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.

High Risk of Substance Use Disorder-Related Outcomes in Veterans Released from Correctional Facilities in Mid to Late Life.

BACKGROUND: Veterans Affairs (VA) is likely to encounter a growing number of veterans returning to the community in mid to late life following incarceration (i.e., experiencing reentry). Yet, rates of negative health outcomes due to substance use disorders (SUDs) in this population are unknown. OBJECTIVE: To determine risk of and risk factors for SUD-related emergency department visits and inpatient hospitalizations (ED/IPH) and overdose death among older reentry veterans compared with never-incarcerated veterans. DESIGN: Retrospective cohort study using national VA and Medicare healthcare systems data. PARTICIPANTS: Veterans age ≥50, incarcerated for ≤5 consecutive years, and released between October 1, 2010, and September 30, 2017 (N = 18,803), were propensity score-matched 1:5 with never-incarcerated veterans (N = 94,015) on demographic characteristics, reason for Medicare eligibility, and SUD history. MAIN MEASURES: SUD-related ED/IPH (overall and substance-specific) were obtained from in-/outpatient VA health services and CMS data within the year following release date/index date (through September 30, 2018). Overdose death within 1 year was identified using the National Mortality Data Repository. Fine-Gray proportional hazards regression compared risk of SUD-related ED/IPH and overdose death between the two groups. RESULTS: The number of SUD-related ED/IPHs and overdose deaths was 2470 (13.1%) and 72 (0.38%) in the reentry sample versus 4402 (4.7%) and 198 (0.21%) in the never-incarcerated sample, respectively. Mid-to-late-life reentry was associated with higher risk of any SUD-related ED/IPH (13,136.2 vs. 2252.8 per 100,000/year; adjusted hazard ratio [AHR] = 2.19; 95% confidence interval [CI] = 2.08, 2.30) and overdose death (382.9 vs. 210.6 per 100,000/year; AHR = 2.24, 95% CI = 1.63, 3.08). CONCLUSIONS: Older reentry veterans have more than double the risk of experiencing SUD-related ED/IPH (overall and substance-specific) and overdose death, even after accounting for SUD history and other likely confounders. These findings highlight the vulnerability of this population. Improved knowledge regarding SUD-related negative health outcomes may help to tailor VA reentry programming.

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.

Association of Race, Ethnicity, Education, and Neighborhood Context With Dementia Prevalence and Cognitive Impairment Severity Among Older Adults Receiving Medicaid-Funded Home and Community-Based Services.

OBJECTIVE: While racial, ethnic, and socioeconomic group disparities in cognitive impairment and dementia prevalence are well-documented among community-dwelling older adults, little is known about these disparity trends among older adults receiving Medicaid-funded home- and community-based services (HCBS) in lieu of nursing home admission. The authors determined how dementia prevalence and cognitive impairment severity compare by race, ethnicity, educational attainment, and neighborhood context in a Medicaid HCBS population. DESIGN/SETTING: A cross-sectional study in Connecticut. PARTICIPANTS: Adults age ≥65 in the HCBS program, January-March 2019 (N = 3,520). MEASUREMENTS: The data source was Connecticut's HCBS program Universal Assessment tool. The authors employed two outcomes: Cognitive Performance Scale (CPS2), a 9-point measure ranging from cognitively intact-very severe impairment; and presence or not of either diagnosed dementia or CPS2 score ≥4 (major impairment). Neighborhood context was measured using the Social Vulnerability Index (SVI). RESULTS: Cohort characteristics: 75.7% female; mean(SD) age = 79.1(8.2); Non-Hispanic White = 47.8%; Hispanic = 33.6%; Non-Hispanic Black = 15.9%. Covariate-adjusted multivariate analyses revealed no dementia/major impairment prevalence differences among White, Black, and Hispanic individuals, but impairment severity was greater among Hispanic participants (b = 0.22; p = 0.02). People with more than HS education had less severe impairment (b = -0.12; p <0.001) and lower likelihood of dementia/major impairment (AOR = 0.61; p <0.001). Dementia/major impairment likelihood and impairment severity were greater in less socially vulnerable neighborhoods. CONCLUSION: Racial and ethnic group differences in cognitive impairment are less pronounced in Medicaid-funded HCBS cohorts than in other community-dwelling older adult cohorts. SVI results suggest that, among other possible explanations, older adults with dementia may move to lower social vulnerability neighborhoods where supportive family members reside.

