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

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 between¹⁸F-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 of¹⁸F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. Results: Among the 25 Aβ– aMCI patients, 10 (40.0%) were¹⁸F-THK5351 positive. The patients in the¹⁸F-THK5351-positive group were older than those in the¹⁸F-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 the¹⁸F-THK5351-positive group deteriorated at a faster rate than those of the¹⁸F-THK5351-negative group (B=0.003, p=0.033). Conclusion: The results of the present study suggest that increased¹⁸F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).