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Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) accompanied by cerebrovascular risk factors (CVRFs) are known to increase the risk of developing dementia. Mind-body practices such as yoga and meditation, have been recognized as safe techniques with beneficial effects on cognitive functions in older adults at risk for cognitive decline. We conducted a randomized, controlled trial to assess the efficacy of Kundalini yoga training (KY) compared to memory enhancement training (MET) on mood and cognitive functioning in a group of older women with CVRFs and SCD (clinicaltrials.gov = NCT03503669). The KY intervention consisted of weekly, 60-min in-person classes with a certified instructor for 12 weeks, with a 12-min guided recording for daily homework practice at home. MET involved 12 weekly in-person group classes with 12-min daily homework exercises. Objective and subjective memory performance were the primary outcomes. Peripheral whole blood samples were collected at baseline, 12-weeks, and 24-weeks follow-up for RNA sequencing and cytokine/chemokine assays. A total of 79 patients (KY = 40; MET = 39) were randomized, and 63 completed the 24-week follow-up (KY = 65% completion rate; MET = 95%; χ2(1) = 10.9, p

BACKGROUND: Social connections have a significant impact on health across age groups, including older adults. Loneliness and social isolation are known risk factors for Alzheimers disease and related dementias (ADRD). Yet, we did not find a review focused on meta-analyses and systematic reviews of studies that had examined associations of social connections with cognitive decline and trials of technology-based and other social interventions to enhance social connections in people with ADRD. STUDY DESIGN: We conducted a scoping review of 11 meta-analyses and systematic reviews of social connections as possible determinants of cognitive decline in older adults with or at risk of developing ADRD. We also examined eight systematic reviews of technology-based and other social interventions in persons with ADRD. STUDY RESULTS: The strongest evidence for an association of social connections with lower risk of cognitive decline was related to social engagement and social activities. There was also evidence linking social network size to cognitive function or cognitive decline, but it was not consistently significant. A number of, though not all, studies reported a significant association of marital status with risk of ADRD. Surprisingly, evidence showing that social support reduces the risk of ADRD was weak. To varying degrees, technology-based and other social interventions designed to reduce loneliness in people with ADRD improved social connections and activities as well as quality of life but had no significant impact on cognition. We discuss strengths and limitations of the studies included. CONCLUSIONS: Social engagement and social activities seem to be the most consistent components of social connections for improving cognitive health among individuals with or at risk for ADRD. Socially focused technology-based and other social interventions aid in improving social activities and connections and deserve more research.

Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions.

Approximately 7% of COVID-19 patients (1.3% children) have exhibited symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC), or Long COVID, and 20% of those present with neuropsychiatric symptoms. While a large number of MRI-based neuroimaging studies in this population have shown cortical atrophy in terms of gray matter volume and cortical thickness in patients, there is a growing body of work showing brain volume enlargements or thickness increases in patients compared to COVID negative controls. To investigate this further, we used structural magnetic resonance imaging (MRI) to examine differences in gray matter thickness for the cortical limbic and the dorsolateral prefrontal cortical regions between patients with Long COVID and healthy controls. Results showed increased cortical thickness in the caudal anterior, isthmus, and the posterior cingulate gyrus as well as the rostral middle frontal gyrus respectively along with higher gray matter volume in the posterior cingulate and the isthmus cingulate in patients with Long COVID. Cortical thickness and gray matter volumes for regions of interest (ROIs) were also associated with the severity measures, clinical dementia rating, and anxiety scores in the Long COVID group. Our findings provide supporting evidence for cortical hypertrophy in Long COVID.

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. RESULTS: In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. CONCLUSIONS: In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).

OBJECTIVE: Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. METHODS: In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition. RESULTS: Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohens d = 0.61), and these improvements were sustained in the continuation phase. CONCLUSION: This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

BackgroundUnderlying inflammation is associated with an increased risk of depression in older adults. In this study, we examined the role of inflammatory biomarkers in antidepressant response in depressed older adults undergoing adjunct Tai Chi Chih (TCC) or Health education interventions.MethodsOlder adults aged 60 years and above with a diagnosis of major depression were randomized to 12 weeks of TCC versus Health and Wellness Education (HEW) as an adjunct therapy to their stable antidepressant treatment regimen. A panel of 19 cytokine/chemokines was measured at baseline and 12 weeks. Five factors were derived using factor analysis. General linear models were estimated to examine the change in factor scores and the association of these changes on depression remission rates, controlling for age, sex, and body mass index.ResultsOf the 170 randomized participants (TCC: n = 85 and HEW: n = 85), 55 TCC and 58 HEW completed the 3-month assessment. The groups did not differ at baseline in any measure. At follow-up, neither the changes in cytokine/chemokines scores nor the depression remission rate differed significantly between TCC and HEW. However, remitters and non-remitters differed significantly in changes in a factor composed of growth-regulated oncogene protein-alpha (GRO-alpha), epidermal growth factor (EGF), and soluble CD40 ligand (sCD40L). GRO-alpha and EGF levels (in both groups) were significantly increased in remitters compared to non-remitters.ConclusionChanges in certain cytokines/chemokines may accompany improvement in depressive symptoms in older adults. Future studies will need to explore the role of these molecules in remission of late-life depression.

BackgroundYoga may be an ideal early intervention for those with modifiable risk factors for Alzheimer's disease (AD) development.ObjectiveTo examine the effects of Kundalini yoga (KY) training versus memory enhancement training (MET) on the resting-state connectivity of hippocampal subregions in women with subjective memory decline and cardiovascular risk factors for AD.MethodsParticipants comprised women with subjective memory decline and cardiovascular risk factors who participated in a parent randomized controlled trial (NCT03503669) of 12-weeks of KY versus MET and completed pre- and post-intervention resting-state magnetic resonance imaging scans (yoga: n = 11, age = 61.45±6.58 years; MET: n = 11, age = 64.55±6.41 years). Group differences in parcellated (Cole-anticevic atlas) hippocampal connectivity changes (post- minus pre-intervention) were evaluated by partial least squares analysis, controlling for age. Correlations between hippocampal connectivity and perceived stress and frequency of forgetting (assessed by questionnaires) were also evaluated.ResultsA left anterior hippocampal subregion assigned to the default mode network (DMN) in the Cole-anticevic atlas showed greater increases in connectivity with largely ventral visual stream regions with KY than with MET (p

