Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine.

Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8+ T cells in the draining lymph nodes are the major producers of this circulating IFN-γ. Analysis of knockout mice revealed that induction of antibody and T cell responses to BNT162b2 was not dependent on signaling via Toll-like receptors 2, 3, 4, 5 and 7 nor inflammasome activation, nor the necroptosis or pyroptosis cell death pathways. Rather, the CD8+ T cell response induced by BNT162b2 was dependent on type I interferon-dependent MDA5 signaling. These results provide insights into the molecular mechanisms by which the BNT162b2 vaccine stimulates immune responses.

Mutations in human DNA methyltransferase DNMT1 induce specific genome-wide epigenomic and transcriptomic changes in neurodevelopment.

DNA methyltransferase type 1 (DNMT1) is a major enzyme involved in maintaining the methylation pattern after DNA replication. Mutations in DNMT1 have been associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). We used fibroblasts, induced pluripotent stem cells (iPSCs) and induced neurons (iNs) generated from patients with ADCA-DN and controls, to explore the epigenomic and transcriptomic effects of mutations in DNMT1. We show cell type-specific changes in gene expression and DNA methylation patterns. DNA methylation and gene expression changes were negatively correlated in iPSCs and iNs. In addition, we identified a group of genes associated with clinical phenotypes of ADCA-DN, including PDGFB and PRDM8 for cerebellar ataxia, psychosis and dementia and NR2F1 for deafness and optic atrophy. Furthermore, ZFP57, which is required to maintain gene imprinting through DNA methylation during early development, was hypomethylated in promoters and exhibited upregulated expression in patients with ADCA-DN in both iPSC and iNs. Our results provide insight into the functions of DNMT1 and the molecular changes associated with ADCA-DN, with potential implications for genes associated with related phenotypes.

Decoding the heterogeneity of Alzheimer's disease diagnosis and progression using multilayer networks.

Alzheimer's disease (AD) is a multifactorial and heterogeneous disorder, which makes early detection a challenge. Studies have attempted to combine biomarkers to improve AD detection and predict progression. However, most of the existing work reports results in parallel or compares normalized findings but does not analyze data simultaneously. We tested a multi-dimensional network framework, applied to 490 subjects (cognitively normal [CN] = 147; mild cognitive impairment [MCI] = 287; AD = 56) from ADNI, to create a single model capable of capturing the heterogeneity and progression of AD. First, we constructed subject similarity networks for structural magnetic resonance imaging, amyloid-ß positron emission tomography, cerebrospinal fluid, cognition, and genetics data and then applied multilayer community detection to find groups with shared similarities across modalities. Individuals were also followed-up longitudinally, with AD subjects having, on average, 4.5 years of follow-up. Our findings show that multilayer community detection allows for accurate identification of present and future AD (≈90%) and is also able to identify cases that were misdiagnosed clinically. From all MCI participants who developed AD or reverted to CN, the multilayer model correctly identified 90.8% and 88.5% of cases respectively. We observed similar subtypes across the full sample and when examining multimodal data from subjects with no AD pathology (i.e., amyloid negative). Finally, these results were also validated using an independent testing set. In summary, the multilayer framework is successful in detecting AD and provides unique insight into the heterogeneity of the disease by identifying subtypes that share similar multidisciplinary profiles of neurological, cognitive, pathological, and genetics information.

Neurocognitive markers of passive suicidal ideation in late-life depression.

OBJECTIVES: (1) To delineate whether cognitive flexibility and inhibitory ability are neurocognitive markers of passive suicidal ideation (PSI), an early stage of suicide risk in depression and (2) to determine whether PSI is associated with volumetric differences in regions of the prefrontal cortex (PFC) in middle-aged and older adults with depression. DESIGN: Cross-sectional study. SETTING: University medical school. PARTICIPANTS: Forty community-dwelling middle-aged and older adults with depression from a larger study of depression and anxiety (NIMH R01 MH091342-05 PI: O'Hara). MEASUREMENTS: Psychiatric measures were assessed for the presence of a DSM-5 depressive disorder and PSI. A neurocognitive battery assessed cognitive flexibility, inhibitory ability, as well as other neurocognitive domains. RESULTS: The PSI group (n = 18) performed significantly worse on cognitive flexibility and inhibitory ability, but not on other neurocognitive tasks, compared to the group without PSI (n = 22). The group with PSI had larger left mid-frontal gyri (MFG) than the no-PSI group. There was no association between cognitive flexibility/inhibitory ability and left MFG volume. CONCLUSIONS: Findings implicate a neurocognitive signature of PSI: poorer cognitive flexibility and poor inhibitory ability not better accounted for by other domains of cognitive dysfunction and not associated with volumetric differences in the left MFG. This suggests that there are two specific but independent risk factors of PSI in middle- and older-aged adults.

