Cross-sectional associations of loneliness with plasma p-tau217 and neurofilament light chain in dementia-free older adults in the INSPIRE-T baseline cohort

Background Loneliness is the subjective feeling of social isolation and evidence suggests that it increases the risk for cognitive decline and Alzheimer's disease (AD). However, studies examining the associations between loneliness and AD biomarkers are limited and inconclusive. Objective We sought to investigate the relationships between loneliness and plasma tau phosphorylated at threonine 217 (p-tau217) and plasma neurofilament light chain (NfL): peripheral biomarkers of central AD pathology. Methods This is a cross-sectional analysis of the ‘INStitute for Prevention’ ‘healthy agIng’ and ‘medicine REjuvenative’ ‘Translational’ (INSPIRE-T) baseline data. Participants were dementia-free (Mini-Mental State Exam score ≥ 24) community-dwellers aged ≥ 65 years (n = 434). Loneliness was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS ® ) Item Bank v2.0, Short Form 8a questionnaire and plasma p-tau217 and plasma NfL were measured using Lumipulse immunoassays. Multiple linear regression was conducted to evaluate the relationships between loneliness (exposure) and plasma biomarkers (outcomes). Results Loneliness was not associated with plasma p-tau217 (β = 0.00458 [95% CI: −0.00328, 0.01243], p = 0.253) or plasma NfL (β = 0.00138 [95% CI: −0.00418, 0.00693], p = 0.626) in multiple linear regression models adjusted for age, sex, education, cognitive performance, depressive score, eyesight, hearing, and apolipoprotein ε4 ( APOE ε4) status (model 2). There was no significant moderating effect of sex, depression, eyesight, hearing or APOE ε4 on these associations. Conclusions Our findings suggest that loneliness is not associated with plasma p-tau217 or plasma NfL in dementia-free older adults. Perspective studies are warranted to examine these associations further.