ObjectivesTwo-thirds of individuals living with Alzheimer's disease are women. Declining estrogen levels influence mood and cognition. Cumulative lifetime estrogen exposure (CLEE) correlates with cognition later in life. We examined the relationship of CLEE to depression and cognition in older women with major depression compared to non-depressed women.DesignOlder women (age ≥60 years) with depression were compared to non-depressed women using a lifetime estrogen exposure questionnaire. CLEE was defined as combined durations of reproductive span (age of menopause minus age of menarche) and any post-menopausal hormone replacement therapy use. Higher vs lower CLEE groups were based on a median of 474 months of estrogen exposure.SettingUniversity hospital outpatient research program.Participants135 women ≥60 years; 64 depressed and 71 non-depressed.MeasurmentsParticipants completed a comprehensive cognitive test battery. General linear models were used to examine the association between cognitive domain scores and CLEE in depressed and non-depressed women, controlling for age, education, and ethnicity.ResultsDepressed and non-depressed groups had significantly different levels of CLEE, measured in months: mean 495.7 (SD 108.6) vs 456.4 (SD 66.0) months, F(1,130) = 5.01, p = .03. Within the non-depressed participants, higher CLEE was associated with improved delayed recall (F(1,59) = 5.94, p = .02, effect size = .61), while no such relationship was observed in the depressed group.ConclusionHigher CLEE was associated with improvement in delayed recall among non-depressed, but not among depressed participants. This suggests a protective role of estrogen on memory in non-depressed older postmenopausal women. Further research should examine the role of the CLEE in antidepressant response and cognitive decline.

BackgroundAs an adjunct to antidepressant treatment, Tai Chi Chih (TCC) is superior to health education and wellness (HEW) training in improving the general health of patients with geriatric depression (GD). This study investigated the brain connectivity changes associated with TCC and HEW in combination with antidepressant treatment in patients with GD.MethodsForty patients with GD under stable antidepressant treatment underwent TCC training (n = 21) or HEW training (n = 19) for 12 weeks, and completed baseline and 3-month follow-up resting state magnetic resonance imaging scans. Within-group and between-group differences in parcel-to-parcel connectivity changes with intervention were evaluated by general linear modeling. Relationships between significant connectivity changes and symptom/resilience improvement were evaluated by partial least squares correlation analysis.ResultsSignificantly greater increases in connectivity with TCC than with HEW (FDR-corrected p

Abstract Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) accompanied by cerebrovascular risk factors (CVRFs) are known to increase the risk of developing dementia. Mind-body practices such as yoga and meditation, have been recognized as safe techniques with beneficial effects on cognitive functions in older adults at risk for cognitive decline. We conducted a randomized, controlled trial to assess the efficacy of Kundalini yoga training (KY) compared to memory enhancement training (MET) on mood and cognitive functioning in a group of older women with CVRFs and SCD (clinicaltrials.gov = NCT03503669). The KY intervention consisted of weekly, 60-min in-person classes with a certified instructor for 12 weeks, with a 12-min guided recording for daily homework practice at home. MET involved 12 weekly in-person group classes with 12-min daily homework exercises. Objective and subjective memory performance were the primary outcomes. Peripheral whole blood samples were collected at baseline, 12-weeks, and 24-weeks follow-up for RNA sequencing and cytokine/chemokine assays. A total of 79 patients (KY = 40; MET = 39) were randomized, and 63 completed the 24-week follow-up (KY = 65% completion rate; MET = 95%; χ2(1) = 10.9, p

Purpose of reviewIntegrative medicine is the practice of combining conventional medical treatments with "alternative" or "complementary" therapies. Integrative psychiatry is a holistic, person-centered approach to neuropsychiatric disorders that emphasizes a person's physical, emotional, interpersonal, behavioral, nutritional, environmental, and spiritual dimensions to achieve well-being. Older adults are more prone to physical injury, interpersonal loss, chronic illnesses, and physical and cognitive decline that can manifest as anxiety, depression, with functional decline and inability to care for self. Additionally, stress of caring for older adults with dementia can adversely affect caregivers' health. Although integrative approaches are perceived as safer and less stigmatizing, it is important to understand the risks and benefits of such therapies for older adults with neurocognitive disorders and their caregivers.Recent findingsHere, we summarize the results of the recent clinical trials and meta-analyses that provide evidence for integrative approaches to treating older adults with cognitive disorders and their caregivers which include the use of diet and supplements, and mind-body therapies. Dietary and mind-body therapies have become increasingly popular and show the strongest evidence of effectiveness for cognitive disorders and caregiver stress. Vitamins and supplements are the most popular integrative intervention, but there is mixed evidence supporting their use and the concern for herb (supplement)-drug interactions. While there is increasing popularity of integrative treatments, information to guide clinicians providing care for older adults remains limited, with variable scientific rigor of the available RCTs for a large number of commonly used integrative interventions particularly for cognitive disorders and caregiver stress and well-being.

ObjectivesDefault mode network (DMN) connectivity is altered in depression. We evaluated the relationship between changes in within-network DMN connectivity and improvement in depression in a subsample of our parent clinical trial comparing escitalopram/memantine (ESC/MEM) to escitalopram/placebo (ESC/PBO) in older depressed adults (NCT01902004).MethodsTwenty-six participants with major depression (age > 60 years) and subjective memory complaints underwent treatment with ESC/MEM (n = 13) or ESC/PBO (n = 13), and completed baseline and 3-month follow-up resting state magnetic resonance imaging scans. Multi-block partial least squares correlation analysis was used to evaluate the impact of treatment on within-network DMN connectivity changes and their relationship with symptom improvement at 3 months (controlling for age and sex).ResultsA significant latent variable was identified, reflecting within-network DMN connectivity changes correlated with symptom improvement (p = .01). Specifically, although overall group differences in within-network DMN connectivity changes failed to reach significance, increased within-network connectivity of posterior/lateral DMN regions (precuneus, angular gyrus, superior/middle temporal cortex) was more strongly and positively correlated with symptom improvement in the ESC/MEM group (r = 0.97, 95% confidence interval: 0.86-0.98) than in the ESC/PBO group (r = 0.36, 95% confidence interval: 0.13-0.72).ConclusionsIncreased within-network connectivity of core DMN nodes was more strongly correlated with depressive symptom improvement with ESC/MEM than with ESC/PBO, supporting an improved engagement of brain circuitry implicated in the amelioration of depressive symptoms with combined ESC/MEM treatment in older adults with depression and subjective memory complaints.

