most associated with poor treatment response. By extension, we suggest that orbitofrontal prefrontal cortex may play a role in sustaining perseverative processing in geriatric depression. [ABSTRACT FROM AUTHOR]

Background: Late-life depression (LLD) is associated with a fragile antidepressant response and high recurrence risk. This study examined what measures predict recurrence in remitted LLD.Methods: Individuals of age 60 years or older with a Diagnostic and Statistical Manual - IV (DSM-IV) diagnosis of major depressive disorder were enrolled in the neurocognitive outcomes of depression in the elderly study. Participants received manualized antidepressant treatment and were followed longitudinally for an average of 5 years. Study analyses included participants who remitted. Measures included demographic and clinical measures, medical comorbidity, disability, life stress, social support, and neuropsychological testing. A subset underwent structural magnetic resonance imaging (MRI).Results: Of 241 remitted elders, approximately over 4 years, 137 (56.8%) experienced recurrence and 104 (43.2%) maintained remission. In the final model, greater recurrence risk was associated with female sex (hazard ratio [HR] = 1.536; confidence interval [CI] = 1.027-2.297), younger age of onset (HR = 0.990; CI = 0.981-0.999), higher perceived stress (HR = 1.121; CI = 1.022-1.229), disability (HR = 1.060; CI = 1.005-1.119), and less support with activities (HR = 0.885; CI = 0.812-0.963). Recurrence risk was also associated with higher Montgomery-Asberg Depression Rating Scale (MADRS) scores prior to censoring (HR = 1.081; CI = 1.033-1.131) and baseline symptoms of suicidal thoughts by MADRS (HR = 1.175; CI = 1.002-1.377) and sadness by Center for Epidemiologic Studies-Depression (HR = 1.302; CI, 1.080-1.569). Sex, age of onset, and suicidal thoughts were no longer associated with recurrence in a model incorporating report of multiple prior episodes (HR = 2.107; CI = 1.252-3.548). Neither neuropsychological test performance nor MRI measures of aging pathology were associated with recurrence.Conclusions: Over half of the depressed elders who remitted experienced recurrence, mostly within 2 years. Multiple clinical and environmental measures predict recurrence risk. Work is needed to develop instruments that stratify risk. [ABSTRACT FROM AUTHOR]

The article comments on the article "Life-span cognitive activity, neuropathologic burden, and cognitive aging" by R. S. Wilson and colleagues that was published in a 2013 issue of "Neurology". It discusses the observed differences in parietotemporal perfusion among Alzheimer's disease patient offered biological evidence. It reflects the association of cognitive activity with decreased rate of global cognitive decline.

Objectives To develop and validate the Dental Activities Test (DAT), a clinical tool for measuring dentally related function in cognitively impaired older adults. Design Cross-sectional study design. Setting Three assisted living residences in North Carolina. Participants Assisted living residents with normal to impaired cognition aged 50 and older; not blind, deaf, or severely physically disabled; and English speaking (N = 90). Measurements Items for the DAT were developed based on focus group discussions, literature review, and clinical relevance. Cronbach alpha, interrater reliability, and test-retest reliability were examined, and construct validity was assessed in relation to correlations with cognitive and functional assessments. Correlations between the DAT and oral health measures were also analyzed to evaluate the concurrent validity of the DAT. Results The DAT has excellent internal consistency reliability (Cronbach alpha 0.90), test-retest reliability (correlation coefficient (r) = 0.84), and interrater reliability (r = 0.90). In terms of construct validity, higher DAT scores were significantly associated with better cognitive function, as well as better activity of daily living and instrumental activity of daily living function. Finally, the DAT was significantly associated with oral hygiene and gingival health. Conclusion The DAT is a reliable and valid instrument to measure dentally-related function in older adults with cognitive impairment. [ABSTRACT FROM AUTHOR]

White matter (WM) lesions have been recognized as a key etiological factor in geriatric depression. However, little is known about the topological pattern changes of WM in geriatric depression in the remitted state (RGD) and its relationship to depressive episodes. To address these questions, we acquired diffusion tensor images in 24 RGD and 24 healthy participants. Among them, 10 patients and 19 healthy controls completed a 1-year follow up. Between-hemisphere connectivity and graph theoretical methods were used to analyze the data. We found significantly reduced WM connectivity between the left and right hemisphere in the RGD group compared with the control group. Those with multiple depression episodes had greater reduction in between-hemisphere connectivity strength than those with fewer episodes. In addition, the RGD group had a reduced global clustering coefficient, global efficiency, and network strength, and an increased shortest path length compared with the controls. A lower clustering coefficient was correlated with poorer memory function. The reduction of nodal clustering coefficient, global efficiency, and network strength in several regions were associated with slower information processing speed. At 1-year follow up, the network properties in the RGD subjects were significantly changed suggesting instability of WM network properties of depressed patients. Together, our study provides direct evidence of reduced between-hemisphere WM connectivity with greater depressive episodes, and of alterations of network properties with cognitive dysfunction in geriatric depression. Hum Brain Mapp 38:53-67, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Resting-state functional magnetic resonance imaging (rs-fMRI) data have been widely used for automated diagnosis of brain disorders such as major depressive disorder (MDD) to assist in timely intervention. Multi-site fMRI data have been increasingly employed to augment sample size and improve statistical power for investigating MDD. However, previous studies usually suffer from significant inter-site heterogeneity caused for instance by differences in scanners and/or scanning protocols. To address this issue, we develop a novel discrepancy-based unsupervised cross-domain fMRI adaptation framework (called UFA-Net) for automated MDD identification. The proposed UFA-Net is designed to model spatio-temporal fMRI patterns of labeled source and unlabeled target samples via an attention-guided graph convolution module, and also leverage a maximum mean discrepancy constrained module for unsupervised cross-site feature alignment between two domains. To the best of our knowledge, this is one of the first attempts to explore unsupervised rs-fMRI adaptation for cross-site MDD identification. Extensive evaluation on 681 subjects from two imaging sites shows that the proposed method outperforms several state-of-the-art methods. Our method helps localize disease-associated functional connectivity abnormalities and is therefore well interpretable and can facilitate fMRI-based analysis of MDD in clinical practice. [Display omitted] • An unsupervised fMRI harmonization framework to reduce inter-site data heterogeneity • An attention-guided spatio-temporal graph convolution module for feature extraction • Locating discriminative functional connectivities and brain regions as biomarkers [ABSTRACT FROM AUTHOR]

