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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.

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.

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)., We provide first line of empirical evidence confirming the theoretical relationship between adaptation capacity, ANS flexibility is a main indictor of which, and neuroplasticity. The identified ANS segment can help determine which individuals may be more responsive to a particular cognitive training.

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

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.

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

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.

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).

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.

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.

Objectives Poor quality of life (QoL) is a major concern among older adults with amnestic mild cognitive impairment (MCI). Maladaptive affective regulation and its relevant frontal dysfunction that are often observed in older adults with MCI may provide an insight into the understanding of their QoL. Methods In this case-controlled study, participants (MCI patients, N = 18; healthy comparisons [HC], N = 21) completed cognitive tasks, and underwent resting-state functional magnetic resonance imaging (rs-fMRI) immediately before and after the tasks. The amplitude of low-frequency fluctuations (ALFF) of rs-fMRI signals was calculated to examine the brain's spontaneous activity. The change in valence from the Self-Assessment Manikin indexed affective reactivity. QoL was assessed using Quality of Life-AD measure. Multiple mediator model was used to examine the mediating effect of frontal regions' ALFF reactivity between the affective reactivity and QoL. Results The MCI group had significantly worse QoL and more negative affective reactivity than HC group. Less negative affective reactivity was significantly associated with better QoL in MCI not HC. ALFF in the anterior cingulate cortex, medial prefrontal cortex (MPFC), and superior frontal gyrus (SFG) increased significantly less after cognitive tasks in MCI than HC. For the entire sample, greater increases of ALFF in MPFC and SFG were significantly associated with better QoL, and SFG alone significantly mediated the association between affective reactivity and QoL. Conclusions Enhancing SFG activation, especially among those with MCI, may provide a therapeutic target for addressing the negative impact of maladaptive affective regulation on QoL.

Locus of control (LOC) measures the extent to which individuals perceive control over their lives. Those with a more “internal” LOC feel self-sufficient and able to determine important aspects of their own future, while those with a more “external” LOC feel that their lives are governed by events beyond their control. Reduced internal LOC and increased external LOC have been found in cognitive disorders, but the neural substrates of these control perceptions are yet unknown. In the present study, we explored the relationship between amygdala functional connectivity and LOC in 18 amnestic mild cognitive impairment (MCI) and age-, sex-, and education-matched, 22 cognitively healthy controls (HC). Participants completed cognitive challenge tasks (Stroop Word Color task and Dual 1-back) for 20 min, and underwent resting-state functional magnetic resonance imaging immediately before and after the tasks. We found significantly lower internal LOC and higher external LOC in the MCI group than the HC group. Compared to HC, MCI group showed significantly stronger positive associations between internal LOC and baseline right amygdala connections (including right middle frontal gyrus and anterior cingulate cortex), and stronger negative associations between internal LOC and change of these right amygdala connections. Across all participants, external LOC explained the relationships between associations of another set of right amygdala connections (including middle cingulate cortex and right superior frontal gyrus), both at baseline and for change, and performance in the cognitive challenge tasks. Our findings indicate that the right amygdala networks might be critical in understanding the neural mechanisms underlying LOC's role in cognitive aging.

Essays about distressing events written by 58 older adults on three occasions ( n = 174) were coded to identify how older adults responded when confronting an emotionally upsetting event. Participants limited the experience of negative emotion by transitioning from negative to positive aspects of the event within a writing session, and across sessions, switched writing topics and moved from writing about past events to current problems. The use of attentional deployment tactics was associated with lower negative affect. This study confirms results found in quantitative studies and uncovers new processes that promote emotion regulation.

