Incorporation of plasma biomarkers for screening and diagnosis in primary care

Abstract Background Plasma biomarkers that reflect Alzheimer’s neuropathological changes are under FDA consideration for approval as diagnostic tests. Their use in primary care will become feasible, and it will be difficult to limit biomarker screening to symptomatic or high risk individuals, especially as symptoms of cognitive decline are often nonspecific. Methods As members of the NIA Advisory Group on Risk Evidence Education for Dementia (AGREED), we have examined analytics of AD biomarkers in asymptomatic and symptomatic contexts, as well as language used in disclosure of biomarker results in research studies. We review recent data and describe key issues in plasma screening for Alzheimer’s Disease in primary care and propose directions for future research. Results Critical issues include: 1. Assessing accuracy of biomarker(s) measurement, and sensitivity and specificity of cutoffs to determine presence or absence of amyloid or other AD pathology. 2. Recognizing the critical need to study biomarkers in population‐based settings and among under‐represented individuals to understand factors that may modify cutoffs and normative data, e.g., age, sex, ethnicity, renal and hepatic function. 3. Data and models regarding the value of amyloid positivity to predict the development of Mild Cognitive Impairment (MCI) or dementia in asymptomatic individuals, and for progression of MCI to dementia. 4. Disclosure of APOE genotype if it is part of a biomarker risk algorithm. 5. Selecting nuanced language for describing positive, negative or indeterminate biomarker results, with clear explanations of what the tests measure, and risks associated with positive or negative results. 6. Current plasma biomarkers do not measure other pathologies and cognitions that may contribute to MCI and dementia, e.g., a‐synuclein, TDP43 or vascular pathology; depression, medical comorbidities, sleep disorders or medications that may adversely impact cognition. Together with biomarker results, the impact of these factors on cognition should be considered and discussed. 7. Screening for cognition is underdeveloped, limited by the types of tests currently used for screening and the time typically available to assess patients in primary care. Conclusions Further research on these topics and support and education of primary care providers is essential for the deployment of blood‐based biomarkers in primary care.