Phenotype-specific metabolic patterns in Posterior cortical atrophy and early-onset typical Alzheimer's disease

Abstract

Objective: Posterior cortical atrophy (PCA) is generally considered an atypical variant of Alzheimer's disease (AD) and is an important component of early-onset AD. Symptomatologic heterogeneity has led to a high rate of misdiagnosis or delayed diagnosis of early-onset AD. We sought to establish the phenotypic-specific metabolic patterns of PCA and early-onset typical AD (tAD) and to assess whether phenotype-specific neuroimaging biomarkers are more valuable for disease recognition.

Methods: Patients accepting ¹⁸F-FDG PET with an onset age younger than 65 years (PCA, n = 40; early-onset tAD, n = 37; behavioral variant frontotemporal dementia (bv-FTD), n = 35) and healthy controls (HCs, n = 30) were enrolled and divided into two cohorts for pattern establishment and validation, respectively. Similarities and differences between patterns were assessed by pattern topography, expression, classification performance and correlation with clinical severity.

Results: PCA-related pattern (PCARP) was characterized by extensively relative hypometabolism in the parietal lobe, occipital lobe, temporal lobe, cingulate gyrus, and relative hypermetabolism mainly in vermis, thalamus. Early-onset tAD-related pattern (EOtADRP) was characterized by relative hypometabolism mainly in the middle frontal gyrus, angular gyrus, precuneus, middle temporal gyrus, cingulate gyrus, caudate, and relative hypermetabolism mainly in vermis, thalamus, postcentral gyrus. PCARP and EOtADRP were closely related in topography (r = 0.909, P < 0.001) and expression (r = 0.862, P < 0.001). High accuracies in distinguishing corresponding patient group from HC were found in both, while only PCARP was capable of phenotype discrimination (PCA versus early-onset tAD; area under the receiver operating characteristic curve [AUC] = 0.84-0.88 for PCARP, AUC = 0.57-0.62 for EOtADRP) and distinguishment between PCA/early-onset tAD and bv-FTD (AUC = 1.00/0.91 for PCARP, AUC = 0.73/0.62 for EOtADRP). PCARP showed great potential in detecting clinical severity in both phenotypes whereas EOtADRP only worked in early-onset tAD.

Conclusion: PCARP outperformed EOtADRP in phenotype discrimination with better potential in severity assessment.

Keywords: 18F-FDG PET; Early-onset typical Alzheimer’s disease; Neuroimaging biomarker; Phenotype; Posterior cortical atrophy.