SARS-CoV-2 RNAemia Predicts Clinical Deterioration and Extrapulmonary Complications from COVID-19.

BACKGROUND: The determinants of coronavirus disease 2019 (COVID-19) disease severity and extrapulmonary complications (EPCs) are poorly understood. We characterized relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia and disease severity, clinical deterioration, and specific EPCs. METHODS: We used quantitative and digital polymerase chain reaction (qPCR and dPCR) to quantify SARS-CoV-2 RNA from plasma in 191 patients presenting to the emergency department with COVID-19. We recorded patient symptoms, laboratory markers, and clinical outcomes, with a focus on oxygen requirements over time. We collected longitudinal plasma samples from a subset of patients. We characterized the role of RNAemia in predicting clinical severity and EPCs using elastic net regression. RESULTS: Of SARS-CoV-2-positive patients, 23.0% (44 of 191) had viral RNA detected in plasma by dPCR, compared with 1.4% (2 of 147) by qPCR. Most patients with serial measurements had undetectable RNAemia within 10 days of symptom onset, reached maximum clinical severity within 16 days, and symptom resolution within 33 days. Initially RNAemic patients were more likely to manifest severe disease (odds ratio, 6.72 [95% confidence interval, 2.45-19.79]), worsening of disease severity (2.43 [1.07-5.38]), and EPCs (2.81 [1.26-6.36]). RNA loads were correlated with maximum severity (r = 0.47 [95% confidence interval, .20-.67]). CONCLUSIONS: dPCR is more sensitive than qPCR for the detection of SARS-CoV-2 RNAemia, which is a robust predictor of eventual COVID-19 severity and oxygen requirements, as well as EPCs. Because many COVID-19 therapies are initiated on the basis of oxygen requirements, RNAemia on presentation might serve to direct early initiation of appropriate therapies for the patients most likely to deteriorate.

Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19.

BACKGROUND: It is unclear whether asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2. METHODS: All patients over 28 days old testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms. RESULTS: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p = .40). Among SARS-CoV-2-positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared with non-allergic asthma (OR 0.52 [0.28, 0.91], p = .026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared with patients with mild or asymptomatic disease, independent of asthma status (p = .0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms. CONCLUSIONS: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared with non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms 3 months post-infection.

Preparing the Next Generation of Academic Researchers During the Pandemic: Lessons from a National Mental Health Research Postdoctoral Fellowship.

OBJECTIVE: The COVID-19 pandemic has severely disrupted all aspects of academic medicine, including post-doctoral research fellowship training. The current survey examined ways in which research fellows across 28 U.S. nationally diverse sites have been impacted. METHODS: Survey participants included 62 M.D. and Ph.D. post-doctoral fellows and 27 local fellowship center directors within the Veterans Affairs (VA) Advanced Fellowship in Mental Illness Research and Treatment (MIRT), a national fellowship program tasked to develop academic clinician researchers within the field of mental health. Survey questions focused on productivity and challenges experienced by fellows during the pandemic. RESULTS: Half of fellows reported working entirely off-site during the COVID-19 pandemic. All fellows reported some level of disruption in productivity during the pandemic; 73% reported a disruption in data collection, 69% reported decreased scholarly output, 41% reported disruption in grant writing, and 73% reported disruption in ability to provide clinical care. Yet, the majority of fellows (66%) reported not having to change their research goals, pivoting to telehealth-based data collection, and employing extant data for research projects and peer-reviewed publications. CONCLUSIONS: The results of the fellow and director surveys highlight the associated disruption of the COVID-19 pandemic on fellowship-related activities and parallel ingenuity of programs to continue conducting research and clinical services in a modified fashion. While many research goals continued unabated, the findings suggest alterations in data collection methodology and a focus on using extant data, which may have a residual influence on future early career research grant applications.

Quantitative measurement of macromolecular tissue properties in white and gray matter in healthy aging and amnestic MCI.

Healthy and pathological aging influence brain microstructure via complex processes. Discerning these processes requires measurements that are sensitive to specific biological properties of brain tissue. We integrated a novel quantitative R1 measure with multi-shell diffusion weighted imaging to map age-associated changes in macromolecular tissue volume (MTV) along major white matter tracts in healthy older adults and patients with amnestic Mild Cognitive Impairment (aMCI). Reduced MTV in association tracts was associated with older age in healthy aging, was correlated with memory performance, and distinguished aMCI from controls. We also mapped changes in gray matter tissue properties using quantitative R1 measurements. We documented a widespread decrease in R1 with advancing age across the cortex and decreased R1 in aMCI compared with controls in regions implicated in episodic memory. Our data are the first to characterize MTV loss along major white matter tracts in aMCI and suggest that qMRI is a sensitive measure for detecting subtle degeneration of white and gray matter tissue that cannot be detected by conventional MRI and diffusion measures.

Guided self-management targeting anxiety and activity participation in older Veterans.

OBJECTIVES: This study examined the acceptance, feasibility, and preliminary effects of a guided self-management intervention using video delivery and a telephone coach on anxiety and activity engagement. METHOD: Ten Veterans aged 60 years or older with anxiety disorders determined by Structured Clinical Interview for Diagnostic and Statistical Manual 5th edition (SCID-5) at baseline visit participated in this non-randomized study examining a 4-week guided self-management intervention for anxiety. Feasibility was examined using participation engagement with the intervention. Measures of anxiety (Geriatric Anxiety Scale, PROMIS Anxiety Scale, Anxiety Control Questionnaire), depression (Patient Health Questionnaire 9-item), and activity participation (modified Activity Card Sort) administered at baseline and final (week 8) visit provided estimates of preliminary intervention effects. The Geriatric Anxiety Scale also was administered by phone at week 4. Participants completed a semi-structured qualitative interview at the final visit, which provided information about the acceptability, benefits of intervention, and barriers to engagement. RESULTS: All participants (N = 10) reported that the intervention somewhat or completely met their expectations, demonstrating intervention acceptability. Intervention completers (n = 9) experienced reduced anxiety over the first 4 weeks, alongside significant improvements in anxiety control and personalized activity goals across 8 weeks. However, anxiety symptoms tended to return to baseline at follow-up. Participants identified the relaxation videos and promotion of a daily relaxation routine as the most helpful intervention components. CONCLUSIONS: Findings indicate that the intervention may improve activity participation and reduce anxiety. Thus, guided self-management interventions show promise for reducing distress and maintaining engagement later in life.

The 5-HTTLPR long allele predicts two-year longitudinal increases in cortisol and declines in verbal memory in older adults.

OBJECTIVES: The short form or s-allele variant of the serotonin transporter polymorphism (5-HTTLPR), as compared with the long-form or l-allele variant, has been associated with the presence of cognitive dysfunction, and particularly memory impairment in older adults. This body of cross-sectional work has culminated in the hypothesis that presence of the s-allele predicts greater memory decline in older adults. Yet, to date, there are no longitudinal studies that have investigated this issue. METHODS/DESIGN: Here, we examine 109 community-dwelling older adults (mean and SD of age = 70.7 ± 8.7 years) who underwent blood draw for genotyping, cognitive, and psychological testing at baseline, 12-, and 24-monthfollow-ups. RESULTS: Multilevel modeling found that s-allele carriers (ss or ls) performed worse than ll homozygotes at baseline on delayed verbal recall. Yet, s-allele carriers' memory performance was stable over the two-yearfollow-up period, while l-allele homozygotes experienced significant memory decline. l-allele homozygote status was associated with both increased cortisol and decreased memory over time, resulting in attenuated verbal memory performance differences compared to s-allele carriers with age. CONCLUSIONS: Overall, our findings do not support the hypothesis that presence of the 5-HTTLPRs-allele is a marker for memory decline in older adults. J Am Geriatr Soc 68:-, 2020.

