Community-Engaged Research With Latino Dementia Caregivers: Overcoming Challenges in Community Advisory Board Development.

BACKGROUND AND OBJECTIVES: Latinos caring for a person with Alzheimer's disease and related dementias (ADRD) have the highest prevalence of caregiving. Yet, they are less likely to benefit from evidence-based interventions given their continued underrepresentation in ADRD-related research. Community advisory boards (CABs) have the potential to address barriers to research for underrepresented communities; however, there are complexities to establishing and sustaining CABs. This article describes how our work addressed challenges in CABs related to unbalanced power relations, language barriers, the value of time, and low research knowledge and health literacy. RESEARCH DESIGN AND METHODS: Nine Latino CAB members, including older Latino caregivers, were trained in a comprehensive program designed to increase knowledge about health research methods and ethics, cognitive health, and cultural adaptation methods. Members completed pre- and post-training measures of Alzheimer's disease knowledge, attitudes, and beliefs toward research, and a satisfaction survey. RESULTS: Results from the satisfaction questionnaire indicated that the program was well received. CAB members increased their knowledge regarding the management of behavioral and psychological symptoms of dementia and dementia-associated risk factors and treatment. Positive changes in members' attitudes toward research included increased willingness to participate in trials and subject protection measures. DISCUSSION AND IMPLICATIONS: Formalized training in research conduct and ethics and health literacy is a promising strategy to reduce challenges in establishing and maintaining CABs and can also optimize CAB impact to address gaps in older Latino ADRD caregiving research.

Antipsychotic use among older patients with dementia receiving home health care services: Prevalence, predictors, and outcomes.

BACKGROUND: Antipsychotic use is a safety concern among older patients in home health care (HHC), particularly for those with Alzheimer's disease and related dementias (ADRD). The objective of this study was to examine the prevalence and predictors of antipsychotic use among older adults with and without ADRD who received HHC, and the association of antipsychotic use with outcomes among patients living with ADRD. METHODS: In this secondary analysis of adults ≥65 years receiving care from an HHC agency in New York in 2019 (N = 6684), we used data from the Outcome and Assessment Information Set, Medicare HHC claims, and home medication review results in the electronic HHC records during a 60-day HHC episode. ADRD was identified by diagnostic codes. Functional outcome was the change in the composite activities of daily living (ADL) score from HHC admission to HHC discharge (measured in 5833 patients), where a positive score means improvement and a negative score means decline. Data were analyzed using logistic (predictors) and linear regression (association with outcome) analyses. RESULTS: The point prevalence of antipsychotic use was 17.2% and 6.6% among patients with and without ADRD, respectively. Among patients living with ADRD, predictors of antipsychotic use included having greater ADL limitations (odds ratio [OR] = 1.30, p = 0.01), taking more medications (OR = 1.04, p = 0.02), having behavioral and psychological symptoms (OR = 5.26, p = 0.002), and living alone (OR = 0.52, p = 0.06). Among patients living with ADRD, antipsychotic use was associated with having less ADL improvement at HHC discharge (ß = -0.70, p < 0.001). CONCLUSIONS: HHC patients living with ADRD were more likely to use antipsychotics and to experience worse functional outcomes when using antipsychotics. Antipsychotics should be systematically reviewed and, if contraindicated or unnecessary, deprescribed. Efforts are needed to improve HHC patients' access to nonpharmacological interventions and to provide education for caregivers regarding behavioral approaches to manage symptoms in ADRD.

Cognitive behavioral therapy for insomnia treatment attrition in patients with weekly nightmares.

