Biomarkers of Alzheimer's Disease and Cerebrovascular Lesions and Clinical Progression in Patients with Subjective Cognitive Decline: A Systematic Review

BACKGROUND: Early identification of Alzheimer's disease (AD) may be extremely beneficial for delaying disease progression. Subjective cognitive decline (SCD) may be an early indicator of AD pathology. Not all individuals with SCD will eventually develop AD, making it critical to identify biomarkers during the SCD stage which indicate likely clinical progression.

OBJECTIVE: The present review aims to summarize available data on structural MRI and cerebrospinal fluid (CSF) biomarkers and their association with clinical progression to mild cognitive impairment (MCI) or AD in people with SCD.

METHODS: Database searches were conducted using Embase and PubMed until June 2020. Longitudinal studies assessing biomarkers in individuals with SCD and assessing clinical progression to MCI/AD were included. Two assessors performed data extraction and assessed the risk of bias in the included studies. Data were synthesized narratively.

RESULTS: An initial search identified 1,065 papers; after screening and review 14 studies were included. Sample size of the included studies ranged from 28-674, mean age was 60.0-68.6 years, and 10.2%-52%of participants converted to MCI/AD. Lower levels of CSF Aβ 42 were consistently associated with clinical progression. Combination measures identifying an AD-like profile of Aβ 42 and tau levels were strongly associated with clinical progression. Biomarkers identified with structural MRI were less conclusive, as some studies found significant associations while others did not.

CONCLUSION: Biomarkers may be able to predict clinical progression in those with cognitive complaints. Aβ 42, or combinations of Aβ 42 and tau may be useful biomarkers in identifying individuals with SCD who will progress to MCI/AD.