Imagine trying to navigate through a maze without a map or compass. That’s exactly what researchers are uncovering about early stages of Alzheimer’s disease (AD). In a recent study, scientists used a virtual version of the Morris Water Maze to evaluate visual-spatial impairments in individuals with amnesic mild cognitive impairment (aMCI) – an early sign of AD. By combining behavioral tests, electroencephalography (EEG) recordings, and eye movement data, they discovered fascinating differences between those with aMCI and healthy controls. Unlike the control group, participants with aMCI did not prefer specific regions of interest and had reduced visual occipital potentials. Furthermore, their brain activity was altered in parietal and frontal regions during the navigation task. Interestingly, the control group showed strong occipital activity during early visual processing, but the aMCI group displayed weakened connectivity between prefrontal cortices in the beta band range. These findings shed light on the impaired visual-spatial processing network in AD, offering potential markers for early diagnosis and intervention. Understanding these mechanisms could lead to improved quality of life and reduced healthcare costs for individuals with AD.

IntroductionAlzheimer’s disease (AD) is the leading cause of dementia worldwide, but its pathophysiological phenomena are not fully elucidated. Many neurophysiological markers have been suggested to identify early cognitive impairments of AD. However, the diagnosis of this disease remains a challenge for specialists. In the present cross-sectional study, our objective was to evaluate the manifestations and mechanisms underlying visual-spatial deficits at the early stages of AD.MethodsWe combined behavioral, electroencephalography (EEG), and eye movement recordings during the performance of a spatial navigation task (a virtual version of the Morris Water Maze adapted to humans). Participants (69–88 years old) with amnesic mild cognitive impairment–Clinical Dementia Rating scale (aMCI–CDR 0.5) were selected as probable early AD (eAD) by a neurologist specialized in dementia. All patients included in this study were evaluated at the CDR 0.5 stage but progressed to probable AD during clinical follow-up. An equal number of matching healthy controls (HCs) were evaluated while performing the navigation task. Data were collected at the Department of Neurology of the Clinical Hospital of the Universidad de Chile and the Department of Neuroscience of the Faculty of Universidad de Chile.ResultsParticipants with aMCI preceding AD (eAD) showed impaired spatial learning and their visual exploration differed from the control group. eAD group did not clearly prefer regions of interest that could guide solving the task, while controls did. The eAD group showed decreased visual occipital evoked potentials associated with eye fixations, recorded at occipital electrodes. They also showed an alteration of the spatial spread of activity to parietal and frontal regions at the end of the task. The control group presented marked occipital activity in the beta band (15–20 Hz) at early visual processing time. The eAD group showed a reduction in beta band functional connectivity in the prefrontal cortices reflecting poor planning of navigation strategies.DiscussionWe found that EEG signals combined with visual-spatial navigation analysis, yielded early and specific features that may underlie the basis for understanding the loss of functional connectivity in AD. Still, our results are clinically promising for early diagnosis required to improve quality of life and decrease healthcare costs.

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