STUDY OBJECTIVES: This study's objective was to evaluate the effect of nightmares (NMs) on attrition and symptom change following cognitive behavioral therapy for insomnia (CBT-I) treatment using data from a successful CBT-I randomized controlled trial delivered to participants with recent interpersonal violence exposure. METHODS: The study randomized 110 participants (107 women; mean age: 35.5 years) to CBT-I or to an attention-control group. Participants were assessed at 3 time periods: baseline, post-CBT-I (or attention control), and at time 3 (T3) post-cognitive processing therapy received by all participants. NM reports were extracted from the Fear of Sleep Inventory. Participants with weekly NMs were compared with those with fewer than weekly NMs on outcomes including attrition, insomnia, posttraumatic stress disorder, and depression. Change in NM frequency was examined. RESULTS: Participants with weekly NMs (55%) were significantly more likely to be lost to follow-up post-CBT-I (37%) compared with participants with infrequent NMs (15.6%) and were less likely to complete T3 (43%) than patients with less frequent NMs (62.5%). NMs were unrelated to differential treatment response in insomnia, depression, or posttraumatic stress disorder. Treatment with CBT-I was not associated with reduced NM frequency; however, change in sleep-onset latency from post-CBT-I to T3 predicted fewer NMs at T3. CONCLUSIONS: Weekly NMs were associated with attrition but not a reduced change in insomnia symptoms following CBT-I. NM symptoms did not change as a function of CBT-I, but change in sleep-onset latency predicted lower NM frequency. CBT-I trials should screen for NMs and consider augmenting CBT-I to specifically address NMs. CITATION: Hamilton NA, Russell JA, Youngren WA, et al. Cognitive behavioral therapy for insomnia treatment attrition in patients with weekly nightmares. J Clin Sleep Med. 2023;19(11):1913-1921.

Autonomic nervous system flexibility for understanding brain aging.

A recent call was made for autonomic nervous system (ANS) measures as digital health markers for early detection of Alzheimer's disease and related dementia (AD/ADRD). Nevertheless, contradictory or inconclusive findings exist. To help advance understanding of ANS' role in dementia, we draw upon aging and dementia-related literature, and propose a framework that centers on the role of ANS flexibility to guide future work on application of ANS function to differentiating the degree and type of dementia-related brain pathologies. We first provide a brief review of literature within the past 10 years on ANS and dementia-related brain pathologies. Next, we present an ANS flexibility model, describing how the model can be applied to understand these brain pathologies, as well as differentiate or even be leveraged to modify typical brain aging and dementia. Lastly, we briefly discuss the implication of the model for understanding resilience and vulnerability to dementia-related outcomes.

Recruiting Socially Disconnected Latinos Caring for a Person with Alzheimer's Disease and Related Dementias During the COVID-19 Pandemic: Lessons Learned.

OBJECTIVES: The purpose of this article is to present conceptual and methodological challenges to recruitment strategies in enrolling socially disconnected middle-aged and older Latino caregivers of a loved one with Alzheimer's disease and related dementias (ADRD). METHODS: Middle-aged and older Latino ADRD caregivers were recruited into two early stage, intervention development studies during the COVID-19 pandemic via online or in-person methods. Recruitment criteria included Latino ADRD caregivers over the age of 40 reporting elevated loneliness on the UCLA 3-item Loneliness Scale (LS) during screening. RESULTS: Middle-aged, Latino caregivers were recruited predominantly from online methods whereas older caregivers were mostly recruited from in-person methods. We report challenges identifying socially disconnected Latino caregivers using the UCLA 3-item LS. CONCLUSIONS: Our findings support previously reported disparities in recruitment by age and language and suggest further methodological considerations to assess social disconnection among Latino caregivers. We discuss recommendations to overcome these challenges in future research. CLINICAL IMPLICATIONS: Socially disconnected Latino ADRD caregivers have an elevated risk for poor mental health outcomes. Successful recruitment of this population in clinical research will ensure the development of targeted and culturally sensitive interventions to improve the mental health and overall well-being of this marginalized group.

Effect of online tDCS to left somatomotor cortex on neuropsychiatric symptoms among older adults at risk for dementia.

