Peter P. Vitaliano - US grants

Dementia of the Alzheimer's Type (DAT) is characterizd by progressive cognitive/behavioral impairment. As DAT progresses the patient is less able to care for him/herself, becoming more dependent on his/her caregiver (usually spouse). Over time the patient becomes more restricted to the home environment and the psychosocial environment of the caregiver/spouse. As such, the patient's functioning may increasingly reflect the functioning of his/her spouse. Simultaneously, via feedback loops, increased cognitive/behavioral decline in the patient may result in increased psychosocial impairment in the spouse. This vicious cycle may lead to patient decline well beyond that due to neuronal degeneration. Unfortunately, much needs to be learned about these dynamics: The vast majority of DAT research has concentrated on the patient or the caregiver, but not on both. In this study longitudinal relationships will be examined to assess the importance of spouse variables on mild DAT patients (Aim 1) and mild DAT patient variables on spouses (Aim 2): 1) Do initial and/or follow-up psychosocial spouse variables account for variance in follow-up cognitive/behavioral functioning of patients beyond that expected from initial cognitive/behavioral functioning of patients? 2) Does initial and/or follow-up cognitive/behavioral functioning of patients account for variance in follow-up psychosocial spouse variables beyond that expected from initial psychosocial spouse variables? A two wave follow-up design will be used: patients/spouses will be first assessed at entry into the Geriatric and Family Services Clinic. Follow-up assessments will be performed 18 months after the respective initial assessments. Criteria for patient inclusion will be: DSM III diagnosis of Primary Degenerative Dementia (no mixed dementias), mild (early) stage of AD, living with one's spouse who is the caregiver, and living within one hour's drive of Seattle. Given these 4 criteria initial/follow-up data will be obtained on 90 dyads. Hierarchical regression will be used to meet the aims. Variables entered will reflect a theoretical model of stress/distress which involves stressors, resources, vulnerability and distress. This research will shed light on two ADAMHA priorities: The interaction of family stress, coping and the management of DAT, and factors in the psychosocial environment that shape and maintain positive behavior in DAT patients.

Dementia of the Alzheimer's Type (DAT) is characterized by progressive cognitive/behavioral impairment. As DAT progresses the patient is less able to care for him/herself becoming more dependent on his/her caregiver (usually spouse). Increased cognitive/behavioral/affective decline in the patient may result in decreased mental/physical health in the spouse. Much needs to be learned about these dynamics. The vast majority of DAT research has concentrated on the patient or the caregiver, but not on both. We recognize the potential effect of DAT patients on the mental/physical health of their spouses. In this multidisciplinary longitudinal study, we will compare psychosocial, immunological, and cardiovascular distress, in 70 spouses of mild DAT patients to the distress in 70 age- sex- and health status-matched spouses of controls. The controls will occur twice, 15 months apart. We believe we can obtain the required samples in the proposed time by using both our DAT Roster and the community sampling procedures practiced in our current studies. Using a theoretical model of distress to guide our research, 4 hierarchical hypotheses will be tested: (1) initially and at follow-up DAT spouses will be more distressed than control spouses on all measures; (2) at follow-up DAT spouses will be more distressed than at baseline, whereas mean differences over time in control spouses partially explained by increases in DAT patient's cognitive/functional decline; however, these relationships will be modified by 3 spouse factors (life stressors, vulnerability, and resources); (4) biological and psychosocial distress will be more correlated at follow-up than at initial assessment; and at both times these relationships will be greater for vulnerable spouses (e.g., hostile/angry, etc.) and less for spouses with resources (e.g., social support and coping). The General Linear Model will be used to statistically test the hypotheses. This research will integrate psychosocial and biological sequelae of stress in DAT spouses and therefore shed light on ADAMHA priorities.

Alzheimer's Disease (AD) is characterized by progressive cognitive and behavioral impairment. Over time, the patient is less able to care for him/herself, becoming more restricted to the home and the psychosocial environment of the caregiver (usually a spouse). As such, the patient's functioning may increasingly reflect the functioning of his or her spouse caregiver. Conversely, increased cognitive and behavioral decline in the patient may result in increased burden in the caregiver. This vicious cycle may lead to patient decline beyond that due to neuronal degeneration. At present, we know relatively little about how initial patient-caregiver dynamics affect long term outcomes. In our progress report we use a theoretical distress model to examine these issues. We demonstrate that caregiver risk (personality, health, distress) and resource (coping, social supports) variables at baseline predict subsequent caregiver burden, patient activities of daily living (ADLs), and nursing home placement. The proposed study will extend this work by interviewing our surviving couples twice (15-18 months apart) over the next 3 years. Although 71 couples are now available for follow-up, our power estimates have been evaluated downward from this figure because of expected attrition between now and the anticipated start date. Three hypotheses will be tested: 1) Caregivers who are most vulnerable to distress at baseline will report the most burden at follow-up; 2) AD patients living with caregivers who are the most vulnerable to distress and have the fewest resources at baseline, will have the lowest ADL levels at follow-up; 3) Caregivers who are more vulnerable to distress at baseline will, over time, admit their AD spouses into nursing homes at a higher rate than caregivers who are less vulnerable to distress. In each analysis, we will control for patient ADL levels and caregiver burden at baseline. Results of this research should have implications for public policy and intervention with caregivers of AD patients.

DESCRIPTION (Adapted from the Applicant's Abstract): This study will use the chronic stress of caregiving as a natural experiment to examine relationships among psychobehavioral processes, race, the metabolic syndrome, and Coronary Heart Disease (CHD) that could not be ethically manipulated in a laboratory. Caregiving is associated with psychosocial (anger/hostility, hassles, depression) problems, which are, in turn, associated with metabolic, cardiovascular, and physical health problems. We have observed that insulin independently distinguishes spouse caregivers and controls (caregivers greater controls) better than other physiological variables and that caregivers greater controls on CHD prevalence. Accordingly, we will compare 130 spouse caregivers of persons with Alzheimer's disease (AD) (n=100 Caucasians, n=30 Blacks) to 130 spouses of non-demented controls matched on sex, race, age, and family history of cardiovascular disease. Assessments will occur at: Time 1, Time 2 (15-18 months after Time 1), and Time 3 (27-30 months after Time 1). We will focus on psychophysiological mediators to understand why chronic stress may increase metabolic problems and CHD in caregivers relative to controls. Our multiple measures will include: medical records (ICD-codes), physical exams, physiology and self reports. A biopsychosocial model will be used to examine 5 aims: Aim 1: To determine whether spouse caregivers of AD victims exhibit more: psychobehavioral, metabolic (greater intraabdominal fat (IAF), insulin, C-peptide, glucose), stress hormone (greater cortisol, catecholamines), plasma viscosity (greater hematocrit), and cardiovascular (greater blood pressure (BP) problems and higher rates of CHD relative to spouses of non-demented controls. Aim 2: To determine whether Blacks have greater problems than do Caucasians; and whether Black caregivers have greater problems than Caucasian caregivers. Aim 3: To determine whether BP differences in caregivers are greater at home than in the laboratory and whether race and psychosocial variables modify such differences. Aim 4: To determine whether psychophysiological changes in caregivers are greater when measured over a longer period (27-30 months) than we studied originally (15-18 months); and whether CHD at Time 1 amplifies these changes. Aim 5: To determine whether over 27-30 months, IAF trajectories are associated with changes in psychophysiological/health variables; and whether such relationships are mediated by insulin changes. This research should elucidate psychophysiological mediators of chronic stress and CHD and, therefore, have clinical implications.

psychological stressor; stress; chronic disease /disorder; psychophysiology; caregivers; Alzheimer's disease; behavioral /social science research tag; clinical research; human subject;

DESCRIPTION (provided by applicant): The proposed research will perform secondary data analyses on 10 waves of data from the Cardiovascular Health Study (CHS). The CHS includes 5,888 community-dwelling older adults sampled from several US regions. At baseline, CHS participants had magnetic resonance imagining scans and other measures. Those with dementia were screened from the follow-up sample for dementia, but were retested on other measures. After 10 years, the dementia-free participants were retested and 480 cases of incident dementia and 577 of Mild Cognitive Impairment (MCI) were observed. We will use this sample to meet our primary goal which is to examine incident life events as risk factors for cognitive decline, MCI, and incident dementia. Our specific aims are to use theoretical models of stress to test hypotheses about direct relationships of four incident stressful life events (SLEs) (i.e., death of a loved one, caregiving, illness of a loved one, poor relationship with loved one) with cognitive decline/incident dementia; and indirect relationships of SLEs, mediators, and cognitive decline/dementia. The mediators have theoretical and empirical support. They include psychosocial (social supports, quality of life, depression, sleep problems), behavioral (drinking, smoking, exercise, diet), and physiological (metabolic syndrome, inflammation) measures, as well as incident illnesses (hypertension, diabetes, etc). We will also examine moderators, namely interactions of SLEs with putative etiologic factors (the above cited mediators) and with genetic (APOE), physical (illnesses) and chemical (medications). Because these measures were repeated several times over the course of 10 years, the CHS allows doubly- prospective analyses. Such analyses are rare in the SLE literature. They provide important information about individuals before they experience a SLE and before they experience cognitive decline and/or incident dementia. For example, if psychophysiological measures mediate relationships of incident SLEs with cognitive decline/dementia, we will be able to estimate whether this was influenced by the SLE itself, the putative mediators before the SLE, or the interaction of the two. We will also be able to assess whether some SLE are acute or chronic (e.g. caregiving) and whether chronic experiences interact with acute events to exacerbate the influence of each other on the outcomes. These relationships could have major implications for the design of programs for persons exposed to potentially harmful stressors. In the next 20 years, the US population over 65 years old will grow much faster than the proportion that is less than 35 years old. Given the relationship between age and dementia, government agencies have warned of a dementia epidemic. Dementia causes suffering for victims and families and is very costly to health care. To mitigate this crisis, we must understand the risks for developing cognitive problems/dementia. Genetic-environmental risks have been identified for dementia, but limited attention has been given to SLEs. This is surprising because SLEs and dementia are associated with cognitive, psychophysiological, and behavioral problems.