Objective Major depression in older adults increases the statistical likelihood of dementia. It is challenging to translate statistical evidence of cognitive decline at the group level into knowledge of individual cognitive outcomes. The objective of the current study is to investigate 2-year reliable cognitive change in late-life depression (LLD), which will enhance understanding of cognitive changes in LLD and provide a means to assess individual change. Methods In a sample of non-depressed cognitively normal older adults or NDCN (n  = 113), we used linear regression to predict tests of global cognition, processing speed-executive functioning, and memory administered 1 and 2 years later. Stepwise regression was used to select covariates among demographics and raw test scores (either baseline or year 1) and we cross-validated the final models using the predicted residual error sum of squares (PRESS). We then derived a z -change score from the difference between actual and predicted follow-up scores and investigated the proportion of LLD patients (n  = 199) and NDCN adults who experienced reliable "decline" (a z -score < −1.645), "stability" (z -scores between + − 1.645), and "improvement" (z scores > +1.645). Results A greater proportion LLD compared with NDCN experienced cognitive decline in processing speed/executive functioning and global cognition over 2 years. When compared to NDCN, a greater proportion of LLD also significantly improved on one test of processing speed over 2 years. Conclusions Older adults with LLD are at risk of meaningful cognitive decline over a relatively short period, particularly in the domain of executive functioning and processing speed. This study provides a series of reliable change equations for common neuropsychological tests that can be applied clinically. [ABSTRACT FROM AUTHOR]

Although major depression has been considered as a manifestation of discoordinated activity between affective and cognitive neural networks, only a few studies have examined the relationships among neural networks directly. Because of the known disconnection theory, geriatric depression could be a useful model in studying the interactions among different networks. In the present study, using independent component analysis to identify intrinsically connected neural networks, we investigated the alterations in synchronizations among neural networks in geriatric depression to better understand the underlying neural mechanisms. Resting-state fMRI data was collected from thirty-two patients with geriatric depression and thirty-two age-matched never-depressed controls. We compared the resting-state activities between the two groups in the default-mode, central executive, attention, salience, and affective networks as well as correlations among these networks. The depression group showed stronger activity than the controls in an affective network, specifically within the orbitofrontal region. However, unlike the never-depressed controls, geriatric depression group lacked synchronized/antisynchronized activity between the affective network and the other networks. Those depressed patients with lower executive function has greater synchronization between the salience network with the executive and affective networks. Our results demonstrate the effectiveness of the between-network analyses in examining neural models for geriatric depression. [ABSTRACT FROM AUTHOR]

Late-life depression (LLD) is a highly prevalent mood disorder occurring in older adults and is frequently accompanied by cognitive impairment (CI). Studies have shown that LLD may increase the risk of Alzheimer's disease (AD). However, the heterogeneity of presentation of geriatric depression suggests that multiple biological mechanisms may underlie it. Current biological research on LLD progression incorporates machine learning that combines neuroimaging data with clinical observations. There are few studies on incident cognitive diagnostic outcomes in LLD based on structural MRI (sMRI). In this paper, we describe the development of a hybrid representation learning (HRL) framework for predicting cognitive diagnosis over 5 years based on T1-weighted sMRI data. Specifically, we first extract prediction-oriented MRI features via a deep neural network, and then integrate them with handcrafted MRI features via a Transformer encoder for cognitive diagnosis prediction. Two tasks are investigated in this work, including (1) identifying cognitively normal subjects with LLD and never-depressed older healthy subjects, and (2) identifying LLD subjects who developed CI (or even AD) and those who stayed cognitively normal over five years. We validate the proposed HRL on 294 subjects with T1-weighted MRIs from two clinically harmonized studies. Experimental results suggest that the HRL outperforms several classical machine learning and state-of-the-art deep learning methods in LLD identification and prediction tasks. • A Hybrid Representation Learning (HRL) framework is developed for longitudinal diagnostic discrimination in late life depression (LLD) using T1-weighted MRI. To the best of our knowledge, this is the first attempt of predicting cognitive diagnosis over 5 years and finding related potential MRI biomarkers. • The HRL integrates data-driven and handcrafted MRI features into a unified framework. A feature fusion module is designed to fuse two types of features more effectively for better prediction. • The feature maps extracted by HRL help to identify potential MRI biomarkers for the assessment of cognitive change in LLD subjects, thus helping to improve clinical diagnosis. [ABSTRACT FROM AUTHOR]

