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.

Molecular Imaging and Updated Diagnostic Criteria in Lewy Body Dementias

“…Proteinopathy imaging studies confirm the spectrum nature of overlapping pathologies in neurodegenerative disorders [52, 53, 72]. Recent FDG PET imaging studies also demonstrate overlapping metabolic changes between DLB and the PCA variant of AD [24].…”

“…Shorter duration of disease was associated with greater AV-1451 uptake in the inferior temporal gyrus and precuneus in the DLB group. A subsequent larger [ 18 F]AV-1451 tau PET imaging study found that AV-1451 uptake was substantially more severe and extensive in AD compared to DLB patients [53]. Medial temporal uptake completely distinguished AD dementia (highest) from probable DLB (lowest).…”

“…Medial temporal uptake completely distinguished AD dementia (highest) from probable DLB (lowest). Probable DLB patients had higher inferior, middle, and superior occipital, lingual, angular, fusiform, middle and inferior temporal gyri, and precuneus and cuneus AV-1451 uptake compared to normal control subjects [53]. These investigators did not find, however, a significant correlation between posterior temporo-parietal and occipital AV-1451 uptake and clinical measures, including cognition, visual hallucinations, motor parkinsonism or presence of RBD.…”

“…These investigators did not find, however, a significant correlation between posterior temporo-parietal and occipital AV-1451 uptake and clinical measures, including cognition, visual hallucinations, motor parkinsonism or presence of RBD. Higher [ 11 C]PIB β-amyloid binding was associated with higher AV-1451 uptake in these regions suggesting an atypical pattern of tau deposition in probable DLB patients [53]. Overall, there appears to be a gradient of increasing tau binding from cognitively normal PD (absent to lowest) to cognitively impaired PD (low) to DLB (intermediate) to AD (highest); Table 1 [52, 54].…”

Clinical and imaging correlates of amyloid deposition in dementia with Lewy bodies

“…Early data from tau imaging studies have reported conflicting findings on the relationships between amyloid deposition, tau deposition, and clinical profile in DLB 36, 37. Other important pathophysiological factors such as the extent and severity of Lewy body pathology remain unquantifiable until postmortem.…”