ObjectivesGeriatric depression is difficult to treat and frequently accompanied by treatment resistance, suicidal ideations and polypharmacy. New adjunctive mind-body treatment strategies can improve clinical outcomes in geriatric depression and reduce risk for side-effects of pharmacological treatments.MethodsWe conducted a 3-month randomized controlled trial to assess the efficacy and tolerability of combining Tai Chi Chih (TCC) or Health Education and Wellness training (HEW) with the stable standard antidepressant treatment on mood and cognitive functioning in depressed older adults (NCT02460666). Primary outcome was change in depression as assessed by the Hamilton Rating Scale for Depression (HAM-D) post-treatment. Remission was defined as HAM-D ≤ 6; naturalistic follow-up continued for 6 months. We also assessed psychological resilience, health-related quality of life and cognition.ResultsOf the 178 randomized participants, 125 completed the 3-month assessment and 117 completed the 6-month assessment. Dropout and tolerability did not differ between groups. Remission rate within TCC was 35.5% and 33.3%, compared to 27.0% and 45.8% in HEW, at 3 and 6 months respectively (χ2(1) = 1.0, p = 0.3; χ2(1) = 1.9, p =0.2). Both groups improved significantly on the HAM-D at 3 and 6 months. TCC demonstrated a greater improvement in general health compared to HEW.ConclusionsBoth TCC and HEW combined with a standard antidepressant treatment improved symptoms of depression in older adults. While TCC was superior to HEW in improving general health, we did not find group differences in improvement in mood and cognition.

Growing evidence supports the concept that bidirectional brain-gut microbiome interactions play an important mechanistic role in aging, as well as in various neuropsychiatric conditions including depression. Gray matter volume (GMV) deficits in limbic regions are widely observed in geriatric depression (GD). We therefore aimed to explore correlations between gut microbial measures and GMV within these regions in GD. Sixteen older adults (>60 years) with GD (37.5% female; mean age, 70.6 (SD = 5.7) years) were included in the study and underwent high-resolution T1-weighted structural MRI scanning and stool sample collection. GMV was extracted from bilateral regions of interest (ROI: hippocampus, amygdala, nucleus accumbens) and a control region (pericalcarine). Fecal microbiota composition and diversity were assessed by 16S ribosomal RNA gene sequencing. There were significant positive associations between alpha diversity measures and GMV in both hippocampus and nucleus accumbens. Additionally, significant positive associations were present between hippocampal GMV and the abundance of genera Family_XIII_AD3011_group, unclassified Ruminococcaceae, and Oscillibacter, as well as between amygdala GMV and the genera Lachnospiraceae_NK4A136_group and Oscillibacter. Gut microbiome may reflect brain health in geriatric depression. Future studies with larger samples and the experimental manipulation of gut microbiome may clarify the relationship between microbiome measures and neuroplasticity.

Causes for genomic and morphological similarities among recently radiated species are often multifaceted and are further convoluted among species that readily interbreed. Here, we couple genomic and morphological trait comparisons to test the extent that ancestry and gene flow explain the retention of mallard-like traits within a sister species, the Mexican duck. First, we confirm that these taxa remain genetically structured, and that Mexican ducks exhibit an isolation-by-distance pattern. Despite the assumption of wide-spread hybridization, we found only a few late-stage hybrids, all from the southwestern USA. Next, assessing 23 morphological traits, we developed a genetically-vetted morphological key that is > 97% accurate in distinguishing across sex-age cohorts of Mexican ducks, mallards, and hybrids. During key development, we determined that 25% of genetically pure, immature male Mexican ducks of the northern population naturally displayed mallard-like traits in their formative plumage. In fact, applying this key to 55 museum specimens, we identified that only four of the 14 specimens originally classified as phenotypic hybrids were truly hybrids. We discuss how genomic and morphological comparisons shed light into the mechanism(s) underlying the evolution of complex phenotypic traits in recent radiations, and how misunderstanding the true morphological diversity within Mexican ducks resulted in taxonomic revisions that hindered conservation efforts.

BackgroundFemale sex, subjective cognitive decline (SCD), and cardiovascular risk factors (CVRFs) are known risk factors for developing Alzheimer's disease (AD). We previously demonstrated that yoga improved depression, resilience, memory and executive functions, increased hippocampal choline concentrations, and modulated brain connectivity in older adults with mild cognitive impairment.ObjectiveIn this study (NCT03503669), we investigated brain gray matter volume (GMV) changes in older women with SCD and CVRFs following three months of yoga compared to memory enhancement training (MET).MethodsEleven women (mean age = 61.45, SD = 6.58) with CVRF and SCD completed twelve weeks of Kundalini Yoga and Kirtan Kriya (KY + KK) while eleven women (mean age = 64.55, SD = 6.41) underwent MET. Anxiety, resilience, stress, and depression were assessed at baseline and 12 weeks, as were T1-weighted MRI scans (Siemens 3T Prisma scanner). We used Freesurfer 6.0 and tested group differences in GMV change, applying Monte-Carlo simulations with alpha = 0.05. Region-of-interest analysis was performed for hippocampus and amygdala.ResultsCompared to KY + KK, MET showed reductions in GMV in left prefrontal, pre- and post-central, supramarginal, superior temporal and pericalcarine cortices, right paracentral, postcentral, superior and inferior parietal cortices, the banks of the superior temporal sulcus, and the pars opercularis. Right hippocampal volume increased after yoga but did not survive corrections.ConclusionYoga training may offer neuroprotective effects compared to MET in preventing neurodegenerative changes and cognitive decline, even over short time intervals. Future analyses will address changes in functional connectivity in both groups.

SARS-CoV-2 has infected hundreds of millions of people with over four million dead, resulting in one of the worst global pandemics in recent history. Neurological symptoms associated with COVID-19 include anosmia, ageusia, headaches, confusion, delirium, and strokes. These may manifest due to viral entry into the central nervous system (CNS) through the blood-brain barrier (BBB) by means of ill-defined mechanisms. Here, we summarize the abilities of SARS-CoV-2 and other neurotropic RNA viruses, including Zika virus and Nipah virus, to cross the BBB into the CNS, highlighting the role of magnetic resonance imaging (MRI) in assessing presence and severity of brain structural changes in COVID-19 patients. We present new insight into key mutations in SARS-CoV-2 variants B.1.1.7 (P681H) and B.1.617.2 (P681R), which may impact on neuropilin 1 (NRP1) binding and CNS invasion. We postulate that SARS-CoV-2 may infect both peripheral cells capable of crossing the BBB and brain endothelial cells to traverse the BBB and spread into the brain. COVID-19 patients can be followed up with MRI modalities to better understand the long-term effects of COVID-19 on the brain.

Abstract The translocation of individuals around the world is leading to rising incidences of anthropogenic hybridization, particularly between domestic and wild congeners. We apply a landscape genomics approach for thousands of mallard (Anas platyrhynchos) samples across continental and island populations to determine the result of over a century of supplementation practices. We establish that a single domestic game-farm mallard breed is the source for contemporary release programs in Eurasia and North America, as well as for established feral populations in New Zealand and Hawaii. In particular, we identify central Europe and eastern North America as epicenters of ongoing anthropogenic hybridization, and conclude that the release of game-farm mallards continues to affect the genetic integrity of wild mallards. Conversely, self-sustaining feral populations in New Zealand and Hawaii not only show strong differentiation from their original stock, but also signatures of local adaptation occurring in less than a half-century since game-farm mallard releases have ceased. We conclude that ‘wild’ is not singular, and that even feral populations are capable of responding to natural processes. Although considered paradoxical to biological conservation, understanding the capacity for wildness among feral and feral admixed populations in human landscapes is critical as such interactions increase in the Anthropocene.

Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions.

Drugs that target glutamate neuronal transmission, such as memantine, offer a novel approach to the treatment of late-life depression, which is frequently comorbid with cognitive impairment. The results of our recently published double-blind, randomized, placebo-controlled trial of escitalopram or escitalopram/memantine in late-life depression with subjective memory complaints (NCT01902004) indicated no differences between treatments in depression remission, but additional benefits in cognition at 12-month follow-up with combination treatment. To identify pathways and biological functions uniquely induced by combination treatment that may explain cognitive improvements, we generated transcriptional profiles of remission compared with non-remission from whole blood samples. Remitters to escitalopram compared with escitalopram/memantine combination treatment display unique patterns of gene expression at baseline and 6 months after treatment initiation. Functional enrichment analysis demonstrates that escitalopram-based remission associates to functions related to cellular proliferation, apoptosis, and inflammatory response. Escitalopram/memantine-based remission, however, is characterized by processes related to cellular clearance, metabolism, and cytoskeletal dynamics. Both treatments modulate inflammatory responses, albeit via different effector pathways. Additional research is needed to understand the implications of these results in explaining the observed superior effects of combination treatment on cognition observed with prolonged treatment.

We call on geriatric brain health care providers, executives and entrepreneurs to embrace our Brain Health Living Lab model-a user-centered, iterative ecosystem, integrating concurrent clinical care, research and innovation processes.

Family dementia caregivers experience high rates of depression and anxiety that often go untreated due to time demands. We aimed to determine the feasibility of a brief, 4-week Mentalizing Imagery Therapy intervention, which couples mindfulness with guided imagery practices aimed at bolstering mentalizing capacity, to reduce caregiver psychological symptoms and to explore potential impact on dorsolateral prefrontal cortex connectivity. Twenty-four family dementia caregivers with moderate depression symptoms (a score of 10 in Patient Health Questionnaire-9) were assigned to either group Mentalizing Imagery Therapy (MIT, n = 12) or a waitlist augmented by optional relaxation exercises (n = 12). Participants completed questionnaires to measure depression and anxiety at baseline and followup, and those eligible also underwent resting state functional magnetic resonance (fMRI) brain imaging at these time points. Eleven of 12 caregivers assigned to MIT completed the intervention and attended weekly groups 98% of the time. MIT home practice logs indicated average practice of 5 ± 2 sessions per week for 23 ± 8 min per session. All participants in waitlist completed the post-assessment. MIT participants exhibited significantly greater improvement than waitlist on self-reported depression and anxiety symptoms (p

ObjectivesGeriatric depression often presents with memory and cognitive complaints that are associated with increased risk for Alzheimer's disease (AD). In a parent clinical trial of escitalopram combined with memantine or placebo for geriatric depression and subjective memory complaints, we found that memantine improved executive function and delayed recall performance at 12 months (NCT01902004). In this report, we used positron emission tomography (PET) to assess the relationship between in-vivo amyloid and tau brain biomarkers and clinical and cognitive treatment response.DesignIn a randomized double-blind placebo-controlled trial, we measured 2-(1-{6-[(2-[F18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile ([18F]FDDNP) binding at baseline and assessed mood and cognitive performance at baseline, posttreatment (6 months), and naturalistic follow-up (12 months).ParticipantsTwenty-two older adults with major depressive disorder and subjective memory complaints completed PET scans and were included in this report.ResultsAcross both treatment groups, higher frontal lobe [18F]FDDNP binding at baseline was associated with improvement in executive function at 6 months (corrected p = .045). This effect was no longer significant at 12 months (corrected p = .12). There was no association of regional [18F]FDDNP binding with change in mood symptoms (corrected p = .2).Conclusions[18F]FDDNP binding may predict cognitive response to antidepressant treatment. Larger trials are required to further test the value of [18F]FDDNP binding as a biomarker for cognitive improvement with antidepressant treatment in geriatric depression.

In this viewpoint, we present an argument for transdisciplinary "precision medicine" approaches that combine studies of basic neurobiology of breathing in animal and human models of stress that can help characterize physiological and neural biomarkers and mechanisms of breathing control and emotion regulation in humans. Such mechanistic research is fundamental for the development of more effective and mechanism-based mind-body therapies. The potential for this research to positively impact public health is high, as breathing techniques are inexpensive, accessible, and cross-culturally accepted, with fewer complications then observed with other standard therapies for stress-related disorders.

Background: Recent evidence suggests that integration of multi-modal data improves performance in machine learning prediction of depression treatment outcomes. Here, we compared the predictive performance of three machine learning classifiers using differing combinations of sociodemographic characteristics, baseline clinical self-reports, cognitive tests, and structural magnetic resonance imaging (MRI) features to predict treatment outcomes in late-life depression (LLD). Methods: Data were combined from two clinical trials conducted with depressed adults aged 60 and older, including response to escitalopram (N = 32, NCT01902004) and Tai Chi (N = 35, NCT02460666). Remission was defined as a score of 6 or less on the 24-item Hamilton Rating Scale for Depression (HAMD) at the end of 24 weeks of treatment. Features subsets were constructed from baseline sociodemographic and clinical features, gray matter volumes (GMVs), or both. Three classification algorithms were compared: (1) Support Vector Machine-Radial Bias Function (SVMRBF), (2) Random Forest (RF), and (3) Logistic Regression (LR). A repeated 5-fold cross-validation approach with a wrapper-based feature selection method was used for model fitting. Model performance metrics included Area under the ROC Curve (AUC) and Matthews correlation coefficient (MCC). Cross-validated performance significance was tested by permutation analysis. Classifiers were compared by Cochran's Q and post-hoc pairwise comparisons using McNemar's Chi-Square test with Bonferroni correction. Results: For the RF and SVMRBF algorithms, the combined feature set outperformed the clinical and GMV feature sets with a final cross-validated AUC of 0.83 ± 0.11 and 0.80 ± 0.11, respectively. Both classifiers passed permutation analysis. The LR algorithm performed best using GMV features alone (AUC 0.79 ± 0.14) but failed to pass permutation analysis using any feature set. Performance of the three classifiers differed significantly for all three features sets. Important predictive features of treatment response included anterior and posterior cingulate volumes, depression characteristics, and self-reported health-related quality scores. Conclusion: This preliminary exploration into the use of ML and multi-modal data to identify predictors of general treatment response in LLD indicates that integration of clinical and structural MRI features significantly increases predictive capability. Identified features are among those previously implicated in geriatric depression, encouraging future work in this arena.

Affective computing (also referred to as artificial emotion intelligence or emotion AI) is the study and development of systems and devices that can recognize, interpret, process, and simulate emotion or other affective phenomena. With the rapid growth in the aging population around the world, affective computing has immense potential to benefit the treatment and care of late-life mood and cognitive disorders. For late-life depression, affective computing ranging from vocal biomarkers to facial expressions to social media behavioral analysis can be used to address inadequacies of current screening and diagnostic approaches, mitigate loneliness and isolation, provide more personalized treatment approaches, and detect risk of suicide. Similarly, for Alzheimer's disease, eye movement analysis, vocal biomarkers, and driving and behavior can provide objective biomarkers for early identification and monitoring, allow more comprehensive understanding of daily life and disease fluctuations, and facilitate an understanding of behavioral and psychological symptoms such as agitation. To optimize the utility of affective computing while mitigating potential risks and ensure responsible development, ethical development of affective computing applications for late-life mood and cognitive disorders is needed.

Dementia prevention interventions that address modifiable risk factors for dementia require extensive lifestyle and behavior changes. Strategies are needed to enhance engagement and personalization of the experience at a population level. Precision Population Brain Health aims to improve brain health across the lifespan at a population level. Psychographic segmentation is a core component of Precision Population Brain Health with untapped potential. Psychographic segmentation applies behavioral and social sciences to understanding people's motivations, values, priorities, decision making, lifestyles, personalities, communication preferences, attitudes, and beliefs. Integrating psychographic segmentation into dementia care could provide a more personalized care experience and increased patient engagement, leading to improved health outcomes and reduced costs. Psychographic segmentation can enhance patient engagement for dementia and shift the clinical paradigm from "What is the matter?" to "What matters to you?" Similar benefits of psychographic segmentation can be provided for dementia caregivers. Developing dementia prevention programs that integrate psychographic segmentation could become the basis for creating a shared framework for prevention of non-communicable diseases and brain health disorders at a population level. Integrating psychographic segmentation into digital health tools for dementia prevention programs is especially critical to overcome current suboptimal approaches. Applying psychographic segmentation to dementia prevention has the potential to help people feel a sense of empowerment over their health and improve satisfaction with their health experience-creating a culture shift in the way brain health is approached and paving the way toward Precision Population Brain Health.

Background and objectivesWomen who breastfeed may experience long-term benefits for their health in addition to the more widely appreciated effects on the breastfed child. Breastfeeding may induce long-term effects on biopsychosocial systems implicated in brain health. Also, due to diminished breastfeeding in the postindustrial era, it is important to understand the lifespan implications of breastfeeding for surmising maternal phenotypes in our species' collective past. Here, we assess how women's breastfeeding history relates to postmenopausal cognitive performance.MethodologyA convenience sample of Southern California women age 50+ was recruited via two clinical trials, completed a comprehensive neuropsychological test battery and answered a questionnaire about reproductive life history. General linear models examined whether cognitive domain scores were associated with breastfeeding in depressed and non-depressed women, controlling for age, education and ethnicity.ResultsWomen who breastfed exhibited superior performance in the domains of Learning, Delayed Recall, Executive Functioning and Processing Speed compared to women who did not breastfeed (P-values 0.0003-0.015). These four domains remained significant in analyses limited to non-depressed and parous subsets of the cohort. Among those depressed, only Executive Functioning and Processing Speed were positively associated with breastfeeding.Conclusions and implicationsWe add to the growing list of lifespan health correlates of breastfeeding for women's health, such as the lower risk of type-2 diabetes, cardiovascular disease and breast cancer. We surmise that women's postmenopausal cognitive competence may have been greater in past environments in which breastfeeding was more prevalent, bolstering the possibility that postmenopausal longevity may have been adaptive across human evolutionary history.Lay summaryBreastfeeding may affect women's cognitive performance. Breastfeeding's biological effects and psychosocial effects, such as improved stress regulation, could exert long-term benefits for the mother's brain. We found that women who breastfed performed better on a series of cognitive tests in later life compared to women who did not breastfeed.

