A pilot study of yogic meditation for family dementia caregivers with depressive symptoms: effects on mental health, cognition, and telomerase activity. Association between hospice care and psychological outcomes in Alzheimer's spousal caregivers. A pilot study of immune and mood outcomes of a community-based intervention for dementia caregivers: the PLST intervention. Effect of Childhood Emotional Abuse and Age on Cortisol Responsivity in Adulthood Yogic meditation reverses NF-κB and IRF-related transcriptome dynamics in leukocytes of family dementia caregivers in a randomized controlled trial Transcendental Meditation for the improvement of health and wellbeing in community-dwelling dementia caregivers [TRANSCENDENT]: a randomised wait-list controlled trial Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers A Yoga and Compassion Meditation Program Reduces Stress in Familial Caregivers of Alzheimer's Disease Patients Acute tryptophan depletion reduces kynurenine levels: implications for treatment of impaired visuospatial memory performance in irritable bowel syndrome Effects of moderate-intensity exercise on physiological, behavioral, and emotional responses to family caregiving: a randomized controlled trial. Accelerated risk of hypertensive blood pressure recordings among Alzheimer caregivers. A randomized clinical trial of Behavioral Activation (BA) therapy for improving psychological and physical health in dementia caregivers: results of the Pleasant Events Program (PEP). Blood pressure, stroke, and coronary heart disease: Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias Spousal Caregivers of Patients With Alzheimer's Disease Show Longitudinal Increases in Plasma Level of Tissue-Type Plasminogen Activator Antigen Cognitive–behavioural group therapy improves a psychophysiological marker of stress in caregivers of patients with Alzheimer's disease Sleep in spousal Alzheimer caregivers: a longitudinal study with a focus on the effects of major patient transitions on sleep. Positive aspects of caregiving and adaptation to bereavement. Effects of placement and bereavement on psychological well-being and cardiovascular risk in Alzheimer's caregivers: a longitudinal analysis. Antidepressant augmentation with metyrapone for treatment-resistant depression (the ADD study): a double-blind, randomised, placebo-controlled trial.
BACKGROUND This study examined the effects of brief daily yogic meditation on mental health , cognitive functioning , and immune cell telomerase activity in family dementia caregivers with mild depressive symptoms . METHODS Thirty-nine family dementia caregivers ( mean age 60.3 years old ( SD = 10.2 ) ) were r and omized to practicing Kirtan Kriya or listening to relaxation music for 12 min per day for 8 weeks . The severity of depressive symptoms , mental and cognitive functioning were assessed at baseline and follow-up . Telomerase activity in peripheral blood mononuclear cells ( PMBC ) was examined in peripheral P BMC pre-intervention and post-intervention . RESULTS The meditation group showed significantly lower levels of depressive symptoms and greater improvement in mental health and cognitive functioning compared with the relaxation group . In the meditation group , 65.2 % showed 50 % improvement on the Hamilton Depression Rating scale and 52 % of the participants showed 50 % improvement on the Mental Health Composite Summary score of the Short Form-36 scale compared with 31.2 % and 19 % , respectively , in the relaxation group ( p < 0.05 ) . The meditation group showed 43 % improvement in telomerase activity compared with 3.7 % in the relaxation group ( p = 0.05 ) . CONCLUSION This pilot study found that brief daily meditation practice s by family dementia caregivers can lead to improved mental and cognitive functioning and lower levels of depressive symptoms . This improvement is accompanied by an increase in telomerase activity suggesting improvement in stress-induced cellular aging . These results need to be confirmed in a larger sample CONTEXT Dementia care giving can lead to increased stress , physical and psychosocial morbidity , and mortality . Anecdotal evidence suggests that hospice care provided to people with dementia and their caregivers may buffer caregivers from some of the adverse outcomes associated with family caregiving in Alzheimer 's Disease ( AD ) . OBJECTIVES This pilot study examined psychological and physical outcomes among 32 spousal caregivers of patients with AD . It was hypothesized that caregivers who utilized hospice services would demonstrate better outcomes after the death of their spouse than caregivers who did not utilize hospice . METHODS The charts of all spousal caregivers enrolled in a larger longitudinal study from 2001 to 2006 ( N=120 ) were review ed , and participants whose spouse had died were