Life-Course Brain Health as a Determinant of Late-Life Mental Health: American Association for Geriatric Psychiatry Expert Panel Recommendations.

This position statement of the Expert Panel on Brain Health of the American Association for Geriatric Psychiatry (AAGP) emphasizes the critical role of life course brain health in shaping mental well-being during the later stages of life. Evidence posits that maintaining optimal brain health earlier in life is crucial for preventing and managing brain aging-related disorders such as dementia/cognitive decline, depression, stroke, and anxiety. We advocate for a holistic approach that integrates medical, psychological, and social frameworks with culturally tailored interventions across the lifespan to promote brain health and overall mental well-being in aging adults across all communities. Furthermore, our statement underscores the significance of prevention, early detection, and intervention in identifying cognitive decline, mood changes, and related mental illness. Action should also be taken to understand and address the needs of communities that traditionally have unequal access to preventive health information and services. By implementing culturally relevant and tailored evidence-based practices and advancing research in geriatric psychiatry, behavioral neurology, and geroscience, we can enhance the quality of life for older adults facing the unique challenges of aging. This position statement emphasizes the intrinsic link between brain health and mental health in aging, urging healthcare professionals, policymakers, and a broader society to prioritize comprehensive strategies that safeguard and promote brain health from birth through later years across all communities. The AAGP Expert Panel has the goal of launching further activities in the coming months and years.

Neuroimaging features of depression-frailty phenotype in older adults: a pilot study.

OBJECTIVE: Frailty and late-life depression (LLD) often coexist and share several structural brain changes. We aimed to study the joint effect LLD and frailty have on brain structure. DESIGN: Cross-sectional study. SETTING: Academic Health Center. PARTICIPANTS: Thirty-one participants (14 LLD+Frail and 17 Never-depressed+Robust). MEASUREMENT: LLD was diagnosed by a geriatric psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition for single episode or recurrent major depressive disorder without psychotic features. Frailty was assessed using the FRAIL scale (0-5), classifying subjects as robust (0), prefrail (1-2), and frail (3-5). Participants underwent T1-weighted magnetic resonance imaging in which covariance analysis of subcortical volumes and vertex-wise analysis of cortical thickness values were performed to access changes in grey matter. Participants also underwent diffusion tensor imaging in which tract-based spatial statistics was used with voxel-wise statistical analysis on fractional anisotropy and mean diffusion values to assess changes in white matter (WM). RESULTS: We found a significant difference in mean diffusion values (48,225 voxels; peak voxel: pFWER=0.005, MINI coord. (X,Y,Z) = -26,-11,27) between the LLD-Frail group and comparison group. The corresponding effect size (f=0.808) was large. CONCLUSION: We showed the LLD+Frailty group is associated with significant microstructural changes within WM tracts compared to Never-depressed+Robust individuals. Our findings indicate the possibility of a heightened neuroinflammatory burden as a potential mechanism underlying the co-occurrence of both conditions and the possibility of a depression-frailty phenotype in older adults.

Comparison of Long-Term Efficacy and Safety of Esketamine Nasal Spray Plus Oral Antidepressant in Younger Versus Older Patients With Treatment-Resistant Depression: Post-Hoc Analysis of SUSTAIN-2, a Long-Term Open-Label Phase 3 Safety and Efficacy Study.

