Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

Abstract

Objectives: Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [(18)F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD.

Methods: Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed.

Results: Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68).

Conclusions: Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET.

Key points: • Similar patterns of hypoperfusion and hypometabolism were observed in patients with dementia. • For both imaging modalities, parietal abnormalities were found in Alzheimer's disease. • For both imaging modalities, prefrontal abnormalities were found in frontotemporal dementia.

Fig. 1

Transversal FDG and ASL images of an FTD (first and second rows, MMSE 26) and an AD (third and fourth rows, MMSE 17) patient with early-onset disease. Both transversal planes show predominantly prefrontal abnormalities in FTD and parietal abnormalities in AD. Red colour reflects normal metabolism and perfusion

Fig. 2

Functional brain abnormalities of AD and FTD compared to controls projected onto a MNI glass brain. Predominantly parietal, precuneus aberrant function is visible in AD compared to controls, while FTD compared to controls shows mostly prefrontal abnormalities with both FDG and ASL. For illustrative purposes, images were thresholded at p < 0.005

Fig. 3

Panel A shows FDG and ASL regional mean z-scores of AD (left) and FTD (right) compared to controls. Panel B shows AD < FTD (left) and FTD < AD (right) perfusion and metabolism abnormalities

Fig. 4

Positive correlations between FDG SUV and ASL derived CBF in (A) medial prefrontal cortex (right, r = .74, p < 0.001) and (B) inferior parietal lobule (left, r = .61, p < 0.001) across groups

Fig. 5

ROC curves for FDG and ASL in AD and FTD. A) Precuneus function for ASL and FDG in discriminating AD from FTD. B) mPFC function in discriminating FTD from AD. Ratios were taken between the mPFC and precuneus and entered into ROC analyses as ‘ratio ROI’