identified . Of these , those who received hospice care ( n=10 ) were compared to those who did not ( n=22 ) for various physiological and psychological measures of stress , both before and after the death of the care recipient . An Analysis of Covariance ( ANCOVA ) , with postdeath scores as the dependent variable and pre-death scores as covariates , was used for all variables . RESULTS Significant group differences were found in postdeath depressive symptoms ( HAM-D ; F(1,29)=6.10 , p<0.05 ) and anxiety symptoms ( HAM-A ; F(1,29)=5.71 , p<0.05 ) . Most psychological outcome variables demonstrated moderate effect sizes with a Cohen 's d of>0.5 between groups . CONCLUSIONS These data suggest that hospice enrollment may ameliorate the detrimental psychological effects in caregivers who have lost a spouse with Alzheimer 's Disease . Based on these pilot data , further prospect i ve investigation is warranted Providing care to a family member with dementia is conceptualized as a chronic stressor with adverse psychological and physical effects . The purpose of this pilot study was to evaluate mood and immune outcomes of caregivers exposed to a community-based psychoeducational nursing intervention based on the progressively lowered stress threshold ( PLST ) model . The PLST intervention is design ed to strengthen the psychological re sources of dementia caregivers by teaching methods of preventing and /or managing behavioral problems exhibited by the person with dementia . Mood and immune outcomes were compared between caregivers r and omly assigned to receive either the PLST or a comparison intervention . Results of this pilot study suggest that caregivers who received the PLST intervention showed significantly stronger T-cell proliferative responses to both PHA and ConA , indicating an improvement in T-cell immune function immediately after the in-home intervention ( T2 ) and again after 6 months of telephone support for application of the PLST model ( T3 ) . Findings do not support the hypothesis that the PLST intervention had a significant effect on total mood disturbance or natural killer cell cytotoxicity over the course of the study BACKGROUND The dexamethasone/corticotropin releasing hormone ( Dex/CRH ) test has been proposed as a potential tool for identifying endophenotypes relevant to mood disorders . Several studies have shown abnormal cortisol reactivity in phenotypically healthy adults without psychiatric disorders as a function of exposure to adverse early environments . METHODS After a battery of self-report and interview assessment s , 230 adults without major Axis I Disorders completed the Dex/CRH test . Childhood maltreatment was evaluated with the Childhood Trauma Question naire . Effect of childhood emotional abuse ( EA ) on cortisol responses to the Dex/CRH test was examined with repeated measures general linear models , including age , gender , and other types of maltreatment . Post hoc models examined the significant interaction between EA and age and tested the stability of the main findings with selected covariates . RESULTS A history of self-reported childhood EA independently and significantly diminished cortisol response . This effect was amplified with advancing subject age and was independent of the effects of other types of childhood maltreatment , lifetime diagnoses , and symptom scores . CONCLUSIONS Dampened cortisol reactivity might be a consequence of childhood EA that is cumulative over time . Prospect i ve longitudinal investigation is needed to evaluate the potential of this proposed endophenotype BACKGROUND Although yoga and meditation have been used for stress reduction with reported improvement in inflammation , little is known about the biological mechanisms mediating such effects . The present study examined if a yogic meditation might alter the activity of inflammatory and antiviral transcription control pathways that shape immune cell gene expression . METHODS Forty-five family dementia caregivers were r and omized to either Kirtan Kriya Meditation ( KKM ) or Relaxing Music ( RM ) listening for 12 min daily for 8 weeks and 39 caregivers completed the study .  