BACKGROUND: Older, compared with younger, patients with treatment-resistant depression (TRD) typically have lower response and remission rates with poorer tolerability to antidepressant treatment. This post-hoc analysis compared outcomes following treatment with esketamine nasal spray (ESK) between younger (18-64 years) and older (≥65 years) patients with TRD. METHODS: SUSTAIN-2, an up to 1-year open-label safety and efficacy study of ESK plus an oral antidepressant, included patients with TRD either directly enrolled (≥18-year) or transferred from a phase 3 double-blind study, TRANSFORM-3 (≥65-year). Patients were treated in two phases: 4-week induction and 48-week optimization/maintenance. RESULTS: Younger (n = 624) and older (n = 178) patients had similar baseline characteristics except for hypertension history (21.5% versus 48.3%, respectively). Patients (younger versus older) had similar mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores and mean (SD) reductions in MADRS total scores for induction (-18.0 [7.19] versus -18.1 [9.37]; p = 0.492 [t = 0.69, df = 701]) and optimization/maintenance (week 12) (-19.9 [7.03] versus -22.2 [9.50]; p = 0.265 [t = -1.12, df = 3470]) phases. Treatment-emergent adverse events (TEAEs) reported in younger versus older patients, respectively, were: induction, 86.1% versus 74.8%; optimization/maintenance, 86.8% versus 81.0%; serious TEAEs: induction, 2.2% versus 1.9%; optimization/maintenance, 6.7% versus 4.8%; TEAEs of increased blood pressure: induction, 6.9% versus 6.5%; optimization/maintenance, 7.1% versus 9.5%; and falls: induction, 0.3% versus 0.6%; optimization/maintenance, 0.2% versus 0.8%. Cognitive tests did not show clinically meaningful differences between the age groups. CONCLUSIONS: Although limited by the open-label design of SUSTAIN-2, this post-hoc analysis showed generally comparable improvement in depression between ESK-treated younger and older adult patients with TRD, with consistent safety outcomes.

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.

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.

Effects of physical exercise on the aging brain across imaging modalities: A meta-analysis of neuroimaging studies in randomized controlled trials.

BACKGROUND: Physical exercise is effective in protecting against age-related neurodegeneration and cognitive decline. Although there are many neuroimaging studies to evaluate the effect of physical exercise on aging brains, consistent conclusions are limited due to the wide variety of measuring techniques and small sample sizes. OBJECTIVE: Identify brain regions that show exercise-induced neuroplasticity consistently across various imaging modalities and correlate regional neuroplasticity with cognitive changes in older adults. METHODS: An electronic literature search for randomized controlled trials with magnetic resonance imaging measures was performed. We conducted a series of quantitative meta-analyses using activation likelihood estimation on included studies with voxel-based neuroimaging findings. Nonvoxelbased findings were summarized as a descriptive review. RESULTS: Out of 839 publications identified from the literature search, 30 experiments including 2670 participants from 22 papers met the criteria of meta-analyses. Overall, physical exercise consistently results in structural and functional changes in the hippocampus/parahippocampusl area and a cluster within the cerebellum. Although changes of medial/superior prefrontal cortex did not pass the stringent threshold, they were associated with cognitive changes. CONCLUSIONS: This study highlights the effectiveness of physical exercise in inducing hippocampus plasticity, which may be crucially relevant for maintaining memory function in older adults.

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.

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.

Associations of loneliness with risk of Alzheimer's disease dementia in the Framingham Heart Study.

INTRODUCTION: The relationship between persistent loneliness and Alzheimer's disease (AD) is unclear. We examined the relationship between different types of mid-life loneliness and the development of dementia and AD. METHODS: Loneliness was assessed in cognitively normal adults using one item from the Center for Epidemiologic Studies Depression Scale. We defined loneliness as no loneliness, transient loneliness, incident loneliness,or persistent loneliness, and applied Cox regression models and Kaplan-Meier plots with dementia and AD as outcomes (n = 2880). RESULTS: After adjusting for demographics, social network, physical health, and apolipoprotein E ε4, persistent loneliness was associated with higher (hazard ratio [HR], 1.91; 95% confidence interval [CI] 1.25-2.90; P < .01), and transient loneliness with lower (HR, 0.34; 95% CI 0.14-0.84; P < .05), risk of dementia onset, compared to no loneliness. Results were similar for AD risk. DISCUSSION: Persistent loneliness in mid-life is an independent risk factor for dementia and AD, whereas recovery from loneliness suggests resilience to dementia risk.

Ethical and Logistical Considerations of Caring for Older Adults on Inpatient Psychiatry During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has brought challenges to delivery of care for older adults on inpatient psychiatry. We describe two cases: patient A, a 62-year-old woman who initially refused screening for potential COVID-19, bringing up questions about threshold for capacity when public health is at risk and questions about whether screening for infection should be different in older adults. The other case, patient B, is that of an 83-year-old man who was on the unit when patient A tested positive, and brought up concerns for risk of dissemination in the context of wandering, spitting behaviors, and inability to adhere to room isolation or masking measures. We review measures taken to decrease risk of transmission and improve screening for infection in older adults.

Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3.

BACKGROUND: Elderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment. METHODS: This phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Analyses included a preplanned analysis by age (65-74 versus ≥75 years) and post-hoc analyses including age at depression onset. RESULTS: For the primary endpoint, the median-unbiased estimate of the treatment difference (95% CI) was -3.6 (-7.20, 0.07); weighted combination test using MMRM analyses z = 1.89, two-sided p = 0.059. Adjusted mean (95% CI) difference for change in MADRS score between treatment groups was -4.9 (-8.96, -0.89; t = -2.4, df = 127; two-sided nominal p = 0.017) for patients 65 to 74 years versus -0.4 (-10.38, 9.50; t = -0.09, two-sided nominal p = 0.930) for those ≥75 years, and -6.1 (-10.33, -1.81; t = -2.8, df = 127; two-sided nominal p = 0.006) for patients with depression onset <55 years and 3.1 (-4.51, 10.80; t = 0.8, two-sided nominal p = 0.407) for those ≥55 years. Patients who rolled over into the long-term open-label study showed continued improvement with esketamine following 4 additional treatment weeks. CONCLUSIONS: Esketamine/antidepressant did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen for younger patients (65-74 years) and patients with earlier onset of depression (<55 years).

Major depressive disorder and impaired health-related quality of life among US older adults.

OBJECTIVES: To examine the association of current and past major depressive disorder (MDD) and measures of health-related quality of life (HRQOL) in a nationally representative sample of older adults. METHODS: Cross-sectional analysis of the 2012 to 2013 National Epidemiological Survey on Alcohol and Related Conditions Wave III (NESARC-III) was used. NESARC-III is a nationally representative health interview survey on substance use and mental health in the US, and we limited our sample to survey respondents aged 65 or older (n = 5806 unweighted). Using DSM-5 criteria, we identified older adults with current MDD, past MDD (ie, prior but not current MDD), and no history of MDD. Using standardized algorithms, we also constructed HRQOL measures: mental component summary (MCS), physical component summary (PCS), and quality-adjusted life years (QALYs). We performed multivariable-adjusted linear regression analyzes to assess the associations of MDD types with HRQOL measures while adjusting for socio-demographics and clinical co-morbidities. RESULTS: Overall, 14.4% of the older adults, representative of 6.0 million nationwide, met criteria for lifetime MDD. About 2.2 million older adults (5.4%) had current MDD and 3.7 million older adults (9.0%) had past MDD. Older adults with current or past MDD had a moderate difference in HRQOL measures compared with never depressed (Cohen's d measures ranging from -1.02 to -0.07). When controlling for other covariates, MCS and QALYs measures were lowest in the current MDD group. CONCLUSION: Current MDD is associated with significantly lower HRQOL than never MDD, while adults with past MDD had minor (often insignificant) residual impairment in HRQOL.

Electrophoresis of megaDalton proteins inside colloidal silica.

With the growth of the biopharmaceutical industry, there is a need for rapid size-analysis of proteins on the megaDalton scale. The large pore sizes needed for such separations cannot be easily reached by pushing the current limits of size-exclusion chromatography or gel electrophoresis. The concept detailed here is the formation of arbitrarily wide pores by packing nonporous colloidal silica in capillaries. This method can be called packed-capillary electrophoresis, or "pCE". Electrophoresis of protein standards (11-155 kDa) by pCE, using 345 nm diameter particles in 100 µm diameter capillaries, gives 2x higher resolution than a typical PAGE gel in 1/6 of the time. The electropherograms show that pCE is highly efficient, with half-micrometer plate heights for all seven standards, giving 105 plates for a 50 mm length. The large pore radius of 65 nm enables baseline resolution of proteins of 0.72, 1.048 and 1.236 MDa in less than 15 min. The short separation time of pCE is attributed to the absence of small pores that restrict protein migration in gels. The pCE separation is applied to the analysis of a stressed pharmaceutical-grade IgG4 sample, giving unprecedented baseline resolution of monomer, dimer, trimer and tetramer in less than 10 min.

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.