BACKGROUND: Neuropsychiatric symptoms (NPS) in mild cognitive impairment (MCI) cause distress to patients and caregivers, and accelerate progression to dementia. Transcranial direct current stimulation (tDCS) is a promising non-invasive treatment for NPS. OBJECTIVE/HYPOTHESIS: This pilot study assessed behavioral and neural effects of a 4-week anodal tDCS intervention targeting left sensorimotor cortex (LSMC: left precentral/postcentral gyri) during visual attention (compared to online sham tDCS), in 40 older adults (24 females, mean age = 71) with MCI. METHODS: A phase 0 double-blinded randomized control trial was conducted. NPS (patient-reported mood symptoms plus a caregiver-reported questionnaire) and fMRI were measured at baseline and immediately post-intervention. RESULTS: Generalized Estimating Equations found no significant group by time interactions for either NPS measure. However, there was evidence of decreased patient-reported NPS (Wald's χ2 = 3.80, p = .051), decreased LSMC activation during visual attention (Wald's χ2 = 2.93, p = .087), and increased LSMC-amygdala resting-state functional connectivity (rsFC; Wald's χ2 = 3.13, p = .077) in intervention group from pre-to post-intervention. Decrease in LSMC activation (Wald's χ2 = 9.20, p = .002) and increase in LSMC-amygdala rsFC (Wald's χ2 = 4.72, p = .030) related to decreased patient-reported NPS. Increased positive valence across sessions was significantly associated with intervention-related NPS improvement (Wald's χ2 = 22.92, p < .001). There were no findings for caregiver-reported NPS. Effects were stronger for left postcentral compared to left precentral gyrus. CONCLUSION: We found tentative evidence that tDCS applied to LSMC during visual attention in older adults with MCI improved NPS via changes in LSMC activation and LSMC-amygdala rsFC, suggesting improved emotion regulation. Patient-reported NPS was more sensitive to these changes than caregiver-reports, and effects were strongest for left postcentral gyrus. Follow-up studies should perform precise mechanistic investigation and efficacy testing.

Promoting Social Connection in Dementia Caregivers: A Call for Empirical Development of Targeted Interventions.

Social connection is an understudied target of intervention for the health of individuals providing care for a family member with Alzheimer's disease and related dementias (ADRD). To guide future research, we discuss considerations for interventions to promote social connection, with a particular focus on reducing loneliness: (a) include caregiver perspectives in designing and delivering interventions; (b) adapt to stages of dementia; (c) consider caregiving demands, including the use of brief interventions; (d) specify and measure mechanisms of action and principles of interventions; (e) consider dissemination and implementation at all stages of research. With support from the National Institute on Aging for a Roybal Center for Translational Research in the Behavioral and Social Sciences of Aging, we are developing a portfolio of mechanism-informed and principle-driven behavioral interventions to promote social connection in ADRD caregivers that can be flexibly applied to meet a diverse set of needs while maximizing resources and reducing demands on caregivers.

A meta-analysis on neural changes of cognitive training for mental disorders in executive function tasks: increase or decrease brain activation?

BACKGROUND: Cognitive impairment is often found in patients with psychiatric disorders, and cognitive training (CT) has been shown to help these patients. To better understand the mechanisms of CT, many neuroimaging studies have investigated the neural changes associated with it. However, the results of those studies have been inconsistent, making it difficult to draw conclusions from the literature. Therefore, the objective of this meta-analysis was to identify consistent patterns in the literature of neural changes associated with CT for psychiatric disorders. METHODS: We searched for cognitive training imaging studies in PubMed, Cochrane library, Scopus, and ProQuest electronic databases. We conducted an activation likelihood estimation (ALE) for coordinate-based meta-analysis of neuroimaging studies, conduct behavioral analysis of brain regions identified by ALE analysis, conduct behavioral analysis of brain regions identified by ALE analysis, and then created a functional meta-analytic connectivity model (fMACM) of the resulting regions. RESULTS: Results showed that CT studies consistently reported increased activation in the left inferior frontal gyrus (IFG) and decreased activation in the left precuneus and cuneus from pre- to post- CT. CONCLUSION: CT improves cognitive function by supporting language and memory function, and reducing neuronal resources associated with basic visual processing.

