Apoe4 gene variant is related to verbal memory and left hippocampus size in adults with autism
Background: Autism Spectrum Disorder (ASD) is a developmental disorder that affects 1 in 59 births within the United States, yet cognitive and brain aging in older adults with ASD is understudied. Cognitive issues can include difficulty with verbal memory, which has been linked to left hippocampal volume. APOE is a gene linked to neuronal development, and can cause cognitive deficits depending on the variant. The ε2 variant is protective, ε3 is standard, and ε4 is detrimental; it has been linked to Alzheimer’s Disease and general cognitive impairment. We hypothesized that the ε4 allele would have a greater detrimental effect on age related changes to verbal memory and hippocampal size in adults with ASD than neurotypical adults.
Methods: We performed Rey Auditory Learning Test to measure verbal memory, and obtained variables for short term memory, long term memory, and learning. Participants underwent Magnetic resonance imaging (MRI) scans to measure volume of left hippocampus, data was processed with Free Surfer and corrected for intracranial volume. DNA isolated from saliva samples were processed via polymerase chain reaction (PCR) and genotyped on an Agilent D1000 tapestation. Sex and IQ were covariates in an ANCOVA to assess the effects between age groups (Young = < 40 vs. Old = >40), diagnosis (ASD vs NT), and APOE status (ε4 carrier vs. non-carrier).
Results: For short term memory, there was a significant interaction between Age*APOE, suggesting that older e4 carriers have worse short term memory performance than older non-carriers [F(1,135)= 4.709, p=0.024], while younger carriers and non-carriers had no difference. There was also a significant interaction between age*diagnosis, suggesting younger ASD group show worse short term memory performance than compared to their NT counterpart [F(1,135)=6.40, p=0.013], while older ASD and NT counterparts showed no difference. There was a main effect of age on long term memory, showing that the younger performed better than the older group [F(1,135)= 6.80, p=0.01]. There was a main effect of diagnosis in long term memory, supporting that the NT group showed better long term memory performance than the ASD group [F=(1,135)= 5.048, p= 0.026]. There was a significant interaction of APOE*age in learning such that older e4 carriers showed worse learning performance than older non-carriers [F(1,135)= 5.64, p= 0.019], while younger carriers and non-carriers showed no difference. There was a main effect of age, such that the younger group displayed better learning performance than the older group [F(1,135)= 6.69, p= 0.01]. The main effect of age on left hippocampal volume was trending as the younger group displayed larger hippocampal volume than the older group [F(1,133)= 2874, p=0.07].
Discussion: While there was an APOE*Age interaction and a Diagnosis*Age interaction, there was no three-way interaction with diagnosis, age, and APOE, therefore our hypothesis was not supported. The interaction between APOE and age on short term memory scores was expected, however, we did not find an exacerbated effect in ASD. The diagnosis and age interaction on short term memory suggests that the younger ASD group, not the older, showed impairment in short term memory, which was surprising. This data is part of a longitudinal study, and is ongoing. With a larger sample size and more power, in the future we may find different results. Earlier awareness of biological factors contributing to brain and cognitive aging can lead to earlier preventative care such as cognitive therapy for individuals with ASD.