Objective Interest in meditation to manage posttraumatic stress disorder (PTSD) symptoms is increasing. Few studies have examined the effectiveness of meditation programs offered to Veterans within Department of Veterans Affairs (VA) mental health services. The current study addresses this gap using data from a multisite VA demonstration project. Method Evaluation data collected at 6 VA sites (N = 391 Veterans) before and after a meditation program, and a treatment-as-usual (TAU) program, were examined here using random effects meta-analyses. Site-specific and aggregate between group effect sizes comparing meditation programs to TAU were determined for PTSD severity measured by clinical interview and self-report. Additional outcomes included experiential avoidance and mindfulness. Results In aggregate, analyses showed medium effect sizes for meditation programs compared to TAU for PTSD severity (clinical interview: effect size (ES) = -0.32; self-report: ES = -0.39). Similarly sized effects of meditation programs were found for overall mindfulness (ES = 0.41) and 1 specific aspect of mindfulness, nonreactivity to inner experience (ES = .37). Additional findings suggested meditation type and program completion differences each moderated program effects. Conclusions VA-sponsored meditation programs show promise for reducing PTSD severity in Veterans receiving mental health services. Where meditation training fits within mental health services, and for whom programs will be of interest and effective, require further clarification. (PsycINFO Database Record

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 on 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 there is a causal influence of PS/A on 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.

Objectives Clinical insomnia is known to affect pain, but mechanisms are unclear. Insomnia can dysregulate inflammatory pathway, and inflammation plays a mediating role in pain. It is unclear whether insomnia-related alterations in inflammation can be modified with insomnia improvement, and if such alterations parallel improvement in pain. The current study objective was to provide proof of concept for the role of insomnia in inflammation and pain by testing whether improving insomnia would reduce pain and related physical function, and, concurrently, modulate inflammatory responses. Materials and methods Thirty adults with osteoarthritis knee pain and insomnia (Insomnia Severity Index >10) provided baseline measures of osteoarthritis and laboratory pain, and serial blood samples for inflammatory biomarkers, interleukin 6, and tumor necrosis factor α, before and after pain testing. To manipulate insomnia, participants were randomly assigned to a 6-week cognitive-behavioral therapy for insomnia (n=16); or wait-list control (n=14). At 8-weeks (time 2), all measures were repeated. To directly test insomnia improvement effects, participants were grouped by insomnia status at time 2 after confirming baseline equivalency on all outcomes. Results Compared with those maintaining insomnia at time 2 (Insomnia Severity Index ≥8; n=18), those whose insomnia improved at time 2 (n=12) had significantly improved physical functioning, decline in knee pain during transfer activities, and attenuated increase in interleukin 6 and less decrease in tumor necrosis factor α across the pain testing session. Discussion These findings suggest further exploration of inflammatory pathways linking clinical insomnia, and its improvement, to chronic pain.

Sleep disturbance is a common feature of posttraumatic stress disorder (PTSD), but is not a focus of standard PTSD treatments. Psychological trauma exposure is associated with considerable physical and mental health morbidity, possibly due to the alterations in neuroendocrine function and inflammation observed in trauma exposed individuals. Although PTSD treatments are efficacious, they are associated with high drop-out rates in clinical trials and clinical practice. Finally, individuals with PTSD stemming from exposure to interpersonal violence represent an especially under-treated population with significant sleep disturbance. Community-based participatory research was utilized to design and prepare a clinical trial that randomizes recent survivors of interpersonal violence who have PTSD, depression, and insomnia to receive either: (1) Cognitive Behavioral Therapy for Insomnia (CBTi) followed by Cognitive Processing Therapy (CPT) for trauma, or (2) attention control followed by CPT. Outcome measures include subjective and objective measures of sleep, clinician-administered PTSD and depression scales, inflammatory cytokines, and salivary cortisol. Assessments are conducted at baseline, following the sleep or control intervention, and again following CPT. The design allows for: (1) the first test of a sleep intervention in this population; (2) the comparison of sequenced CBTi and CPT to attention control followed by CPT, and (3) assessing the roles of neuroendocrine function, inflammatory processes, and objective sleep markers in mediating treatment outcomes. The study's overarching hypothesis is that treating insomnia will produce reduction in insomnia, PTSD, and depression severity, allowing patients to more fully engage in, and derive optimal benefits from, cognitive processing therapy.

