Preclinical cognitive markers of Alzheimer’s disease and early diagnosis using virtual reality and artificial intelligence: a systematic review. (Preprint)
Authors: Scribano Parada María de la Paz , Gonzalez Palau Fatima , Gonzalez Palau Fatima , Valladares Rodríguez Sonia , Rincon Mariano , Rico Barroeta Maria José , García Rodriguez Marta , Bueno Aguado. Yolanda , Herrero Blanco Ana , Díaz-López Estela , Bachiller Mayoral Margarita , Losada Durán Raquel 
Published: June 2024

BACKGROUND

In today's context, widespread healthcare access and changing living conditions contribute to an aging population, escalating the prevalence of Neurocognitive Disorders (NCD). This shift poses societal challenges and strains healthcare systems, emphasizing the urgent need for pharmacological interventions to address Alzheimer's Disease (AD) progression. Despite efforts, a universally effective pharmacological solution remains elusive. Simultaneously, studies highlight that factors like education, healthy lifestyles, and social engagement can delay AD onset. Identifying early markers, particularly in the preclinical stage, becomes crucial. The preclinical stage, characterized by evidence of AD pathology without cognitive or behavioral impairment, prompts the quest for early biomarkers. Current biomarkers, while valuable, face challenges of cost, limited availability, and inconclusive correlation with clinical manifestations. This underscores the necessity for alternative cognitive-behavioral markers, with recent studies exploring domains beyond episodic memory. Moreover, advancements incorporating Artificial Intelligence (AI) and Machine Learning (ML) aim to integrate neuroimaging, neuropsychological variables, and biomarkers for early AD diagnosis. Additionally, the exploration of Virtual Reality (VR) environments presents a novel avenue for diagnostics

OBJECTIVE

This project systematically reviews neurocognitive markers in preclinical AD diagnosis, emphasizing recent studies involving VR. A secondary objective is to discern tests with the highest evidentiary support for each proposed domain.

METHODS

Methods: The article selection process involved an initial search using specific keywords, such as "memory AND longitudinal AND Alzheimer's disease," "mild cognitive impairment AND (Alzheimer's disease OR dementia) AND neuropsychology AND (prediction OR longitudinal)," and "Alzheimer's disease AND conversion AND neuropsychology." However, this initial search did not yield any papers discussing virtual reality tools for diagnosis. To address this, additional terms, including "virtual reality," were incorporated into the search strategy. This adjustment resulted in the identification of 13 new papers, with 11 fully integrated into the study. Notably, two review papers from this subset are discussed in the later sections. Two papers were excluded due to their focus on rehabilitation rather than the intended diagnostic scope

RESULTS

Results: Selected articles highlight verbal episodic memory, measured by various tests, as the earliest, most sensitive marker for preclinical Alzheimer's Disease (AD). Neuroimaging, genetic profiling (APOE), and CSF markers (A$beta$, tau, p-tau) complement this assessment. Notable studies detail the sequence of cognitive decline, with executive functions preceding memory failure. Speed of processing emerges as a significant correlate, surpassing MRI patterns for functional outcomes. Limited literature explores virtual reality's potential for early diagnosis, with some studies demonstrating its efficacy in assessing visuospatial and memory functions. Promisingly, AI algorithms, coupled with advanced diagnostic tools, offer a multidimensional approach for accurate early diagnosis of neurocognitive disorders.

CONCLUSIONS

The preclinical diagnosis of neurocognitive disorders is challenging, with emerging tools like VR and AI offering potential but also posing obstacles such as cost, rigorous validation, and the need for expert interpretation. Ethical concerns regarding patient data in virtual environments require attention. Despite challenges, the evolving role of VR in Alzheimer's diagnosis signifies a promising advancement in healthcare. Continued technological refinement is expected to enhance early identification and management, demanding thorough validation and regulation for clinical efficacy and safety.