Pain and the Alzheimer's Disease and Related Dementia Spectrum in Community-Dwelling Older Americans: A Nationally Representative Study.

CONTEXT: Pain is a significant concern among older adults with Alzheimer's disease and related dementias (ADRD). OBJECTIVES: Examine the association between cognitive impairment across the ADRD spectrum and pain assessment and treatment in community-dwelling older Americans. METHODS: This cross-sectional, population-based study included 16,836 community-dwelling participants ≥ 50 years in the 2018 Health and Retirement Study. ADRD, assessed by validated cognitive measures, was categorized into "dementia," "cognitive impairment, no dementia (CIND)" and "intact cognition." Pain assessment included pain presence (often being troubled with pain), pain severity (degree of pain most of the time [mild/moderate/severe]), and pain interference (pain making it difficult to do usual activities). Pain treatment included recent use of over-the-counter pain medications and opioids (past 3 months), and regular intake of prescriptions for pain. RESULTS: Dementia were associated with lower likelihood of reporting pain presence (Odds Ratio [OR]= 0.61, P = 0.01), pain interference (OR = 0.46, P < 0.001), reporting lower pain severity (e.g., moderate vs. no: Relative Risk Ratio = 0.38, P < 0.001), and lower likelihood of receiving pain treatment, that is, recent use of over-the-counter pain medications (OR = 0.60, P = 0.02) and opioids (OR = 0.33, P < 0.001), and regular intake of prescriptions for pain (OR = 0.461, P = 0.002). CIND was associated with reporting lower pain severity (e.g., moderate vs. no: Relative Risk Ratio = 0.75, P = 0.021), lower likelihood of reporting pain interference (OR = 0.79, P = 0.045) and recent over-the-counter pain medication use (OR = 0.74, P = 0.026). CONCLUSION: CIND and dementia increased the risk of under-report and under-treatment of pain. Systematic efforts are needed to improve pain recognition and treatment among older adults with cognitive impairment, regardless of dementia diagnosis.

Subjective memory in adults over 50 years of age: associations with affective and physiological markers of emotion regulation.

OBJECTIVES: To examine associations among subjective memory reports, psychophysiological markers of emotion regulation, and cognitive performance in healthy adults over 50 years of age. METHOD: A cross-sectional laboratory study was conducted with healthy, community-dwelling, non-depressed adults (M age = 60.4 years, SD = 8.4). The Metamemory in Adulthood (MIA) questionnaire provided reports of subjective memory capacity and stability (versus decline) and anxiety about memory. Poorer emotion regulation was marked by greater negative affect (NA) and lower high frequency heart rate variability (HF-HRV) responses to a challenging working memory task. Regression models were used to identify associations between subjective memory and emotion regulation markers, and structural equation modeling was used to explore whether emotion regulation mediated associations between subjective memory and objective task performance. RESULTS: A total of 115 participants were included in the final sample. Subjective memory decline (indicated by lower scores on memory stability) was associated with lower HF-HRV response and worse working memory performance. Poorer subjective memory capacity and more anxiety about memory were both associated with greater negative affect in response to the working memory task. There was an indirect effect of subjective memory capacity on working memory performance through negative affect response. CONCLUSIONS: The findings here suggest that worse subjective memory may signal reduced capacity for emotion regulation. Along with known cognitive risks of depression and anxiety, more subtle emotion regulation difficulties may be involved in pathways of poor cognitive aging.

A Randomized Clinical Trial of Cognitive-Behavioral Therapy for Insomnia to Augment Posttraumatic Stress Disorder Treatment in Survivors of Interpersonal Violence.

INTRODUCTION: Individuals exposed to interpersonal violence (IPV) commonly develop posttraumatic stress disorder (PTSD) with co-occurring depression and insomnia. Standard PTSD interventions such as cognitive processing therapy (CPT) do not typically lead to remission or improved insomnia. Cognitive behavioral therapy for insomnia (CBTi) improves insomnia in individuals with PTSD, but PTSD severity remains elevated. OBJECTIVE: To determine whether sequential treatment of insomnia and PTSD is superior to treatment of only PTSD. METHODS: In a 20-week trial, 110 participants exposed to IPV who had PTSD, depression and insomnia were randomized to CBTi followed by CPT or to attention control followed by CPT. Primary outcomes following CBTi (or control) were the 6-week change in score on the Insomnia Severity Index (ISI), the Clinician-Administered PTSD Scale (CAPS), and the Hamilton Rating Scale for Depression (HAM-D). Primary outcomes following CPT were the 20-week change in scores. RESULTS: At 6 weeks, the CBTi condition had greater reductions in ISI, HAM-D, and CAPS scores than the attention control condition. At 20 weeks, participants in the CBTi+CPT condition had greater reductions in ISI, HAM-D, and CAPS scores compared to control+CPT. Effects were larger for insomnia and for depression than for PTSD. Similar patterns were observed with respect to clinical response and remission. A tipping point sensitivity analyses supported the plausibility of the findings. CONCLUSIONS: The sequential delivery of CBTi and CPT had plausible, significant effects on insomnia, depression, and PTSD compared to CPT alone. The effects for PTSD symptoms were moderate and clinically meaningful.

Pain treatment and functional improvement in home health care: Relationship with dementia.

BACKGROUND: Pain management is important to post-acute functional recovery, yet older persons with Alzheimer's disease and related dementias (ADRD) are often undertreated for pain. The main objectives were (1) to examine the relationship between ADRD and analgesic use among Medicare home health care (HHC) recipients with daily interfering pain, and (2) to examine the impact of analgesic use on functional outcome in patients with and without ADRD. METHODS: We analyzed longitudinal data from the Outcome and Assessment Information Set, Medicare HHC claims, and HHC electronic medical records during a 60-day HHC episode. The sample included 6048 Medicare beneficiaries ≥65 years receiving care from an HHC agency in New York in 2019 who reported daily interfering pain. Analgesic use was assessed during HHC medication reconciliation and included any analgesic, non-opioid analgesic, and opioid. ADRD was identified from ICD-10 codes (HHC claims) and cognitive impairment symptoms (Outcome and Assessment Information Set [OASIS]). Functional outcome was measured as change in the composite Activity of Daily Living (ADL) limitation score in the HHC episode. RESULTS: ADRD was related to a lower likelihood of using any analgesic (odds ratio [OR] = 0.66, 95% confidence interval [CI]: 0.49, 0.90, p = 0.008) and opioids (OR = 0.54, 95% CI: 0.47, 0.62, p < 0.001), but not related to non-opioid analgesic use (OR = 0.94, 95% CI: 0.74, 1.18, p = 0.58). Stratified analyses showed that any analgesic use (ß = -0.43, 95% CI: -0.73, -0.13, p = 0.004) and non-opioid analgesic use (ß = -0.31, 95% CI: -0.56, -0.06, p = 0.016) were associated with greater ADL improvement in patients with ADRD, but not in patients without ADRD. Opioid use was not significantly related to ADL improvement regardless of ADRD status. CONCLUSIONS: HHC patients with ADRD may be undertreated for pain, yet pain treatment is essential for functional improvement in HHC. HHC clinicians and policymakers should ensure adequate pain management for older persons with ADRD for improved functional outcomes.

Targeting autonomic flexibility to enhance cognitive training outcomes in older adults with mild cognitive impairment: study protocol for a randomized controlled trial.

