In the last decade, extensive research has emerged into understanding the impact of risk factors for Alzheimer's Disease (AD) on brain in pre-symptomatic stages. We investigated the neuroimaging correlates of the APOEe4 genetic risk factor for AD in young adulthood, its relationship with cognition, and potential effects of other variables on the findings. While conventional volumetric analyses revealed no consistent differences, more sophisticated analyses identified subtle structural differences between APOEe4 carriers and non-carriers. Findings from diffusion studies were limited, but functional studies demonstrated consistent alterations in connectivity and activity. The complex relationship between APOE genotype, neuroimaging variables, and cognition revealed no consensus on the directionality of findings. Methodological choices, including analytical approaches, sample size, and the influence of other genes, gender, and ethnicity, varied across studies, impacting comparability and generalizability. Recommendations for future research include multimodal and longitudinal imaging, standardisation of pipelines, advanced analytical techniques, and collaborative data pooling.
Keywords: APOE; Alzheimer's; Brain function; Brain structure; Early identification; Neuroimaging; Presymptomatic; Risk factors.
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