Background: Vision-based speed of processing (VSOP) training can result in broad cognitive improvements in older adults with amnestic mild cognitive impairment (aMCI). What remains unknown, however, is what neurophysiological mechanisms account for the observed training effect. Much of the work in this area has focused on the central nervous system, neglecting the fact that the peripheral system can contributes to changes of the central nervous system and vice versa. Objective: We examined the prospective relationship between an adaptive parasympathetic nervous system response to cognitive stimuli and VSOP training-induced plasticity. Method: Twenty-one participants with aMCI (10 for VSOP training, and 11 for mental leisure activities (MLA) control) were enrolled. We assessed high-frequency heart rate variability (HF-HRV) during training sessions, and striatum-related neural networks and cognition at baseline and post-training. Results: Compared to MLA, the VSOP group showed a significant U-shaped pattern of HF-HRV response during training, as well as decreases in connectivity strength between bilateral striatal and prefrontal regions. These two effects were associated with training-induced improvements in both the trained (attention and processing speed) and transferred (working memory) cognitive domains. Conclusion: This work provides novel support for interactions between the central and the peripheral nervous systems in relation to cognitive training, and motivates further studies to elucidate the causality of the observed link.

Objective: To better understand age and gender differences in associations of social relationships with chronic inflammation. Method: Using a sample of middle-aged and older adults ( N = 963) from the Midlife Development in the United States (MIDUS) biomarker project, we examined interactions of age and gender with structural and functional social network measures in predicting interleukin-6 (IL-6) and C-reactive protein (CRP). Results: Significant interactions involving age and gender showed that social support was associated with lower IL-6 in older women, whereas perceived positive relationships and social integration were related to lower IL-6 in both men and women of advanced age. Functional measures were associated with higher CRP in both men and women after adjustment for health conditions and behaviors, with some further variation by age. Discussion: Greater social support may be related to lower IL-6 in older women. Further research is needed to understand observed associations of social support with higher CRP.

Objectives Recent evidence suggests that younger and middle-age adults who show greater cardiovascular reactivity (CVR) to acute mental stress demonstrate better reasoning and memory skills. The purpose of this study was to examine whether older adults would exhibit a similar positive association between CVR and executive function and whether regular engagement in mentally stimulating activities (MSA) would moderate this association. Design Secondary cross-sectional analysis. Setting Three clinical research centers in the Midwest and on the West Coast and East Coast. Participants A total of 487 older adults participating in an ongoing national survey. Measurements Heart rate (HR) and low-frequency (LF) and high-frequency (HF) domains of heart rate variability (HRV) were measured at baseline and in response to standard mental stress tasks (Stroop color word task and mental arithmetic). Executive function was measured separately from the stress tasks by using five neuropsychological tests. MSA was measured by self-reported frequency of six common MSA. Results Higher HR reactivity was associated with better executive function after controlling for demographic and health characteristics and baseline HR, and the interaction between HR reactivity and MSA was significant for executive function. Higher LF-HRV reactivity was also associated with executive function, but subsequent analyses indicated that frequency of MSA was the strongest predictor of executive function in models that included LF-HRV or HF-HRV. Conclusions Higher HR reactivity to acute psychological stress is related to better executive function in older adults. For those with lower HR reactivity, engaging frequently in MSA produced compensatory benefits for executive function.

Summary Objectives Accumulating evidence suggests an adverse association between depressive symptoms and cognition, but a positive association between insulin-like growth factor (IGF)-1 and cognition. The present study examined the influence of IGF-1 in the relationship between depressive symptoms and learning and memory. Methods A cross-sectional study of 94 healthy fit older adults. Blood was collected and plasma IGF-1 was measured. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS), and learning and memory were assessed using the Rey Auditory Verbal Learning Test (AVLT). Results Among older adults with lower IGF-1 levels, higher depressive symptoms scores were associated with lower AVLT delayed recall and recognition. Older adults with higher IF-1 levels showed no associations between depressive symptoms and memory. Conclusions The association between depressive symptoms and cognition is stronger among older adults with lower levels of circulating IGF-1. Further validation studies on groups with depression or different stages of cognitive impairment are needed. IGF-1 may be a novel intervention target for slowing cognitive decline in older adults with depressive symptoms.

