Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI

Landau, Susan M.; Horng, Andy; Fero, Allison; Jagust, William J.; Stern, Yaakov; Alzheimer's Disease Neuroimaging Initiative

Objective: To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a prospective cohort study. Methods: We first investigated the reliability of florbetapir2 PET in patients with AD and patients with MCI using CSF-Ab1–42 as a comparison amyloid measurement. We then compared florbetapir2 vs florbetapir1 patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data. Results: Florbetapir and CSF-Ab1–42 1/2 status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir2 scans were a reliable representation of amyloid status. Florbetapir2 AD (n 5 27/177; 15%) and MCI (n 5 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir1 counterparts (MCI 30%, AD 24%). Florbetapir2 patients also had less AD-specific hypometabolism, lower CSF p-tau and t-tau, and better longitudinal cognitive performance, and were more likely to be taking medication for depression. In MCI only, florbetapir2 participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir1 participants. Conclusions: Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir2 ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir1 counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype. Neurology® 2016;86:1377–1385



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February 11, 2022