Higher cerebellum florbetapir uptake in cerebral amyloid angiopathy compared to Alzheimer's disease: A dual florbetapir and FDG PET study

Abstract

Background: Amyloid-β (Aβ) is the primary amyloidogenic protein involved in various diseases associated with cognitive dysfunction, including Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA).

Objective: This cross-sectional study aimed to investigate the characteristics of ¹⁸F-florbetapir PET, which detects Aβ deposition, and ¹⁸F-FDG PET, which measures glucose metabolism in patients with CAA and AD.

Methods: 30 patients with AD, 37 with probable CAA, and 14 control subjects (CSs) underwent ¹⁸F-florbetapir and ¹⁸F-FDG PET imaging within a one-month period. Region of interest and voxel-wise analyses were performed to compare Aβ deposition and glucose metabolism patterns among the three study groups. Standardized uptake value ratios were calculated using brainstem as the reference region for ¹⁸F-florbetapir and ¹⁸F-FDG PET, respectively.

Results: Patients with CAA exhibited significantly higher ¹⁸F-florbetapir uptake in the cerebellum, global cerebral cortex, and various cortical regions compared to CSs. Compared to patients with AD, those with CAA showed predominantly higher ¹⁸F-florbetapir uptake in the cerebellum but lower uptake in the insular cortex and posterior cingulate gyrus. Glucose hypometabolism patterns in CAA did not differ significantly from those observed in AD.

Conclusions: Distinct Aβ deposition patterns, particularly the increased amyloid burden in the cerebellum, could serve as a valuable biomarker for differentiating CAA from AD.

Keywords: Alzheimer's disease; amyloid; cerebral amyloid angiopathy; glucose metabolism; positron emission tomography.

Figure 1.

Comparative analysis of ¹⁸F-florbetapir standardized uptake value ratios in the three study groups. (A) Box plot displaying greater global cerebral cortex flobetapir SUVr in patients with CAA than CSs (p < 0.001), in patients with AD than CSs (p < 0.001), and no significant difference between CAA and AD. (B) Elevated cerebellar cortex flobetapir SUVr in patients with CAA relative to both CSs (p < 0.001) and patients with AD (p < 0.001). (C)-(F) Greater ¹⁸F-florbetapir SUVr in patients with CAA compared to CSs in (C) the occipital cortex (p < 0.001), (D) temporal cortex (p < 0.01), (E) frontal cortex (p < 0.01), (F) parietal cortex (p < 0.01). Greater ¹⁸F-florbetapir SUVr in patients with AD compared to CSs in these four regional cortices (p < 0.001). No significant differences were observed between CAA and AD in these regional cortices. (G) Lower SUVr of the insular cortex in CAA compared to AD (p < 0.01). Higher SUVr of that in AD relative to CSs (p < 0.001). No significant difference between CAA and CSs. (H) Lower posterior cingulate gyrus SUVr in patients with CAA compared to AD (p < 0.05). Higher SUVr of that in patients with AD than CSs (p < 0.01). (I) Higher O/PC SUVr of that in CAA compared to AD (p < 0.001) and CSs (p < 0.001). Statistical significance is denoted as follows: *p < 0.05, **p < 0.01, and ***p < 0.001. The upper and lower whiskers of the box represent the maximum and minimum values, respectively. Each point represents a sample. CAA: cerebral amyloid angiopathy; AD: Alzheimer's disease; CS: control subject; SUVr: standardized uptake value ratio; PC: posterior cingulate cortex; O/PC: Occipital cortex/Posterior cingulate cortex.

Figure 2.

