The Role of State Versus Trait Anxiety on Cognition in Older Adults With Major Depressive Disorder.

OBJECTIVE: Anxiety superimposed on late life depression (LLD) results in greater changes to prefrontal and medial temporal brain regions compared to depression alone. Yet, the combined impact of anxiety and depression on cognition in LLD has not been thoroughly investigated. The current study investigated whether annual changes in state and trait anxiety were associated with cognitive changes in older adults with major depression. We hypothesized that the presence of anxiety among older depressed adults would be associated with worse cognitive performance in the domains of memory and executive functioning over time. DESIGN: Three-year longitudinal observational study of older adults with LLD who were offered antidepressant treatment. SETTING: Academic Health Center. METHODS: Participants included 124 adults aged 60+ who met criteria for major depression at baseline. The association between anxiety and cognition was examined with separate multilevel linear models that addressed both between-subject and within-person effects of state and trait anxiety on cognitive functioning tests. RESULTS: Individuals who experienced annual increases in anxiety above his/her personal average also experienced cognitive decline. Increases in state anxiety were associated with declines in memory and global cognition. By contrast, increases in trait anxiety were associated with declines in mental flexibility and memory. These findings remained significant even when controlling for changes in depression over time. CONCLUSION: In LLD, individual increases in state and trait anxiety were associated with cognitive declines in different domains.

Neuropsychological Assessments of Cognitive Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis with Meta-Regression.

INTRODUCTION: Cognitive dysfunction or deficits are common in patients with major depressive disorder (MDD). The current study systematically reviews and meta-analyzes multiple domains of cognitive impairment in patients with MDD. METHODS: PubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, Web of Science, and Google Scholar were searched from inception through May 17, 2023, with no language limits. Studies with the following inclusion criteria were included: (1) patients with a diagnosis of MDD using standardized diagnostic criteria; (2) healthy controls (i.e., those without MDD); (3) neuropsychological assessments of cognitive impairment using Cambridge Neuropsychological Test Automated Battery (CANTAB); and (4) reports of sufficient data to quantify standardized effect sizes. Hedges' g standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were used to quantify effect sizes of cognitive impairments in MDD. SMDs were estimated using a fixed- or random-effects models. RESULTS: Overall, 33 studies consisting of 2,596 subjects (n = 1,337 for patients with MDD and n = 1,259 for healthy controls) were included. Patients with MDD, when compared to healthy controls, had moderate cognitive deficits (SMD, -0.39 [95% CI, -0.47 to -0.31]). In our subgroup analyses, patients with treatment-resistant depression (SMD, -0.56 [95% CI, -0.78 to -0.34]) and older adults with MDD (SMD, -0.51 [95% CI, -0.66 to -0.36]) had greater cognitive deficits than healthy controls. The effect size was small among unmedicated patients with MDD (SMD, -0.19 [95% CI, -0.37 to -0.00]), and we did not find any statistical difference among children. Cognitive deficits were consistently found in all domains, except the reaction time. No publication bias was reported. CONCLUSION: Because cognitive impairment in MDD can persist in remission or increase the risk of major neurodegenerative disorders, remediation of cognitive impairment in addition to alleviation of depressive symptoms should be an important goal when treating patients with MDD.

Olfactory Dysfunction and Depression Trajectories in Community-Dwelling Older Adults.