We examined the frequency and course of cognitive impairment, no dementia among a group of older patients enrolled in a longitudinal study of depression. Among 230 participants, 29 with baseline dementia diagnosis were excluded from further analyses. Among the remaining 201 participants, 69 were classified with cognitive impairment, no dementia-broadly defined (34.3%) and 28 (13.9%) with cognitive impairment, no dementia-narrowly defined. At 2-year follow-up, individuals with cognitive impairment, no dementia either narrowly or broadly defined had varied outcomes including (1) improvement to normal cognition, (2) continued cognitive impairment, and (3) progression to dementia. Patients with cognitive impairment, no dementia were more likely to be assigned a later diagnosis of dementia. Our results characterize the concept of cognitive impairment, no dementia as a risk factor for dementia among older individuals with current and past depression; however, just as with the general population, the course of this condition is heterogeneous. [ABSTRACT FROM AUTHOR]

Objective To examine the contribution of medication adherence to 12-month depression scores in the context of other psychosocial and clinical predictors of depression in a sample of older adults treated for depression. Methods Secondary analysis of a prospective cohort study involving 241 older patients undergoing depression treatment using a standardized algorithm. Depression was measured at baseline and 12-months post-baseline. Baseline predictor variables included antidepressant adherence, barriers to antidepressant adherence, four domains of social support, basic and instrumental activities of daily living (BADLs and IADLs), and clinical factors including past history of depression and medical comorbidities. Results Nearly 28% of patients reported being nonadherent with their antidepressant medication. In bivariate analyses, greater antidepressant medication nonadherence, more medication barriers, poorer subjective social support, less non-family interaction, greater BADL and IADL limitations, poor self-rated health, higher baseline depression scores, and not having diabetes were related to higher 12-month depression scores. In multivariable analyses, greater medication nonadherence, not having diabetes, poorer subjective social support, greater BADL limitations, and higher baseline depression scores were related to higher 12-month depression scores. Conclusion Interventions should be directed toward improving antidepressant adherence and modifiable psychosocial variables. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: This study examined trends over time in the prevalence of anxiety and depression among Canadian nurses: 6 months before, 1-month after, and 3 months after COVID-19 was declared a pandemic.Methods: This study adopted a repeated cross-sectional design and surveyed unionized nurses in British Columbia (BC), Canada on three occasions: September 2019 (Time 1, prepandemic), April 2020 (Time 2, early-pandemic) and June 2020 (Time 3).Results: A total of 10,117 responses were collected across three timepoints. This study found a significant increase of 10% to 15% in anxiety and depression between Time 1 and 2, and relative stability between Time 2 and 3, with Time 3 levels still higher than Time 1 levels. Cross-sector analyses showed similar patterns of findings for acute care and community nurses. Long-term care nurses showed a two-fold increase in the prevalence of anxiety early pandemic, followed by a sharper decline mid pandemic.Conclusions: COVID-19 has had short- and mid-term mental health implications for BC nurses particularly among those in the long-term care sector. Future research should evaluate the impact of COVID-19 on the mental health of health workers in different contexts, such as jurisdictional analyses, and better understand the long-term health and labor market consequences of elevated mental health symptoms over an extended time period. [ABSTRACT FROM AUTHOR]

Objective: The concept of cognitive reserve (CR) explains why individuals with higher education, intelligence, or occupational attainment exhibit less severe cognitive changes in the presence of age-related or neurodegenerative pathology. CR may be a useful construct in understanding the cognitive performance of patients with late life depression (LLD), a cohort who are twice as likely to later receive a clinical diagnosis of dementia. It follows that depressed older adults with low CR may be at greater risk of cognitive decline compared to non-depressed older adults matched for CR. However, the literature on CR and LLD is limited to cross-sectional studies with mixed findings as to whether proxies of CR moderate cognitive outcomes in LLD. For example, both higher and lower education levels in LLD are associated with greater cognitive impairment in LLD compared to similarly educated non-depressed older adults. Longitudinal studies may help disentangle the association between CR and cognitive outcomes in LLD. The current study investigated the interaction between proxies of CR (e.g., education) and depression status on cognitive functioning over three years. We hypothesized that depressed older adults with low CR would demonstrate greater cognitive impairment and decline compared to depressed elders with high CR and non-depressed older adults with comparable CR. Participants and Methods: Older adults with LLD and non-depressed older adults age 59+ participated. All participants were free of dementia at baseline. We divided both patients and non-depressed participants into low (<16) and high (>=16) education groups based upon the median years of education (16) of the entire sample. All participants underwent detailed neuropsychological testing. Composite measures of episodic memory (CERAD Wordlist and recall, LM I and LM II, BVRT), processing speed-executive functioning (SDMT and Trail Making Part B), working memory (forward, reverse, ascending Digit Span), and verbal fluency (Animal Naming and COWA) were calculated based on the non-depressed older adults. Results: The baseline sample included 210 non-depressed older adults and 465 older adults with major depression (LLD). 150 non-depressed older adults and 235 LLD patients provided three-year follow-up data. Separate ANOVAs revealed a statistically significant interaction between education and depression status at baseline on the composite score of executive functioning F (1, 668) = 8.74, p <.003. Consistent with our hypothesis, LLD with low education performed significantly worse compared to non-depressed with low education (z-score difference -1.35) and this effect was significantly greater than the difference between LLD patients and non-depressed with high education (z-score difference -0.36). No other interactions were found at baseline. Longitudinal analyses also revealed significant interactions between education and depression on memory over time, although sensitivity analyses did not suggest findings consistent with our hypothesis. Conclusions: Cognitive reserve contribute to group differences between LLD and non-depressed older adults in cognitive performance but may not alter cognitive trajectories over time. Future studies should further explore structural and functional brain changes associated with CR in LLD. [ABSTRACT FROM AUTHOR]