Genome-wide transcriptional profiles were collected from peripheral blood leukocytes sample d at baseline and 8-week follow-up . Promoter-based bioinformatics analyses tested the hypothesis that observed transcriptional alterations were structured by reduced activity of the pro-inflammatory nuclear factor (NF)-κB family of transcription factors and increased activity of Interferon Response Factors ( IRFs ; i.e. , reversal of patterns previously linked to stress ) . RESULTS In response to KKM treatment , 68 genes were found to be differentially expressed ( 19 up-regulated , 49 down-regulated ) after adjusting for potentially confounded differences in sex , illness burden , and BMI . Up-regulated genes included immunoglobulin-related transcripts . Down-regulated transcripts included pro-inflammatory cytokines and activation-related immediate-early genes . Transcript origin analyses identified plasmacytoid dendritic cells and B lymphocytes as the primary cellular context of these transcriptional alterations ( both p<.001 ) . Promoter-based bioinformatic analysis implicated reduced NF-κB signaling and increased activity of IRF1 in structuring those effects ( both p<.05 ) . CONCLUSION A brief daily yogic meditation intervention may reverse the pattern of increased NF-κB-related transcription of pro-inflammatory cytokines and decreased IRF1-related transcription of innate antiviral response genes previously observed in healthy individuals confronting a significant life stressor Background Dementia is a prevalent neurodegenerative disorder affecting an estimated 24.3 million people across the globe . The burden on those caring for people with dementia is substantial , with widespread implication s for the caregiver , the care recipient and the community . Relaxation techniques , such as Transcendental Meditation ® ( TM ) , have been shown to reduce stress and anxiety in healthy workers ; similar benefits are anticipated in dementia caregivers . The objective of this study was to ascertain whether TM can improve psychological stress , quality of life , affect and cognitive performance in dementia caregivers . Methods The study was conducted as a pilot prospect i ve , multi-centre , community-based , r and omised wait-list controlled trial . Community-dwelling caregivers of persons with diagnosed dementia were r and omly assigned to a 12-week ( 14-hour ) TM training program or wait-list control . Participants were assessed for quality of life , stress , affect , cognitive performance and adverse effects . The feasibility of the study was also evaluated . Results Seventeen caregivers were recruited and r and omised .  Improvements in WebNeuro response speed scores over time were significantly ( p = 0.03 ) greater in the TM group relative to control . Changes between groups over time in all other primary and secondary outcome measures did not reach statistical significance . However , there was a trend toward greater improvement in WebNeuro stress , depression and negativity bias scores in the TM group . Adverse events were reported amongst 63 % of TM-treated subjects ; however , events were generally transient , of mild-moderate intensity and only ‘ possibly ’ related to TM . Conclusions Dementia caregivers exposed to TM demonstrated varying degrees of improvement in several measures of cognitive function , mood , quality of life and stress following exposure to TM . However , as the pilot study was underpowered , no firm conclusions can be made about the effectiveness of TM in this caregiver population . Findings from full-scale trials are now warranted . Trial registration Australian New Zeal and Clinical Trial Registry ACTRN12613000184774 ( Registered 15th February 2013 ) The emerging concept of psychobiotics — live microorganisms with a potential mental health benefit — represents a novel approach for the management of stress-related conditions . The majority of studies have focused on animal models . Recent pre clinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors , physiology and cognitive performance . Whether such pre clinical effects could be translated to healthy human volunteers remains unknown . We tested whether psychobiotic consumption could affect the stress response , cognition and brain activity patterns . In a within- participants design , healthy volunteers ( N=22 ) completed cognitive assessment s , resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline , post-placebo and post-psychobiotic . Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated . Furthermore , daily reported stress was reduced by psychobiotic consumption . We also observed subtle improvements in hippocampus-dependent visuospatial memory performance , as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption . These subtle but clear benefits are in line with the predicted impact from pre clinical screening platforms . Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory . Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects Familial  caregivers of patients with Alzheimer 's disease exhibit reduced quality of life and increased stress levels . The aim of this study was to investigate the effects of an 8-week yoga and compassion meditation program on the perceived stress , anxiety , depression , and salivary cortisol levels in familial caregivers . A total of 46 volunteers were r and omly assigned to participate in a stress-reduction program for a 2-month period ( yoga and compassion meditation program — YCMP group ) ( n = 25 ) or an untreated group for the same period of time ( control group ) ( n = 21 ) . The levels of stress , anxiety , depression , and morning salivary cortisol of the participants were measured before and after intervention . The groups were initially homogeneous ; however , after intervention , the groups diverged significantly . The YCMP group exhibited a reduction of the stress ( P < 0.05 ) , anxiety ( P < 0.000001 ) , and depression ( P < 0.00001 ) levels , as well as a reduction in the concentration of salivary cortisol ( P < 0.05 ) . Our study suggests that an 8-week yoga and compassion meditation program may offer an effective intervention for reducing perceived stress , anxiety , depression , and salivary cortisol in familial caregivers Rationale A visuospatial episodic memory impairment has recently been identified in irritable bowel syndrome . Increased tryptophan metabolism along the kynurenine pathway has also been reported in irritable bowel syndrome , which may play a role in altered cognitive performance as peripheral kynurenine can cross the blood brain barrier and lead to the production of neuroactive metabolites , which modulate glutamatergic and cholinergic signalling , key neurotransmitter systems involved in cognitive function . Objectives Utilising the acute tryptophan depletion ( ATD ) protocol , the aim of this study was to examine if manipulating peripheral levels of tryptophan regulates cognitive performance in irritable bowel syndrome and also to determine for the first time if the ATD protocol alters kynurenine supply to the central nervous system . Methods In this double-blind , placebo-controlled , crossover design study , nine female patients with irritable bowel syndrome and 14 matched female healthy controls participant completed a range of tests from the CANTAB ® following ATD and placebo .  Plasma tryptophan and kynurenine , self-report measures of gastrointestinal symptoms , mood and arousal were determined pre- and post-treatment on each study day . Results Following placebo ( p = 0.016 ) but not ATD ( p > 0.05 ) , patients with irritable bowel syndrome exhibited impaired visuospatial memory performance ( Paired Associates Learning ( PAL ) test ) . In addition , ATD significantly decreased ( p < 0.001 ) and placebo significantly increased ( p < 0.001 ) plasma kynurenine levels in both groups . Conclusions Manipulating peripheral tryptophan and kynurenine levels using ATD modulates hippocampal-mediated cognitive performance in irritable bowel syndrome but not healthy controls . These data may have important implication s for reducing cognitive impairment in irritable bowel syndrome BACKGROUND The study objective was to determine the health and quality -of-life effects of moderate-intensity exercise among older women family caregivers . METHODS This 12-month r and omized controlled trial involved a volunteer sample of 100 women aged 49 to 82 years who were sedentary , free of cardiovascular disease , and caring for a relative with dementia . Participants were r and omized to 12 months of home-based , telephone-supervised , moderate-intensity exercise training or to an attention-control ( nutrition education ) program . Exercise consisted of four 30- to 40-minute endurance exercise sessions ( brisk walking ) prescribed per week at 60 % to 75 % of heart rate reserve based on peak treadmill exercise heart rate . Main outcomes were stress-induced cardiovascular reactivity levels , rated sleep quality , and reported psychological distress . RESULTS Compared with nutrition participants ( NU ) , exercise participants ( EX ) showed significant improvements in the following : total energy expenditure ( baseline and post-test means [ SD ] for EX = 1.4 [ 1.9 ] and 2.2 [ 2.2 ] kcal/kg/day ; for NU = 1.2 [ 1.7 ] and 1.2 [ 1.6 ] kcal/kg/day ; p < .02 ) ; stress-induced blood pressure reactivity ( baseline and post-test systolic blood pressure reactivity values for EX = 21.6 [ 12.3 ] and 12.4 [ 11.2 ] mm Hg ; for NU = 17.9 [ 10.2 ] and 17.7 [ 13.8 ] mm Hg ; p < .024 ) ; and sleep quality ( p < .05 ) . NU showed significant improvements in percentages of total calories from fats and saturated fats relative to EX ( p values < .01 ) . Both groups reported improvements in psychological distress . Conclusions . Family caregivers can benefit from initiating a regular moderate-intensity exercise program in terms of reductions in stress-induced cardiovascular reactivity and improvements in rated sleep quality The purpose of this study was to determine whether the stress of caregiving for the Alzheimer 's disease ( AD ) patient accelerates the likelihood of exceeding hypertensive blood pressure ( BP ) criteria in periodic longitudinal home assessment s. In this cohort study , participants consisted of spousal caregivers of AD patients ( n = 144 ) and demographically equivalent non-caregiving controls ( n = 47 ) . Thirty percent of caregivers and 33 % of controls were receiving antihypertensive treatment at study entry .  