BACKGROUND/STUDY CONTEXT: Vascular and myocardial activation can each increase blood pressure responses to stressors, but vascular responses are uniquely associated with negative affect, pernicious coping processes, and cardiovascular risk. These hemodynamic correlates of coping in response to acute stressors have not been well characterized in older adults.Adults 65 to 97 years of age (N = 74) either engaged in written disclosure about a distressing event (acute stressor) or wrote objectively about a neutral topic (control). Blood pressure, impedance cardiography, and affect measures were assessed at baseline and in response to writing. Moderating effects of age on affect, blood pressure, and vascular and myocardial responses to the acute stressor were tested using multiple linear regression models.Follow-up tests of Age × Writing Group interactions indicated that the expected effects of written disclosure on systolic and diastolic blood pressure responses were diminished with increasing age. Regardless of age, compared with neutral writing, written disclosure increased negative affect and vascular responses, but not myocardial responses.Blood pressure responses to an acute, emotionally evocative stressor were indistinguishable from blood pressure responses to a control condition among the eldest older adults in our sample. In contrast, characterizing the hemodynamic mechanisms of blood pressure responses revealed notable vascular effects of the acute, emotional stressor across a wide age range. Such characterization may be particularly useful for clarifying the psychophysiological pathways to older adults' cardiovascular health.

Posttraumatic stress disorder (PTSD) is a chronic and debilitating disorder that affects the lives of 7-8% of adults in the U.S. Although several interventions demonstrate clinical effectiveness for treating PTSD, many patients continue to have residual symptoms and ask for a variety of treatment options. Complementary health approaches, such as meditation and yoga, hold promise for treating symptoms of PTSD. This meta-analysis evaluates the effect size (ES) of yoga and meditation on PTSD outcomes in adult patients. We also examined whether the intervention type, PTSD outcome measure, study population, sample size, or control condition moderated the effects of complementary approaches on PTSD outcomes. The studies included were 19 randomized control trials with data on 1,173 participants. A random effects model yielded a statistically significant ES in the small to medium range (ES = −.39, p < .001, 95% CI [−.57, −.22]). There were no appreciable differences between intervention types, study population, outcome measures, or control condition. There was, however, a marginally significant higher ES for sample size ≤ 30 (ES = −.78, k = 5). These findings suggest that meditation and yoga are promising complementary approaches in the treatment of PTSD among adults and warrant further study.

ObjectivesTo examine the cognitive and neural effects of vision-based speed-of-processing (VSOP) training in older adults with amnestic mild cognitive impairment (aMCI) and contrast those effects with an active control (mental leisure activities (MLA)).DesignRandomized single-blind controlled pilot trial.SettingAcademic medical center.ParticipantsIndividuals with aMCI (N=21).InterventionSix-week computerized VSOP training.MeasurementsMultiple cognitive processing measures, instrumental activities of daily living (IADLs), and two resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN).ResultsVSOP training led to significantly greater improvements in trained (processing speed and attention: F1,19 =6.61, partial η(2) =0.26, P=.02) and untrained (working memory: F1,19 =7.33, partial η(2) =0.28, P=.01; IADLs: F1,19 =5.16, partial η(2) =0.21, P=.03) cognitive domains than MLA and protective maintenance in DMN (F1, 9 =14.63, partial η(2) =0.62, P=.004). VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z=-2.37, P=.02).ConclusionTarget and transfer effects of VSOP training were identified, and links between VSOP training and two neural networks associated with aMCI were found. These findings highlight the potential of VSOP training to slow cognitive decline in individuals with aMCI. Further delineation of mechanisms underlying VSOP-induced plasticity is necessary to understand in which populations and under what conditions such training may be most effective.

Objectives Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. Design Observational study of community-dwelling, healthy older adults. Setting Participants completed the study in a clinical research laboratory of a mid-sized university. Participants Generally healthy, community-dwelling men and women age 50 and older. Measurements IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. Results Participants categorized as poor sleepers on the basis of Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors than good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. Conclusions Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation.

Sleep disturbance is a common comorbidity of chronic pain. Inflammatory processes are dysregulated in sleep disturbance and also contribute to pain sensitivity. Thus, inflammation may play an important role in bidirectional associations between pain and sleep. Little is known about concurrent relationships among chronic pain, sleep, and inflammation. The aim of our study was to examine associations between sleep disturbance and circulating levels of the inflammatory cytokine, interleukin-6 (IL-6), in individuals with and without chronic low back pain.Sex-matched and age-matched adults with chronic low back pain (CLBP; n=25) or without chronic pain (controls; n=25)completed measures of sleep quality in the past month and depressive symptoms in the past week, and provided a blood sample for IL-6. The next morning, participants reported their sleep quality the previous night and their current experience of morning pain.Individuals with CLBP had more sleep disturbance than controls. Circulating IL-6 levels were similar for the 2 groups; however, in adults with CLBP, poorer sleep quality was associated with higher IL-6 levels, and both sleep and IL-6 related to pain reports. Unlike CLBP participants, controls showed normal, age-related increases in IL-6 levels, whereas sleep quality was unrelated to IL-6 levels. Depressive symptoms could not fully explain the observed associations.Inflammatory processes may play a significant role in the cycles of pain and sleep disturbance. Clinical interventions that improve sleep and reduce concomitant inflammatory dysregulation hold promise for chronic pain management.

Summary Allergic rhinitis (AR) is the fifth most common chronic disease, and the association between allergic disorders and anxiety is well-documented. To investigate how anxiety and stressors modulate skin prick test (SPT) responses and associated inflammatory responses, 28 men and women with AR were selected by clinical history and skin test responses. The participants were admitted twice to a hospital research unit for 4 h in a crossover trial. Changes in SPT wheals were assessed before and after a standardized laboratory speech stressor, as well as again the following morning; skin responses assessed twice during a lab session without a stressor and again the following morning served as the contrast condition. Anxiety heightened the magnitude of allergen-induced wheals following the stressor. As anxiety increased, SPT wheal diameters increased after the stressor, compared to a slight decrease following the control task. Anxiety also substantially enhanced the effects of stress on late phase responses: even skin tests performed the day after the stressor reflected the continuing impact of the speech stressor among the more anxious participants. Greater anxiety was associated with more IL-6 production by Con A-stimulated leukocytes following the stressor compared to the control visit. The data suggest that stress and anxiety can enhance and prolong AR symptoms.

Objectives Adaptive physiological stress regulation is rarely studied in mild cognitive impairment (MCI). Here we targeted mental fatigability (MF) as a determinant of altered high frequency heart rate variability (HF-HRV) reactivity in individuals with MCI, and examined frontobasal ganglia circuitry as a neural basis supporting the link between MF and HF-HRV reactivity. Methods We measured mental fatigability and HF-HRV during a 60-minute cognitive stress protocol in 19 individuals with MCI. HF-HRV responses were modeled using a quadratic equation. Resting state functional connectivity of intra- and inter-network frontobasal ganglia circuitry was assessed using blood-oxygen-level-dependent magnetic resonance imaging among seven of the participants. Results Lower MF was associated with faster and greater rebound in U-shape HF-HRV reactivity, which linked to a stronger connectivity between right middle frontal gyrus and left putamen. Conclusions Results suggest that MF may contribute to abnormal physiological stress regulation in MCI, and fronto basal ganglia circuitry may support the link.

Background: Human and animal laboratory studies have shown that stress delays healing of standardized punch biopsy wounds. Purpose: This 5-week prospective study of 17 women who underwent elective gastric bypass surgery addressed the association between postsurgical pain intensity and subsequent healing of a standard 2.0-mm punch biopsy wound. Methods: Participants were assessed 1 week before surgery, within 3 hr before surgery, 1 to 3 days postsurgery, and at weekly intervals for 4 weeks following surgery. Results: Patient ratings of greater acute postsurgical pain, averaged over Days 1 and 2 postsurgery, and greater persistent postsurgical pain, averaged over 4 weekly postsurgery pain ratings, were significantly associated with subsequent delayed healing of the punch biopsy wound. Presence of depressive symptoms on the day of surgery, pre-existing persistent pain, and medical complications following initial discharge from the hospital were not related to wound healing. Depressive symptoms on the day of surgery and pre-existing persistent pain did predict persistent postsurgical pain intensity. Conclusions: These findings extend the previous laboratory models of wound healing to a surgical population, providing the first evidence that pain plays an important role in postsurgery wound healing, a key variable in postsurgical recovery.

