Increasing empathic concern relates to salience network hyperconnectivity in cognitively healthy older adults with elevated amyloid-β burden

Enhanced emotional empathy, the ability to share others' affective experiences, can be a feature of Alzheimer's disease (AD), but whether emotional empathy increases in the preclinical phase of the disease is unknown. We measured emotional empathy over time (range = 0 - 7.3 years, mean = 2.4 years) in 86 older adults during a period in which they were cognitively healthy, functionally normal, and free of dementia symptoms. For each participant, we computed longitudinal trajectories for empathic concern (i.e., an other-oriented form of emotional empathy that promotes prosocial actions) and emotional contagion (i.e., a self-focused form of emotional empathy often accompanied by feelings of distress) from informant ratings of participants' empathy on the Interpersonal Reactivity Index. Amyloid-beta (A beta) positron emission tomography (PET) scans were used to classify participants as either A beta positive (A beta+, n = 23) or negative (A beta-, n = 63) based on A beta-PET cortical binding. Participants also underwent structural and task-free functional magnetic resonance imaging approxi-mately two years on average after their last empathy assessment, at which time most participants remained cognitively healthy. Results indicated that empathic concern, but not emotional contagion, increased more over time in A beta+ participants than in A beta-participants despite no initial group difference at the first measurement. Higher connectivity between certain salience network node-pairs (i.e., pregenual anterior cingulate cortex and periaqueductal gray) predicted longitudinal increases in empathic concern in the A beta+ group but not in the A beta-group. The A beta+ participants also had higher overall salience network connectivity than A beta-participants despite no differences in gray matter volume. These results suggest gains in empathic concern may be a very early feature of AD pathophysiology that relates to hyperconnectivity in the salience network, a system that supports emotion generation and interoception. A better understanding of emotional empathy trajectories in the early stages of AD pathophysiology will broaden the lens on preclinical AD changes and help clinicians to identify older adults who should be screened for AD biomarkers.