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Backgrounds  Although neurofibrillary tangles (NFTs) mainly accumulate in the medial temporal lobe with human aging, only a few imaging studies have investigated correlations between NFT accumulation and gray matter (GM) volume in cognitively normal older adults. Here, we investigated the correlations between  18 F-THK5351 accumulation and GM volume at the voxel level.    Material and methods  We recruited 47 amyloid-negative, cognitively normal, older adults (65.0 ± 7.9 years, 26 women), who underwent structural magnetic resonance imaging,  11 C-Pittsburgh compound-B and  18 F-THK5351 PET scans, and neuropsychological assessment. The magnetic resonance and  18 F-THK5351 PET images were spatially normalized using Statistical Parametric Mapping 12. Voxel-wise correlations between  18 F-THK5351 accumulation and GM volume were evaluated using the Biological Parametric Mapping toolbox.    Results  A significant negative correlation ( p  < 0.001) between  18 F-THK5351 accumulation and GM volume was detected in the bilateral medial temporal lobes.    Conclusions  Voxel-wise correlation analysis revealed a significant negative correlation between  18 F-THK5351 accumulation and GM volume in the medial temporal lobe in individuals without amyloid-β deposits. These results may contribute to a better understanding of the pathophysiology of primary age-related tauopathy in human aging.

Voxel-based correlation of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults