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
Background and Objectives The risk of developing Alzheimer disease is increased after stroke, and this association may not solely be driven by traditional vascular risk factors. Neuronal death leads to the release of tau proteins, which can become dephosphorylated, rephosphorylated, or hyperphosphorylated in the setting of ischemia, possibly leading to formation of neurofibrillary tangles (NFT). Therefore, a potential synergistic effect between development of tauopathy and cerebrovascular lesion burden may contribute to cognitive decline after stroke. We explored the spatial and temporal distribution of NFT after ischemic stroke in vivo by using 18F-MK-6240 PET.
Methods We included patients with a first ischemic stroke to undergo longitudinal 18F-MK-6240 PET/MR within 2–4 weeks and 6 months after stroke. For cross-sectional analyses, we also included age-matched healthy controls. We delineated 5 volumes of interest based on T2 FLAIR and T1 MR data: the ischemic lesion, 3 consecutive peri-ischemic areas, and the remaining ipsilesional hemisphere. We performed region-based voxel-wise partial volume correction on the PET data and calculated standardized uptake value ratios (SUVRs) with the cerebellum as the reference region.
Results We did not quantify PET scans of patients within the first month after stroke (n = 17; median age 73 years [interquartile range {IQR}: 62–82 years]) because the signal intensity was influenced by blood-brain barrier breakdown hampering a reliable data analysis. At 6 months after the event (n = 13; median age 71 years [IQR: 60–79 years]), 18F-MK-6240 SUVR was increased in the ischemic lesion compared with 20 age-matched healthy controls (median age 71.5 years [IQR: 66–76 years]; ratiolesion/controls = 1.62 ± 0.54; 1-sample t test: p = 0.0015) and gradually decreased in the surrounding tissue (1-way within-subject analysis of variance [F{1.2, 14.8} = 18.0, p = 0.00043]).
Discussion These findings suggest that NFT may form after ischemic stroke and spread in the peri-ischemic brain parenchyma. Further follow-up is required to gain more insight into the spatial and temporal dynamics of this tauopathy after ischemic stroke.
Glossary
- ANOVA=
- analysis of variance;
- MNI=
- Montreal Neurologic Institute;
- MMSE=
- Mini-Mental State Examination;
- NFT=
- neurofibrillary tangles;
- NIHSS=
- NIH Stroke Scale;
- TE=
- echo time;
- TI=
- inversion time;
- TR=
- repetition time;
- VOI=
- volume of interest
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.
Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD, FAAN.
- Received March 25, 2022.
- Accepted in final form August 17, 2022.
- © 2022 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
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
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.