Supine systolic and diastolic blood pressure ( SBP and DBP ) was assessed by semi-automated recordings taken in the home every 6 months for 2 to 6 years . Survival analyses ( Cox proportional hazards models ) were used to determine whether the hazard for developing hypertension ( DBP>140 , SBP>90 ) was greater in caregivers than in controls , and whether increased hazards were related to background characteristics or the extent of caregiving dem and s. Based on periodic 6-month assessment s of BP over 6 years , the hazards of meeting criteria for borderline hypertension were greater for caregivers than for controls ( Cox Proportional Hazards , chi2 [ 1 , N = 174 ] = 4.86 , p = 0.03 ) . This difference remained statistically significant ( p<0.05 ) after controlling for age , gender , education , socioeconomic status , body mass index , and use of antihypertensive medications . Increased risk of hypertension was not related to the extent of daily living assistance provided , patient problem behaviors , or caregiver distress . The chronic stress of caring for an AD spouse may have adverse effects on blood pressure ; however , the mechanism for this relationship remains unclear Dementia caregiving is associated with elevations in depressive symptoms and increased risk for cardiovascular diseases ( CVD ) . This study evaluated the efficacy of the Pleasant Events Program ( PEP ) , a 6-week Behavioral Activation intervention design ed to reduce CVD risk and depressive symptoms in caregivers . One hundred dementia family caregivers were r and omized to either the 6-week PEP intervention ( N = 49 ) or a time-equivalent Information-Support ( IS ) control condition ( N = 51 ) . Assessment s were completed pre- and post-intervention and at 1-year follow-up . Biological assessment s included CVD risk markers Interleukin-6 ( IL-6 ) and D-dimer . Psychosocial outcomes included depressive symptoms , positive affect , and negative affect . Participants receiving the PEP intervention had significantly greater reductions in IL-6 ( p = .040 ) , depressive symptoms ( p = .039 ) , and negative affect ( p = .021 ) from pre- to post-treatment . For IL-6 , clinical ly significant improvement was observed in 20.0 % of PEP participants and 6.5 % of IS participants . For depressive symptoms , clinical ly significant improvement was found for 32.7 % of PEP vs 11.8 % of IS participants . Group differences in change from baseline to 1-year follow-up were non-significant for all outcomes . The PEP program decreased depression and improved a measure of physiological health in older dementia caregivers . Future research should examine the efficacy of PEP for improving other CVD biomarkers and seek to sustain the intervention 's effects The associations of  diastolic blood pressure ( DBP )  with  stroke  and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally " hypertensive " or " normotensive " , a lower blood pressure should eventually confer a lower risk of vascular disease Objective : To determine if  caregivers of spouses with Alzheimer 's disease demonstrate greater increase in tissue plasminogen activator ( t-PA ) antigen relative to noncaregiving controls . Caring for a spouse with Alzheimer 's disease has been associated with increased mortality and reduced time to developing cardiovascular disease ( CVD ) , possibly due to impaired fibrinolysis result ing from chronic stress . Methods : Annual in-home assessment s of plasma t-PA antigen were collected from 165 participants ( 112 caregivers and 53 noncaregivers ) enrolled in the University of California , San Diego Alzheimer caregiver study . Participants were married , living with their spouses , at least 55 years of age , and free of serious medical conditions ( e.g. , cancer ) . Caregivers provided in-home care for their spouse with Alzheimer 's disease  at the time of enrollment . Exclusion criteria included taking anticoagulant medication or evidence d severe hypertension ( > 200/120 mm Hg ) . Mixed ( r and om effects ) regression was used to assess slopes for t-PA antigen over the study period at the same time controlling for medical and demographic characteristics associated with t-PA antigen . Results : Caregivers demonstrated significantly greater increases in t-PA antigen over the 5-year study period compared with noncaregiving controls ( p = .02 ) , even when controlling for body mass index , mean blood pressure , age , gender , and use of CVD medication . Conclusions : The accelerated rate of developing a prothrombotic environment including elevated t-PA antigen may provide one mechanism by which caregiving is associated with greater morbidity and mortality and the development of CVD . CVD = cardiovascular disease ; IL-6 = interleukin-6 ; t-PA = tissue plasminogen activator ; PAI-1 = plasminogen activator inhibitor ; CHD = coronary heart disease ; MAP = mean arterial pressure ; BMI = body mass index ; BP = blood pressure ; HAM-D = Hamilton Scale for Depression Background : Family caregivers of patients with dementia frequently experience psychological stress , depression and disturbed psychophysiological activity , with increased levels of diurnal cortisol secretion . Objectives : To compare the effects of a cognitive – behavioural group therapy ( CBT ) to a psychoeducation group programme ( EDUC ) on cortisol secretion in caregivers of patients with moderate Alzheimer 's disease ( AD ) . Method : Caregivers of AD out patients were semi-r and omly allocated to one of two intervention programmes ( CBT or EDUC ) consisting of eight weekly sessions . Twenty-six participants completed the study . Before and after intervention , salivary cortisol was collected at four different times of the day . Effects of the interventions were evaluated with self-report psychological scales and question naires related to functional abilities and neuropsychiatric symptoms of the AD relative . Results : Only in the CBT group did salivary cortisol levels significantly decrease after intervention , with a large effect size and high achieved power . Both groups reported a reduction of neuropsychiatric symptoms of their AD relative after intervention . Conclusion : Psychoeducation for caregivers may contribute to a reduction of neuropsychiatric symptoms of AD patients while CBT additionally attenuates psychophysiological responses to stressful situations in caregivers , by reducing diurnal cortisol levels . This may lead to a positive impact in the general health of the caregiver , eventually result ing in better care of the AD patient STUDY OBJECTIVES Findings on sleep disturbances in family dementia caregivers are conflicting . We studied the longitudinal effects of  dementia caregiving  and major transitions in the caregiving situation on caregivers ' sleep and the effect of moderating variables . DESIGN AND SETTING Community-based longitudinal study with assessment s about once a year for up to three years . PARTICIPANTS A sample of 109 elderly spousal Alzheimer caregivers and 48 non-caregiving age- and gender-matched controls . MEASUREMENTS AND RESULTS R and om regression models with fixed and time-variant effects for covariates known to affect sleep were used to evaluate changes in the Pittsburgh Sleep Quality Index ( PSQI ) and in four actigraphy measures over time in relation to caregiving status and transitions ( i.e. , nursing home placement or death of the Alzheimer disease spouse ) . Multivariate-adjusted sleep characteristics did not significantly differ between caregivers and non-caregivers over time . Spousal death increased caregivers ' nighttime wake after sleep onset ( WASO ) by 23 min ( P = 0.002 ) and daytime total sleep time ( TST ) by 29 min ( P = 0.003 ) , while nighttime sleep percent decreased by 3.2 % ( P = 0.009 ) and nighttime TST did not change . Placement of the spouse had no significant effect on caregivers ' sleep . Older age , male gender , role overload , depressive symptoms , and proinflammatory cytokines variously emerged as significant moderators of the relationships between caregiving and transitions with poor subjective and objective sleep . CONCLUSIONS Alzheimer caregivers and non-caregiving controls had similar trajectories of sleep . However , there may be subgroups of caregivers who are vulnerable to develop sleep disturbances , including those whose spouses have died This study examined how positive aspects of caregiving affect adaptation to bereavement among older adults who cared for a family member with dementia . The sample consisted of 217 caregivers who were part of the Re sources for Enhancing Alzheimer 's Caregiver Health Study . Using pre- and postloss data , hierarchical regressions were carried out to examine the effects of positive aspects of caregiving ( caregiving benefit ) on postloss depression and grief . Findings show that preloss caregiving benefit was associated with higher levels of postloss depression and grief , even after controlling for caregiver demographic characteristics , context ual factors , and caregiving burden . This effect was particularly strong for the relation between benefit and grief . Results demonstrate the importance of study ing both positive and negative aspects of caregiving and their relation to bereavement outcomes OBJECTIVE We examined the impact of  Alzheimer caregiver transitions ( i.e. ,  placement and bereavement )  on psychological outcomes and on plasma D-dimer levels , an end product of the coagulation cascade associated with increased cardiovascular risk . METHODS This was a prospect