Despite increased rates of disease, disability, and social losses with aging, seniors consistently report higher levels of subjective well-being (SWB), a construct closely related to happiness, than younger adults. In this exploratory study, we utilized an available dataset to investigate how aspects of health commonly deteriorating with age, including sensory (i.e., vision and hearing) and cognitive status, relate to variability in self-described contributors to happiness. Community-dwelling seniors (n = 114) responded to a single-item prompt: "name things that make people happy." 1731 responses were categorized into 13 domains of SWB via structured content analysis. Sensory health and cognition were assessed by Snellen visual acuity, pure-tone audiometry, and in-person administration of the Brief Test of Adult Cognition by Telephone (BTACT) battery. A subset of eligible participants (n = 57) underwent functional magnetic resonance imaging (fMRI) to assess resting state functional connectivity (FC) within a previously described dopaminergic network associated with reward processing. SWB response patterns were relatively stable across gender, sensory status, and cognitive performance with few exceptions. For example, hearing-impaired participants listed fewer determinants of SWB (13.59 vs. 17.16; p<0.001) and were less likely to name things in the "special events" category. Participants with a higher proportion of responses in the "accomplishments" domain (e.g., winning, getting good grades) demonstrated increased FC between the ventral tegmental area and nucleus accumbens, regions implicated in reward and motivated behavior. While the framework for determinants of happiness among seniors was largely stable across the factors assessed here, our findings suggest that subtle changes in this construct may be linked to sensory loss. The possibility that perceptions about determinants of happiness might relate to differences in intrinsic connectivity within reward-related brain networks also warrants further investigation. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a retinal disease associated with significant vision loss among older adults. Previous large-scale behavioral studies indicate that people with AMD are at increased risk of cognitive deficits in language processing, particularly in verbal fluency tasks. The neural underpinnings of any relationship between AMD and higher cognitive functions, such as language processing, remain unclear. This study aims to address this issue using independent component analysis of spontaneous brain activity at rest. In 2 components associated with visual processing, we observed weaker functional connectivity in the primary visual cortex and lateral occipital cortex in AMD patients compared with healthy controls, indicating that AMD might lead to differences in the neural representation of vision. In a component related to language processing, we found that increasing connectivity within the right inferior frontal gyrus was associated with better verbal fluency performance across all older adults, and the verbal fluency effect was greater in AMD patients than controls in both right inferior frontal gyrus and right posterior temporal regions. As the behavioral performance of our patients is as good as that of controls, these findings suggest that preservation of verbal fluency performance in AMD patients might be achieved through higher contribution from right hemisphere regions in bilateral language networks. If that is the case, there may be an opportunity to promote cognitive resilience among seniors with AMD or other forms of late-life vision loss. [ABSTRACT FROM AUTHOR]

Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults. NFL and GCIPL thicknesses on optical coherence tomography (OCT) were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) and Spectralis software. We demonstrated that regional thicknesses of NFL or GCIPL on macular or nerve OCTs did not differ between groups. However, a multi-variate regression analysis identified macular areas with a significant thickening or thinning in NFL and GCIPL in MCI and AD patients. Our primary findings controvert previous reports of thinner NFL in moderate-to-severe AD. The areas of thickening of GCIPL and NFL in the macula adjacent to areas of thinning, as revealed by a more complex statistical model, suggest that NFL and GCIPL may undergo dynamic changes during AD progression. [ABSTRACT FROM AUTHOR]

Background: Individuals with major depressive disorder (MDD) may exhibit smaller striatal volumes reflecting deficits in the reward circuit. Deficits may change with age and be more pronounced among the melancholic subtype. Limited research has investigated striatal volume differences in older adults and by depression subtypes.Method: We used baseline data from the Neurocognitive Outcomes of Depression in the Elderly study. We examined volumetric differences in the putamen and caudate nucleus among older adults (60 years and older), comparing healthy control participants (n = 134) to depressed participants (n = 226), and comparing nonmelancholic depressed participants (n = 93) to melancholic depressed participants (n = 133). Group-by-age interactions were examined.Results: There were no significant group differences for the caudate nucleus. For the left putamen, investigation of the significant group-by-age interaction revealed that volume size was greater for the healthy controls compared to the depressed participants but only at younger ages (60-65 years); group differences diminished with increasing age. Examining volume by depression subtype revealed that the melancholic depressed participants had a smaller left putamen compared to the nonmelancholic depressed participants. Anhedonia symptoms were related to both smaller left and right putamen.Conclusion: Structural abnormalities in reward regions may underlie the anhedonic phenotype. Volume loss associated with MDD may attenuate in older age. [ABSTRACT FROM AUTHOR]

