Regional cerebral THK5351 accumulations correlate with neuropsychological test scores in Alzheimer continuum

Objective(s): We evaluated the relationship between regional accumulations of the tau positron emission tomography (PET) tracer THK5351 and cognitive dysfunction in the Alzheimer's disease (AD) continuum. Methods: The cases of 18 patients with AD or mild cognitive impairment (MCI) due to AD who underwent three-dimensional MRI, fluoro-2-deoxyglucose (FDG)-(PET), Pittsburgh compound B (PiB)-amyloid PET, and THK5351-tau PET were analyzed. Their mean age was 70.6±11.3, their mean Mini-Mental State Examination (MMSE) score was 22.3±6.8, and their mean Alzheimer Disease Assessment Scale-Cognitive Subtest (ADAS) score was 12.5±7.3. To determine the correlation between each patient's four imaging results and their MMSE and ADAS scores, we performed a voxel-wise statistical analysis with statistical parametric mapping (SPM). Results: The SPM analysis showed that the bilateral parietotemporal FDG accumulations and MMSE scores were positively correlated, and the bilateral parietotemporal FDG accumulations were negatively correlated with ADAS scores. There were significant correlations between bilateral parietotemporal and left posterior cingulate/precuneus THK5351 accumulations and MMSE/ADAS scores. Conclusion: In the AD brain, THK5351 correlates with neuropsychological test scores as well as or more additional than FDG due to its affinity for both tau and monoamine oxidase-B (MAO-B), and measurements of THK5351 may thus be useful in estimating the progression of AD.

[1]  L. Ai,et al.  Neuropsychological Performance Is Correlated With Tau Protein Deposition and Glucose Metabolism in Patients With Alzheimer’s Disease , 2022, Frontiers in Aging Neuroscience.

[2]  Y. Kimura,et al.  Relationship between F-18 florbetapir uptake in occipital lobe and neurocognitive performance in Alzheimer’s disease , 2021, Japanese Journal of Radiology.

[3]  M. Mintun,et al.  Relationships Between Cognition and Neuropathological Tau in Alzheimer's Disease Assessed by 18F Flortaucipir PET. , 2021, Journal of Alzheimer's disease : JAD.

[4]  Y. Kimura,et al.  Regional gray matter-dedicated SUVR with 3D-MRI detects positive amyloid deposits in equivocal amyloid PET images , 2020, Annals of Nuclear Medicine.

[5]  H. Matsuda,et al.  Neuroimaging of Alzheimer’s disease: focus on amyloid and tau PET , 2019, Japanese Journal of Radiology.

[6]  Stephen F. Carter,et al.  Astrocyte Biomarkers in Alzheimer's Disease. , 2019, Trends in molecular medicine.

[7]  Christopher G Schwarz,et al.  Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease , 2018, Human brain mapping.

[8]  Clifford R. Jack,et al.  The National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease: Perspectives from the Research Roundtable , 2018, Alzheimer's & Dementia.

[9]  H. Arai,et al.  Correlations of 18F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease , 2017, The Journal of Nuclear Medicine.

[10]  H. Nishida,et al.  Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI , 2016, Physics in medicine and biology.

[11]  H. Arai,et al.  18F-THK5351: A Novel PET Radiotracer for Imaging Neurofibrillary Pathology in Alzheimer Disease , 2016, The Journal of Nuclear Medicine.

[12]  Takamichi Murakami,et al.  Investigation of 11C-PiB equivocal PET findings , 2015, Annals of Nuclear Medicine.

[13]  K. Ishii PET Approaches for Diagnosis of Dementia , 2014, American Journal of Neuroradiology.

[14]  P. Scheltens,et al.  Atrophy of medial temporal lobes on MRI in “probable” Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates , 2012, Journal of Neurology, Neurosurgery & Psychiatry.

[15]  M. Albert,et al.  Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[16]  Nick C Fox,et al.  The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[17]  Denise C. Park,et al.  Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[18]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[19]  Gianmario Sambuceti,et al.  Unawareness of memory deficit in amnestic MCI: FDG-PET findings. , 2010, Journal of Alzheimer's disease : JAD.

[20]  W. Klunk,et al.  Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents. , 2003, Journal of medicinal chemistry.

[21]  P. Scheltens,et al.  Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[22]  Vijaya L. Melnick,et al.  Alzheimer’s Dementia , 1985, Contemporary Issues in Biomedicine, Ethics, and Society.