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.

翻译：背景：痴呆导致高残疾负担，1990年至2016年间全球痴呆患者数量翻倍。然而，部分研究提示痴呆风险可能下降，这或许源于传统分析方法未能充分校正因死亡导致的疾病信息缺失所造成的偏倚。方法：本研究重新检验弗雷明汉心脏研究中跨越四十年的痴呆发病率潜在趋势。我们采用针对区间删失疾病-死亡数据定制的多状态建模框架，并定义三个非重叠出生队列（1915-1924年、1925-1934年及1935-1944年）。以年龄为时间尺度，分别基于痴呆患病率和痴呆风险评估趋势变化。同时估算了按性别分层的年龄条件性痴呆概率。结果：3828名参与者中共有731人被诊断为痴呆。多状态模型分析显示，无论性别如何，各出生队列的痴呆风险均未呈现随时间下降的趋势。按性别分层并校正教育水平后，女性在整个研究期间始终表现出比男性更高的终生年龄条件性风险（46%-50%对30%-34%）。结论：我们建议在队列研究中结合多状态方法与出生队列分层策略，以准确评估疾病风险趋势，并有效传达如年龄条件性疾病风险等与患者相关的结局指标。