BACKGROUND: We examined the relationship between baseline olfactory performance and incident significant depressive symptoms and longitudinal depression trajectories in well-functioning older adults. Inflammation and cognitive status were examined as potential mediators. METHODS: Older adults (n = 2 125, 71-82 years, 51% female, 37% Black) completed an odor identification task at Year 3 (our study baseline) of the Health, Aging, and Body Composition study. Cognitive assessments, depressive symptoms, and inflammatory markers were ascertained across multiple visits over 8 years. Discrete-time complementary log-log models, group-based trajectory models, and multivariable-adjusted multinomial logistic regression were employed to assess the relationship between baseline olfaction and incident depression and longitudinal depression trajectories. Mediation analysis assessed the influence of cognitive status on these relationships. RESULTS: Individuals with lower olfaction had an increased risk of developing significant depressive symptoms at follow-up (hazard ratio = 1.04, 95% confidence interval [CI]: 1.00, 1.08). Of the 3 patterns of longitudinal depression scores identified (stable low, stable moderate, and stable high), poorer olfaction was associated with a 6% higher risk of membership in the stable moderate (relative risk ratio [RRR] = 1.06, 95% CI: 1.02, 1.10)/stable high (RRR = 1.06, 95% CI: 1.00, 1.12) groups, compared to the stable low group. Poor cognitive status, but not inflammation, partially mediated the relationship between olfactory performance and incident depression symptom severity. CONCLUSIONS: Suboptimal olfaction could serve as a prognostic indicator of vulnerability for the development of late-life depression. These findings underscore the need for a greater understanding of olfaction in late-life depression and the demographic, cognitive, and biological factors that influence these relationships over time.

Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90-0.96, p = 3.37 × 10-7 ). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.

Exposure to ultrafine particles and cognitive decline among older people in the United States.

BACKGROUND: Some studies suggest that ambient particulate air pollution is associated with cognitive decline. However, the findings are mixed, and there is no relevant research examining the influences of ultrafine particles (UFP), which may have more toxicity than larger particles. We therefore conducted this study to investigate whether residential UFP exposure is associated with cognitive decline using data from the Alzheimer's Disease Research Centers in the United States. METHODS: This is a longitudinal study of participants who were aged 65 years and older and had normal cognitive status at baseline. Residential UFP exposure, expressed as particle number concentrations (PNC), was assessed in 2016-2017 using a nationwide land use regression model, and was assigned to each participant using their 3-digit residential ZIP codes. Cognitive functions including memory, attention, language, executive function, and global function were assessed annually using 15 neuropsychological tests from March 2015 to February 2022. Linear mixed-effects models were used to examine the associations after adjustment for covariates including baseline age, sex, APOE ε4 status, race, education, smoking status, history of diabetes, quartiles of neighborhood median household income, and interaction terms of follow-up time with each covariate. RESULTS: This study included 5646 participants (mean age 76 years, 65% female). On average, each participant had 4 annual visits. When PNC was treated as a continuous variable, there were no statistically or clinically significant changes in annual decline of each cognitive function in relation to an interquartile range elevation in PNC (4026 particles/cm3). Similarly, when PNC was treated as a categorical variable including five exposure groups, there were no linear exposure-response trends in annual decline of each cognitive function across the five exposure groups. CONCLUSIONS: This study found no meaningful associations between residential UFP exposure and cognitive decline in global and domain-specific functions. There is a need for further research that assigns UFP exposure at a finer geographic scale.

Reliable Cognitive Decline in Late-Life Major Depression.

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.

Effects of Longitudinal Changes in Neuroticism and Stress on Cognitive Decline.

