Inequalities in accelerated cognitive decline: Resolving observational window bias using nested non-linear regression.

Abstract

Limited observational windows lead to conflicting results in studies examining educational differences in Alzheimer's disease and related dementias (ADRD) risk, due to observational window bias relative to onset of accelerated cognitive decline. This study tested a novel model to address observational window bias and tested for the presence and sources of disparities in accelerated cognitive declines due to ADRD. The sample examined 167,314 cognitive assessments from 32,441 Health and Retirement Study participants. We implemented a parametric non-linear nested longitudinal regression and reported multivariable-adjusted nodal incidence ratios (aNIR). University degrees were associated with lower incidence (aNIR=0.253, 95% confidence interval [CI]=[0.221 to 0.289], p<0.001), while black participants had a higher incidence (aNIR=1.995, [1.858 to 2.141], p<0.001) of accelerated cognitive decline, adjusting for demographic, sociobehavioral, and medical risk factors. Sex-stratified analyses identified diminished educational returns for women and increased incidence among minoritized women. Addressing observational window bias reveals large social inequalities in the onset of accelerated cognitive declines indicative of ADRD. This study identifies observational window bias as a source of conflicting results among previous studies of educational achievement in Alzheimer's disease and related dementias (ADRD) disparities. The study locates preclinical accelerated cognitive decline, which is indicative of ADRD while occurring 10+ years prior to symptom onset, as a site to study ADRD disparities that mitigates observational window bias. A novel method, nested non-linear regression, is developed to test for differences in the onset of accelerated cognitive decline. Educational and racial/ethnic disparities are demonstrated in the onset of accelerated cognitive decline, as are their intersecting differences with sex/gender.