Temporal Trends in Incidence of Dementia in a Birth Cohorts Analysis of the Framingham Heart Study

Background: Dementia leads to a high burden of disability and the number of dementia patients worldwide doubled between 1990 and 2016. Nevertheless, some studies indicated a decrease in dementia risk which may be due to a bias caused by conventional analysis methods that do not adequately account for missing disease information due to death. Methods: This study re-examines potential trends in dementia incidence over four decades in the Framingham Heart Study. We apply a multistate modeling framework tailored to interval-censored illness-death data and define three non-overlapping birth cohorts (1915-1924, 1925-1934, and 1935-1944). Trends are evaluated based on both dementia prevalence and dementia risk, using age as the underlying timescale. Additionally, age-conditional dementia probabilities stratified by sex are estimated. Results: A total of 731 out of 3828 individuals were diagnosed with dementia. The multistate model analysis revealed no temporal decline in dementia risk across birth cohorts, irrespective of sex. When stratified by sex and adjusted for education, women consistently exhibited higher lifetime age-conditional risks (46%-50%) than men (30%-34%) over the study period. Conclusions: We recommend using a combination of multistate approach and separation into birth cohorts to adequately estimate trends of disease risk in cohort studies as well as to communicate patient-relevant outcomes such age-conditional disease risks.

💡 Research Summary

Background
Dementia imposes a substantial global burden, with the number of affected individuals doubling between 1990 and 2016, largely driven by population ageing. Recent reports from high‑income countries, however, suggest a modest decline in dementia incidence over the past few decades. Such an apparent trend may be artefactual, arising from methodological shortcomings—particularly the failure of conventional survival analyses (e.g., Cox models) to account for missing disease information caused by death, a problem termed “Missing Disease Information due to Death” (MDID).

Objective
The authors re‑examined temporal trends in dementia incidence using the Framingham Heart Study (FHS) cohort, applying a multistate (illness‑death) model that explicitly handles interval‑censored disease onset and MDID, and organizing participants into non‑overlapping birth cohorts rather than arbitrary calendar epochs.

Data and Cohort Construction
FHS comprises an original cohort (recruited 1948, ages 28‑74) and an offspring cohort (recruited 1971, ages 5‑70). Cognitive screening began in 1975 (original) and 1979 (offspring) using the MMSE, followed by detailed neurological and neuropsychological assessments for those flagged as possibly impaired. The authors extracted data in 2025, identified participants born between 1915 and 1944, and required at least one dementia‑free assessment at age ≥ 60. This yielded 3,828 individuals (1,360 in birth cohort 1