The Role of Chronic Stress as a Trigger for the Alzheimer Disease Continuum

Abstract

Alzheimer disease (AD) is the most prevalent type of dementia that appears late in life and has devastating effects both in society and patients. This is a silent disorder in which neurodegeneration occurs in the brain decades before the diagnosis of the disease (Bateman et al., 2012). This long period of time between the appearance of the first pathophysiological changes and the presentation of clinical symptoms suggests that there is an AD continuum in which different transition stages can be distinguished. Thus, prior to the onset of dementia, it appears a prodromal stage called mild cognitive impairment (MCI) which is characterized by the presence of cognitive deficits, but not severe enough to significantly affect everyday activities (Petersen et al., 1999). In addition, earlier in the continuum and before the appearance of MCI, a preclinical AD phase has been described. This preclinical stage is defined by the accumulation of biomarkers in the brain as well as the appearance of a state termed subjective cognitive decline (SCD). SCD is defined as the presence of self-reported subtle cognitive complaints despite normal performance in standard cognitive testing (Jessen et al., 2014). The difficulty in pharmacologically modifying the course of AD continuum has fostered the consensus that therapeutic interventions are more likely to be effective at the earliest possible phase. Then, early markers are urgently needed to identify how the silent neurodegeneration is taking place before the onset of clinical signs of dementia. For this purpose many candidates have been proposed so far. In the presentmanuscript we would like to highlight the role of stress, amuch less explored risk factor for AD

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