‘I have not found among my possessions anything which I hold more dear than, or value so much as, my knowledge of the actions of great people, acquired by long experience in contemporary affairs, and a continual study of antiquity.’ The Prince, Machiavelli

PurposeThe use of complementary and integrative medicine (CIM) is on the rise among diverse populations of older adults in the USA. CIM is commonly perceived as safer, less expensive, and more culturally acceptable. There is a growing body of evidence to support the use of CIM, especially mind-body therapies, diet and nutritional supplements used for mental disorders of aging.Recent findingsWe summarize the results of the recent clinical trials and meta-analyses that provide the evidence for the role of CIM in treating older adults with mood or cognitive disorders that includes the use of diet and supplements, and mind-body therapies.SummaryDietary and mind-body therapies have become increasingly popular and show the strongest evidence of efficacy for mood and cognitive disorders. Although the use of vitamins and supplements is the most popular CIM practice, only mixed evidence supports their use with additional concerns for herb (supplement)-drug interactions. Despite increasing use of CIM by the general population, information to guide clinicians providing care for older adults remains limited with variable scientific rigor of the available RCTs for a large number of commonly used CIM interventions for the mental health of older adults.

IntroductionGeriatric depression is frequently accompanied by cognitive complaints and inflammation that increase risk for treatment-resistant depression and dementia. Memantine, a neuroprotective drug, can improve depression, inflammation, and help prevent cognitive decline. In our six-month clinical trial, escitalopram/memantine (ESC/MEM) improved mood and cognition compared to escitalopram/placebo treatment (ESC/PBO; NCT01902004). In this report, we examined the impact of baseline inflammation on mood and cognitive outcomes.Materials and methodsWe measured a panel of inflammatory cytokine markers using Human 38-plex magnetic cytokine/chemokine kits (EMD Millipore, HCYTMAG-60K-PX38) in 90 older adults 60 years and older with major depression enrolled in a 6-month double-blind placebo-controlled trial of escitalopram ​+ ​memantine (ESC/MEM) in depressed older adults with subjective memory complaints. Four cytokine factors were derived and linear models were estimated to examine the predictive ability of cytokine levels on treatment induced change in depression and cognition.ResultsOf the 90 randomized participants, 62 completed the 6-month follow up assessment. Both groups improved significantly on depression severity (HAM-D score), but not on cognitive outcomes at six months. Cytokine factor scores were not significantly different between ESC/MEM (n ​= ​45) and ESC/PBO (n ​= ​45) at baseline. Pro-inflammatory biomarkers at baseline predicted a decline in executive functioning in the ESC/PBO group but not in the ESC/MEM group, interaction F(1,52) ​= ​4.63, p ​= ​.04.DiscussionIn this exploratory analysis, the addition of memantine to escitalopram provided a protective effect on executive functioning in older depressed adults. Future studies are needed to replicate the association of cytokine markers to antidepressant and neuroprotective treatment-related change in cognition in geriatric depression.

BackgroundAlmost half of people living with HIV (PLWH) in the USA are over 50 years of age; this is expected to increase to 70% by 2020. Yet, few interventions exist for older PLWH that address psychological and physical symptoms combined, both prevalent in this population. There is a need to find innovative and accessible interventions that can help older PLWH to manage their symptoms. Mind-body interventions, like tai chi/qigong (TCQ), improve both physical and psychological health. TCQ is a series of slow, low-impact meditative movements that integrates breathwork, meditation, and stances.MethodsThe present study is an exploratory clinical trial that will evaluate the acceptability and feasibility of a 12-week, small group TCQ intervention (n = 24), a sham qigong control condition (n = 24), and a standard of care control condition (n = 24) for older people living with HIV/AIDS. It will also explore any preliminary associations between the TCQ intervention and symptom alleviation. Participants will be recruited from community-based health and social services organizations in Miami, FL, and randomized to one of the 3 conditions.DiscussionWe will assess feasibility and acceptability through questionnaires and adherence to TCQ. We will assess preliminary associations with symptoms such as depression, anxiety, social support, chronic HIV-related fatigue, and clinical outcomes. These will be described through proportions, means, and changes over time through graphing techniques. Outcomes will be assessed at baseline, at post-intervention, and at 3 months follow-up. These preliminary analyses also will provide information necessary to estimate effect size and power needed for a larger clinical trial.Trial registrationClinicalTrials.gov NCT03840525 . Registered on 16 July 2018.

INTRODUCTION: Numerous issues in mental health benefit from technological innovation. An example involves the mental health challenges of long-duration spaceflight (such as a Mars mission), including prolonged confinement, microgravity, and different sunlight exposure lengths. Persisting on Earth are global mental health challenges stemming from disease burdens, limited interview-based diagnostic systems, trial-and-error treatment approaches, and suboptimal access. There is potential for cross-pollinating solutions between these seemingly disparate challenges using a range of emerging technologies such as sensors, omics, and big data. In this review, we highlight the bidirectional value of mental health technology transfer aimed to address issues both on Earth and in space.METHODS: We prepared a systematic review of studies pertaining to mental health technological innovation and space medicine.RESULTS: For Earth mental health technologies translatable to long-duration space missions, we cite several example technologies, including device-based psychotherapy and social support, conversational agents aka chatbots, and nutritional and physical activity focused mental health. Space technologies translatable to Earth mental health include remote sensing devices, global navigation satellite systems, satellite communications, chronotherapies, and nutritional advances.DISCUSSION: There is a rich history of space technologies informing Earth technological trends, including general health care on Earth, and vice versa. To avoid the traditional happenstance approach that results in delays, missed opportunities, and increased cost, and to improve outcomes for both Earth and space utilization of these technologies, we propose increased dialogue and training opportunities to enhance innovation and outcomes.Chang DD, Storch EA, Black L, Berk M, Pellis N, Lavretsky H, Sutton J, Ternes K, Shepanek M, Smith E, Abbott R, Eyre HA. Promoting tech transfer between space and global mental health. Aerosp Med Hum Perform. 2020; 91(9):737745.

