Project Summary/Abstract
Autistic adults have a 2.6 times higher risk for Alzheimer’s disease compared to those without autism,
and less than 0.001% of autism research publications include older autistic adults. Previously, in both cross-
sectional and longitudinal designs, we published that middle-aged and older (MA+) autistic adults experience
accelerated cognitive and brain aging compared to neurotypical adults. Thousands of risk alleles have been
identified in autism spectrum disorder, and it is not known whether they impact cognitive aging risk. Instead of
assessing each risk allele separately, polygenic risk scores (PRS) enable the computation of a “genomic dosage”
unique to each individual. This project assesses the central hypothesis that autism PRS scores contribute to
accelerated age-related: Aim 1) memory decline; Aim 2) temporal lobe aging; and Exploratory Aim 3) sex
differences in cognitive and brain aging in MA+ autistic adults. The proposed research will significantly impact
biological understanding of cognitive and brain aging and sex differences in autism by incorporating both
molecular and systems-level approaches. We will use powered multilevel mixed models to evaluate age by
autism PRS interactions in predicting Aim 1) verbal and visual short-term and long-term memory and Aim 2)
cortical thickness and hippocampal volume in MA+ autistic adults. Exploratory Aim 3 will identify the contribution
of autism risk genes on autism-related sex differences in these measures.
Ms. Harker is determined to become a tenure-track professor at an R1 university and an expert in the
neurogenomics of autism and aging. Her long-term goal is to direct a cross-disciplinary clinical laboratory that
emphasizes inclusion and diversity in autism research by understanding the relationship between brain aging
and genetic risk in autistic individuals across the lifespan, especially women. Ms. Harker’s past training and
experiences of 1) being autistic, 2) writing autism advocacy articles, 3) being an autistic research participant,
and 4) doctoral coursework have prepared her to assume the role of a doctoral candidate and attain her
academic and professional career goals in autism research. In her current laboratories, she has gained
foundational knowledge in neuroimaging statistics/neuropsychology, genomics, autism ethics, and professional
development. Through this proposal, she can translate these developing skills into expertise to discover and
compare aging differences for neurotypical and autistic adults. Training will occur primarily at Arizona State
University (ASU). ASU is a well-regarded R1 institution with collaborations at Barrow Neurological Institute’s top-
notch neuroimaging facilities. This is an optimal, supportive training environment for Ms. Harker to hone her skills
in interdisciplinary neuroscience. In addition to the proposed goals, training will focus on professional
development and dissemination of findings to the broader autism community and will be empowered by Ms.
Harker’s unique perspective as an openly autistic adult.