Subjective cognitive decline: differentiating pathological from normal brain aging

Abstract

Background: By 2050, USA alone will spend over $1 trillion on dementia care, and the impact of dementia will exceed that of heart disease, cancer and stroke combined. Alarmingly, nothing can halt or even modify disease progression. According to the NIA-AA criteria, stage 3 of pre-clinical Alzheimer’s Disease (AD) is defined by the presence of biomarker evidence plus very subtle cognitive impairment, but not severe enough to be mild cognitive impairment, which is the next clinical stage before dementia. This very early stage is termed subjective cognitive decline (SCD), and it refers to the earliest clinically apparent pre-clinical stage of AD. Patients with SCD acknowledge there is some cognitive decline, but their performance on routine cognitive assessment (e.g. MMSE or MOCA) is within normal limits. Methods: Patients with SCD are at a higher risk of biomarker abnormalities indicative of AD pathogenesis, conveying a higher future risk of AD. Theoretically, any efficacious interventions at this SCD stage could preserve cognitive function at a higher baseline level. Accurately diagnosing this SCD stage and differentiating it from normal brain aging is one of the most important goals of modern AD research. However, SCD is not easy to confirm using routinely available cognitive assessments because of their low sensitivity and specificity, variable intra- and inter-rater variability, and ceiling effects. Results: Much better cognitive assessment tools are needed, and other supporting evidence from blood or neuroimaging biomarkers are necessary to support and confirm a diagnosis of truly pathological SCD (i.e. pre-clinical AD), and to reliably differentiate it from normal brain aging. Conclusion: In this lecture, I will explore the importance of recognising SCD, the potential scientific methods of differentiating it from normal brain aging, and the new clinical trials of early disease-modifying interventions that are aimed at this early pre-clinical stage of AD.