Reducing CVD Risk in Caregivers: A Brief Behavioral Activation Intervention

Study Overview
=================
Brief Summary
-----------------
Cardiovascular disease and depression are some of the most costly illnesses to society, and caring for a loved-one with Alzheimer's disease has been associated with increased risk for both depression and cardiovascular disease. Indeed, depressive symptoms have been linked with elevated plasma concentrations of D-dimer and Interleukin-6 (IL-6), both of which are associated with increased risk for cardiovascular disease (CVD). The present research tests a brief behavioral intervention for reducing both depressive symptoms and CVD biomarkers in Alzheimer caregivers. We hypothesize that caregivers receiving a brief Behavioral Activation (BA) therapy will show greater reductions in depressive symptoms and in CVD biomarkers relative to those randomized to a time-equivalent Information and Support (IS) therapy.

Detailed Description
-----------------
Due to an aging society, the number of people diagnosed with dementia is expected to increase dramatically over the next two decades, with a concomitant rise in the number of family members providing informal care for their loved ones. The stresses associated with this care have been well-documented in the scientific literature, and are noted to be associated with increased risk for psychological and physical morbidity, particularly cardiovascular disease. Indeed, caregiving is associated with elevations in negative affect (e.g., depressive and anxiety symptoms), which in turn is associated with biological indicators that are thought to predict CVD risk (e.g., markers of coagulation and inflammation). The primary goal of this study is to examine the efficacy of a brief Behavioral Activation (BA) Treatment, called the Pleasant Events Program (PEP), for reducing biological CVD risk indicators in a sample of Alzheimer caregivers. We will enroll 100 dementia caregivers and randomly assign them to receive 4-sessions of PEP or 4-sessions of support + information. Our PEP intervention will be conducted in caregivers' homes and will emphasize the importance of monitoring and increasing activities that help individuals make contact with natural reinforcers in their environments, identifying and reducing negative coping responses, and selection and achievement of behavioral goals for healthier living. Caregivers will be assessed for our biological outcomes at baseline, post-treatment, and 1-year to determine intervention efficacy. Given the brief nature of the PEP intervention, the ease with which it can be applied in real-world settings (e.g., community agencies providing services to caregivers), and lack of difficult skills for interventionists and caregivers to acquire, we believe our PEP intervention will be easily transferred to real-world settings. If our PEP intervention is efficacious, it may have a considerable impact on both the physical and mental health of caregivers, and will likely have public health implications.

Official Title
-----------------
Reducing CVD Risk in Caregivers: A Brief Behavioral Activation Intervention

Conditions
-----------------
Inflammation, Depressive Symptoms

Intervention / Treatment
-----------------
* Behavioral: Pleasant Events Program (PEP)
* Behavioral: Information Support (IS)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 55 or older and providing at-home care for a care recipient (CR) with a physician-diagnosis of Alzheimer's disease (AD) or related dementia. Exclusion Criteria: Receiving beta-blocking medications at enrollment Receiving treatment with Anticoagulant medications Severe hypertension (>200/120 mmHg) Diagnosed with a terminal illness with a life expectancy <6 months Enrolled in another intervention study

Ages Eligible for Study
-----------------
Minimum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pleasant Events Program (PEP)<br>The Pleasant Events Program (PEP) is a Behavioral Activation (BA) treatment for depression. Participants receive 4 weekly sessions of face-to-face therapy (60 minutes each) to increase caregiver participation in pleasurable activities. Two additional phone sessions focus on continued behavioral activation for caregivers as well as problem-solving barriers to activation. | Behavioral: Pleasant Events Program (PEP)<br>* Behavioral Activation Therapy<br>|
| Active Comparator: Information-Support (IS)<br>Participants in the Information-Support (IS) control condition were provided with a resource manual consisting of topics commonly covered in support groups or information packets provided by community agencies. Topics included problem-solving and communication skills, cognitive reframing and behavioral management, self-care help, caregiver fact sheets on a range of social and mental health issues, placement information, financial and legal issues, and lists of local organizations and community resources available. Each IS session allowed caregivers to select issue(s) from the resource manual to discuss. The therapist covered the material based on the caregivers' needs. When requested by the caregiver, supportive psychotherapy was also provided. | Behavioral: Information Support (IS)<br>* Information-Support (IS) condition consisted of supportive psychotherapy and informational brochures.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Center for Epidemiologic Studies Depression Scale (CESD) | The Brief CESD is a measure of depressive symptoms. The scale's minimum score is 0 and maximum score is 30. Lower scores represent fewer depressive symptoms and thus better outcomes. | Change from Baseline CESD at 8-weeks | 
| D-dimer | D-dimer is an indicator of fibrin formation and its subsequent lysis and is a useful biomarker representing overall activation of blood coagulation. High concentrations of D-dimer have been linked prospectively to onset of Coronary Heart Disease. Blood was collected by a research nurse in the caregivers' homes through a 22 gauge forearm catheter after a 20 minute rest. Blood for D-dimer was dispensed into polypropylene tubes with 3.8 percent sodium citrate and spun at 1600 g for 10 minutes at room temperature. Obtained plasma was stored at minus 80 degrees Celsius until analyzed. Plasma D-dimer (Asserachrom Stago, Asnieres, France) was determined via high sensitive enzyme-linked immunosorbent assays. Intra- and interassay coefficients of variation were less than 5 percent. | Change from Baseline D-dimer at 8-weeks | 
| Interleukin-6 (IL-6) | IL-6 is one of many biomarkers represented in the inflammatory cascade which is initiated during an immune response. Prospectively, increased plasma IL-6 is also associated with future myocardial infarction in healthy men and increasing concentrations of IL-6 have been associated with both nonfatal myocardial infarction and fatal Coronary Heart Disease (CHD) in longitudinal studies of population-based cohorts. Higher concentrations of IL-6 raise CHD risk. Blood was collected by a research nurse in the caregivers' homes through a 22-gauge forearm catheter after a 20 min rest. Blood for IL-6 was dispensed in Ethylenediaminetetraacetic acid (EDTA) tubes and spun at 3000 g for 10 minutes at 4 to 8 degrees Celsius. Obtained plasma was stored at minus 80 degrees Celsius until analyzed. Plasma IL-6 (Meso Scale Discovery, Gaithersburg, MD) was determined via highsensitive enzyme-linked immunosorbent assays. Intra- and interassay coefficients of variation were less than 5 percent. | Change from Baseline IL-6 at 8-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Affect Schedule | This scales contains ten items assessing Positive Affect. Items included are adjectives, such as interested, strong, and inspired. Participants rated each adjective based on how they felt over the past few weeks using a 5-point scale with responses ranging from 1 (very slightly to not at all) to 5 (extremely). The scale's minimum score is 10 and maximum score is 50. Higher scores represent better outcomes. | Change from Baseline Positive Affect at 8-weeks | 
| Positive and Negative Affect Schedule | This scales contains ten items assessing Negative Affect. Items included are adjectives, such as distressed, ashamed, and Participants rated each adjective based on how they felt over the past few weeks using a 5-point scale with responses ranging from 1 (very slightly to not at all) to 5 (extremely). The scale's minimum score is 10 and maximum score is 50. Lower scores represent better outcomes. | Change from Baseline Negative Affect at 8-weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Behavioral Activation, Caregiver, Dementia, Cardiovascular Disease, Alzheimer's Disease, Coagulation