A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease

Abstract

There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.

Keywords: Alzheimer's disease; Mild cognitive impairment; Preclinical Alzheimer's disease; Prodromal Alzheimer 's disease; Research criteria; Subjective cognitive decline.

Fig. 1

Depicted is the course of cognitive decline in relation to progressive disease pathology in Alzheimer’s disease (AD). After a phase of stable cognitive performance in the presence of increasing pathology, cognitive decline occurs. After crossing the threshold of below normal age-, sex-, and education-adjusted performance, the stage of mild cognitive impairment (MCI) or prodromal AD is reached. Subsequently, cognitive decline progresses onward to the stage of dementia. It is proposed that SCD occurs at the late stage of preclinical AD, which is characterized by increasing compensatory cognitive efforts and subtle cognitive decline. Thus, SCD may indicate the late-stage preclinical AD before the threshold of MCI/prodromal AD is reached. There is evidence that the subjective experience of decline levels off as disease progresses into dementia. That stage, however, is not part of the conceptualization of SCD in preclinical AD and is not addressed in the present publication.