BackgroundGeriatric depression with subjective cognitive complaints increases the risk of Alzheimer's Disease (AD). Memantine is a cognitive enhancer used to treat AD. In a 6-month double-blind randomized placebo-controlled trial of escitalopram and memantine (ESC/MEM), ESC/MEM improved cognition at 12 month in geriatric depression (NCT01902004). We now investigated structural neuroplastic changes at 3 months.MethodsForty-one older depressed adults (mean age=70.43, SD=7.33, 26 female) were randomized to receive ESC/MEM or ESC/PBO. Mood scores (Hamilton Depression Rating Scale, HAMD) and high-resolution structural T1-weighted images were acquired at baseline and 3 months. Freesurfer 6.0 for image processing and General Linear Models was used to examine group differences in symmetrized percent change gray matter volume (GMV) and cortical thickness, controlling for age and intracranial volume. Nonparametric tests were used to investigate group differences in mood and subcortical volume change.ResultsAmong 27 completers (ESC/MEM n = 13; ESC/PBO n = 14), 62% achieved remission (HAMD≤6) with ESC/MEM and 43% with ESC/PBO (Fisher's exact p=.45). Change in HAMD did not differ between groups (F(1,23)=0.14, p=.7). GMV and thickness increased more with ESC/MEM than with ESC/PBO in the left middle and inferior temporal lobe, right medial, and lateral orbito-frontal cortex (OFC).Limitationsincluded small sample size, dropout, and the lack of cognitive data at 3 months.ConclusionsAlthough significant group differences in mood improvement were not observed, ESC/MEM resulted in increased GMV and cortical thickness in several brain regions compared to placebo. Larger longitudinal clinical trials can further examine the neuroprotective effect of memantine in geriatric depression.

ObjectiveTo determine the effect of the COVID-19 pandemic on the mental health of older adults with pre-existing major depressive disorder (MDD).ParticipantsParticipants were 73 community-living older adults with pre-existing MDD (mean age 69 [SD 6]) in Los Angeles, New York, Pittsburgh, and St Louis.Design and measurementsDuring the first 2 months of the pandemic, the authors interviewed participants with a semistructured qualitative interview evaluating access to care, mental health, quality of life, and coping. The authors also assessed depression, anxiety, and suicidality with validated scales and compared scores before and during the pandemic.ResultsFive themes from the interviews highlight the experience of older adults with MDD: 1) They are more concerned about the risk of contracting the virus than the risks of isolation. 2) They exhibit resilience to the stress and isolation of physical distancing. 3) Most are not isolated socially, with virtual contact with friends and family. 4) Their quality of life is lower, and they worry their mental health will suffer with continued physical distancing. 5) They are outraged by an inadequate governmental response to the pandemic. Depression, anxiety, and suicidal ideation symptom scores did not differ from scores before the pandemic.ConclusionMost older adults with pre-existing MDD show resilience in the first 2 months of the COVID-19 pandemic but have concerns about the future. Policies and interventions to provide access to medical services and opportunities for social interaction are needed to help to maintain mental health and quality of life as the pandemic continues.

BackgroundBrain health diplomacy aims to influence the global policy environment for brain health (i.e. dementia, depression, and other mind/brain disorders) and bridges the disciplines of global brain health, international affairs, management, law, and economics. Determinants of brain health include educational attainment, diet, access to health care, physical activity, social support, and environmental exposures, as well as chronic brain disorders and treatment. Global challenges associated with these determinants include large-scale conflicts and consequent mass migration, chemical contaminants, air quality, socioeconomic status, climate change, and global population aging. Given the rapidly advancing technological innovations impacting brain health, it is paramount to optimize the benefits and mitigate the drawbacks of such technologies.ObjectiveWe propose a working model of Brain health INnovation Diplomacy (BIND).MethodsWe prepared a selective review using literature searches of studies pertaining to brain health technological innovation and diplomacy.ResultsBIND aims to improve global brain health outcomes by leveraging technological innovation, entrepreneurship, and innovation diplomacy. It acknowledges the key role that technology, entrepreneurship, and digitization play and will increasingly play in the future of brain health for individuals and societies alike. It strengthens the positive role of novel solutions, recognizes and works to manage both real and potential risks of digital platforms. It is recognition of the political, ethical, cultural, and economic influences that brain health technological innovation and entrepreneurship can have.ConclusionsBy creating a framework for BIND, we can use this to ensure a systematic model for the use of technology to optimize brain health.

ObjectiveGeriatric depression is difficult to treat and frequently accompanied by cognitive complaints that increase risk for dementia. New treatment strategies targeting both depression and cognition are urgently needed.MethodsWe conducted a 6-month double-blind placebo-controlled trial to assess the efficacy and tolerability of escitalopram + memantine (ESC/MEM) compared to escitalopram + placebo (ESC/PBO) for improving mood and cognitive functioning in depressed older adults with subjective memory complaints (NCT01902004). Primary outcome was change in depression as assessed by the HAM-D post-treatment (at 6 months). Remission was defined as HAM-D ≤6; naturalistic follow-up continued until 12 months.ResultsOf the 95 randomized participants, 62 completed the 6-month assessment. Dropout and tolerability did not differ between groups. Mean daily escitalopram dose was 11.1 mg (SD = 3.7; range: 5-20 mg). Mean daily memantine dose was 19.3 mg (SD = 2.6; range 10-20 mg). Remission rate within ESC/MEM was 45.8% and 47.9%, compared to 38.3% and 31.9% in ESC/PBO, at 3 and 6 months, respectively (χ2(1) = 2.0, p = 0.15). Both groups improved significantly on the HAM-D at 3, 6, and 12 months, with no observed between-group differences. ESC/MEM demonstrated greater improvement in delayed recall (F(2,82) = 4.3, p = 0.02) and executive functioning (F(2,82) = 5.1, p = 0.01) at 12 months compared to ESC/PBO.ConclusionsThe combination of memantine with escitalopram was well tolerated and as effective as escitalopram and placebo in improving depression using HAM-D. Combination memantine and escitalopram was significantly more effective than escitalopram and placebo in improving cognitive outcomes at 12 months. Future reports will address the role of biomarkers of aging in treatment response.

