LEGENNDS

The primary outcome variable of interest is the presence of dementia as determined from the core HRS interview
that includes a Telephone Interview for Cognitive Status (TICS). Secondary outcomes of interest include cognitive
scores and change in scores. The primary predictor variables of interest are polygenic risk scores for autism,
ADHD, and intelligence. The covariates considered in this study include age at study entry, sex, race/ethnicity,
socioeconomic status at baseline, education, and genetic ancestry. Cox proportional hazards models will evaluate
time to event, operationalized as the time from study entry to the time of the first instance of dementia status.
Those who did not receive a status of dementia by the end of the follow-up period were termed censored.
Similarly, individuals who died before receiving a diagnosis of dementia were also censored, as well as those who
were lost to follow-up. Each censored individual also had a time to event from the time of study entry to the time
of censoring. Statistical models will estimate the association of polygenic risk scores for autism, ADHD, and
intelligence and dementia/cognitive scores and change in scores. This is a collaboration with Drexel University (PI: Brian K Lee)

Emerging evidence suggests that certain neurodevelopmental disorders – autism, attention-deficit hyperactive
disorder (ADHD), and intellectual disability – may increase the risk of later life neurodegenerative disorders such
as Alzheimer’s disease or related dementia (ADRD). The goal of this proposed study is to elucidate the genetic link
between autism, ADHD, and intellectual disability and ADRD. As part of this, we will examine the relationship
between genetic susceptibility to neurodevelopmental disorders and future risk of ADRD. This study will make use
of genetic data from over 18,000 participants in the Health and Retirement Study.