Burnout is a syndrome occurring mainly in individuals with long-term stressful work. The main complaints are emotional exhaustion and reduced performance. Burnout also largely overlaps with depression. Both are characterized by increased incidence of infections due to dysregulation of the immune system, overexpression of pro-inflammatory cytokines and cognitive deficits, particularly related to executive functions. To distinguish between burnout and depression already at the pre-clinical stage, the present double-blinded study compared immunological and cognitive parameters in seventy-six employees from emotionally demanding occupations who were post-hoc subdivided into two groups scoring low (EE−) and high (EE+) in emotional exhaustion and low (DE−) and high (DE+) in depression. Immunological parameters were measured from blood samples. Executive functions were studied by analyzing event-related brain potentials (ERPs) and performance during a task switching paradigm. Psychosocial job parameters were measured with standardized questionnaires. Burnout and mild to moderate depression largely overlapped. However, several subjects showed burnout without depressive symptoms. Higher levels of the pro-inflammatory cytokines IL-6 and IL-12 were correlated with burnout severity and depressive symptoms in male individuals. In the switch task a trend for lower performance in the EE+ vs. EE− group and no difference between DE+ and DE− groups were found. In the ERPs, however, differences were observed which distinguished between subclinical burnout and depression: the terminal contingent negative variation (CNV), indicating preparatory activity and the P3b, related to allocation of cognitive resources were generally reduced in EE+ vs. EE−, whereas no differences were found in the DE+ vs. DE− groups. The frontal P3a was selectively reduced in switch trials in the EE+ vs. EE− group and showed only a trend in DE+ vs. DE−, indicating impairment of executive control in subclinical burnout. Taken together, the results unveil specific immunological changes and declines in brain functions in employees with subclinical burnout that are not apparent in persons with moderate depression. Hence, the combination of immunological, behavioral and ERP methods renders a promising method for distinguishing both syndromes and for improving an early diagnosis of burnout before a clinical stage is reached. [ABSTRACT FROM AUTHOR]

Burnout is a pattern of complaints in individuals with emotionally demanding jobs that is often seen as a precursor of depression. One often reported symptom of burnout is cognitive decline. To analyze cognitive control and to differentiate between subclinical burnout and mild to moderate depression a double-blinded study was conducted that investigates changes in the processing of performance errors and feedback in a task switching paradigm. Fifty-one of 76 employees from emotionally demanding jobs showed a sufficient number of errors to be included in the analysis. The sample was subdivided into groups with low (EE-) and high (EE+) emotional exhaustion and no (DE-) and mild to moderate depression (DE+). The behavioral data did not significantly differ between the groups. In contrast, in the EE+ group, the error negativity (Ne/ERN) was enhanced while the error positivity (Pe) did not differ between the EE+ and EE- groups. After negative feedback the feedback-related negativity (FRN) was enhanced, while the subsequent positivity (FRP) was reduced in EE+ relative to EE-. None of these effects were observed in the DE+ vs. DE-. These results suggest an upregulation of error and negative feedback processing, while the later processing of negative feedback was attenuated in employees with subclinical burnout but not in mild to moderate depression. [ABSTRACT FROM AUTHOR]

Previous functional magnetic resonance imaging (fMRI) studies have reported that task-irrelevant, emotionally salient events can disrupt target discrimination, particularly when attentional demands are low, while others demonstrate alterations in the distracting effects of emotion in behavior and neural activation in the context of attention-demanding tasks. We used fMRI, in conjunction with an emotional oddball task, at different levels of target discrimination difficulty, to investigate the effects of emotional distractors on the detection of subsequent targets. In addition, we distinguished different behavioral components of target detection representing decisional, nondecisional, and response criterion processes. Results indicated that increasing target discrimination difficulty led to increased time required for both the decisional and nondecisional components of the detection response, as well as to increased target-related neural activation in frontoparietal regions. The emotional distractors were associated with activation in ventral occipital and frontal regions and dorsal frontal regions, but this activation was attenuated with increased difficulty. Emotional distraction did not alter the behavioral measures of target detection, but did lead to increased target-related frontoparietal activation for targets following emotional images as compared to those following neutral images. This latter effect varied with target discrimination difficulty, with an increased influence of the emotional distractors on subsequent target-related frontoparietal activation in the more difficult discrimination condition. This influence of emotional distraction was in addition associated specifically with the decisional component of target detection. These findings indicate that emotion-cognition interactions, in the emotional oddball task, vary depending on the difficulty of the target discrimination and the associated limitations on processing resources. [ABSTRACT FROM AUTHOR]

Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the 3 imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function. [ABSTRACT FROM AUTHOR]

We conducted functional magnetic resonance imaging (fMRI) with a visual search paradigm to test the hypothesis that aging is associated with increased frontoparietal involvement in both target detection and bottom-up attentional guidance (featural salience). Participants were 68 healthy adults, distributed continuously across 19 to 78 years of age. Frontoparietal regions of interest (ROIs) were defined from resting-state scans obtained prior to task-related fMRI. The search target was defined by a conjunction of color and orientation. Each display contained one item that was larger than the others (i.e., a size singleton) but was not informative regarding target identity. Analyses of search reaction time (RT) indicated that bottom-up attentional guidance from the size singleton (when coincident with the target) was relatively constant as a function of age. Frontoparietal fMRI activation related to target detection was constant as a function of age, as was the reduction in activation associated with salient targets. However, for individuals 35 years of age and older, engagement of the left frontal eye field (FEF) in bottom-up guidance was more prominent than for younger individuals. Further, the age-related differences in left FEF activation were a consequence of decreasing resting-state functional connectivity in visual sensory regions. These findings indicate that age-related compensatory effects may be expressed in the relation between activation and behavior, rather than in the magnitude of activation, and that relevant changes in the activation-RT relation may begin at a relatively early point in adulthood. Hum Brain Mapp 38:2128-2149, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The objective of the study was to examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. We compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: (a) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N = 4,115), (b) Spanish and English Neuropsychological Assessment Scales (N = 525), (c) Duke Memory, Health, and Aging study (N = 578), and (d) Neurocognitive Outcomes of Depression in the Elderly (N = 585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. The results found that for baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. In this diverse set of datasets, non-Hispanic Whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed. [ABSTRACT FROM AUTHOR]

