Lifelong associations between childhood multimorbidity and early-onset and late-onset dementia: A multi-cohort study

Abstract

Objectives

Previous studies have investigated associations between childhood illness and health outcomes in early adulthood. Nevertheless, little evidence is available on the associations of childhood chronic conditions and multimorbidity with Alzheimer's disease and related dementias (ADRD) in mid-to-old age.

Study design

Multi-cohort study.

Methods

We conducted a multi-cohort study using the Survey of Health, Ageing and Retirement in Europe, English Longitudinal Study of Ageing and Health and Retirement Study. We included eight retrospectively reported childhood chronic diseases that were diagnosed by a doctor before 15/16y and defined multimorbidity as≥2 diseases. The associations with new-onset, early-onset (<65y) and late-onset (≥65y) ADRD were estimated using subdistribution hazard ratios (sHRs) and Aalen's additive hazard model (i.e., absolute risk). Results were pooled across cohorts using weighted random-effect meta-analysis.

Results

A total of 135,588 participants aged ≥ 50y were followed up for an average of around eight years. Childhood multimorbidity was associated with higher risk of new-onset ADRD: sHR = 1.44 (95 % CI: 1.25–1.66) after adjusting for demographic and early-life factors, corresponding to excess incidence density of 223.3 per 100,000 person-years. The association was stronger with early-onset ADRD than late-onset ADRD: sHR = 2.50 (1.84–3.41) vs 1.25 (1.07–1.47), corresponding to the excess incidence density of 217.1 and 230.7 per 100,000 person-years. Of individual childhood chronic diseases, migraine, epilepsy and psychiatric disorders showed the strongest association with ADRD.

Conclusions

Childhood multimorbidity was associated with increased risk of ADRD in late life, highlighting the importance of preventing childhood diseases, especially neuropsychiatric conditions, to mitigate the burden of ADRD in older adults.