Voxel-wise analysis comparing ¹⁸F-florbetapir uptake in three study groups using Gaussian random field (GRF) theory correction of voxel-level p < 0.001, cluster-level p < 0.05. (A) Patients with CAA exhibited diffusely greater ¹⁸F-florbetapir uptake in the global cerebral cortex (primarily frontal cortex, parietal cortex, temporal cortex, and occipital cortex) and cerebellum compared to CSs (labelled in orange, white arrows for some regions). (B) Patients with AD demonstrated diffusely higher ¹⁸F-florbetapir uptake in the global cerebral cortex compared to CSs (labelled in yellow). (C) Patients with CAA exhibited higher retention of ¹⁸F-florbetapir primarily in the cerebellum (labelled in orange, white arrows), and lower uptake of that in the white matter compared to patients with AD (labelled in gray). All the color-coded regions in the figure depict areas of statistically significant differences in radiotracer uptake between groups. The age, sex, and APOE genotype (the carriage of APOE ε2 and ε4) were included as covariates to control for potential confounding effects, for 36 CAA, 28 AD, and 13 CS with APOE genotype available. The color bar in the figure reflects the parameters of t-values. The color-coded regions depict areas of statistically significant differences in radiotracer uptake between groups using Gaussian Random Field (GRF) theory correction of voxel-level p < 0.001, cluster-level p < 0.05. CAA: cerebral amyloid angiopathy; AD: Alzheimer’s disease; CS: control subject.

Figure 3.

Comparative analysis of ¹⁸F-FDG standardized uptake value ratios in the three study groups. (A) Box plot displaying lower global cerebral cortex FDG SUVr in patients with CAA than CSs (p < 0.001), in patients with AD than CSs (p < 0.001), and no significant difference between CAA and AD. (B) The box plots demonstrate no statistical difference of cerebellar cortex FDG SUVr across the three groups. Lower FDG SUVr in patients with CAA compared to CSs in (C) occipital cortex (p < 0.01), (D) the temporal cortex (p < 0.01), (E) frontal cortex (p < 0.05), (F) parietal cortex (p < 0.01), (G) insular cortex (p < 0.01), (H) posterior cingulate cortex (p < 0.01). Lower FDG SUVr in patients with AD compared to CSs in (C) occipital cortex (p < 0.05), (D) temporal cortex (p < 0.01), (E) frontal cortex (p < 0.05), (F) parietal cortex (p < 0.01), (G) insular cortex (p < 0.05), and (H) posterior cingulate cortex (p < 0.01). (I) No significant difference of O/PC across the three groups. Statistical significance is denoted as follows: *p < 0.05, **p < 0.01, ***p < 0.001. The upper and lower whiskers of the box represent the maximum and minimum values, respectively. Each point represents a sample. FDG: fluorodeoxyglucose; CAA: cerebral amyloid angiopathy; AD: Alzheimer’s disease; CS: control subject; FDG: fluorodeoxyglucose; SUVr: standardized uptake value ratio; PC: posterior cingulate cortex; O/PC: occipital cortex/posterior cingulate cortex.

Figure 4.

Voxel-wise analysis comparing ¹⁸F-FDG uptake in three study groups using Gaussian random field (GRF) theory correction of voxel-level p < 0.001, cluster-level p < 0.05. (A) Patients with CAA exhibited reduced glucose metabolism in precuneus, inferior parietal lobule, angular gyrus, middle occipital gyrus, superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and calcarine cortex compared to CSs (labelled in green, white arrows for typical regions). (B) Patients with AD demonstrated significant glucose hypometabolism primarily in precuneus, inferior parietal lobule, superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, middle cingulate gyrus, angular gyrus, posterior cingulate gyrus, superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, hippocampus, para hippocampus, and temporal pole compared to CSs (labelled in blue, white arrows for typical regions). (C) No significant difference of FDG uptake was found between CAA and AD. The age, sex, and APOE genotype (the carriage of APOE ε2 and ε4) were included as covariates to control for potential confounding effects, for 36 CAA, 28 AD, and 13 CS with APOE genotype available. The color bar in the figure reflects the parameters of t-values. The color-coded regions depict areas of statistically significant differences in radiotracer uptake between groups using Gaussian Random Field (GRF) theory correction of voxel-level p < 0.001, cluster-level p < 0.05. FDG: fluorodeoxyglucose; CAA: cerebral amyloid angiopathy; AD: Alzheimer's disease; cs: control subject.