Objective The objective of this study is to determine whether differential item functioning (DIF) due to cognitive status impacted three depressive symptoms measures commonly used with older adults. Methods Differential item functioning in depressive symptoms was assessed among participants ( N = 3558) taking part in four longitudinal studies of cognitive aging, using the Geriatric Depression Scale, the Montgomery-Åsberg Depression Rating Scale, and the Center for Epidemiologic Studies Depression Scale. Participants were grouped by cognitive status using a general cognitive performance score derived from each study's neuropsychological battery and linked to a national average using a population-based survey representative of the US population. The Clinical Dementia Rating score was used as an alternate grouping variable in three of the studies. Results Although statistically significant DIF based on cognitive status was found for some depressive symptom items (e.g., items related to memory complaints, appetite loss, lack of energy, and mood), the effect of item bias on the total score for each scale was negligible. Conclusions The depressive symptoms scales in these four studies measured depression in the same way, regardless of cognitive status. This may reduce concerns about using these depression measures in cognitive aging research, as relationships between depression and cognitive decline are unlikely to have been due to item bias, at least in the ways that were measured in the datasets we considered. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Previous studies have identified differential item function (DIF) in depressive symptoms measures, but the impact of DIF has been rarely reported. Given the critical importance of depressive symptoms assessment among older adults, we examined whether DIF due to demographic characteristics resulted in salient score changes in commonly used measures. Methods Four longitudinal studies of cognitive aging provided a sample size of 3754 older adults and included individuals both with and without a clinical diagnosis of major depression. Each study administered at least one of the following measures: the Center for Epidemiologic Studies Depression scale (20-item ordinal response or 10-item dichotomous response versions), the Geriatric Depression Scale, and the Montgomery-Åsberg Depression Rating Scale. Hybrid logistic regression-item response theory methods were used to examine the presence and impact of DIF due to age, sex, race/ethnicity, and years of education on the depressive symptoms items. Results Although statistically significant DIF due to demographic factors was present on several items, its cumulative impact on depressive symptoms scores was practically negligible. Conclusions The findings support substantive meaningfulness of previously reported demographic differences in depressive symptoms among older adults, showing that these individual differences were unlikely to have resulted from item bias attributable to demographic characteristics we examined. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Activation of frontal and parietal brain regions is associated with attentional control during visual search. We used fMRI to characterize age-related differences in frontoparietal activation in a highly efficient feature search task, detection of a shape singleton. On half of the trials, a salient distractor (a color singleton) was present in the display. The hypothesis was that frontoparietal activation mediated the relation between age and attentional capture by the salient distractor. Participants were healthy, community-dwelling individuals, 21 younger adults (19–29 years of age) and 21 older adults (60–87 years of age). Top-down attention, in the form of target predictability, was associated with an improvement in search performance that was comparable for younger and older adults. The increase in search reaction time (RT) associated with the salient distractor (attentional capture), standardized to correct for generalized age-related slowing, was greater for older adults than for younger adults. On trials with a color singleton distractor, search RT increased as a function of increasing activation in frontal regions, for both age groups combined, suggesting increased task difficulty. Mediational analyses disconfirmed the hypothesized model, in which frontal activation mediated the age-related increase in attentional capture, but supported an alternative model in which age was a mediator of the relation between frontal activation and capture. [ABSTRACT FROM AUTHOR]