i ve study in which 126 spousal caregivers of Alzheimer 's patients were assessed each year for 5 years . We used r and om regression models to evaluate discontinuous change in our outcomes over time , with emphasis on the impact of caregiver transitions on psychological and physical well-being . RESULTS Caregivers experienced immediate improvement in overload and mastery following transitions , and these improvements were maintained over time . There was also a significant drop in depressive symptoms immediately following placement of spouses . D-dimer rose significantly over time but began to significantly decline at 6-months posttransitions . CONCLUSIONS Caregiver transitions appear to produce immediate and long-term " normalization " of psychological health in caregivers . This normalization also appears related to " downstream " reductions in D-dimer BACKGROUND Many patients with major depressive disorder have treatment-resistant depression , defined as no adequate response to two consecutive courses of antidepressants . Some evidence suggests that antiglucocorticoid augmentation of antidepressants might be efficacious in patients with major depressive disorder . We aim ed to test the proof of concept of metyrapone for the augmentation of serotonergic antidepressants in the clinical ly relevant population of patients with treatment-resistant depression . METHODS This double-blind , r and omised , placebo-controlled trial recruited patients from seven UK National Health Service ( NHS ) Mental Health Trusts from three areas ( northeast Engl and , northwest Engl and , and the Leeds and Bradford area ) . Eligible patients were aged 18 - 65 years with treatment-resistant depression ( Hamilton Depression Rating Scale 17-item score of ≥18 and a Massachusetts General Hospital Treatment-Resistant Depression staging score of 2 - 10 ) and taking a single-agent or combination antidepressant treatment that included a serotonergic drug .  Patients were r and omly assigned ( 1:1 ) through a central ised web-based system to metyrapone ( 500 mg twice daily ) or placebo , in addition to their existing antidepressant regimen , for 21 days . Permuted block r and omisation was done with a block size of two or four , stratified by centre and primary or secondary care setting . The primary outcome was improvement in Montgomery-Åsberg Depression Rating Scale ( MADRS ) score 5 weeks after r and omisation , analysed in the modified intention-to-treat population of all r and omly assigned patients that completed the MADRS assessment at week 5 . The study has an International St and ard R and omised Controlled Trial Number ( IS RCT N45338259 ) and is registered with the EU Clinical Trial register , number 2009 - 015165 - 31 . FINDINGS Between Feb 8 , 2011 , and Dec 10 , 2012 , 165 patients were recruited and r and omly assigned ( 83 to metyrapone and 82 to placebo ) , with 143 ( 87 % ) completing the primary outcome assessment ( 69 [ 83 % ] in the metyrapone and 74 [ 90 % ] in the placebo group ) . At 5 weeks , MADRS score did not significantly differ between groups ( 21·7 points [ 95 % CI 19·2 - 24·4 ] in the metyrapone group vs 22·6 points [ 20·1 - 24·8 ] in the placebo group ; adjusted mean difference of -0·51 points [ 95 % CI -3·48 to 2·46 ] ; p=0·74 ) . 12 serious adverse events were reported in four ( 5 % ) of 83 patients in the metyrapone group and six ( 7 % ) of 82 patients in the placebo group , none of which were related to study treatment . 134 adverse events occurred in 58 ( 70 % ) patients in the metyrapone group compared with 95 events in 45 ( 55 % ) patients in the placebo group , of which 11 ( 8 % ) events in the metyrapone group and four ( 4 % ) in the placebo group were judged by principle investigators at the time of occurrence to be probably related to the study drug . INTERPRETATION Metyrapone augmentation of antidepressants is not efficacious in a broadly representative population of patients with treatment-resistant depression within the NHS and therefore is not an option for patients with treatment-resistant depression in routine clinical practice at this time . Further research is needed to clarify if such augmentation might benefit sub population s with demonstrable hypothalamic-pituitary-adrenal axis abnormalities . FUNDING Efficacy and Mechanism Evaluation ( EME ) programme , a UK Medical Research Council and National Institute for Health Research partnership
HighlightsMuch research has examined biomarkers of chronic stress in dementia caregivers .
NA ; As the physiological impact of chronic stress is difficult to study in humans , naturalistic stressors are invaluable sources of information in this area .
This review systematic ally evaluates the research literature examining biomarkers of chronic stress , including neurocognition , in informal dementia caregivers .