IMPORTANCE: Cognitive training with components that can further enhance the transferred and long-term effects and slow the progress of dementia is needed for preventing dementia. OBJECTIVE: The goal of the study is to test whether improving autonomic nervous system (ANS) flexibility via a resonance frequency breathing (RFB) training will strengthen the effects of a visual speed of processing (VSOP) cognitive training on cognitive and brain function, and slow the progress of dementia in older adults with mild cognitive impairment (MCI). DESIGN: Stage II double-blinded randomized controlled trial. The study was prospectively registered at ClinicalTrials.gov, with registration approved on 21 August 2020 (No. NCT04522791). SETTING: Study-related appointments will be conducted on-site at University of Rochester Medical Center locations. Data collection will be conducted from August 2020 to February 2025. PARTICIPANTS: Older adults with MCI (n = 114) will be randomly assigned to an 8-week combined intervention (RFB+VSOP), VSOP with guided imagery relaxation (IR) control, and a IR-only control, with periodical booster training sessions at follow-ups. Mechanistic and distal outcomes include ANS flexibility, measured by heart rate variability, and multiple markers of dementia progress. Data will be collected across a 14-month period. DISCUSSION: This will be among the first RCTs to examine in older persons with MCI a novel, combined intervention targeting ANS flexibility, an important contributor to overall environmental adaptation, with an ultimate goal for slowing neurodegeneration. TRIAL REGISTRATION: ClinicalTrials.gov NCT04522791 . Registered on 21 August 2020 Protocol version: STUDY00004727; IRB protocol version 2, approved on 30 July 2020.

Decoding individual identity from brain activity elicited in imagining common experiences.

Everyone experiences common events differently. This leads to personal memories that presumably provide neural signatures of individual identity when events are reimagined. We present initial evidence that these signatures can be read from brain activity. To do this, we progress beyond previous work that has deployed generic group-level computational semantic models to distinguish between neural representations of different events, but not revealed interpersonal differences in event representations. We scanned 26 participants' brain activity using functional Magnetic Resonance Imaging as they vividly imagined themselves personally experiencing 20 common scenarios (e.g., dancing, shopping, wedding). Rather than adopting a one-size-fits-all approach to generically model scenarios, we constructed personal models from participants' verbal descriptions and self-ratings of sensory/motor/cognitive/spatiotemporal and emotional characteristics of the imagined experiences. We demonstrate that participants' neural representations are better predicted by their own models than other peoples'. This showcases how neuroimaging and personalized models can quantify individual-differences in imagined experiences.

Effects of mindfulness training on posttraumatic stress symptoms from a community-based pilot clinical trial among survivors of intimate partner violence.

Objective: Exposure to intimate partner violence (IPV) is a significant public health issue associated with deleterious mental and medical health comorbidities, including posttraumatic stress disorder (PTSD). The hallmark symptoms of posttraumatic stress (PTS), even when not meeting the threshold for a diagnosis of PTSD, appear to be underpinned by poor self-regulation in multiple domains, including emotion, cognitive control, and physiological stress. Mindfulness-based stress reduction (MBSR) holds promise for treating PTS symptoms because evidence suggests it targets these domains. The current study was a pilot randomized clinical trial designed to examine changes in emotion regulation, attentional function, and physiological stress dysregulation among women IPV survivors with elevated PTS symptoms after participation in a group-based, 8-week MBSR program. Method: In total, 29 participants were randomized to receive MBSR (n = 19) or an active control (n = 10). Assessments were conducted at study entry, as well as 8 and 12 weeks later. Results: Between-group differences on primary outcomes were nonsignificant; however, when exploring within groups, statistically significant decreases in PTS symptoms, F(1.37, 16.53) = 5.19, p < .05, and emotion dysregulation, F(1.31, 14.46) = 9.36, p < .01, were observed after MBSR but not after the control intervention. Further, decreases in PTSD and emotion dysregulation were clinically significant for MBSR participants but not control participants. Conclusions: These preliminary data signal that MBSR may improve PTS symptoms and emotion regulation and suggest further study of the effectiveness of PTSD interventions guided by integrative models of MBSR mechanisms and psychophysiological models of stress regulation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Autonomic flexibility reflects learning and associated neuroplasticity in old age.