Technology use and preferences for mental health self-management interventions among older veterans.

OBJECTIVES: The United States Department of Veterans Affairs offers numerous technology-delivered interventions to self-manage mental health problems. It is unknown, however, what barriers older military veterans face to using these technologies and how willing they would be to use technologies for mental health concerns. METHODS: Seventy-seven veterans (Mage = 69.16 years; SD = 7.10) completed interviews in a concurrent mixed methods study. Interviewers asked about technology ownership and described four modalities of delivering self-management interventions: printed materials, DVDs, Internet, and mobile apps. Interviewers obtained feedback about each modality's benefits, barriers, and facilitators. Participants ranked their self-management modalities preferences alone and compared with counseling. Multivariable adjusted logistic regression and qualitative analyses were conducted to investigate the reasons contributing to preferences. RESULTS: Most reported owning a computer (84.4%), having home Internet (80.5%), and a smartphone (70.1%). Participants preferred printed materials (35.1%) over mobile apps (28.6%), Internet (24.7%), and DVDs (13.0%). Lower computer proficiency was associated with preferring DVDs; higher proficiency was associated with Internet and mobile interventions. Residing in an urban area was associated with mobile apps. When counseling was an option, 66% identified this as their first preference. Qualitative findings showed veterans' desire for information, training, and provider support with technology. CONCLUSIONS: Older veterans reported high technology ownership rates but varied preferences for self-management interventions. Notably, two-thirds preferred some form of technology, which points to the importance of ensuring that providers offer existing technology-delivered interventions to older veterans. Veterans' strong preference for counseling emphasizes the need for human support alongside self-management.

Sleep-wake disorders in Alzheimer's disease: further genetic analyses in relation to objective sleep measures.

This paper presents updated analyses on the genetic associations of sleep disruption in individuals with Alzheimer's disease (AD). We published previously a study of the association between single nucleotide polymorphisms (SNPs) found in eight genes related to circadian rhythms and objective measures of sleep-wake disturbances in 124 individuals with AD. Here, we present new relevant analyses using polygenic risk scores (PRS) and variable number tandem repeats (VNTRs) enumerations. PRS were calculated using the genetic data from the original participants and relevant genome wide association studies (GWAS). VNTRs for the same circadian rhythm genes studied with SNPs were obtained from a separate cohort of participants using whole genome sequencing (WGS). Objectively (wrist actigraphy) determined wake after sleep onset (WASO) was used as a measure of sleep disruption. None of the PRS were associated with sleep disturbance. Computer analyses using VNTRseek software generated a total of 30 VNTRs for the circadian-related genes but none appear relevant to our objective sleep measure. In addition, of 71 neurotransmitter function-related genes, 29 genes had VNTRs that differed from the reference VNTR, but it was not clear if any of these might affect circadian function in AD patients. Although we have not found in either the current analyses or in our previous published analyses of SNPs any direct linkages between identified genetic factors and WASO, research in this area remains in its infancy.

Subjective but Not Objective Sleep is Associated with Subsyndromal Anxiety and Depression in Community-Dwelling Older Adults.

OBJECTIVE: To examine the relationship between subclinical anxiety and depressive symptoms and objective sleep architecture measures and subjective sleep reports in older adults. METHODS: Community-dwelling older adults (N = 167) self-rated their current severity of anxiety symptoms, depressive symptoms, daytime sleepiness, and global sleep quality. Participants received overnight ambulatory polysomnography to assess sleep architecture. Multivariate linear regression models examined associations between anxiety and depressive symptoms and objective and subjective sleep measures. RESULTS: Significant findings emerged for subjective sleep, with higher depression and anxiety scores associated with worse global sleep quality and greater anxiety scores associated with greater daytime sleepiness. No significant associations were observed between subclinical levels of anxiety or depressive symptoms with sleep architecture. CONCLUSION: Subclinical levels of late-life anxiety and depression have distinct associations with subjective sleep disturbance. Findings implicate subjective measures of sleep quality and daytime sleepiness as stronger trait markers for subthreshold psychiatric symptoms than objective sleep biomarkers.

