MRI and flortaucipir relationships in Alzheimer's phenotypes are heterogeneous.

Abstract

OBJECTIVE:

To assess the relationships between MRI volumetry and [18 F]flortaucipir PET of typical and atypical clinical phenotypes of Alzheimer's disease, by genarian (age by decade).

METHODS:

Five-hundred and sixty-four participants including those with typical (n = 86) or atypical (n = 80) Alzheimer's dementia and normal controls (n = 398) underwent apolipoprotein E genotyping, MRI, flortaucipir, and 11 C-PiB; all 166 Alzheimer's participants were beta-amyloid positive and all controls were beta-amyloid negative. Grey matter volume and flortaucipir standard uptake value ratios were calculated for hippocampus, entorhinal cortex, and neocortex. Ratios of hippocampal-to-neocortical and entorhinal-to-neocortical volume and flortaucipir uptake were also calculated. Linear regression models assessed relationships among regional volume, flortaucipir uptake, and ratios and phenotypes, within three genarians (50-59, 60-69, and 70+). Voxel-level analyses were also performed.

RESULTS:

For 50-59 greater medial temporal atrophy and flortaucipir uptake was observed in the typical compared with atypical phenotype. The typical phenotype also showed greater frontal neocortex uptake with the voxel-level analysis. For 60-69 and 70+ there was greater hippocampal volume loss in the typical compared with atypical phenotype while only the 60-69, but not the 70+ group, showed a difference in hippocampal flortaucipir uptake. We also observed a pattern for higher neocortical flortaucipir uptake to correlate with younger age decade for both phenotypes.

INTERPRETATION:

MRI volumetry versus flortaucipir PET relationships differ across Alzheimer's clinical phenotypes, and also within phenotype across age decades. This suggests that there is potential risk of masked effects by not accounting for genarian in participants with beta-amyloid and tau-positive biomarker defined Alzheimer's disease.

• Authors: Keith A Josephs, Nirubol Tosakulwong, Jonathan Graff-Radford, Stephen D Weigand, Marina Buciuc, Mary M Machulda, David T Jones, Christopher G Schwarz, Matthew L Senjem, Nilufer Ertekin-Taner, Kejal Kantarci, Bradley F Boeve, David S Knopman, Clifford R Jack Jr, Ronald C Petersen, Val J Lowe, Jennifer L Whitwell
• Journal: Annals of clinical and translational neurology (Ann Clin Transl Neurol) Vol. 7 Issue 5 Pg. 707-721 (05 2020) ISSN: 2328-9503 [Electronic] United States
• PMID: 32293805 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Chemical References

• Carbolines
• Contrast Media
• MAPT protein, human
• tau Proteins
• 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Alzheimer Disease (classification, diagnostic imaging, metabolism, pathology)
• Atrophy (pathology)
• Carbolines (pharmacokinetics)
• Contrast Media (pharmacokinetics)
• Entorhinal Cortex (diagnostic imaging, metabolism, pathology)
• Female
• Hippocampus (diagnostic imaging, metabolism, pathology)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neocortex (diagnostic imaging, metabolism, pathology)
• Phenotype
• Positron-Emission Tomography
• tau Proteins (metabolism)