We investigated linkages between spousal support satisfaction and affective, cortisol, and blood pressure responses to conflict in two samples, 85 newlyweds and 31 older couples, married an average of 42 years. Couples were admitted to a hospital research unit and provided self-reports regarding the support received from their spouses. After a baseline period, couples engaged in a 30-min conflict discussion during which time blood was drawn for cortisol assessment. After the conflict, newlyweds' blood pressure was measured. Among newlywed wives, greater spousal support satisfaction was associated with smaller changes in negative affect and cortisol responses to conflict. Notably, newlywed wives and husbands demonstrated lower blood pressure after conflict when spousal support satisfaction was higher. In contrast, older husbands (but not wives) exhibited greater cortisol responses when spousal support satisfaction was lower. These relationships provide a window on mechanisms linking marriage and health for men and women across the life span.

Objectives Mental fatigability refers to the failure to sustain participation in tasks requiring mental effort. Older adults with vascular risk are at particular risk for experiencing mental fatigability. The present study (1) tested a new way of measuring objective mental fatigability by examining its association with perceived mental fatigability; and (2) identified associated psychological, physiological, and situational predictors. Methods A cross-sectional study was conducted with 49 community-dwelling participants aged 75 + years with vascular risk. A 20-minute fatigability-manipulation task was used to induce mental fatigability and develop objective and perceived mental fatigability measures. Objective fatigability was calculated by the change of reaction time over the course of the task. Perceived fatigability was calculated by the change of fatigue self-reported before and after the task. A set of potential psychological, physiological, and situational predictors were measured. Results There was a significant increase in reaction time and self-reported fatigue to the fatigability manipulation task, indicating occurrence of objective and perceived mental fatigability. Reaction time and self-reported fatigue were moderately, but significantly correlated. Higher levels of executive control and having a history of more frequently engaging in mental activities were associated with lower objective mental fatigability. None of the examined factors were associated with perceived mental fatigability. Conclusion Objective and perceived mental fatigability were sensitive to our fatigability-manipulation task. While these two measures were correlated, they were not associated with the same factors. These findings need to be validated in studies with a more heterogeneous sample and a greater variety of fatigability-manipulation tasks.

Anxiety and psychological stress affect allergy-related immune function. How these relations influence the evaluations of patients with allergic rhinitis is unknown.To examine whether anxiety and stress exposure affect skin prick test (SPT) responses to common allergens for which patients with atopy showed no prior positive SPT response.Patients with allergic rhinitis, evidenced by clinical history and SPT results, were admitted twice to a hospital research unit for 4 hours. In a crossover design, SPT wheals were assessed before and after the Trier Social Stress Test and then the following morning; for comparison, SPT wheals were assessed before and after a laboratory session without a stressor. Analyses focused on wheal responses for common allergens that tested negative (wheal size3 mm larger than saline) from SPTs performed at multiple baseline assessments.After the Trier Social Stress Test, more anxious patients with atopy had a higher incidence of positive SPT reactions to antigens that previously tested negative. Anxiety was unrelated to positive SPT incidence under nonstressful conditions. Based on clinical symptom reports, newly positive SPT reactions after the stressor were apparently corrections of previously false-negative SPT reactions. The SPT wheal responses for allergens previously testing negative were enhanced after a stressor. Histamine (positive control) or saline (negative control) SPT responses were not affected.A laboratory stressor affected allergen SPT responses in more anxious patients with allergic rhinitis. In addition to clinical history, assessment of anxiety and current stress at the time of the SPT may provide valuable information about a patient's allergic status and aid in clinical decision making.

