AV-1451 tau and β-amyloid positron emission tomography imaging in dementia with Lewy bodies

Abstract

Objective: Patients with probable dementia with Lewy bodies (DLB) often have Alzheimer's disease (AD)-related pathology. Our objective was to determine the pattern of positron emission tomography (PET) tau tracer AV-1451 uptake in patients with probable DLB, compared to AD, and its relationship to β-amyloid deposition on PET.

Methods: Consecutive patients with clinically probable DLB (n = 19) from the Mayo Clinic Alzheimer's Disease Research Center underwent magnetic resonance imaging, AV-1451, and Pittsburgh compound-B (PiB) PET examinations. Age- and sex-matched groups of AD dementia (n = 19) patients and clinically normal controls (n = 95) from an epidemiological cohort served as a comparison groups. Atlas- and voxel-based analyses were performed.

Results: The AD dementia group had significantly higher AV-1451 uptake than the probable DLB group, and medial temporal uptake completely distinguished AD dementia from probable DLB. Patients with probable DLB had greater AV-1451 uptake in the posterior temporoparietal and occipital cortex compared to clinically normal controls, and in probable DLB, the uptake in these regions correlated with global cortical PiB uptake (Spearman rho = 0.63; p = 0.006).

Interpretation: Medial temporal lobe AV-1451 uptake distinguishes AD dementia from probable DLB, which may be useful for differential diagnosis. Elevated posterior temporoparietal and occipital AV-1451 uptake in probable DLB and its association with global cortical PiB uptake suggest an atypical pattern of tau deposition in DLB. ANN NEUROL 2017;81:58-67.

Figure 1

Regional pattern of AV‐1451 uptake in probable DLB patients compared to the clinically normal controls and probable AD dementia. Voxel‐based analysis comparing patients with probable DLB to the clinically normal control group indicate greater uptake in the posterior and inferior temporoparietal lobes and medial frontal cortex in probable DLB patients compared to controls. Higher uptake in the choroid plexus is seen on the left side (p < 0.001; uncorrected for multiple comparisons). Correction for multiple comparisons revealed no findings. (A) Voxel‐based analysis comparing patients with probable DLB to AD dementia showed significant differences throughout the brain relatively sparing the somatosensory and primary visual cortices (p < 0.001; family‐wise error corrected for multiple comparisons). (B) Color bars show the t‐value range. AD = Alzheimer's disease; DLB = dementia with Lewy bodies.

Figure 2

AV‐1451 uptake in individual ROIs in patients with probable DLB compared to controls and patients with AD dementia. Median AV‐1451 SUVr from the atlas ROIs and the interquartile ranges are presented with box plots in the three groups. ROIs are ordered according to the area under the receiver operating characteristic curve (AUROC) from highest to lowest with confidence intervals and the p value of the difference between the probable DLB and control (A); probable DLB and AD dementia (B) groups. AD = Alzheimer's disease; CN = clinically normal controls; DLB = dementia with Lewy bodies; ROIs = regions of interest; SUVr = standard value uptake unit ratio.

Figure 3

Box plots show the AV‐1451 SUVr values in each subject from the posterior temporoparietal and occipital lobe meta‐ROI (inferior, middle and superior occipital, lingual, angular, fusiform, middle and inferior temporal gyri, and precuneus and cuneus ROIs) (A) and the medial temporal lobe meta‐ROI (parahippocampal gyrus, entorhinal cortex, and hippocampus) (B). AD = Alzheimer's disease; CN = clinically normal controls; DLB = dementia with Lewy bodies; ROI = region of interest; SUVr = standard value uptake unit ratio.

Figure 4

AV‐1451 uptake in probable DLB patients with high and low uptake on PiB PET scans. AV‐1451 PET scans are registered to T₁‐weighted MRI. Each AV‐1451 PET voxel was referenced to the median value of the right and left cerebellar crus uptake. The color scale in the AV‐1451 PET images indicates a range of standard value uptake unit ratio (SUVr) in each PET voxel. Case 1 is a 65‐year‐old man with parkinsonism, fluctuations, probable rapid eye movement sleep behavior disorder (RBD), and a disease duration of 6.6 years. He has high uptake on the PiB PET scan with a global cortical SUVr of 1.71. There is significant AV‐1451 uptake in the right inferior occipital lobe and moderate uptake in the inferior temporal lobes. Case 2 is a 78‐year‐old man with parkinsonism, fluctuations, probable RBD, and a disease duration of 5.0 years. He has low uptake on PiB PET scan, with a global cortical SUVr of 1.30. There is moderate AV‐1451 uptake in the inferior temporal and occipital lobes. DLB = dementia with Lewy bodies; MRI = magnetic resonance imaging; PET = positron emission tomography; PiB = Pittsburgh compound‐B.

Figure 5

Correlations between AV‐1451 SUVr in the posterior temporoparietal and occipital meta‐ROI and global cortical PiB SUVr in patients with probable DLB (n = 18; because 1 DLB patient did not have PiB PET). The global cortical PiB SUVr is scaled with log transformation attributed to the skewing at lower SUVr levels (Spearman rho = 0.63; p = 0.006). DLB = dementia with Lewy bodies; PET = positron emission tomography; PiB = Pittsburgh compound‐B; SUVr = standard value uptake unit ratio.