Agreement between clinical diagnosis and blood biomarkers of Alzheimer's disease in a real-world peripheral memory clinic

Background Blood-based biomarkers (BBM) are promising to help diagnose Alzheimer's disease (AD) and are on the verge of implementation in diagnostic dementia workups. However, evaluating BBM performance in peripheral memory clinics is essential to establish their real-world clinical utility. Objective To evaluate the diagnostic concordance of BBMs with clinically established diagnoses in an unselected peripheral memory clinic population using predefined, validated thresholds. Methods In a peripheral memory clinic, plasma levels of phosphorylated Tau217 (pTau217), amyloid-β 42/40 ratio (Aβ 42 /Aβ 40 ), glial fibrillary acidic protein, and neurofilament light (NfL) were measured in patients (mean age 75.2 ± 8.8 years, 48.3% female) clinically diagnosed with subjective cognitive decline (SCD; n = 108), mild cognitive impairment (MCI; n = 55), AD dementia (n = 132), or non-AD dementia (non-AD; n = 28). BBM levels were compared across diagnostic groups and concordance between clinical diagnoses and BBM test results, based on thresholds developed in an academic memory clinic, were analyzed. Results The levels of all four BBMs differed between SCD and AD dementia (p < 0.001). Between AD dementia and non-AD dementia, only PTau217 levels differed (p = 0.03). In SCD participants, 50% (pTau217) to 79% (NfL) showed abnormality in at least one BBM. In AD dementia patients, this ranged from 83% (pTau217) to 97% (NfL); all had at least one abnormal BBM, and 68% had abnormalities in all four BBMs. Conclusions In a peripheral real-world memory clinic setting the BBMs demonstrated high concordance with clinically diagnosed dementia due to AD. Our findings suggest utility of BBMs in peripheral memory clinic practice, in patients with suspected dementia.