Changes in Loneliness, BDNF, and Biological Aging Predict Trajectories in a Blood-Based Epigenetic Measure of Cortical Aging: A Study of Older Black Americans

Abstract

A recent epigenetic measure of aging has developed based on human cortex tissue. This cortical clock (CC) dramatically outperformed extant blood-based epigenetic clocks in predicting brain age and neurological degeneration. Unfortunately, measures that require brain tissue are of limited utility to investigators striving to identify everyday risk factors for dementia. The present study investigated the utility of using the CpG sites included in the CC to formulate a peripheral blood-based cortical measure of brain age (CC-Bd). To establish the utility of CC-Bd, we used growth curves with individually varying time points and longitudinal data from a sample of 694 aging African Americans. We examined whether three risk factors that have been linked to cognitive decline—loneliness, depression, and BDNFm—predicted CC-Bd after controlling for several factors, including three new-generation epigenetic clocks. Our findings showed that two clocks—DunedinPACE and PoAm—predicted CC-BD, but that increases in loneliness and BDNFm continued to be robust predictors of accelerated CC-Bd even after taking these effects into account. This suggests that CC-Bd is assessing something more than the pan-tissue epigenetic clocks but that, at least in part, brain health is also associated with the general aging of the organism.

Racial discrimination during middle age predicts higher serum phosphorylated tau and neurofilament light chain levels a decade later: A study of aging black Americans

“…4 An abundance of recent research has documented the way that chronic exposure to such events takes a toll on biological systems and compromises health. Several studies have shown, for example, that exposure to racial mistreatment promotes onset of chronic illness, 5,6 an increased speed of biological aging, 7 and risk for stroke and mortality. 8 Building upon these findings, some have argued that the impact of stress and trauma likely extends to the brain and onset of dementia.…”

“…8 Building upon these findings, some have argued that the impact of stress and trauma likely extends to the brain and onset of dementia. 2,3,7 For example, high levels of stress are associated with reductions in hippocampal 9,10 and prefrontal cortex 11 volumes. These brain structures are critical for episodic memory and executive function and are among the first to show neurodegenerative changes in ADRD.…”

“…In support of this idea, several recent studies have reported a link between exposure to racial discrimination and ADRD. 7 , 13 , 14 , 15 However, the underlying biological mechanisms by which stress and discrimination contribute to cognitive decline are not yet understood. For example, it is not clear whether racial discrimination impacts biomarkers of AD pathology, more general biomarkers of neurodegeneration, or both.…”

“…We expected that exposure to chronic racial discrimination during middle‐age, assessed between 2002 and 2008, would show little association with the serum biomarkers assessed in 2008 when the participants were still relatively young (aged 40–50) and ADRD pathology is not highly prevalent. However, past research has shown that early exposure to racial discrimination predicts later onset of a wide variety of chronic illnesses, 5 , 6 speed of epigenetic aging, 7 and mortality. 8 We hypothesized that a similar pattern likely exists for ADRD and corresponding biomarkers.…”