Effective learning in old age, particularly in those at risk for dementia, is essential for prolonging independent living. Individual variability in learning, however, is remarkable; that is, months of cognitive training to improve learning may be beneficial for some individuals but not others. So far, little is known about which neurophysiological mechanisms account for the observed variability in learning induced by cognitive training in older adults. By combining Lövdén et al.'s (2010, A theoretical framework for the study of adult cognitive plasticity. Psychological Bulletin, 136, 659-676) framework proposing the role of adaptation capacity in neuroplasticity and a neurovisceral integration model of the relationship between autonomic nervous system (ANS) and brain with a novel shapelet analytical approach that allows for accurate and interpretable analysis of time series data, we discovered an acute, ECG-derived ANS segment in response to cognitive training tasks at baseline that predicted learning outcomes from a 6-week cognitive training intervention. The relationship between the ANS segment and learning was robust in both cross-participant and cross-task analyses among a group of older adults with amnestic mild cognitive impairment. Furthermore, the revealed ANS shapelet significantly predicted training-induced neuroplasticity in the dorsal anterior cingulate cortex and select frontal regions during task fMRI. Across outcome measures, individuals were less likely to prospectively benefit from the cognitive training if their ECG data were more similar to this particular ANS segment at baseline. Our findings are among the first empirical evidence to confirm that adaptation capacity, indexed by ANS flexibility, predicts individual differences in learning and associated neuroplasticity beyond individual characteristics (e.g., age, education, neurodegeneration, total training).

Dysregulation of inflammation, neurobiology, and cognitive function in PTSD: an integrative review.

Compelling evidence from animal and human research suggest a strong link between inflammation and posttraumatic stress disorder (PTSD). Furthermore, recent findings support compromised neurocognitive function as a key feature of PTSD, particularly with deficits in attention and processing speed, executive function, and memory. These cognitive domains are supported by brain structures and neural pathways that are disrupted in PTSD and which are implicated in fear learning and extinction processes. The disruption of these supporting structures potentially results from their interaction with inflammation. Thus, the converging evidence supports a model of inflammatory dysregulation and cognitive dysfunction as combined mechanisms underpinning PTSD symptomatology. In this review, we summarize evidence of dysregulated inflammation in PTSD and further explore how the neurobiological underpinnings of PTSD, in the context of fear learning and extinction acquisition and recall, may interact with inflammation. We then present evidence for cognitive dysfunction in PTSD, highlighting findings from human work. Potential therapeutic approaches utilizing novel pharmacological and behavioral interventions that target inflammation and cognition also are discussed.

Processing speed and attention training modifies autonomic flexibility: A mechanistic intervention study.

Adaptation capacity is critical for maintaining cognition, yet it is understudied in groups at risk for dementia. Autonomic nervous system (ANS) is critical for neurovisceral integration and is a key contributor to adaptation capacity. To determine the central nervous system's top-down regulation of ANS, we conducted a mechanistic randomized controlled trial study, using a 6-week processing speed and attention (PS/A)-targeted intervention. Eighty-four older adults with amnestic mild cognitive impairment (aMCI) were randomized to a 6-week PS/A-targeted intervention or an active control without PS/A. Utilizing repeated measures (i.e., PS/A test different from the intervention, resting and cognitive task-based ECG, and resting fMRI) at baseline, immediately post-intervention (post-test), and 6-month follow-up, we aimed to test whether PS/A causally influences vagal control of ANS via their shared central neural pathways in aMCI. We indexed vagal control of ANS using high-frequency heart rate variability (HF-HRV) extracted from ECG data. Functional brain connectivity patterns were extracted from fMRI using advanced statistical tools. Compared to the control group, the intervention group showed significant improvement in PS/A, HF-HRV, salience network (SN), central executive network (CEN), and frontal parietal network (FPN) connectivity at post-test; the effect on SN, CEN, and FPN remained at 6-month follow-up. Changes in PS/A and SN connectivity significantly predicted change in HF-HRV from baseline to post-test and/or 6-month-follow-up. Age, neurodegeneration, nor sex did not affect these relationships. This work provides novel support for top-down regulation of PS/A and associated SN on vagal control of ANS. Intervening PS/A may be a viable approach for promoting adaptation capacity in groups at risk for dementia.

