Neuropsychological Performance Is Correlated With Tau Protein Deposition and Glucose Metabolism in Patients With Alzheimer's Disease

Abstract

Objective: This study characterizes glucose metabolism and tau protein deposition distribution in patients with Alzheimer's disease (AD) and to evaluate the relationships between neuropsychological performance and tau protein deposition or glucose metabolism using ¹⁸F-FDG and ¹⁸F-AV1451 positron emission tomography/computed tomography (PET/CT).

Methods: Sixty-four patients with β-amyloid-positive (Aβ+) AD and twenty-five healthy participants were enrolled in this study. All participants underwent ¹⁸F-FDG and ¹⁸F-AV1451 PET/CT. Clinical data and neuropsychological scores were collected. Patients with AD were divided into mild, moderate, and severe groups according to mini-mental state examination (MMSE) scores. The standardized uptake value ratios (SUVRs) for both FDG and AV1451 PET images were calculated using the cerebellar vermis as reference. The SUVRs of the whole cerebral cortex and each brain region were calculated. The volume of interest (VOI) was obtained using automated anatomical atlas (AAL) and Brodmann regions. Student's t-test was used to perform intergroup comparisons of SUVR. The partial correlation coefficient between SUVR and neuropsychological scores was computed in an inter-subject manner using age and education as covariates.

Results: The mild subgroup showed a reduction in glucose metabolism and aggregation of tau protein in the temporoparietal cortex. With a decline in neuropsychiatric performance, the SUVR on FDG PET decreased and SUVR on tau PET increased gradually. The areas of glucose metabolism reduction and tau protein deposition appeared first in the parietal cortex, followed by the temporal and frontal cortex, successively. Both FDG and tau SUVRs significantly correlated with MMSE, Montreal cognitive assessment (MOCA), auditory verbal learning test (AVLT), Boston naming test (BNT), clock drawing task (CDT), and verbal fluency test (VFT) (p < 0.05). The SUVR on FDG PET significantly correlated with activities of daily living (ADL) and the Hamilton depression scale (HAMD). There was no significant correlation between the tau SUVRs and ADL or HAMD.

Conclusion: The extension of tau protein deposition was similar but not exactly consistent with the area of glucose metabolism reduction. Both tau and FDG SUVRs correlated with cognitive function in domain-specific patterns, and the results of FDG PET more closely correlated with neuropsychological function than tau PET results did.

Keywords: Alzheimer’s disease; glucose metabolism; neuropsychological domain; neuropsychological scores; positron emission tomography; tau protein.