Tau Positron Emission Tomographic Imaging in the Lewy Body Diseases

Abstract

IMPORTANCEThe causes of cognitive impairment in dementia with Lewy bodies (DLB) and Parkinson disease (PD) are multifactorial. Tau pathologic changes are commonly observed at autopsy in individuals with DLB and PD dementia, but their contribution to these diseases during life is unknown.OBJECTIVE To contrast tau aggregation in DLB, cognitively impaired persons with PD (PD-impaired), cognitively normal individuals with PD (PD-normal), and healthy persons serving as control participants, and to evaluate the association between tau aggregation, amyloid deposition, and cognitive function. DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional study was conducted from January 1, 2014, to April 28, 2016, in a tertiary care center's memory and movement disorders units. Twenty-four patients with Lewy body disease (7 DLB, 8 PD-impaired, and 9 PD-normal) underwent multimodal brain imaging, cognitive testing, and neurologic evaluation, and imaging measures were compared with those of an independently acquired group of 29 controls with minimal brain amyloid burden as measured with carbon 11-labeled Pittsburgh Compound B ([ 11 C]PiB) positron emission tomography (PET). EXPOSURES Imaging with fluorine 18-labeled AV-1451 ([ 18 F]AV-1451) (formerly known as [ 18 F]T807), [ 11 C]PiB PET, magnetic resonance imaging (MRI), neurologic examination, and detailed cognitive testing using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale. MAIN OUTCOMES AND MEASURES Main outcomes were differentiation of diagnostic groups on the basis of [ 18 F]AV-1451 binding, the association of [ 18 F]AV-1451 binding with [ 11 C]PiB binding, and the association of [ 18 F]AV-1451 binding with cognitive impairment. All but 3 individuals underwent amyloid imaging with [ 11 C]PiB PET. The hypotheses being tested were formulated before data collection. Mini-Mental State Examination (range, 0-30, with 30 being best) and Clinical Dementia Rating scale sum-of-boxes scale (range, 0-18, with 0 being best) were used for assessment of cognitive function. RESULTSIn patients with DLB, cortical [ 18 F]AV-1451 uptake was highly variable and greater than in the controls, particularly in the inferior temporal gyrus and precuneus. Foci of increased [ 18 F]AV-1451 binding in the inferior temporal gyrus and precuneus were also evident in PD-impaired patients. Elevated cortical [ 18 F]AV-1451 binding was observed in 4 of 17 patients with Lewy body disease with low cortical [ 11 C]PiB retention. For DLB and PD-impaired patients, greater [ 18 F]AV-1451 uptake in the inferior temporal gyrus and precuneus was associated with increased cognitive impairment as measured with the MMSE and the Clinical Dementia Rating scale sum-of-boxes score.CONCLUSIONS AND RELEVANCE Patients with Lewy body disease manifest a spectrum of tau pathology. Cortical aggregates of tau are common in patients with DLB and in PD-impaired patients, even in those without elevated amyloid levels. When present, tau deposition is associated with cognitive impairment. These findings support...

Extremely Low Prevalence of Amyloid Positron Emission Tomography Positivity in Parkinson's Disease without Dementia

“…The results of these studies indicate that Aβ deposition may be suppressed in PD with Lewy body, but tau accumulation and cognitive dysfunction, which are correlated with tau tangles [32,33], appear even with low Aβ deposition and/or rapidly after deposition in patients with PD. This speculation was supported by a recent study on tau imaging showing that cortical aggregates of tau are common in patients with DLB and PD, even in those with low Aβ depositions [34]. Although future cohort studies on cognitive function and tau imaging in PD without dementia are required, we propose that the curves of Aβ deposition and tau-mediated neuronal injury shift to the right and left, respectively, in the dynamic biomarker model of AD as described by Jack et al [35], with the result that the preclinical stage of asymptomatic cerebral Aβ deposition in PD may be shorter and the symptoms of dementia may appear earlier (Fig.…”

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.…”

Imaging in Parkinson's Disease

“…Cortical [ 18 F]T807 uptake was higher in the DLB and PD with cognitive impairment than healthy controls with in low-amyloid pathology, and higher uptake was observed in the inferolateral temporal and parietal/ precuneus regions (Gomperts et al, 2016). Tau deposition was more variable in DLB patients and was lower in magnitude and extent in PD with cognitive impairment, whereas PD patients without cognitive impairment showed no evidence for tau deposition (Gomperts et al, 2016).…”

“…A recent PET study using [ 18 F]T807 investigated tau deposition in DLB, PD with and without cognitive impairment (Gomperts et al, 2016). Cortical [ 18 F]T807 uptake was higher in the DLB and PD with cognitive impairment than healthy controls with in low-amyloid pathology, and higher uptake was observed in the inferolateral temporal and parietal/ precuneus regions (Gomperts et al, 2016).…”