Abstract
Objective To describe the phenomenon of tau-negative amnestic dementia mimicking Alzheimer disease (AD) clinically and radiologically and to highlight the importance of biomarkers in AD research. Methods Eight participants with amnestic mild cognitive impairment or AD dementia were evaluated by a behavioral neurologist and had a standardized neuropsychological battery performed. All participants completed structural (MRI) and molecular (amyloid and tau PET) imaging. AD-signature thickness and adjusted hippocampal volume served as structural biomarkers, while standardized uptake value ratios (SUVRs) from validated regions of interest for amyloid and tau PET were used to determine molecular biomarker status. Results All participants were thought to have AD as the primary driver of their symptoms before any PET imaging. All participants had hippocampal atrophy, and 2 participants fell below the AD-signature thickness cutoff for elderly controls (2.57), with a further 3 falling below the more stringent cutoff based on young controls (2.67). Four participants were amyloid positive (SUVR >1.42), and all were tau negative (SUVR <1.33). Conclusions The participants presented here were clinically impaired, with structural imaging evidence of neurodegeneration, in the absence of any significant tau accumulation. Therefore, AD is unlikely as a cause of their clinical presentation and neurodegenerative imaging findings. Several implications are discussed, including the need to establish amyloid and tau positivity in N+ participants before enrolling them in trials of disease-modifying therapy agents for AD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | e940-e946 |
| Journal | Neurology |
| Volume | 90 |
| Issue number | 11 |
| DOIs | |
| State | Published - Mar 13 2018 |
Bibliographical note
Funding Information:H. Botha, W. Mantyh, and J. Graff-Radford report no disclosures relevant to the manuscript. M. Machulda receives research support from the NIH and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation. S. Przybelski, H. Wiste, M. Senjem, and J. Parisi report no disclosures relevant to the manuscript. R. Petersen works as a consultant for Merck Inc, Roche Inc, Biogen Inc, Eli Lily and Company, and Genentech Inc; receives publishing royalties for Mild Cognitive Impairment (Oxford University Press, 2003); and receives research support from the NIH and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation. M. Murray has served on the editorial boards of BMC Neurology and Frontiers in Neurology and has been a consultant for Avid Radiopharmaceuticals. B. Boeve has served as an investigator for clinical trials sponsored by GE Healthcare and FORUM Pharmaceuticals; receives royalties from the publication of a book titled Behavioral Neurology of Dementia (Cambridge Medicine, 2009); serves on the Scientific Advisory Board of the Tau Consortium; has consulted for Isis Pharmaceuticals; and receives research support from the NIH, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation, and the Mangurian Foundation. V. Lowe is a consultant for Bayer Schering Pharma, Merck Research, and Piramal Imaging Inc and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, the NIH (National Institute on Aging, National Cancer Institute), the Elsie and Marvin Dekelboum Family Foundation, the Liston Family Foundation, and the MN Partnership for Biotechnology and Medical Genomics. D. Knopman receives research support from the NIH and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation. He serves on a Data Safety Monitoring Board for Lundbeck Pharmaceuticals and for the Dominantly Inherited Alzheimer Network study and is an investigator in clinical trials sponsored by Biogen, TauRX Pharmaceuticals, Lilly Pharmaceuticals, and the Alzheimer’s Disease Treatment and Research Institute, University of Southern California. C. Jack receives research funding from the NIH and the Alexander Family Alzheimer’s Disease Research Professorship at Mayo Clinic. D. Jones reports no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Funding Information:
This study was funded by the NIH and the Mayo Foundation’s Robert H. and Clarice Smith and Abigail van Buren AD Research Program. Some authors report performing consultancy work, serving on data monitoring committees, and supervising clinical trials for various pharmaceutical companies; receiving research support from government agencies, pharmaceutical companies, and medical research foundations; and receiving book royalties. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© 2018 American Academy of Neurology.