Early detection of Alzheimer’s disease (AD) and related dementias is critical for timely intervention and disease management. Mild cognitive impairment represents a transitional state between normal aging and dementia, but diagnosis remains challenging. Biomarkers offer promising tools for identifying early neurodegenerative changes, potentially years before clinical symptoms appear. This systematic review examined studies published between 2012 and 2025 from PubMed and Ovid MEDLINE, focusing on the role of biomarkers in the early diagnosis of AD. Search terms included "biomarkers," "Alzheimer’s disease," "early diagnosis," and "early detection." Included studies were systematic reviews that had been peer-reviewed and emphasized early-stage diagnostic utility. Observational studies, meta-analyses, and systematic reviews were included and screened using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. Biomarkers identified included cerebrospinal fluid (CSF) markers (amyloid beta, total tau, phosphorylated tau), genetic markers (ApoE4, presenilin mutations), and neuroimaging techniques (MRI, PET, fNIRS). Novel biomarkers such as miRNAs and biosensors, while still largely investigational, also show emerging potential. Phosphorylated tau, particularly p-tau 217, and the amyloid beta 42:40 ratio demonstrate high sensitivity in some studies for early AD pathology. In certain experimental studies, genetic and imaging biomarkers can detect risk or structural changes well before symptom onset. While biomarkers cannot currently replace clinical diagnosis, they significantly enhance early detection and risk stratification. Further research is needed to establish standardized thresholds and to evaluate the ethical implications of widespread biomarker testing. Non-invasive, cost-effective tools such as CSF (minimally invasive) and plasma-based (non-invasive) assays and biosensors represent the future of early dementia diagnostics.
Putnam et al. (Thu,) studied this question.