Neuropsychological Functioning in Older Adults with Mild Cognitive Impairment and Insomnia Randomized to CBT-I or Control Group.

OBJECTIVES: Improving the sleep of older adults with mild cognitive impairment (MCI) represents a first step in discovering whether interventions directed at modifying this risk factor also have the potential to alter the cognitive decline trajectory. METHODS: A six-session, adapted version of a cognitive behavioral therapy for insomnia (CBT-I) was administered to older adults (N = 28; 14 per group) with MCI across two residential facilities. Participants were randomly assigned to either the sleep intervention or an active control group and completed a neuropsychological battery at three time points (e.g., baseline-T1, post-intervention-T2, 4 month follow-up-T3). RESULTS: Results showed a significant improvement in sleep and a change (p < .05) on a key measure of executive functioning sub task of inhibition (Condition 3 of D-KEF Color-Word Interference Test), a positive trend on the inhibition-switching task (p < .10; Condition 4 of D-KEF Color-Word Interference Test), an no change in a measure of verbal memory (HVLT-R Delayed Recall) compared with the active control group. CONCLUSIONS: CBT-I is a nonpharmacological intervention that has the potential to cognitively benefit individuals with MCI suffering from comorbid insomnia. CLINICAL IMPLICATIONS: Results suggest that a non-pharmacological intervention to improve sleep in older adults with MCI also improve cognitive functioning. Further exploration of the mechanisms underlying these improvements is warranted.

Information-Seeking about Anxiety and Perceptions about Technology to Teach Coping Skills in Older Veterans.

OBJECTIVE: We sought to learn where older veterans seek information about anxiety and coping. Due to increasing use of technology in health care, we also explored benefits and barriers of using technology to teach coping skills. METHODS: Twenty veterans (mean age = 69.5 years, SD = 7.3) participated in semi-structured interviews in which we inquired about where they seek information about anxiety. We explored quantitative and qualitative differences for veterans with high versus low anxiety. In follow-up focus groups, we examined opinions about learning coping skills using technology. RESULTS: Though veterans primarily named health care professionals as sources of information about anxiety, online searches and reading books were frequently mentioned. Reported benefits of using technology were convenience and standardized instruction of coping skills. Barriers included lack of interaction and frustration with technology usability. CONCLUSION: Older veterans use multiple sources, heavily rely on interpersonal sources (e.g., professionals, friends), and employ varied search strategies regarding how to cope with anxiety. Using technology to teach coping skills was generally acceptable to older veterans. CLINICAL IMPLICATIONS: Health care professionals could guide patients towards credible online and book sources. Providing instruction about using technology may help older adults use technology to learn coping skills.

Disentangling cognition and emotion in older adults: the role of cognitive control and mental health in emotional conflict adaptation.

OBJECTIVE: Recent research suggests cognition has a bidirectional relationship with emotional processing in older adults, yet the relationship is still poorly understood. We aimed to examine a potential relationship between late-life cognitive function, mental health symptoms, and emotional conflict adaptation. We hypothesized that worse cognitive control abilities would be associated with poorer emotional conflict adaptation. We further hypothesized that a higher severity of mental health symptoms would be associated with poorer emotional conflict adaptation. METHODS: Participants included 83 cognitively normal community-dwelling older adults who completed a targeted mental health and cognitive battery, and emotion and gender conflict-adaptation tasks. RESULTS: Consistent with our hypothesis, poorer performance on components of cognitive control, specifically attention and working memory, was associated with poorer emotional conflict adaptation. This association with attention and working memory was not observed in the non-affective-based gender conflict adaptation task. Mental health symptoms did not predict emotional conflict adaptation, nor did performance on other cognitive measures. CONCLUSION: Our findings suggest that emotion conflict adaptation is disrupted in older individuals who have poorer attention and working memory. Components of cognitive control may therefore be an important potential source of inter-individual differences in late-life emotion regulation and cognitive affective deficits. Copyright © 2016 John Wiley & Sons, Ltd.

Development of a video-delivered relaxation treatment of late-life anxiety for veterans.

