Family Member Deaths in Childhood Predict Systemic Inflammation in Late Life

Abstract

Biological and epidemiological evidence has linked early-life psychosocial stress with late-life health, with inflammation as a potential mechanism. We report here the association between familial death in childhood and adulthood and increased levels of high-sensitivity C-reactive protein (CRP), a marker of systemic inflammation. The Cache County Memory Study is a prospective study of persons initially aged 65 and older in 1995. In 2002, there were 1,955 persons in the study with data on CRP (42.3 percent male, mean [SD] age = 81.2 [5.8] years), linked with objective data on family member deaths. Using logistic regression, high (> 10 mg/L) versus low (≤ 10 mg/L) CRP was regressed on cumulative parental, sibling, spouse, and offspring deaths during childhood and during early adulthood, adjusted for family size in each period (percentage family depletion; PFD). Findings revealed PFD during childhood to be significantly associated with CRP (OR = 1.02, 95% CI [1.01, 1.04]). Individuals with two or more family deaths were 79 percent more likely to have elevated CRP than those with zero family deaths (OR = 1.79, 95% CI [1.07, 2.99]). Early adulthood PFD was not related to CRP. This study demonstrates a link between significant psychosocial stress in early life and immune-inflammatory functioning in late life, and suggests a mechanism explaining the link between early-life adversity and late-life health.

Early parental death and psychosocial risk factors for dementia: A case–control study in Europe

“…13 In terms of physical health, early parental death has been associated with worse health perception 14 and more somatic symptoms, 15 as well as higher mortality, 16 cardiovascular disease, 4,5,17 self-harm, 18 and an increased risk of dementia. [19][20][21][22][23][24][25][26] Previous studies have identified certain mechanisms involved in the association between early parental death and the risk of dementia and other pathologies associated with older age: stress, 27,28 increased inflammatory processes, 29 alterations of the hypothalamic-pituitaryadrenal axis, 30 and shorter telomeres on chromosomes. 31,32 Research into the relationship between early parental death and dementia and/or severe cognitive impairment in the elderly has confirmed a general increased risk (odds ratios [OR]: 1.52-6.41), [19][20][21][22][23][24][25][26] although the results vary according to gender and age at the time of parental death.…”

“…Previous studies have identified certain mechanisms involved in the association between early parental death and the risk of dementia and other pathologies associated with older age: stress, 27,28 increased inflammatory processes, 29 alterations of the hypothalamic‐pituitary‐adrenal axis, 30 and shorter telomeres on chromosomes 31,32 …”

The Long Harm of Childhood: Childhood Exposure to Mortality and Subsequent Risk of Adult Mortality in Utah and The Netherlands

“…Research shows that exposure to sibling deaths is related to later-life stress (Norton et al 2017) and increases mortality in early and late childhood and early adulthood (Yu et al 2017). In line with these results, we found that sibling deaths are related to reduced survival at adult ages.…”

“…In addition, sibling mortality may lead to chronically increased levels of stress (Yu et al 2017), which, in turn, is a risk factor for diseases such as asthma, diabetes, gastrointestinal disorders, cancer and myocardial infection (McEwen 1998; McEwen and Stellar 1993). Similarly, Norton et al (2017) found that sibling deaths during childhood predict systemic inflammation in later life, linking stress responses to adult life expectancy. To gain further insights into the causal mechanisms linking sibling mortality to mortality hazards in adulthood, in this paper, we employ cause of death information and competing risk models.…”

Early life exposures associated with risk of small intestinal neuroendocrine tumors

“…Data resources at the University of Utah offer a unique opportunity to explore the relationship between early life environmental exposures and subsequent cancer risks. Multiple studies have used these statewide resources to consider early life conditions including socioeconomic status, parental mortality, religion and birth order on long-term health outcomes including cancer, mortality and systemic inflammation [18][19][20]. Early life exposures based on place of birth has not, to our knowledge, been explored using the Utah state-wide resources.…”