期刊
NEUROLOGY
卷 86, 期 15, 页码 1377-1385出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000002576
关键词
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资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH) [U01 AG024904]
- National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Rev December, Health Research
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 florbetapir- PET in patients with AD and patients with MCI using CSF-A(1-42) as a comparison amyloid measurement. We then compared florbetapir- vs florbetapir+ patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data.Results:Florbetapir and CSF-A(1-42) +/- status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir- scans were a reliable representation of amyloid status. Florbetapir- AD (n = 27/177; 15%) and MCI (n = 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir+ counterparts (MCI 30%, AD 24%). Florbetapir- 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, florbetapir- participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir+ participants.Conclusions:Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir- ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype.
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