APOE ε4-Allele in Middle-Aged and Older Autistic Adults: Associations with Verbal Learning and Memory

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disability and recent evidence suggests that autistic adults are more likely to develop Alzheimer’s disease (Alz) and other dementias compared to neurotypical (NT) adults. The ε4-allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alz and negatively impacts cognition in middle-aged and older (MA+) adults. This study aimed to determine the impact of the APOE ε4-allele on verbal learning and memory in MA+ autistic adults (ages 40–71 years) compared to matched NT adults. Using the Auditory Verbal Learning Test (AVLT), we found that ε4 carriers performed worse on short-term memory and verbal learning across diagnosis groups, but there was no interaction with diagnosis. In exploratory analyses within sex and diagnosis groups, only autistic men carrying APOE ε4 showed worse verbal learning (p = 0.02), compared to autistic men who were not carriers. Finally, the APOE ε4-allele did not significantly affect long-term memory in this sample. These findings replicate previous work indicating that the APOE ε4-allele negatively impacts short-term memory and verbal learning in MA+ adults and presents new preliminary findings that MA+ autistic men may be vulnerable to the effects of APOE ε4 on verbal learning. Future work with a larger sample is needed to determine if autistic women may also be vulnerable.

Cognitive and brain morphological deviations in middle-to-old aged autistic adults: A systematic review and meta-analysis

“…In this review, most studies confirmed diagnosis following DSM-IV ( Braden et al, 2017 ; Davids et al, 2016 ; Geurts et al, 2020 ; Groenman et al, 2024 ; Groot et al, 2021 ; Lever and Geurts, 2016 ; Spek et al, 2017 ; Torenvliet et al, 2023b , 2024 ; Tse et al, 2019 ), DSM-5 ( Braden et al, 2017 ; Davids et al, 2016 ; Groenman et al, 2024 ; Groot et al, 2021 ; Harker et al, 2023 ; Kohli et al, 2019 ; Pagni et al, 2022 ; Torenvliet et al, 2022 , 2023a , 2023b , 2024 ; Tse et al, 2019 ; Walsh et al, 2022 ), or NICE guidelines for the diagnosis and management of autistic adults ( https://www.nice.org.uk/guidance/cg142 ) ( Koolschijn and Geurts, 2016 ; Koolschijn et al, 2017 ). In confirming diagnosis, the Autism Diagnostic Observation Schedule (ADOS) was used by the majority of selected studies ( Braden et al, 2017 ; Davids et al, 2016 ; Groot et al, 2021 ; Harker et al, 2023 ; Kohli et al, 2019 ; Koolscjihn & Geurts, 2016 ; Koolschijn et al, 2017 ; Lever et al, 2016 ; Powell et al, 2017 ; Pagni et al, 2022 ; Torenvliet et al, 2022 ; Walsh et al, 2022 ), with some of the studies using ADOS in addition to screening instruments such as the Autism Spectrum Quotient (AQ) ( Bathelt et al, 2022 ; Groenman et al, 2024 ; Groot et al, 2021 ; Koolschijn and Geurts, 2016 ; Koolschijn et al, 2017 ; Lever and Geurts, 2016 ; Torenvliet et al, 2023a , 2023b , 2024 ) or Social Responsiveness Scale (SRS) ( Braden et al, 2017 ; Pagni et al, 2022 ; Powell et al, 2017 ;…”

“…Twenty-two studies were selected. A summary of extracted data is shown in Table 1 for cognitive studies ( Bathelt et al, 2022 ; Davids et al, 2016 ; Geurts et al, 2020 ; Geurts and Vissers, 2012 ; Groenman et al, 2024 ; Groot et al, 2021 ; Harker et al, 2023 ; Klein et al, 2023 ; Lever and Geurts, 2016 ; Powell et al, 2017 ; Spek et al, 2017 ; Torenvliet et al, 2022 , 2023a , 2023b , 2024 ; Tse et al, 2019 ) and Table 2 for brain imaging studies ( Braden et al, 2017 ; Kohli et al, 2019 ; Koolschijn et al, 2017 ; Koolschijn and Geurts, 2016 ; Pagni et al, 2022 ; Walsh et al, 2022 ) Twenty-one studies [except for Klein et al, (2023) ] included more male than female participants, of which two cognitive ( Geurts et al, 2020 ; Spek et al, 2017 ) and one imaging article ( Braden et al, 2017 ) only recruited male participants. All studies focused on autistic adults without intellectual disability.…”

“…A range of cognitive domains were examined, including global cognitive function ( Bathelt et al, 2022 ; Braden et al, 2017 ; Groenman et al, 2024 ; Groot et al, 2021 ; Harker et al, 2023 ; Klein et al, 2023 ; Koolschijn and Geurts, 2016 ; Lever and Geurts, 2016 ; Powell et al, 2017 ; Pagni et al, 2022 ; Torenvliet et al, 2022 , 2023a , 2023b , 2024 ; Walsh et al, 2022 ), executive control ( Braden et al, 2017 ; Davids et al, 2016 ; Geurts and Vissers, 2012 ; Geurts et al, 2020 ; Kohli et al, 2019 ; Powell et al, 2017 ; Spek et al, 2017 ; Torenvliet et al, 2022 , 2023a , 2023b ; Tse et al, 2019 ), memory ( Braden et al, 2017 ; Geurts and Vissers, 2012 ; Groenman et al, 2024 ; Harker et al, 2023 ; Klein et al, 2023 ; Lever and Geurts, 2016 ; Pagni et al, 2022 ; Powell et al, 2017 ; Torenvliet et al, 2022 , 2023a , 2023b , 2024 ; Walsh et al, 2022 ; Tse et al, 2019 ), attention ( Geurts and Vissers, 2012 ), and visuospatial skills ( Bathelt et al, 2022 ; Braden et al, 2017 ). No study assessed perceptual speed in middle-to-old aged autistic adults.…”

“…The retention rate of the three mixed-design studies ( Pagni et al, 2022 ; Walsh et al, 2022 ; Torenvliet et al, 2023a ) was high (>86 %) at the first follow-up, although significantly decreased at the second follow-up with a rate of 30.42 % ( Torenvliet et al, 2023a ). Only Nine studies (40 % of identified articles) included sample size justification and the analysis for effect size and statistical power ( Braden et al, 2017 ; Groenman et al, 2024 ; Harker et al, 2023 ; Pagni et al, 2022 ; Torenvliet et al, 2023a , 2023b , 2024 ; Tse et al, 2019 ; Walsh et al, 2022 ).…”

“…Common exclusion criteria included IQ ( Braden et al, 2017 ; Geurts et al, 2020 ; Groenman et al, 2024 ; Groot et al, 2021 ; Harker et al, 2023 ; Koolschijn and Geurts, 2016 ; Koolschijn et al, 2017 ; Lever and Geurts, 2016 ; Pagni et al, 2022 ; Powell et al, 2017 ; Spek et al, 2017 ; Torenvliet et al, 2022 , 2023a , 2023b , 2024 ; Tse et al, 2019 ; Walsh et al, 2022 ), neurological or neurodegenerative conditions ( Bathelt et al, 2022 ; Braden et al, 2017 ; Davids et al, 2016 ; Groenman et al, 2024 ; Groot et al, 2021 ; Harker et al, 2023 ; Kohli et al, 2019 ; Koolschijn and Geurts, 2016 ; Koolschijn et al, 2017 ; Lever and Geurts, 2016 ; Pagni et al, 2022 ; Spek et al, 2017 ; Torenvliet et al, 2022 , 2024 ; Torenvliet et al, 2023a , Torenvliet et al, 2023b ; Walsh et al, 2022 ), major psychiatric disorders ( Bathelt et al, 2022 ; Geurts et al, 2020 ; Groenman et al, 2024 ; Groot et al, 2021 ; Koolschijn and Geurts, 2016 ; Koolschijn et al, 2017 ; Lever and Geurts, 2016 ; Spek et al, 2017 ; Torenvliet et al, 2022 , 2024 ; Torenvliet et al, 2023a , Torenvliet et al, 2023b ), MMSE score ( Braden et al, 2017 ; Groenman et al, 2024 ; Groot et al, 2021 ; Harker et al, 2023 ; Koolschijn and Geurts, 2016 ; Lever and Geurts, 2016 ; Pagni et al, 2022 ; Torenvliet et al, 2022 ,…”