Objective: Genetic factors confer risk for neuropsychiatric phenotypes, but the polygenic etiology of these phenotypes makes identification of genetic culprits challenging. An approach to this challenge is to examine the effects of genetic variation on relevant endophenotypes, such as hippocampal volume loss. A smaller hippocampus is associated with gene variants of the renin-angiotensin system (RAS), a system implicated in vascular disease. However, no studies to date have investigated longitudinally the effects of genetic variation of RAS on the hippocampus.Method: The authors examined the effects of polymorphisms of AGTR1, the gene encoding angiotensin-II type 1 receptor of RAS, on longitudinal hippocampal volumes of older adults. In all, 138 older adults (age ≥60 years) were followed for an average of about 4 years. The participants underwent repeated structural MRI and comprehensive neurocognitive testing, and they were genotyped for four AGTR1 single-nucleotide polymorphisms (SNPs) with low pairwise linkage disequilibrium values and apolipoprotein E (APOE) genotype.Results: Genetic variants at three AGTR1 SNPs (rs2638363, rs1492103, and rs2675511) were independently associated with accelerated hippocampal volume loss over the 4-year follow-up period in the right but not left hemisphere. Intriguingly, these AGTR1 risk alleles also predicted worse episodic memory performance but were not related to other cognitive measures. Two risk variants (rs2638363 and rs12721331) interacted with the APOE4 allele to accelerate right hippocampal volume loss.Conclusions: Risk genetic variants of the RAS may accelerate memory decline in older adults, an effect that may be conferred by accelerated hippocampal volume loss. Molecules involved in this system may hold promise as early therapeutic targets for late-life neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Objectives To examine whether performance on a brief memory test is related to functional outcomes in older individuals undergoing low-vision rehabilitation ( LVR) for macular disease. Design Observational cohort study of individuals receiving outpatient LVR. Setting Academic center. Participants Ninety-one individuals (average age 80.1) with macular disease. Measurements Memory was assessed at baseline using a 10-word list; memory deficit was defined as immediate recall of two or fewer words. Vision-related function was measured using the 25-item Visual Function Questionnaire ( VFQ-25) administered at baseline and during subsequent interviews (mean follow-up, 115 days). Linear mixed models were constructed to compare average trajectories of four VFQ-25 subscales: near activities, distance activities, dependency, and role difficulty. Results The 29.7% of participants with memory deficits tended to decline in ability to accomplish activities that involved near vision. Controlling for age, sex, and education, the functional trajectory of participants with memory deficit differed significantly from that of those with better memory ( P = .002), who tended to report improvements in ability to accomplish near activities. Conclusion Of older adults receiving LVR for macular disease, those with memory deficits experienced worse functional trajectories in their ability to perform specific visually mediated tasks. A brief memory screen may help explain variability in rehabilitation outcomes and identify individuals who might require special accommodations. [ABSTRACT FROM AUTHOR]

In this paper, a high-dimensional pattern classification framework, based on functional associations between brain regions during resting-state, is proposed to accurately identify MCI individuals from subjects who experience normal aging. The proposed technique employs multi-spectrum networks to characterize the complex yet subtle blood oxygenation level dependent (BOLD) signal changes caused by pathological attacks. The utilization of multi-spectrum networks in identifying MCI individuals is motivated by the inherent frequency-specific properties of BOLD spectrum. It is believed that frequency specific information extracted from different spectra may delineate the complex yet subtle variations of BOLD signals more effectively. In the proposed technique, regional mean time series of each region-of-interest (ROI) is band-pass filtered (0:025⩽f⩽0:100 Hz) before it is decomposed into five frequency sub-bands. Five connectivity networks are constructed, one from each frequency sub-band. Clustering coefficient of each ROI in relation to the other ROIs are extracted as features for classification. Classification accuracy was evaluated via leave-one-out cross-validation to ensure generalization of performance. The classification accuracy obtained by this approach is 86.5%, which is an increase of at least 18.9% from the conventional full-spectrum methods. A cross-validation estimation of the generalization performance shows an area of 0.863 under the receiver operating characteristic (ROC) curve, indicating good diagnostic power. It was also found that, based on the selected features, portions of the prefrontal cortex, orbitofrontal cortex, temporal lobe, and parietal lobe regions provided the most discriminant information for classification, in line with results reported in previous studies. Analysis on individual frequency sub-bands demonstrated that different sub-bands contribute differently to classification, providing extra evidence regarding frequency-specific distribution of BOLD signals. Our MCI classification framework, which allows accurate early detection of functional brain abnormalities, makes an important positive contribution to the treatment management of potential AD patients. [ABSTRACT FROM AUTHOR]

Abstract: In this article we review recent research on diffusion tensor imaging (DTI) of white matter (WM) integrity and the implications for age-related differences in cognition. Neurobiological mechanisms defined from DTI analyses suggest that a primary dimension of age-related decline in WM is a decline in the structural integrity of myelin, particularly in brain regions that myelinate later developmentally. Research integrating behavioral measures with DTI indicates that WM integrity supports the communication among cortical networks, particularly those involving executive function, perceptual speed, and memory (i.e., fluid cognition). In the absence of significant disease, age shares a substantial portion of the variance associated with the relation between WM integrity and fluid cognition. Current data are consistent with one model in which age-related decline in WM integrity contributes to a decreased efficiency of communication among networks for fluid cognitive abilities. Neurocognitive disorders for which older adults are at risk, such as depression, further modulate the relation between WM and cognition, in ways that are not as yet entirely clear. Developments in DTI technology are providing a new insight into both the neurobiological mechanisms of aging WM and the potential contribution of DTI to understanding functional measures of brain activity. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. [Copyright &y& Elsevier]

Abstract: Different imaging modalities provide essential complementary information that can be used to enhance our understanding of brain disorders. This study focuses on integrating multiple imaging modalities to identify individuals at risk for mild cognitive impairment (MCI). MCI, often an early stage of Alzheimer''s disease (AD), is difficult to diagnose due to its very mild or insignificant symptoms of cognitive impairment. Recent emergence of brain network analysis has made characterization of neurological disorders at a whole-brain connectivity level possible, thus providing new avenues for brain diseases classification. Employing multiple-kernel Support Vector Machines (SVMs), we attempt to integrate information from diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI) for improving classification performance. Our results indicate that the multimodality classification approach yields statistically significant improvement in accuracy over using each modality independently. The classification accuracy obtained by the proposed method is 96.3%, which is an increase of at least 7.4% from the single modality-based methods and the direct data fusion method. A cross-validation estimation of the generalization performance gives an area of 0.953 under the receiver operating characteristic (ROC) curve, indicating excellent diagnostic power. The multimodality classification approach hence allows more accurate early detection of brain abnormalities with greater sensitivity. [Copyright &y& Elsevier]