OBJECTIVE: The relationships among depression, personality factors, stress, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Independently, the presence of neuroticism and the number of stressful life events are each associated with worsening cognitive decline in depressed older adults. Yet little is known about combined effects of changes in neuroticism and changes in stress on cognitive decline among older depressed adults. DESIGN: Longitudinal observational study. SETTING: Academic Health Center. PARTICIPANTS: The authors examined 62 participants in the Neurobiology of Late-life depression (NBOLD) study to test the hypothesis that, compared with older depressed subjects who experience improved neuroticism and lower psychosocial stressors over time, those with worsening neuroticism and greater psychosocial stressors will demonstrate more cognitive decline. MEASUREMENTS: The authors measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Ǻsberg Depression Rating Scale. At annual assessments, subjects reported the number of psychosocial stressors in the prior year and completed a neuropsychological evaluation. Participants completed a detailed neuropsychological battery at baseline and annually over 3 years. The battery included a test of delayed story memory (Logical Memory-2 or LMII). The outcome 3-year change in cognitive scores was regressed against 3-year change scores of neuroticism and number of psychosocial stressors, plus their interaction, while adjusting for sex, age, race, education, baseline cognitive score, and 3-year change in MADRS score as covariates. RESULTS: In multivariable linear regression analysis with the above covariates, the interaction effect of 3-year change in Total Neuroticism score and 3-year change in Total Stressors on change in LMII performance was statistically significant (B = -0.080[95%CL: -0.145 to -0.015], T = -2.48, df = 52, p = 0.017). Further exploration of this finding showed that 1) when total stressors increased by 2 or more over 3 years, LMII change was inversely associated with neuroticism change; and 2) when neuroticism improved less, LMII change score was inversely associated with total stressor change. There were no other significant interactions between stress and neuroticism on cognition. CONCLUSION: Our findings document the importance of tracking change in neuroticism and monitoring psychosocial stress over the long-term course of treatment in geriatric depression. Both factors exert important combined effects on memory over time. Future studies in larger samples are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

The neurobiology of apathy in depression and neurocognitive impairment in older adults: a review of epidemiological, clinical, neuropsychological and biological research.

Apathy is a common condition that involves diminished initiative, diminished interest and diminished emotional expression or responsiveness. It is highly prevalent in the context of a variety of neuropsychiatric disorders and is related to poor health outcomes. Presence of apathy is associated with cognitive and functional decline in dementia. Despite its negative impact on health, there is no definitive treatment for apathy, a clinical reality that may be due in part to lack of knowledge about assessment, neuropsychological features and neurobiological underpinnings. Here, we review and synthesize evidence from clinical, epidemiological, neuropsychological, peripheral biomarker and neuroimaging research. Apathy is a common feature of depression and cognitive disorders and is associated with impairment in executive function. Neuropsychological and neuroimaging studies point to dysfunction of brain circuitry involving the prefrontal cortex, especially the dorsolateral prefrontal cortex circuit, the dorsomedial prefrontal cortex circuit, and the ventromedial prefrontal cortex circuit. However, inconsistent findings, particularly in neuroimaging may be due to heterogeneity of apathy symptoms (with a need to better elucidate subtypes), neuropsychiatric comorbidities, the severity of cognitive impairment and other factors. These factors need to be accounted for in future studies so that biomarker research can make progress. On the whole, the literature on apathy has identified likely neurocognitive, peripheral biomarker and neuroimaging targets for understanding apathy, but also points to the need to address methodological issues that will better inform future studies. In turn, as we learn more about the underpinning of apathy and its subtypes, subsequent research can focus on new neurally based interventions that will strengthen the clinical management of apathy in the context of its comorbidities.

Older adult driving performance assessed under simulated and on-road conditions.

Simulated driving offers a convenient test of driving ability for older drivers, although the viability of using simulated driving with this population is mixed. The relative weighting of the relevant perceptual, cognitive, and physical factors may vary between simulated and on-road driving. The current study was designed to assess this possibility. We conducted simulated and on-road driving tests of 61 older adults aged 66-92 years. To ensure that the driving performance was measured similarly between the two driving modalities, we employed the Record of Driving Errors (RODE) driving assessment system during both driving tests. Correlation and random weights analysis (RWA) results indicated only modest evidence of correspondence between the simulated and on-road driving performances. The primary factors operative in both simulated and on-road driving was Useful Field of View and a measure of basic cognition. Unique factors for simulated driving included a measure of physical mobility (Time-Up-and-Go) and spatial reasoning (Line), and for on-road driving included chronological age and sensorimotor processing (Trail-Making Task A). Chronological age was correlated primarily the on-road rather than simulated test, was greatly reduced with the inclusion of additional explanatory factors, and likely reflects driving efficiency rather than driving safety. We conclude that simulated driving in healthy older drivers can be beneficial for research purposes to assess cognitive and perceptual factors that underly driving effectiveness, although it cannot serve as a clear proxy for on-road driving.

