The Significance of Subjective Cognitive Decline in Primary Care and Memory Clinic Patients

Abstract

Subjective Cognitive Decline (SCD) is defined as an individual’s perception of worsening cognitive function compared to his/her earlier performance level. In the elderly, SCD may occur as a common phenomenon of regular cognitive ageing processes. However, previous studies have also shown that cognitively unimpaired individuals who experience SCD are at increased risk of future Alzheimer’s disease (AD) dementia and of having abnormal values in biomarkers indicative of AD pathology. This has led to the hypothesis that SCD may emerge as a first clinical symptom in the transient stage between a completely asymptomatic stage and a pre-dementia clinical stage of AD commonly referred to as Mild Cognitive Impairment (MCI). Importantly, individuals with pre-MCI SCD represent a particularly relevant target population for early prevention approaches as they are enriched for risk of AD but still in a disease stage where interventions might be most effective. On the other hand, the usefulness of SCD for prediction of AD has been questioned, mainly because there is little cross-sectional correlation with objective cognitive performance and, more importantly, because of potential confounding factors such as depressive symptomatology, reduced symptom awareness (in MCI), and, to a lesser degree of evidence, anxiety and personality factors.<br /> This thesis presents empirical studies which examined the significance of SCD as a predictor of incident AD dementia and of AD biomarkers in the pre-MCI and the MCI stage. Study 1 evaluated the AD dementia risk of individuals with memory related SCD in the German study on Ageing, Cognition and Dementia (AgeCoDe). Results showed that cognitively normal individuals who reported SCD in the memory domain and who had concerns related to their experienced memory decline were at a significantly elevated risk to develop AD dementia over time. Their risk was similar to that of very mildly impaired MCI patients. These results highlight the relevance of subjective memory decline to predict future dementia at the very early stage of AD. They further suggest that concerns regarding the self-experienced memory decline may be a particularly important qualitative feature of AD-related SCD.<br /> Study 2 and study 3 investigated the significance of SCD in a memory clinic sample of patients with MCI (Competence Network Dementia MCI cohort). In the MCI population, the diagnostic and prognostic relevance of SCD has been questioned as its validity may be limited due to the potential of reduced symptom awareness in patients with more advanced cognitive impairment. As a consequence, the assessment of SCD in MCI is much less elaborated compared to objective cognitive testing. However, studies 2 and 3 found quantitative and qualitative aspects (again in the form of concerns about memory decline) of SCD to be significant predictors of incident AD dementia and of abnormal AD biomarkers. Further, results suggested that the significance of SCD as a predictor of AD may indeed decrease with decreasing memory performance, thereby providing evidence of a dynamic interplay of SCD and objective cognitive impairment in AD dementia prediction. Both studies suggest that a refined and improved SCD assessment in the MCI stage could contribute to improved prediction of AD dementia and prove useful for enrichment of MCI samples for underlying AD pathology.<br /> The thesis starts with a general introduction followed by a detailed presentation of the three empirical studies. In the last section, a discussion of the studies’ contributions to the field of AD research will be outlined together with directions for future research.