Compensatory Mechanisms in Early Alzheimer’s Disease and Clinical Setting: The Need for Novel Neuropsychological Strategies

Despite advances in the detection of biomarkers and in the design of drugs that can slow the progression of Alzheimer’s disease (AD), the underlying primary mechanisms have not been elucidated. The diagnosis of AD has notably improved with the development of neuroimaging techniques and cerebrospinal fluid biomarkers which have provided new information not available in the past. Although the diagnosis has advanced, there is a consensus among experts that, when making the diagnosis in a specific patient, many years have probably passed since the onset of the underlying processes, and it is very likely that the biomarkers in use and their cutoffs do not reflect the true critical points for establishing the precise stage of the ongoing disease. In this context, frequent disparities between current biomarkers and cognitive and functional performance in clinical practice constitute a major drawback in translational neurology. To our knowledge, the In-Out-test is the only neuropsychological test developed with the idea that compensatory brain mechanisms exist in the early stages of AD, and whose positive effects on conventional tests performance can be reduced in assessing episodic memory in the context of a dual-task, through which the executive auxiliary networks are ‘distracted’, thus uncover the real memory deficit. Furthermore, as additional traits, age and formal education have no impact on the performance of the In-Out-test.