Association of 1-year change in neuroticism and 3-year change in cognitive performance among older depressed adults.

OBJECTIVES: The relationships among depression, personality factors, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Presence of neuroticism worsens cognitive decline in depressed older adults. Yet little is known about changes in neuroticism among older adults being treated for depression and the impact of these changes on cognitive decline. DESIGN: Longitudinal observational study. SETTING: Academic Health Center. PARTICIPANTS: We examined 68 participants in the neurobiology of late-life depression (LLD) study to test the hypothesis that older depressed subjects with more improvement in neuroticism would experience less cognitive decline compared with those with less change in neuroticism. MEASUREMENTS: We measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Åsberg depression rating scale (MADRS). Global cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery at baseline and annually over 3 years. Regression models of 1-year change in neuroticism and 3-year change in CERAD included sex, age, race, education, and 1-year change in MADRS score as covariates. RESULTS: We found that among older adults, 1-year change in neuroticism was inversely associated with 3-year change in CERAD total score. CONCLUSIONS: Our findings challenge the notion of longitudinal stability of measures of personality, especially among older depressed individuals. They highlight the importance of repeated personality assessment, especially of neuroticism, in the management of LLD. Future studies in larger samples followed for longer periods are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.

Cognitive Impairment in Older Incarcerated Males: Education and Race Considerations.

OBJECTIVE: Assess cognitive impairment (global cognition and executive functioning) in older incarcerated males overall, and according to education and race. DESIGN: Cross-sectional PARTICIPANTS: The sample included 239 racially diverse (37.7% White, 41.4% Black, 20.9% Hispanic/Other) incarcerated males age ≥50 (mean age = 56.4 ± 6.1; range 50-79 years). MEASUREMENTS: Global cognitive impairment assessed using the Montreal Cognitive Assessment (MoCA) - standard MoCA scoring (1-point adjustment for ≤12 years education, and score <26 indicating cognitive impairment) versus education- and race-specific cutpoints. Trail Making Test (TMT) assessed executive functioning. The relationship between race and cognitive impairment was evaluated using Chi-Square, One-Way ANOVA, and Tukey's HSD post-hoc analyses. Chi-Square was also used to evaluate the relationship between race and frequency of missed MoCA items. RESULTS: Average MoCA score was 24.12 ± 3.38. Overall, 62.8% and 38.5% of participants met criteria for cognitive impairment using standard scoring and education- and race-specific cutpoints, respectively. This difference was largely attributed to the change in proportion of Blacks who met criteria for cognitive impairment after applying education- and race-specific cutpoints (62.6% versus 19.2%). Fewer White inmates were impaired (51.1% versus 36.7%) after applying demographically-adjusted norms; however, the proportion of Hispanics/Others remained largely unchanged (84% versus 80%). A considerable proportion of participants were mildly impaired on TMT-A (18.2% Whites, 7.1% Blacks) and TMT-B (20.5% Whites, 4.1% Blacks). Race differences were observed in missed MoCA items. CONCLUSIONS: Cognitive impairment is common in older incarcerated persons, despite applying education- and race-specific norms. Notable race differences highlight need for validated assessments for this diverse population.

Structural brain changes and neuroticism in late-life depression: a neural basis for depression subtypes.