BACKGROUND: Behavioral treatments reduce anxiety, yet many older adults may not have access to these efficacious treatments. To address this need, we developed and evaluated the feasibility and acceptability of a video-delivered anxiety treatment for older Veterans. This treatment program, BREATHE (Breathing, Relaxation, and Education for Anxiety Treatment in the Home Environment), combines psychoeducation, diaphragmatic breathing, and progressive muscle relaxation training with engagement in activities. METHODS: A mixed methods concurrent study design was used to examine the clarity of the treatment videos. We conducted semi-structured interviews with 20 Veterans (M age = 69.5, SD = 7.3 years; 55% White, Non-Hispanic) and collected ratings of video clarity. RESULTS: Quantitative ratings revealed that 100% of participants generally or definitely could follow breathing and relaxation video instructions. Qualitative findings, however, demonstrated more variability in the extent to which each video segment was clear. Participants identified both immediate benefits and motivation challenges associated with a video-delivered treatment. Participants suggested that some patients may need encouragement, whereas others need face-to-face therapy. CONCLUSIONS: Quantitative ratings of video clarity and qualitative findings highlight the feasibility of a video-delivered treatment for older Veterans with anxiety. Our findings demonstrate the importance of ensuring patients can follow instructions provided in self-directed treatments and the role that an iterative testing process has in addressing these issues. Next steps include testing the treatment videos with older Veterans with anxiety disorders.

Multimorbidity is associated with anxiety in older adults in the Health and Retirement Study.

OBJECTIVES: The present study determined whether the number of medical conditions was associated with increased occurrence of anxiety and whether triads of medical conditions were associated with anxiety in a nationally representative sample of older Americans. We determined whether multimorbidity findings were unique to anxiety as compared with depressive symptoms. METHODS: A sample of 4219 participants (65 years or older) completed anxiety and depression measures in the Health and Retirement Study 2006 wave. The logistic regression models' outcome was elevated anxiety (≥12 on five-item Beck Anxiety Inventory) or depressive symptoms (≥12 on eight-item Center for Epidemiological Studies Depression Scale). The predictor variable was a tally of seven self-report of doctor-diagnosed conditions: arthritis, cancer, diabetes, heart conditions, high blood pressure, lung disease, and stroke. Analyses were adjusted for age, gender, and depressive or anxiety symptoms. Associations among elevated anxiety or depressive symptoms and 35 triads of medical conditions were examined using Bonferroni corrected chi-square analyses. RESULTS: Three or more medical conditions conferred a 2.30-fold increase in elevated anxiety (95% confidence interval: 1.44-4.01). Twenty triads were associated with elevated anxiety as compared with 13 associated with depressive symptoms. Six of seven medical conditions, with the exception being stroke, were present in the majority of triads. CONCLUSION: Number of medical conditions and specific conditions are associated with increased occurrence of elevated anxiety. Compared with elevated depressive symptoms, anxiety is associated with greater multimorbidity. As anxiety and depression cause significant morbidity, it may be beneficial to consider these mental health symptoms when evaluating older adults with multimorbidity. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

The impact of executive function on response to cognitive behavioral therapy in late-life depression.

OBJECTIVE: Late-life depression (LLD) is a common and debilitating condition among older adults. Cognitive behavioral therapy (CBT) has strong empirical support for the treatment of depression in all ages, including in LLD. In teaching patients to identify, monitor, and challenge negative patterns in their thinking, CBT for LLD relies heavily on cognitive processes and, in particular, executive functioning, such as planning, sequencing, organizing, and selectively inhibiting information. It may be that the effectiveness of CBT lies in its ability to train these cognitive areas. METHODS: Participants with LLD completed a comprehensive neuropsychological battery before enrolling in CBT. The current study examined the relationship between neuropsychological function prior to treatment and response to CBT. RESULTS: When using three baseline measures of executive functioning that quantify set shifting, cognitive flexibility, and response inhibition to predict treatment response, only baseline Wisconsin Card Sort Task performance was associated with a significant drop in depression symptoms after CBT. Specifically, worse performance on the Wisconsin Card Sort Task was associated with better treatment response. CONCLUSIONS: These results suggest that CBT, which teaches cognitive techniques for improving psychiatric symptoms, may be especially beneficial in LLD if relative weaknesses in specific areas of executive functioning are present.