human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Although adverse effects of severe chronic stress on immunocompetence and physical well-being in older adults have been reported , the immune response to less severe life stress among healthy older adults , particularly among women , is not well understood . Interleukin-6 ( IL-6 ) has been considered a good overall indicator of immune functioning in older adults because of its contribution to the pathogenesis of several age-related conditions such as osteoporosis . Regulation of IL-6 is impaired in elderly adults , and levels of IL-6 increase with stress and depression . This research cross-sectionally examined levels of IL-6 in three groups of healthy older women with varying levels of life stress and mood disturbance and a healthy group of young women . METHODS Subjects included 18 caregivers of Alzheimer 's patients , 17 older women assessed one month before relocation of their residence , 15 nonmoving and noncaregiving older women , and 20 younger women . Subjects completed the  Profile of Mood States ( POMS )  and had early morning blood draws . RESULTS Alzheimer 's caregivers reported significantly greater distress than women of all other groups . IL-6 levels in caregivers were significantly higher than those of all other women . The older women had significantly higher IL-6 than young controls , but there were no significant differences in IL-6 between movers and older controls . Among all women , greater depression and distress were related to higher levels of IL-6 . CONCLUSIONS These findings suggest that in older women , chronic stressors are associated with significant elevations in IL-6 over and above the elevations associated with normal aging , but that moderate stressors may not be related to appreciable elevations in IL-6 PURPOSE We set out to assess whether a high sense of coherence ( SOC ) protects from adverse health outcomes in patients aged 80 years and older who have multiple chronic diseases . METHODS A population -based prospect i ve cohort study  in 29 primary care practice s throughout Belgium included 567 individuals aged 80 years and older . We plotted the highest tertile of SOC scores in Kaplan-Meier curves representing 3-year mortality and time to first hospitalization . Using Cox proportional hazard regression analyses and multiple logistic regression analyses adjusted for sociodemographic characteristics , depression , cognition , disability , and multimorbidity we examined the relationship between  SOC and mortality , hospitalization , and decline in performance of activities of daily living ( ADL ) . RESULTS Subjects with  high SOC scores  showed a higher cumulative survival than others ( Log rank = 0.004 ) independent of other prognostic characteristics ( adjusted hazard ratio 0.62 ( 95 % CI , 0.38–1.00 ) , P = .049 ) . For ADL decline , a high SOC was shown to be protective , and this effect tended to be independent from the covariates under study ( adjusted odds ratio 0.56 ( 95 % CI , 0.31–1.0 ) , P = .05 ) . CONCLUSION Even very elderly persons with  high SOC scores  were shown to have lower mortality rates and less functional decline . These effects were independent of multimorbidity , depression , cognition , disability , and sociodemographic characteristics Background : Providing care to a spouse with Alzheimer ’s disease ( AD ) may contribute to cardiovascular disease ( CVD ) . The acute phase reactant C-reactive protein ( CRP ) is a well-established biomarker of an increased CVD risk . Objective : To investigate the hypothesis that dementia caregiving is associated with elevated circulating levels of CRP and possibly other biomarkers of CVD risk . Methods : We examined 118 elderly spousal Alzheimer caregivers and 51 noncaregiving controls about once a year for up to 3 years .  R and om regression models with fixed and time-variant effects for a range of covariates known to affect biomarker levels were used to evaluate changes in CRP and in 12 additional measures of inflammation , cellular adhesion , endothelial function , and hemostasis in relation to caregiving status , years of caregiving , and major transitions in the caregiving situation . Results : During the study period , longer duration of caregiving was associated with elevated CRP levels ( p = 0.040 ) and caregivers showed greater tumor necrosis factor (TNF)-α levels than controls ( p = 0.048 ) . Additionally , 3 months after the death of the AD spouse , caregivers showed a significant drop in CRP levels ( p = 0.003 ) and levels of soluble intercellular adhesion molecule (sICAM)-1 ( p = 0.008 ) . Conclusion : Duration of caregiving and being a caregiver per se were both associated with chronic low- grade inflammation as indicated by elevated CRP and TNF-α levels , respectively . Conversely , death of the AD spouse was associated with lower CRP and sICAM-1 levels . The findings indicate that chronic caregiving of those with dementia may result in increased inflammation and , thereby , possibly increased CVD risk CONTEXT The decision to institutionalize a patient with dementia is complex and is based on patient and caregiver characteristics and the sociocultural context of patients and caregivers . Most studies have determined predictors of nursing home placement primarily according to patient or caregiver characteristics alone . OBJECTIVE To develop and vali date a prognostic model to determine the comprehensive