Objective: Estimates of incident dementia, and cognitive impairment, not dementia (CIND) (or the related mild cognitive impairment) are important for public health and clinical care policy. In this paper, we report US national incidence rates for dementia and CIND. Methods: Participants in the Aging, Demographic, and Memory Study (ADAMS) were evaluated for cognitive impairment using a comprehensive in-home assessment. A total of 456 individuals aged 72 years and older, who were not demented at baseline, were followed longitudinally from August 2001 to December 2009. An expert consensus panel assigned a diagnosis of normal cognition, CIND, or dementia and its subtypes. Using a population-weighted sample, we estimated the incidence of dementia, Alzheimer disease (AD), vascular dementia (VaD), and CIND by age. We also estimated the incidence of progression from CIND to dementia. Results: The incidence of dementia was 33.3 (standard error [SE], 4.2) per 1,000 person-years and 22.9 (SE, 2.9) per 1,000 person-years for AD. The incidence of CIND was 60.4 (SE, 7.2) cases per 1,000 person-years. An estimated 120.3 (SE, 16.9) individuals per 1,000 person-years progressed from CIND to dementia. Over a 5.9-year period, about 3.4 million individuals aged 72 and older in the United States developed incident dementia, of whom approximately 2.3 million developed AD, and about 637,000 developed VaD. Over this same period, almost 4.8 million individuals developed incident CIND. Interpretation: The incidence of CIND is greater than the incidence of dementia, and those with CIND are at high risk of progressing to dementia, making CIND a potentially valuable target for treatments aimed at slowing cognitive decline. ANN NEUROL 2011; [ABSTRACT FROM AUTHOR]

To examine the association between neuropsychiatric symptoms and risk of institutionalization and death. Analysis of longitudinal data. The Aging, Demographics, and Memory Study (ADAMS). Five hundred thirty-seven adults aged 71 and older with cognitive impairment drawn from the Health and Retirement Study (HRS). Neuropsychiatric symptoms (delusions, hallucinations, agitation, depression, apathy, elation, anxiety, disinhibition, irritation, and aberrant motor behaviors) and caregiver distress were identified using the Neuropsychiatric Inventory. A consensus panel in the ADAMS assigned cognitive category. Date of nursing home placement and information on death, functional limitations, medical comorbidity, and sociodemographic characteristics were obtained from the HRS and ADAMS. Overall, the presence of one or more neuropsychiatric symptoms was not associated with a significantly higher risk for institutionalization or death during the 5-year study period, although when assessing each symptom individually, depression, delusions, and agitation were each associated with a significantly higher risk of institutionalization (hazard rate (HR)=3.06, 95% confidence interval (CI)=1.09-8.59 for depression; HR=5.74, 95% CI=1.94-16.96 for clinically significant delusions; HR=4.70, 95% CI=1.07-20.70 for clinically significant agitation). Caregiver distress mediated the association between delusions and agitation and institutionalization. Depression and hallucinations were associated with significantly higher mortality (HR=1.56, 95% CI=1.08-2.26 for depression; HR=2.59, 95% CI=1.09-6.16 for clinically significant hallucinations). Some, but not all, neuropsychiatric symptoms are associated with a higher risk of institutionalization and death in people with cognitive impairment, and caregiver distress also influences institutionalization. Interventions that better target and treat depression, delusions, agitation, and hallucinations, as well as caregiver distress, may help delay or prevent these negative clinical outcomes. [ABSTRACT FROM AUTHOR]

To compare the characteristics and outcomes of caregivers of adults with dementia with those of caregivers of adults with cognitive impairment, not dementia (CIND). Cross-sectional. In-home assessment for cognitive impairment and self-administered caregiving questionnaire. One hundred sixty-nine primary family caregivers of participants in the Aging, Demographics, and Memory Study (ADAMS). ADAMS participants were aged 71 and older drawn from the nationally representative Health and Retirement Study. Neuropsychological testing, neurological examination, clinical assessment, and medical history were used to assign a diagnosis of normal cognition, CIND, or dementia. Caregiving measures included caregiving time, functional limitations, depressive symptoms, physical and emotional strain, caregiving rewards, caregiver health, and demographic characteristics. Dementia caregivers spent approximately 9 hours per day providing care, compared with 4 hours per day for CIND caregivers ( P=.001). Forty-four percent of dementia caregivers exhibited depressive symptoms, compared with 26.5% of CIND caregivers ( P=.03). Physical and emotional strains were similar in both groups of caregivers. Regardless of the strains, nearly all caregivers reported some benefits from providing care. Behavioral problems ( P=.01) and difficulty with instrumental activities of daily living ( P=.01) in persons with CIND partially explained emotional strain experienced by CIND caregivers. For those with dementia, behavioral problems predicted caregiver emotional strain ( P<.001) and depressive symptoms ( P=.01). Although support services are available to dementia caregivers, CIND caregivers also expend considerable time and experience strains. The real caregiver burden of cognitive impairment in the U.S. population may therefore be greatly underestimated if people who have reached the diagnostic threshold for dementia are focused on exclusively. [ABSTRACT FROM AUTHOR]