The neurobiological basis of neuroticism in late-life depression (LLD) is understudied. We hypothesized that older depressed subjects scoring high in measures of neuroticism would have smaller hippocampal and prefrontal volumes compared with non-neurotic older depressed subjects and with nondepressed comparison subjects based on previous research. Non-demented subjects were recruited and were either depressed with high neuroticism (n = 65), depressed with low neuroticism (n = 36), or never depressed (n = 27). For imaging outcomes focused on volumetric analyses, we found no significant between-group differences in hippocampal volume. However, we found several frontal lobe regions for which depressed subjects with high neuroticism scores had smaller volumes compared with non-neurotic older depressed subjects and with nondepressed comparison subjects, controlling for age and gender. These regions included the frontal pole, medial orbitofrontal cortex, and left pars orbitalis. In addition, we found that non-neurotic depressed subjects had a higher volume of non-white matter hypointensities on T1-weighted images (possibly related to cerebrovascular disease) than did neurotic depressed subjects. Our finding that depressed subjects low in neuroticism had higher volumes of non-white matter hypointensities is consistent with prior literature on "vascular depression." In contrast, the finding that those high in neuroticism had smaller frontal volume than depressed subjects low in neuroticism and never-depressed subjects highlight the importance of frontal circuitry in the subgroup of older depressed individuals with comorbid neuroticism. Together, these results implicate different neural mechanisms in older neurotic and non-neurotic depressed groups and suggest that multiple biological pathologies may lead to different clinical expressions of LLD.

The Interaction of Personality and Social Support on Prospective Suicidal Ideation in Men and Women With Late-Life Depression.

OBJECTIVE: Evidence suggests a cross-sectional association between personality traits and suicidal ideation in LLD. Yet, it is unclear how personality may influence suicidal ideation over time in LLD, or whether such an association would be moderated by psychosocial and biological individual differences. The present study had three aims: 1) to examine whether personality traits increase suicidal ideation in LLD over time, 2) to understand whether this relationship is influenced by subjective social support, and 3) to determine whether the potential relationship between social support, personality, and suicidal ideation is different for men and women. DESIGN: Participants were enrolled in the Duke University Neurocognitive Outcomes of Depression in the Elderly (NCODE), a longitudinal investigation of the predictors of poor illness course in LLD. Patients were initially enrolled in the NCODE study between December 1994 and June 2000 and were followed for an average of six years. SETTING: NCODE operates in a naturalistic treatment milieu. PARTICIPANTS: One hundred twelve participants aged 60 and older with a current diagnosis of major depressive disorder. MEASUREMENTS: Annual assessments of depression, suicidal ideation, and social support (measured with the Duke Social Support Index). Participants also completed the NEO Personality Inventory-Revised (NEO-PI-R) providing measures of the five major personality dimensions (neuroticism, extraversion, openness, conscientiousness, and agreeableness). RESULTS: Univariate logistic generalized linear mixed modeling (GLMM) analyses revealed that higher levels of depression at baseline, less subjective social support, higher neuroticism, and lower extraversion were significantly associated with an increased likelihood of suicidal ideation over time. While the relationship between these dimensions and suicidal ideation were no longer significant in multivariate analyses, there was a significant moderating effect of social support on the association between suicidal ideation and certain neuroticism and extraversion personality facets. Decreased subjective social support was associated with an increased likelihood of suicidal ideation in LLD patients with high (but not low) impulsiveness and low (but not high) gregariousness and positive emotions. Across all models, social support was beneficial to women, but not men, in decreasing the likelihood of future suicidal ideation. CONCLUSION: Changes in social support may contribute to suicidal ideation in older depressed adults with certain personality traits. Irrespective of personality traits, changes in social support had a significant effect on the suicidal ideation of women but not men. These relationships were apparent even when controlling for depression severity, age, and history of suicide attempt.

Cognitive variability, brain aging, and cognitive decline in late-life major depression.