predictors of placement among an ethnically diverse population of patients with dementia . DESIGN , SETTING , AND PARTICIPANTS The Medicare Alzheimer 's Disease Demonstration and Evaluation study , a prospect i ve study at 8 sites in the United States , with enrollment between December 1989 and December 1994 of 5788 community-living persons with advanced dementia . MAIN OUTCOME MEASURES Time to nursing home placement throughout a 36-month follow-up period , assessed by interview and review of Medicare records , and its association with patient and caregiver characteristics , obtained by interview at enrollment . RESULTS Patients were divided into a development ( n = 3859 ) and validation ( n = 1929 ) cohort . In the development cohort , the Kaplan-Meier estimates of nursing home placement throughout 1 , 2 , and 3 years were 22 % , 40 % , and 52 % , respectively . After multivariate adjustment , patient characteristics that were associated with nursing home placement were as follows : black ethnicity ( hazard ratio , 0.60 ; 95 % confidence interval [ CI ] , 0.48 - 0.74 ) , Hispanic ethnicity ( HR , 0.40 ; 95 % CI , 0.28 - 0.56 ) ( both ethnicities were inversely associated with placement ) , living alone ( HR , 1.74 ; 95 % CI , 1.49 - 2.02 ) , 1 or more dependencies in activities of daily living ( HR , 1.38 ; 95 % CI , 1.20 - 1.60 ) , high cognitive impairment ( for Mini-Mental Status Examination score < or = 20 : HR , 1.52 ; 95 % CI , 1.33 - 1.73 ) , and 1 or more difficult behaviors ( HR , 1.30 ; 95 % CI , 1.11 - 1.52 ) . Caregiver characteristics associated with patient placement were age 65 to 74 years ( HR , 1.17 ; 95 % CI , 1.01 - 1.37 ) , age 75 years or older ( HR , 1.55 ; 95 % CI , 1.31 - 1.84 ) , and high Zarit Burden Scale score ( for highest quartile : HR , 1.73 ; 95 % CI , 1.49 - 2.00 ) . Patients were assigned to quartiles of risk based on this model . In the development cohort , patients in the first , second , third , and fourth quartile had a 25 % , 42 % , 64 % , and 91 % rate of nursing home placement at 3 years , respectively . In the validation cohort , the respective rates were 21 % , 50 % , 64 % , and 89 % . The C statistic for 3-year nursing home placement was 0.66 in the development cohort and 0.63 in the validation cohort . CONCLUSIONS Patient and caregiver characteristics are both important determinants of long-term care placement for patients with dementia . Interventions directed at delaying placement , such as reduction of caregiver burden  or  difficult patient behaviors  , need to take into account the patient and caregiver as a unit 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 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 = interle 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Although adverse effects of severe chronic stress on immunocompetence and physical well-being in older adults have been reported , the immune response to less severe life stress among healthy older adults , particularly among women , is not well understood . Interleukin-6 ( IL-6 ) has been considered a good overall indicator of immune functioning in older adults because of its contribution to the pathogenesis of several age-related conditions such as osteoporosis . Regulation of IL-6 is impaired in elderly adults , and levels of IL-6 increase with stress and depression . This research cross-sectionally examined levels of IL-6 in three groups of healthy older women with varying levels of life stress and mood disturbance and a healthy group of young women . METHODS Subjects included 18 caregivers of Alzheimer 's patients , 17 older women assessed one month before relocation of their residence , 15 nonmoving and noncaregiving older women , and 20 younger women . Subjects completed the  Profile of Mood States ( POMS )  and had early morning blood draws . RESULTS Alzheimer 's caregivers reported significantly greater distress than women of all other groups . IL-6 levels in caregivers were significantly higher than those of all other women . The older women had significantly higher IL-6 than young controls , but there were no significant differences in IL-6 between movers and older controls . Among all women , greater depression and distress were related to higher levels of IL-6 . CONCLUSIONS These findings suggest that in older women , chronic stressors are associated with significant elevations in IL-6 over and above the elevations associated with normal aging , but that moderate stressors may not be related to appreciable elevations in IL-6 PURPOSE We set out to assess whether a high sense of coherence ( SOC ) protects from adverse health outcomes in patients aged 80 years and older who have multiple chronic diseases . METHODS A population -based prospect i ve cohort study  in 29 primary care practice s throughout Belgium included 567 individuals aged 80 years and older . We plotted the highest tertile of SOC scores in Kaplan-Meier curves representing 3-year mortality and time to first hospitalization . Using Cox proportional hazard regression analyses and multiple logistic regression analyses adjusted for sociodemographic characteristics , depression , cognition , disability , and multimorbidity we examined the relationship between  SOC and mortality , hospitalization , and decline in performance of activities of daily living ( ADL ) . RESULTS Subjects with  high SOC scores  showed a higher cumulative survival than others ( Log rank = 0.004 ) independent of other prognostic characteristics ( adjusted hazard ratio 0.62 ( 95 % CI , 0.38–1.00 ) , P = .049 ) . For ADL decline , a high SOC was shown to be protective , and this effect tended to be independent from the covariates under study ( adjusted odds ratio 0.56 ( 95 % CI , 0.31–1.0 ) , P = .05 ) . CONCLUSION Even very elderly persons with  high SOC scores  were shown to have lower mortality rates and less functional decline . These effects were independent of multimorbidity , depression , cognition , disability , and sociodemographic characteristics Background : Providing care to a spouse with Alzheimer ’s disease ( AD ) may contribute to cardiovascular disease ( CVD ) . The acute phase reactant C-reactive protein ( CRP ) is a well-established biomarker of an increased CVD risk . Objective : To investigate the hypothesis that dementia caregiving is associated with elevated circulating levels of CRP and possibly other biomarkers of CVD risk . Methods : We examined 118 elderly spousal Alzheimer caregivers and 51 noncaregiving controls about once a year for up to 3 years .  R and om regression models with fixed and time-variant effects for a range of covariates known to affect biomarker levels were used to evaluate changes in CRP and in 12 additional measures of inflammation , cellular adhesion , endothelial function , and hemostasis in relation to caregiving status , years of caregiving , and major transitions in the caregiving situation . Results : During the study period , longer duration of caregiving was associated with elevated CRP levels ( p = 0.040 ) and caregivers showed greater tumor necrosis factor (TNF)-α levels than controls ( p = 0.048 ) . Additionally , 3 months after the death of the AD spouse , caregivers showed a significant drop in CRP levels ( p = 0.003 ) and levels of soluble intercellular adhesion molecule (sICAM)-1 ( p = 0.008 ) . Conclusion : Duration of caregiving and being a caregiver per se were both associated with chronic low- grade inflammation as indicated by elevated CRP and TNF-α levels , respectively . Conversely , death of the AD spouse was associated with lower CRP and sICAM-1 levels . The findings indicate that chronic caregiving of those with dementia may result in increased inflammation and , thereby , possibly increased CVD risk CONTEXT The decision to institutionalize a patient with dementia is complex and is based on patient and caregiver characteristics and the sociocultural context of patients and caregivers . Most studies have determined predictors of nursing home placement primarily according to patient or caregiver characteristics alone . OBJECTIVE To develop and vali date a prognostic model to determine the comprehensive predictors of placement among an ethnically diverse population of patients with dementia . DESIGN , SETTING , AND PARTICIPANTS The Medicare Alzheimer 's Disease Demonstration and Evaluation study , a prospect i ve study at 8 sites in the United States , with enrollment between December 1989 and December 1994 of 5788 community-living persons with advanced dementia . MAIN OUTCOME MEASURES Time to nursing home placement throughout a 36-month follow-up period , assessed by interview and review of Medicare records , and its association with patient and caregiver characteristics , obtained by interview at enrollment . RESULTS Patients were divided into a development ( n = 3859 ) and validation ( n = 1929 ) cohort . In the development cohort , the Kaplan-Meier estimates of nursing home placement throughout 1 , 2 , and 3 years were 22 % , 40 % , and 52 % , respectively . After multivariate adjustment , patient characteristics that were associated with nursing home placement were as follows : black ethnicity ( hazard ratio , 0.60 ; 95 % confidence interval [ CI ] , 0.48 - 0.74 ) , Hispanic ethnicity ( HR , 0.40 ; 95 % CI , 0.28 - 0.56 ) ( both ethnicities were inversely associated with placement ) , living alone ( HR , 1.74 ; 95 % CI , 1.49 - 2.02 ) , 1 or more dependencies in activities of daily living ( HR , 1.38 ; 95 % CI , 1.20 - 1.60 ) , high cognitive impairment ( for Mini-Mental Status Examination score < or = 20 : HR , 1.52 ; 95 % CI , 1.33 - 1.73 ) , and 1 or more difficult behaviors ( HR , 1.30 ; 95 % CI , 1.11 - 1.52 ) . Caregiver characteristics associated with patient placement were age 65 to 74 years ( HR , 1.17 ; 95 % CI , 1.01 - 1.37 ) , age 75 years or older ( HR , 1.55 ; 95 % CI , 1.31 - 1.84 ) , and high Zarit Burden Scale score ( for highest quartile : HR , 1.73 ; 95 % CI , 1.49 - 2.00 ) . Patients were assigned to quartiles of risk based on this model . In the development cohort , patients in the first , second , third , and fourth quartile had a 25 % , 42 % , 64 % , and 91 % rate of nursing home placement at 3 years , respectively . In the validation cohort , the respective rates were 21 % , 50 % , 64 % , and 89 % . The C statistic for 3-year nursing home placement was 0.66 in the development cohort and 0.63 in the validation cohort . CONCLUSIONS Patient and caregiver characteristics are both important determinants of long-term care placement for patients with dementia . Interventions directed at delaying placement , such as reduction of caregiver burden  or  difficult patient behaviors  , need to take into account the patient and caregiver as a unit 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 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 = interle 
    Output:
    