Background: Geriatric depression with subjective memory complaints increases the risk for Alzheimer's Disease. Memantine, a neuroprotective drug, can improve depression and help prevent cognitive decline. In our 6-months clinical trial, escitalopram/memantine (ESC/MEM) improved mood and cognition compared to escitalopram/placebo treatment (ESC/PBO; NCT01902004). In this report, we investigated whether baseline brain white matter integrity in fronto-limbic-striatal tracts can predict clinical outcomes using fractional anisotropy (FA). Methods: Thirty-eight older depressed adults (mean age = 70.6, SD = 7.2) were randomized to ESC/MEM or ESC/PBO and underwent diffusion-weighted imaging (DWI) at 3 Tesla at baseline. Mood was assessed using the Hamilton Depression Rating Scale (HAMD), apathy using the Apathy Evaluation Scale (AES) and anxiety using the Hamilton Anxiety Scale (HAMA) at baseline and 6-months follow-up. FA was extracted from seven tracts of interest (six in each hemisphere and one commissural tract) associated with geriatric depression. Non-parametric General Linear Models were used to examine group differences in the association between FA and symptom improvement, controlling for age, sex, baseline symptom scores and scanner model, correcting for false discovery rate (FDR). Post-hoc tests further investigated group differences in axial, mean and radial diffusivity (AD, MD, and RD, respectively). Lastly, we performed an exploratory whole-brain model to test whether FA might be related to treatment response with memantine. Results: There were no differences in remission rates or HAMD change between groups. In bilateral anterior and posterior internal capsule tracts and bilateral inferior and right superior fronto-occipital (IFO and SFO) fasciculus, higher FA was associated with larger improvements in depressive symptoms for ESC/MEM, but not ESC/PBO, correcting for FDR. Lower MD in the left IFO and RD in the right anterior internal capsule were associated with improved treatment responses. We found no significant associations in the whole-brain analysis. Limitations: Included small sample size and high dropout. Conclusions: Higher baseline FA and lower RD and MD in hypothesized fronto-limbic-striatal tracts predicted greater improvement in mood and anxiety with ESC/MEM compared to ESC/PBO in geriatric depression. FA as a biomarker for white matter integrity may serve as a predictor of treatment response but requires confirmation in larger future studies.

As marine ecosystems respond to climate change and other stressors, it is necessary to evaluate current and past hybridization events to gain insight on the outcomes and drivers of such events. Ancestral introgression within the gadids has been suggested to allow cod to inhabit a variety of habitats. Little attention has been given to contemporary hybridization, especially within cold-water-adapted cod (Boreogadus saida Lepechin, 1774 and Arctogadus glacialis Peters, 1872). We used whole-genome, restriction-site associated, and mitochondrial sequence data to explore the degree and direction of hybridization between these species where previous hybridization had not been reported. Although nearly identical morphologically at certain life stages, we detected very distinct nuclear and mitochondrial lineages. We detected one potential hybrid with a Arctogadus mitochondrial haplotype and Boreogadus nuclear genotype, but no early generational hybrids. The presence of a late generation hybrid suggests that at least some hybrids survive to maturity and reproduce. However, a historical introgression event could not be excluded. Contemporary gene flow appears asymmetrical from Arctogadus into Boreogadus, which may be due to overlap in timing of spawning, environmental heterogeneity, or differences in population size. This study provides important baseline information for the degree of potential hybridization between these species within Alaska marine environments.

BackgroundIncreasing understanding of the neural correlates of anxiety symptoms in late-life depression (LLD) could inform the development of more targeted and effective treatments.MethodsGrey matter volume (GMV) was assessed with volumetric magnetic resonance imaging in a sample of 113 adults ≥60 years with MDD using the following regions of interest: amygdala, anterior cingulate cortex (ACC), insula, orbitofrontal cortex (OFC), and temporal cortex.ResultsAfter controlling for demographic (age, sex, education) and clinical variables (antidepressant use, anxiolytic use, duration of illness, medical comorbidity, cognitive functioning), greater severity of anxiety symptoms was associated with lower GMV bilaterally in the insula, F(1,102) = 6.63, p = 0.01, and OFC, F(1,102) = 8.35, p = 0.005. By contrast, depressive symptom severity was significantly associated with lower bilateral insula volumes, F(1,102) = 6.43, p = 0.01, but not OFC volumes, F(1,102) = 5.37, p = 0.02.LimitationsLimitations include (1) the relatively mild nature of anxiety symptoms in our sample; (2) the cross-sectional research design, which prohibits inferences of directionality; (3) the relatively homogenous demographic of the sample, and (4) the exclusion of participants with significant psychiatric comorbidity, suicidality, or cognitive impairment.ConclusionsDecreased OFC volumes may serve as a unique biomarker of anxiety symptoms in LLD. Future longitudinal and clinical studies with long-term follow up and more diverse samples will help further elucidate the biological, psychological, and social factors affecting associations between anxiety and brain morphology in LLD.

In contrast to traditional perspectives of resilience as a stable, trait-like characteristic, resilience is now recognized as a multidimentional, dynamic capacity influenced by life-long interactions between internal and environmental resources. We review psychosocial and neurobiological factors associated with resilience to late-life depression (LLD). Recent research has identified both psychosocial characteristics associated with elevated LLD risk (e.g., insecure attachment, neuroticism) and psychosocial processes that may be useful intervention targets (e.g., self-efficacy, sense of purpose, coping behaviors, social support). Psychobiological factors include a variety of endocrine, genetic, inflammatory, metabolic, neural, and cardiovascular processes that bidirectionally interact to affect risk for LLD onset and course of illness. Several resilience-enhancing intervention modalities show promise for the prevention and treatment of LLD, including cognitive/psychological or mind-body (positive psychology; psychotherapy; heart rate variability biofeedback; meditation), movement-based (aerobic exercise; yoga; tai chi), and biological approaches (pharmacotherapy, electroconvulsive therapy). Additional research is needed to further elucidate psychosocial and biological factors that affect risk and course of LLD. In addition, research to identify psychobiological factors predicting differential treatment response to various interventions will be essential to the development of more individualized and effective approaches to the prevention and treatment of LLD.

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