OBJECTIVES: Older adults with late-life major depression (LLMD) are at increased risk of dementia. Dispersion, or within-person performance variability across cognitive tests, is a potential marker of cognitive decline. This study examined group differences in dispersion between LLMD and nondepressed healthy controls (HC) and investigated whether dispersion was a predictor of cognitive performance 1 year later in LLMD. We also explored demographic, clinical, and structural imaging correlates of dispersion in LLMD and HC. We hypothesized that dispersion would be greater in LLMD compared with HC and would be associated with worse cognitive performance 1 year later in LLMD. DESIGN: Participants were enrolled in the Neurobiology of Late-Life Depression, a naturalistic longitudinal investigation of the predictors of poor illness course in LLMD. PARTICIPANTS: The baseline sample consisted of 121 older adults with LLMD and 39 HC; of these subjects, 94 LLMD and 35 HC underwent magnetic resonance imaging (MRI). One-year cognitive data were available for 107 LLMD patients. MEASUREMENTS: All participants underwent detailed clinical and structural MRI at baseline. LLMD participants also completed a comprehensive cognitive evaluation 1 year later. RESULTS: Higher test dispersion was evident in LLMD when compared with nondepressed controls. Greater baseline dispersion predicted 1-year cognitive decline in LLMD patients even when controlling for baseline cognitive functioning and demographic and clinical confounders. Dispersion was correlated with white matter lesions in LLMD but not HC. Dispersion was also correlated with anxiety in both LLMD and HC. CONCLUSIONS: Dispersion is a marker of neurocognitive integrity that requires further exploration in LLMD.

Recent advances in the use of imaging in psychiatry: functional magnetic resonance imaging of large-scale brain networks in late-life depression.

Advances in neuroimaging have identified neural systems that contribute to clinical symptoms that occur across various psychiatric disorders. This transdiagnostic approach to understanding psychiatric illnesses may serve as a precise guide to identifying disease mechanisms and informing successful treatments. While this work is ongoing across multiple psychiatric disorders, in this article we emphasize recent findings pertaining to major depression in the elderly, or late-life depression (LLD), a common and debilitating neuropsychiatric illness. We discuss how neural functioning of three networks is linked to symptom presentation, illness course, and cognitive decline in LLD. These networks are (1) an executive control network responsible for complex cognitive processing, (2) a default mode network normally deactivated during cognitive demanding when individuals are at rest, and a (3) salience network relevant to attending to internal and external emotional and physiological sensations. We discuss how dysfunction in multiple networks contributes to common behavioral syndromes, and we present an overview of the cognitive control, default mode, and salience networks observed in LLD.

Training the Next Generation of Geriatric-Focused Clinical Neuroscientists.

It remains challenging to integrate clinical neuroscience into clinical practice. Hindrances at the training level (e.g., lack of qualified faculty and curriculum) contribute to this impasse. To help address this, we present a model of training in clinical neuroscience. We expand on a growing literature on incorporating neuroscience into psychiatry training by emphasizing two points. That is, 1) we propose a training model designed for the geriatric-minded clinician; and 2) that extends across several phases of education and career development. Considering the relevance of dementia to our population of interest, and the potential impact expertise in clinical neuroscience can have in elders with cognitive impairment, we provide relevant curriculum examples at various training stages. Clinical research, both as a practitioner and consumer, figures prominently into our training model. We discuss two mentoring programs, T32 fellowships and Research Career Institute in the Mental Health of Aging, as ways to engage geriatric psychiatrists early in their training and transition them successfully to post-residency clinical investigator positions. Although there is increasing opportunity for geriatric psychiatrists and other clinicians to become leaders in the field of neuroscience, this remains a work in progress; ours and others' training programs continue to evolve based on input from trainers and trainees alike, as well as from the increasing literature on this important topic.

State of the Science of Neural Systems in Late-Life Depression: Impact on Clinical Presentation and Treatment Outcome.

Major depression in older adults, or late-life depression (LLD), is a common and debilitating psychiatric disorder that increases the risk of morbidity and mortality. Although the effects of LLD make it important to achieve a diagnosis and start treatment quickly, individuals with LLD are often inadequately or unsuccessfully treated. The latest treatment developments suggest that interventions targeting executive dysfunction and neuroticism, constructs associated with poor response to antidepressants in older adults, are successful in treating LLD. Specific behavioral interventions (computerized cognitive training, mindfulness meditation, aerobic exercise) appear to decrease depressive symptoms and ameliorate executive dysfunction and neuroticism, but we do not fully understand the mechanisms by which these treatments work. We review recent research on neural network changes underlying executive dysfunction and neuroticism in LLD and their association with clinical outcomes (e.g., treatment response, cognitive functioning).