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

Yonsei Med J. 2022 Mar;63(3):259-264. doi: 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).

Keywords: Positron emission tomography; amyloid; inflammation; mild cognitive impairment; tau proteins.

Publication types

  • Clinical Trial

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / metabolism
  • Aminopyridines
  • Amyloid beta-Peptides / metabolism
  • Cognition
  • Cognitive Dysfunction* / diagnostic imaging
  • Humans
  • Positron-Emission Tomography
  • Quinolines

Substances

  • Aminopyridines
  • Amyloid beta-Peptides
  • Quinolines
  • THK5351

Associated data

  • ClinicalTrials.gov/NCT02656498