Value of ophthalmological psychophysical test and MEG in subjects at high risk for sporadic Alzheimer's disease

Purpose: The aim of this work was to analyse in subjects at high risk of developing Alzheimer's disease (AD) the possible correlation between psychophysical tests and magnetoencephalography (MEG) in comparison with control subjects. Methods: Extensive ophthalmological analysis, MEG recording, genotyping and magnetic resonance imaging (MRI) were performed on 149 healthy subjects, of whom 109 had a family history of the disease and 40 did not. This sample was subdivided into subgroups aged 40–60 years with an increased risk of AD based on the presence of the ApoEɛ4 allele (ApoEɛ4+) and family history (FH+). 28 participants as higher risk group (ApoEɛ4+ and FH+) and 16 participants as lower risk group (FH‐ and ApoEɛ4‐). Results: In the ApoEɛ4+ and FH+ group, a significant increase in visual acuity was observed, as well as an increase in some spatial frequencies of contrast sensitivity. In addition, in this group, some areas of the inner plexiform layer and the inner nuclear layer were thinned. Between the risk groups, when directly comparing M100 latency or temporal frequency activity associated with the visual response, no significant differences were found. However, there was an association between higher visual acuity and earlier M100 latency and increased activity in the high‐risk groups. Conclusions: There seems to exist an early hyperactivation of the visual system, which would act as a compensatory mechanism, or be a manifestation of a biological malfunction that ultimately leads to toxicity. This hyperactivation represents the first evidence of the consequences of early retinal damage, associated with genetic risk, on visual processing. These changes observed by readily available and non‐invasive techniques could constitute a set of biomarkers for early detection of the disease and assessment of the efficacy of possible future treatments.