This research was concerned with two issues: first, whether cardiovascular response patterns to a social stressor (i.e. self-presentation under evaluative circumstances) differ as a function of one's ability to control the impression one makes on others; second, whether cognitive appraisals are necessary or sufficient for the cardiovascular components of emotional arousal. Forty-two male subjects (Ss), monitored for cardiac impedance and blood pressure, were shown a previously recorded videotape of themselves in which each S verbally described personal aspects about himself. Ss in an Active condition were allowed to mark segments of the tape they wanted to re-shoot before the tape was evaluated by reviewers. Ss in a Passive condition viewed their tape but could not indicate whether to revise it. Control conditions allowed assessment of the activity entailed in tape marking and of evaluation per se. Self-reports of stress, threat, and coping ability regarding the upcoming task were taken. Blood pressure elevations occurred equally in both experimental conditions, but apparently through different underlying mechanisms. The Active condition produced myocardial responses (increased ejection fraction), while the Passive condition produced a vascular response (increased total peripheral resistance). However, while cardiovascular reactivity patterns did differ as a function of the opportunity to control the impression one could make on evaluative others, they did not differ as a function of having appraised the task as a challenge or as a threat. Consideration also is given to the conditions necessary for cognitive appraisal to occur and to influence reactivity.

Objective Pain, chronic medical morbidity, and depression are highly prevalent problems that frequently co-occur in primary care. Elevated levels of inflammatory markers are linked with all three of these conditions and may play an important role in patients' comorbidities. The current study aimed to examine if the associations among pain, chronic medical morbidity, and the inflammatory marker interleukin (IL)-6 are dependent on depression status in primary care patients. Setting, Subjects, and Outcome Measures Primary care patients (N = 106) aged 40 and older were assessed for pain (36-item Medical Outcomes Study Survey Form), chronic medical morbidity (checklist of chronic health conditions), and depressive symptoms (Center for Epidemiologic Studies Depression Scale), and provided a blood sample for the measurement of serum IL-6. Results Among patients with elevated depressive symptoms, higher IL-6 levels were associated with both greater pain and greater chronic medical comorbidity. IL-6 was unrelated to pain or chronic medical comorbidity among patients without clinically significant depressive symptoms. In mediation analyses, chronic medical morbidity did not mediate the association between IL-6 and pain, and depression severity and pain remained independently associated after adjustment for chronic medical comorbidity. Conclusions Depression may increase primary care patients' vulnerability to pain and elevated levels of inflammatory markers such as IL-6.

Objective To determine whether the relationship between interleukin (IL)-6 and depressive symptoms is moderated by participation in moderate-intensity physical activity in a sample of primary care patients. Elevated inflammation has been associated with a number of poor health outcomes. Depressive symptoms may be related to higher levels of the inflammatory marker IL-6; however, previous findings are inconsistent, possibly due to unidentified moderating factors. Methods A total of 107 participants, aged ≥ 40 years, were recruited in Rochester, New York, in 2006 to 2007. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale-Revised, participation in moderate-intensity physical activity was measured using a modified version of the Community Health Activities Model Program for Seniors Activity Questionnaire for Older Adults, and serum IL-6 concentrations were determined using standard enzyme-linked immunosorbent assay protocols and high-sensitivity, anti-cytokine antibody pairs. A hierarchical multiple regression analysis was conducted. Results The correlation between IL-6 and depressive symptoms was nonsignificant (r = .086, p = .40). The association between IL-6 and depressive symptoms was moderated by participation in moderate-intensity physical activity (p = .02). Among those who did not engage in moderate-intensity physical activity, higher levels of depressive symptoms were significantly associated with higher levels of IL-6 (r = .28, p = .05), whereas this association was not significant among those who did participate in moderate-intensity physical activity (r = -.13, p = .38). Conclusion Participation in moderate-intensity physical activity may buffer the risk of higher inflammation often associated with higher levels of depressive symptoms.

Prior studies have suggested a relationship between dehydration and poor cognitive performance. The present study examined the relationships among hydration status, declarative memory and working memory skills, and blood pressure in a sample of older community dwelling females.Data was analyzed from a larger study; relationships among hydration status, blood pressure, and cognitive measures were assessed with correlation and meditational analyses.Laboratory.21 postmenopausal women (mean age 60.3, SD 8.03).Hydration status was measured using bioelectrical impedance, baseline blood pressure was assessed using a Colin Pressmate, and cognition was examined using the Auditory Verbal Learning Test and Auditory Consonant Trigrams.Bioelectrical impedance total body water by weight was found to be related to working memory, r = .47, p = .04, and memory skills, r = .54, p = .01. Total body water by weight was also found to be related to diastolic blood pressure, r = -.56, p = .01, which in turn was related to working memory, r = -.67, p = .002, and declarative memory, r = -.57, p = .009, skills. When diastolic blood pressure was accounted for, the relationship between hydration status and cognitive skills was attenuated. A similar pattern of results was seen for systolic blood pressure, although findings did not reach statistical significance.Results emphasize the importance of considering hydration status and blood pressure when interpreting cognitive performance in older adults.

