Subjective Cognitive Decline as a Preclinical Marker for Alzheimer's Disease: The Challenge of Stability Over Time

Subjective Cognitive Decline (SCD) refers to a self-experienced persistent decline in cognitive abilities in comparison with a prior normal status and independent of the objective performance on neuropsychological tests (Jessen et al., 2014). It has been proposed that SCDmight appear at the end of the preclinical phase of Alzheimer’s Disease (AD) even in the absence of significant objective impairment detectable on standardized neuropsychological assessment (Rabin et al., 2017). This fact explains why SCD is gaining increased prominence in neurodegenerative research as a potential marker for future Mild Cognitive Impairment (MCI) due to AD. Nevertheless, in our opinion SCD has to face up to a challenge in order to aspire to become a reliable marker of preclinical AD. This challenge is related to the temporal stability of self-reported complaints over time. This manuscript describes this challenge. SCD is considered a sign of preclinical AD that occurs even before objective cognitive impairment appears (Figure 1). A recent meta-analysis has revealed that about 25% of cognitively healthy older adults who report SCDwill developMCI due to AD in the next 4 years (Mitchell et al., 2014). In addition, these individuals have two-fold risk of progression to dementia during a 5-year follow-up period. To increase the potential usefulness of SCD the international working group called Subjective Cognitive Decline Initiative (SCD-I) agreed to a common framework and research procedures to study the role of SCD as a marker of preclinical AD (Jessen et al., 2014). Following these new standards, cognitively healthy individuals who accomplish certain conditions of SCD have been probed to have four times higher risk for developing prodromal AD in just 1-year compared to those subjects without complaints (Fernández-Blázquez et al., 2016). Despite its outstanding clinical value, recently the SCD-I also pointed out some limitations of SCD when it comes to investigating this concept (Rabin et al., 2015; Molinuevo et al., 2017). These limitations could be summarized in three different blocks: