Neuropsychological profiles and neural correlates in typical and atypical variants of Alzheimer disease: A systematic qualitative review

Introduction: Neuropsychological symptoms and cortical atrophy patterns show similarities between typical Alzheimer’s Disease (AD) and its variants. Thus, correct diagnosis is difficult, leading to errors in the therapeutic process. Indeed, the challenge in cognitive neuroscience focuses on identifying key features of cognitive-linguistic profiles and improving the knowledge of neural correlates for accurate differential diagnosis between the heterogeneous profiles of typical and atypical AD. Aim: This systematic review aims to describe different AD profiles, considering their neuropsychological symptoms and neural correlates. Methods: The present study followed the PRISMA guidelines and included studies from the PubMed, ScienceDirect, Scopus, and Web of Science databases, published between 2011 and 2021. Results: Thirty-one articles were included in this systematic review for critical analysis. Results suggest significant declines in episodic and working memory and executive function. Likewise, in all groups, verbal fluency and visuospatial/visuoconstructive skills declined. However, these symptoms overlap between typical AD, logopenic variant primary progressive aphasia, posterior cortical atrophy, behavioural/dysexecutive or frontal variant AD, and corticobasal syndrome. On the other hand, the neural correlate showed a pattern of atrophy in frontal, temporal, parietal, and occipital areas, even compromising the cuneus and precuneus. Conclusion: Spontaneous language and semantic and phonological verbal fluency could be an important biomarker for differential diagnosis between typical AD and its atypical variants. Likewise, clinical assessment should consider using advanced neuroimaging techniques to establish early associations between brain dysfunction and neuropsychological performance, with particular attention to brain areas such as the cuneus and precuneus