Social isolation confers increased risk for coronary heart disease (CHD) events and mortality. In two recent studies, low levels of social integration among older adults were related to higher levels of C-reactive protein (CRP), a marker of inflammation, suggesting a possible biological link between social isolation and CHD. The current study examined relationships among social isolation, CRP, and 15-year CHD death in a community sample of US adults aged 40 years and older without a prior history of myocardial infarction. A nested case-cohort study was conducted from a parent cohort of community-dwelling adults from the southeastern New England region of the United States (N = 2,321) who were interviewed in 1989 and 1990. CRP levels were measured from stored sera provided by the nested case-cohort (n = 370), which included all cases of CHD death observed through 2005 (n = 48), and a random sample of non-cases. We found that the most socially isolated individuals had two-and-a-half times the odds of elevated CRP levels compared to the most socially integrated. In separate logistic regression models, both social isolation and CRP predicted later CHD death. The most socially isolated continued to have more than twice the odds of CHD death compared to the most socially integrated in a model adjusting for CRP and more traditional CHD risk factors. The current findings support social isolation as an independent risk factor of both high levels of CRP and CHD death in middle-aged adults without a prior history of myocardial infarction. Prospective study of inflammatory pathways related to social isolation and mortality are needed to fully delineate whether and how CRP or other inflammatory markers contribute to mechanisms linking social isolation to CVD health.

We examined 31 older couples’ wife demand/husband withdraw communication patterns and cortisol responses to marital conflict. Regression analyses indicated that wife demand/husband withdraw sequences during conflict related to cortisol responses only for wives. Based on a mixed model that accounted for the interdependence of spouses’ perceptions of communication patterns and outcomes, older spouses who reported greater wife demand/husband withdraw patterns in their marriage had greater cortisol responses during a conflict discussion; actual demand-withdraw did not relate to cortisol responses in this model. Findings suggest that perceived communication patterns contribute to neuroendocrine responses to marital conflict, and implications for marriage and health research with older couples are discussed.

A growing body of research linking psychological and behavioral factors to the incidence and progression of cancer suggests that psychosocial factors may have an impact on some types of cancer [1–6]. In this paper, we suggest that it is through the impact these behavioral and psychological factors have on the cellular immune response, including natural killer (NK) cell function, that they may ultimately affect the occurrence and progression of certain tumors. Our discussion of this link begins with a brief overview of the evidence that psychoneuroimmunology (PNI) research with healthy individuals may be relevant to cancer. Next, to link extant PNI research findings with tumorigenesis, we draw upon two important PNI findings relating psychological distress to two important aspects of carcinogenesis: (i) poorer repair of damaged cellular DNA and (ii) modulation of apoptosis. Finally, we focus on the implications of intervention research in cancer patients for cancer progression and treatment. Before reviewing the evidence regarding stress-related immunological changes, it should be noted that one recurrent concern in the literature is the question of the significance of the immune system for cancer. Cancer is comprised of a heterogeneous group of diseases with multiple etiologies [1], and immunological involvement varies across different cancers. Those cancers that are induced by chemical carcinogens (e.g. lung cancer) may be less influenced by psychological, behavioral and immunological factors than cancers that are associated with a virus, such as Epstein–Barr Virus (EBV), which are immunogenic. Suppression of cellular immunity is associated with a higher incidence of certain types of tumors, particularly EBV-associated lymphoproliferative diseases in organ transplant patients, and Kaposi’s sarcoma and EBVassociated B-cell lymphoma in AIDS patients [7]. Additionally, some researchers have questioned whether stress-related immune changes are of either the type or the magnitude to influence tumor growth and metastases [3, 8]. While such issues are beyond the scope of this paper, compelling evidence exists for the role of cells, such as NK cells, in resisting the progression and metastatic spread of tumors once they have developed [7]. Stress and immune dysregulation