Stress adaptation in older adults with and without cognitive impairment: an fMRI pattern-based similarity analysis.

BACKGROUND: The capacity to adapt to environmental stressors is essential for older adults' health and well-being. It is unclear how cognitive impairment may disrupt the capacity. Here we examined the relationship between self-perceptions of stress and the neurobiological response to a laboratory model of stress adaptation in amnestic mild cognitive impairment (aMCI), a group at high risk for dementia. RESULTS: aMCI group and cognitively healthy controls did not differ in neurobiological acute stress recovery (indexed by similarity in neural patterns at baseline and after recovery from cognitive challenges). However, compared to controls, aMCI group had significantly lower scores on PSS-PW. Notably, higher PSS-PW was associated with greater acute neural recovery in controls, but not aMCI. METHODS: We assessed self-perceptions of stress adaptation with the Perceived Stress Scale subscales, measuring perceived helplessness (i.e., negatively worded items, PSS-NW) and self-efficacy (i.e., positively worded items, PSS-PW) in response to stress. At a subsequent laboratory fMRI visit, we indexed neurobiological stress adaptation by assessing and comparing functional network connectivity at baseline and immediately following, and after recovery from, cognitive challenges. CONCLUSIONS: Studying stress adaptation in aMCI may shed light on pathways that contribute to the onset and progress of cognitive deterioration in aging.

Cognitive Behavioral Therapy for Insomnia Reduces Depression in Cancer Survivors.

STUDY OBJECTIVES: The current archival analyses examine the direct and indirect effects of cognitive behavioral therapy for insomnia (CBT-I) on depression in cancer survivors. METHODS: We report on 67 cancer survivors from a 2 × 2 randomized controlled trial of CBT-I and armodafinil for insomnia, after collapsing across the noneffective study medication conditions (armodafinil/placebo) to create CBT-I (yes/no). Depression and insomnia were assessed before, during the 7-week CBT-I intervention, at postintervention, and 3 months later by the Patient Health Questionnaire and the Insomnia Severity Index, respectively. RESULTS: Mean depression at baseline for all participants was 6.44 (standard error = 0.41, range 0-15). Paired t tests showed that depression improved from baseline to postintervention by 48% (P < .001) in the CBT-I group versus 15% (P = .016) in the non-CBT-I group. Analysis of covariance controlling for baseline found that participants receiving CBT-I had significantly less depression at postintervention (effect size = -0.62; P = .001), compared to those who did not receive CBT-I. These benefits were maintained at the 3-month follow-up. Spearman rank correlations showed that changes in insomnia severity from baseline to postintervention were significantly correlated with concurrent changes in depression (r = .73; P < .001). Path analysis revealed that improvement in depression was mediated by improvement in insomnia severity (P < .001). CONCLUSIONS: Our findings provide preliminary support that in cancer survivors, CBT-I reduces depression via improvement in insomnia. Further, this reduction in depression remained stable 3 months after completing CBT-I. This suggests that a CBT-I intervention has a meaningful effect on depression. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Cognitive Behavioral Therapy +/- Armodafinil for Insomnia and Fatigue Following Chemotherapy; Identifier: NCT01091974; URL: https://clinicaltrials.gov/ct2/show/record/NCT01091974.