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

Abstract

Purpose Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18 F-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 18 F-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: 18 F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18 F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. Results Among the 25 Aβ– aMCI patients, 10 (40.0%) were 18 F-THK5351 positive. The patients in the 18 F-THK5351-positive group were older than those in the 18 F-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 18 F-THK5351-positive group deteriorated at a faster rate than those of the 18 F-THK5351-negative group (B=0.003, p =0.033). Conclusion The results of the present study suggest that increased 18 F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498 ).

Comparative assessment of regional tau distribution by Tau-PET and Post-mortem neuropathology in a representative set of Alzheimer’s & frontotemporal lobar degeneration patients

“…We also found evidence that flortaucipir detects at least some 4R tau although we cannot exclude the possibility that uptake is due to neurodegeneration-associated pathologies, as has been reported to occur with other tau PET markers such as 18F-THK5351 PET [ 52 ]. Regardless, we did find flortaucipir uptake to be higher in the frontal lobes of the PSP-SL patients compared to the PSP-RS patient which matched the higher burden in the frontal lobes of the PSP-SL patients observed with AT8.…”

Long-term results on the suppression of secondary brain injury by early administered low-dose baclofen in a traumatic brain injury mouse model

“…Particularly, some researchers observed the accumulation of tau protein in the contralateral hippocampus 6 weeks after TBI occurrence 58 . This extensive damage may potentially contribute to cognitive decline in TBI-induced long-term damage [61][62][63] . Nevertheless, the primary objective of our study was to ascertain whether baclofen demonstrates therapeutic efficacy in a TBI model.…”

Leveraging Technology To Diagnose Alzheimer's Disease: A Meta Analysis

“…Frequency PET [24,28,30,33,37,38,41,42,44 25,27,29,33,[35][36][37][38][39][40][41][43][44][45] In 11/53 (21%) occurrences, the intervention was identi ed as non-invasive. [21, 22, 26-29, 34, 36, 37, 39, 42] In 8/53 (15%) of the occurrences, two themes emerged: The intervention was identi ed as non-stressful for the patient; [26-29, 34, 36, 37, 42] and, the intervention as identi ed as inexpensive to implement.…”

“…Of the 28 studies analyzed over the 10-year period, 0 were from 2012, 3 from 2013, [18-20] 2 were from 2014, [21,22] 0 were from 2015, 1 was from 2016, [23] 2 were from 2017, [24,25] 5 were from 2018, [26-30] 3 were from 2019, [31][32][33] 3 were from 2020, [34][35][36] 7 were from 2021, [37][38][39][40][41][42][43] and 2 were from 2022. [44,45] All involved older adults, 61% were quasi-experimental, 21% were observational, and 14% were true experiments. Of those analyzed, 9/28 (32%) used positron emission tomography (PET) to examine tau (plaque) on the brain, 6/28 (21%) examined blood-based biomarkers, 4/28 (14%) used some form of telehealth (video teleconferencing, virtual reality, or telemonitoring), 3/28 (11%) used arti cial intelligence or machine learning to recognize patters from MRI or PET scans, while the other six interventions stood on their own without repeats (MRI, MRI + PET, arterial pulse, RNA, EEG, and spectral domain optical coherence tomography).…”

“…PET was identi ed 9/28 (32%) of the studies analyzed. [24,28,30,33,37,38,41,42,44] PET can identify tau plaque on the brain. This intervention is less invasive, but the con ned space of the machine can cause stress.…”