Yonsei Med J.  2022 Mar;63(3):259-264. 10.3349/ymj.2022.63.3.259.

¹⁸F-THK5351 PET Positivity and Longitudinal Changes in Cognitive Function in β-Amyloid-Negative Amnestic Mild Cognitive Impairment

• Chun MY
• Lee J
• Jeong JH
• Roh JH
• Oh SJ
• Oh M
• Oh JS
• Kim JS
• Moon SH
• Woo Sy
• Kim YJ
• Choe YS
• Kim HJ
• Na DL
• Jang H
• Seo SW

• KMID: 2526558
• DOI: http://doi.org/10.3349/ymj.2022.63.3.259

Abstract

Purpose
Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. ¹⁸F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer’s disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ–) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer’s disease pathophysiology. Accordingly, we investigated associations between ¹⁸F-THK5351 PET positivity and cognitive decline among Aβ– aMCI patients.
Materials and Methods
The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: ¹⁸F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of ¹⁸F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients.
Results
Among the 25 Aβ– aMCI patients, 10 (40.0%) were ¹⁸F-THK5351 positive. The patients in the ¹⁸F-THK5351-positive group were older than those in the ¹⁸F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the ¹⁸F-THK5351-positive group deteriorated at a faster rate than those of the ¹⁸F-THK5351-negative group (B=0.003, p=0.033).
Conclusion
The results of the present study suggest that increased ¹⁸F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

Keyword

Positron emission tomography; mild cognitive impairment; amyloid; tau proteins; inflammation