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Regional tau deposition measured by [F-18]THK5317 positron emission tomography is associated to cognition via glucose metabolism in Alzheimer's disease
Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, Novum 5th Floor, S-14157 Huddinge, Sweden..
Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, Novum 5th Floor, S-14157 Huddinge, Sweden.;Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden.;Stockholm Univ, Dept Psychol, Stockholm, Sweden..
Karolinska Inst, Dept NVS, Ctr Alzheimer Res, Div Translat Alzheimer Neurobiol, Novum 5th Floor, S-14157 Huddinge, Sweden..
Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
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2016 (English)In: Alzheimer's Research & Therapy, ISSN 0065-6755, E-ISSN 1758-9193, Vol. 8, 38Article in journal (Refereed) Published
Abstract [en]

Background: The recent development of tau-specific positron emission tomography (PET) tracers has allowed in vivo quantification of regional tau deposition and offers the opportunity to monitor the progression of tau pathology along with cognitive impairment. In this study, we investigated the relationships of cerebral tau deposition ([F-18]THK5317-PET) and metabolism ([F-18]FDG-PET) with concomitant cognitive function in patients with probable Alzheimer's disease (AD). Methods: Nine patients diagnosed with AD dementia and 11 with prodromal AD (mild cognitive impairment, amyloid-positive on [C-11]PiB-PET) were included in this study. All patients underwent PET scans using each tracer, as well as episodic memory and global cognition assessment. Linear models were used to investigate the association of regional [F-18]THK5317 retention and [F-18]FDG uptake with cognition. The possible mediating effect of local metabolism on the relationship between tau deposition and cognitive performance was investigated using mediation analyses. Results: Significant negative associations were found between [F-18]THK5317 regional retention, mainly in temporal regions, and both episodic memory and global cognition. Significant positive associations were found between [F-18]FDG regional uptake and cognition. The association of [F-18]FDG with global cognition was regionally more extensive than that of [F-18]THK5317, while the opposite was observed with episodic memory, suggesting that [F-18]THK5317 retention might be more sensitive than [F-18]FDG regional uptake to early cognitive impairment. Finally, [F-18]FDG uptake had a mediating effect on the relationship between [F-18]THK5317 retention in temporal regions and global cognition. Conclusions: These findings suggest a mediating role for local glucose metabolism in the observed association between in vivo tau deposition and concomitant cognitive impairment in AD.

Place, publisher, year, edition, pages
2016. Vol. 8, 38
Keyword [en]
Tau imaging, Positron emission tomography (PET), Cognition, Memory, Metabolism
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-306258DOI: 10.1186/s13195-016-0204-zISI: 000384362400001PubMedID: 27683159OAI: oai:DiVA.org:uu-306258DiVA: diva2:1040284
Funder
Swedish Research Council, 05817Stockholm County CouncilThe Karolinska Institutet's Research FoundationStiftelsen Gamla TjänarinnorThe Swedish Brain FoundationThe Dementia Association - The National Association for the Rights of the DementedWenner-Gren FoundationsEU, FP7, Seventh Framework Programme, HEALTH-F2-2011-278850Swedish Foundation for Strategic Research
Available from: 2016-10-27 Created: 2016-10-26 Last updated: 2016-10-27Bibliographically approved

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