Chronic Perceived Stress, Social Isolation, and Perceived Loneliness as a Symptom Cluster among Dementia Caregivers Mariya Kovaleva BSN RN,1 Sydney A. Spangler PhD MSN CNM RN,1 Kenneth Hepburn PhD1,2 Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA 2Emory Alzheimer’s Disease Research Center, Atlanta, GA Background Literature Search Strategy Link Between Endogenous Mechanisms & Exogenous Factors Search terms: dement*, caregiv*, Alzheimer* disease, carer, family, family members, informal, unpaid, stress, chronic stress, health, biomarker, • 15.5 million unpaid dementia caregivers in the immunology, inflammation, social isolation, loneliness, perceived loneliness • Association between social isolation & morbidity, incl. U.S.; over 5 million individuals living with diseases of inflammatory pathogenesis Alzheimer’s disease (AD), projected to reach up to Results • Association between perceived loneliness & altered gene transcription 16 million in 2050; most live in the community, Caregivers’ Multifactorial Stress • Chronically high subjective social isolation altered gene assisted by unpaid caregivers • ADLs & neuromotor disturbance: more intense caregiver involvement needed transcription in leukocytes: • $9.7 million/year in healthcare costs compared to older care recipients with non-dementing illnesses • Underexpression of genes that carry anti-inflammatory Caregivers’ • Contribute $217 billion/year in labor • Behavioral & psychological symptoms of dementia (BPSD): more supervision glucocorticoid response elements & genes required for economic & • Experience chronic stress, depressive • BPSD may trigger caregivers’ acute stress antibody synthesis & B lymphocyte maturation • Overexpression of genes that carry response elements for psychological symptoms, anxiety, burden, quality of • Caregiving hours: employment & family difficulties; sandwich caregivers the pro-inflammatory transcription factor – nuclear factor • Employment risks: work hours, financial insecurity well-being life, social isolation & perceived kappa B protein complex & genes that regulate pro- loneliness • Social isolation and/or perceived loneliness: potentially changed relationships inflammatory cytokine signaling, cellular transcription Disruption of Neuroendocrine & Immune Regulatory Pathways with Chronic Stress events, cell cycle course, & prostaglandin formation • Similar findings among individuals living with chronic stress Hypothalamic-Pituitary-Adrenal Chronic stress Acute Stress Chronic Stress – caregivers for persons with glioblastoma Endogenous (HPA) Axis Low-grade systemic inflammation Paraventricular • Heart rate, blood pressure, cortisol secretion Underlying mechanism nuclei of the Stress 2 Morbidity hypothalamus cardiovascular output downregulation of “Transcriptional fingerprint” of chronic stress & perceived & mortality Chronic diseases: cardiovascular disease, cancer, Corticotropin- Negative • Blood glucose expression & function of loneliness arthritis, diabetes, depression, osteoporosis, frailty, releasing factor feedback • Production, secretion, & receptors on WBCs that bind Anterior • Healthy adults who self-perceive as lonely exhibit greater functional decline pituitary Melanocortin type 2 efficacy of cytokines cortisol receptors, zona synthesis of TNF-α & IL-6 by PBMCs stimulated by Adrenocorticotropic fasciculata, adrenal ACTH • Migration of white blood Persistent hormone (ACTH) cortex lipopolysaccharide, following acute stress Social isolation: cells (WBCs) to cellular hypercortisolemina • Dementia caregivers who perceive themselves as lonely may • May contribute to chronic stress injury sites exhibit similar inflammatory phenotype Exogenous Glucocorticoids, • ≠ perceived loneliness incl. cortisol Adaptive Maladaptive • Relevant given high risk of acutely stressful events • Both documented in this population associated with BPSD: agitation, aggression, wandering Chronic Stress: Other Cellular Sympathetic Adrenal Medullary Neuroimmunological Dysregulation • Dementia caregivers who perceive themselves as lonely: Changes Axis & Depressive Symptoms Objectives at a risk for a three-component symptom cluster – I. Review evidence on dementia caregivers’ health through • Proinflammatory • Activated during stress • Depression: overactivity fatigue, pain, & depression cytokines TNF-α & IL-10; the lens of endogenous mechanisms of chronic stress & norephinephrine & Locus of the HPA axis • proliferation of T Secretes epinephrine coeruleus in • “Counterregulatory”1 exogenous factors that may contribute to social isolation lymphocytes – active pons • Chronically physically demanding work of caregiving: fatigue and perceived loneliness. II. Examine whether chronic response of WBCs • Chronic pain likelihood (e.g., arthritis) immunity Proinflammatory Sympathetic similar to chronic stress stress, social isolation, and perceived loneliness may occur • Shortened telomere cytokines fibers’ nerve • Depression likelihood terminals • Chronic exposure to • Likelihood of perceived loneliness due to social isolation as a symptom cluster, and what may serve as a marker of length in peripheral blood proinflammatory the proposed cluster. mononuclear cells Immune system cytokines depressive (PBMCs) Methods communicates with brain symptoms morbidity Discussion & Implications • Study design: Review: randomized controlled trials • Caregivers’ chronic stress & social isolation are common Exogenous Factors (RCTs), systematic reviews of RCTs, meta-analyses, • Social isolation linked to perceived loneliness, which may quasi-experimental investigations, case-control or cohort Perceived Loneliness & Social Dementia Caregivers’ Chronic Diseases exacerbate adverse outcomes of chronic stress Isolation • A possible social isolation-linked three-component cluster studies, systematic reviews of qualitative or descriptive • HTN & arthritis: most • Need to investigate & intervene on caregiver social isolation studies, single qualitative or descriptive studies, expert • Change in family roles prevalent conditions • Arthritis: may instrumental • Proliferation of on-line education & support programs may opinions. Publication years & language: 1980 – 2015, • Likely loss of relationship among caregivers who are ADL performance help mitigate social isolation & linked adverse outcomes English. Search strategy: PubMed, PsycINFO, CINAHL, with the care recipient baby boomers ability to engage in social • Prevalence of conflict in Web of Science, & EMBASE databases; reference lists. • HTN: may lead to acute activities caregiving families • Study selection: i. Report endogenous mechanisms of events or heart failure References • Reduction of work hours may ability to maintain • Financial burden of 1 Miller, G. E., Cohen, S., & Ritchey, A. K. (2002). Chronic psychological stress and the regulation of pro-inflammatory cytokines: A chronic stress and/or exogenous factors that contribute may further limit non- glucocorticoid-resistance model. Health Psychology, 21, 531-541 social connections; not caregivers’ own illnesses 2 to dementia caregivers’ social isolation or perceived Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007). Social regulation of gene expression family social connections willing to be seen ill coupled with expenses of in human leukocytes. Genome Biology, 8(9), R189. loneliness. ii. Aimed at informal caregivers of community- may worsen social caregiving . dwelling persons with dementia (AD, frontotemporal, isolation and/or perceived Acknowledgments Lewy body, vascular, or mixed). loneliness Ms. Carolyn Brown, Dr. Elizabeth Corwin, Dr. Ann Rogers