Intra-individual correlations between quantitative THK-5351 PET and MRI-derived cortical volume in Alzheimer's disease differ according to disease severity and amyloid positivity

Abstract

Purpose: To assess the in vivo whole-brain relationship between uptake of [18F]THK-5351 on PET and cortical atrophy on structural MRI according to the presence and severity of Alzheimer's disease (AD).

Materials and methods: Sixty-five participants (21 normal controls, 32 mild cognitive impairment [MCI] subjects, and 12 AD patients) were enrolled from a prospective multicenter clinical trial (NCT02656498). Structural MRI and [18F]THK-5351 PET were performed within a 2-month interval. Cortical volume and standardized uptake value ratios (SUVR) were calculated from MRI and PET images, respectively, for 35 FreeSurfer-derived cortical regions. Pearson's correlation coefficients between SUVR and cortical volume were calculated for the same regions, and correlated regions were compared according to disease severity and β-amyloid PET positivity.

Results: No significantly correlated regions were found in the normal controls. Negative correlations between SUVR and cortical volume were found in the MCI and AD groups, mainly in limbic locations in MCI and isocortical locations in AD. The AD group exhibited stronger correlations (r = -0.576-0.781) than the MCI group (r = 0.368-0.571). Hippocampal atrophy did not show any correlation with SUVR in the β-amyloid PET-negative group, but negatively correlated with SUVR (r = -0.494, P = .012) in the β-amyloid PET-positive group.

Conclusions: Regional THK-5351 uptake correlated more strongly with cortical atrophy in AD compared with MCI, thereby demonstrating a close relationship between the neuro-pathologic process and cortical atrophy. Hippocampal atrophy was associated with both β-amyloid and THK-5351 uptake, possibly reflecting an interaction between β-amyloid and tau deposition in the neurodegeneration process.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Flow diagram of the participant inclusion process of the study.

Fig 2

Regions exhibiting a significant negative relationship between THK5351 uptake and cortical atrophy in patients with mild cognitive impairment (MCI; A) and Alzheimer’s disease (AD; B). In MCI, the locations showing correlation occurred in one transentorhinal region (entorhinal), three limbic regions (parahippocampal, middle temporal, temporal), and two isocortical regions (pars triangularis and lateral orbitofrontal). In AD, correlated locations were found in one transentorhinal region (entorhinal), two limbic regions (middle temporal and isthmus cingulate), and six isocortical regions (superior frontal, superior temporal, precuneus, supramarginal, inferior parietal, and superior parietal). More widespread and stronger correlations were observed in the AD group.

Fig 3. Representative cases of the relationship between THK5351 uptake and cortical atrophy in normal control, mild cognitive impairment, and Alzheimer’s disease.

Note that the correlated locations propagate from transentorhinal to isocortical locations according to the AD spectrum.

Fig 4

Differences in regions exhibiting significant negative relationships between THK5351 uptake and cortical atrophy in the β-amyloid positive (A) and -negative (B) groups. More widespread significant negative relationships were found in the β-amyloid positive group. Hippocampal atrophy was associated with THK5351 uptake only in the amyloid beta-positive group.