This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Objective To evaluate FDG-PET as an antemortem diagnostic tool for Alzheimer-related TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy.
Methods We conducted a cross-sectional neuroimaging–histologic analysis of patients with antemortem FDG-PET and postmortem brain tissue from the Mayo Clinic Alzheimer's Disease Research Center and Study of Aging with Alzheimer spectrum pathology. TDP-43-positive status was assigned when TDP-43-immunoreactive inclusions were identified in the amygdala. Statistical parametric mapping (SPM) analyses compared TDP-43-positive (TDP-43[+]) with TDP-43-negative cases (TDP-43[−]), correcting for field strength, sex, Braak neurofibrillary tangle, and neuritic plaque stages. Cross-validated logistic regression analyses were used to determine whether regional FDG-PET values predict TDP-43 status. We also assessed the ratio of inferior temporal to medial temporal (IMT) metabolism as this was proposed as a biomarker of hippocampal sclerosis.
Results Of 73 cases, 27 (37%) were TDP-43(+), of which 6 (8%) had hippocampal sclerosis. SPM analysis showed TDP-43(+) cases having greater hypometabolism of medial temporal, frontal superior medial, and frontal supraorbital (FSO) regions (punc < 0.001). Logistic regression analysis showed only FSO and IMT to be associated with TDP-43(+) status, identifying up to 81% of TDP-43(+) cases (p < 0.001). An IMT/FSO ratio was superior to the IMT in discriminating TDP-43(+) cases: 78% vs 48%, respectively.
Conclusions Alzheimer-related TDP-43 proteinopathy is associated with hypometabolism in the medial temporal and frontal regions. Combining FDG-PET measures from these regions may be useful for antemortem prediction of Alzheimer-related TDP-43 proteinopathy.
Classification of evidence This study provides Class II evidence that hypometabolism in the medial temporal and frontal regions on FDG-PET is associated with Alzheimer-related TDP-43 proteinopathy.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- FDG-PET=
- [18F]-fluorodeoxyglucose PET;
- FSM=
- frontal superior medial;
- FSO=
- frontal supraorbital;
- FWHM=
- full-width at half maximum;
- HS=
- hippocampal sclerosis;
- IMT=
- inferior temporal to medial temporal ratio;
- IT=
- inferior temporal gyrus;
- MCALT=
- Mayo Clinic Adult Lifespan Template;
- MT=
- medial temporal;
- NACC=
- National Alzheimer's Coordinating Center;
- NACCLEWY=
- Lewy bodies staged according to National Alzheimer's Coordinating Center;
- NACCNEUR=
- neuritic plaques staged according to National Alzheimer's Coordinating Center;
- NFT=
- neurofibrillary tangle;
- NIA-AA=
- National Institute on Aging–Alzheimer Association;
- PVC=
- partial volume correction;
- ROC=
- receiver operating characteristic;
- ROI=
- region of interest;
- SUVR=
- standard uptake value ratio;
- TDP-43=
- trans-active response DNA-binding protein of 43 kDa
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
- Received July 11, 2019.
- Accepted in final form December 7, 2019.
- © 2020 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Topics Discussed
Alert Me
Recommended articles
β-Amyloid PET and neuropathology in dementia with Lewy bodies
Longitudinal anatomic, functional, and molecular characterization of Pick disease phenotypes
Clinical, Imaging, and Pathologic Characteristics of Patients With Right vs Left Hemisphere–Predominant Logopenic Progressive Aphasia
Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults