Tau PET and relative cerebral blood flow in dementia with Lewy bodies: A PET study.

Alpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. Regional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stβ = 0.72) and category fluency (stβ = 0.69) tests. Lower parietal R1 was related to lower delayed (stβ = 0.50) and immediate (stβ = 0.48) recall, VOSP number location (stβ = 0.70) and fragmented letters (stβ = 0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stβ = 0.61), all p < 0.05. The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.

Wolters EE ，van de Beek M ，Ossenkoppele R ，Golla SSV ，Verfaillie SCJ ，Coomans EM ，Timmers T ，Visser D ，Tuncel H ，Barkhof F ，Boellaard R ，Windhorst AD ，van der Flier WM ，Scheltens P ，Lemstra AW ，van Berckel BNM ... -  《NeuroImage-Clinical》

Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer's disease.

Visser D ，Wolters EE ，Verfaillie SCJ ，Coomans EM ，Timmers T ，Tuncel H ，Reimand J ，Boellaard R ，Windhorst AD ，Scheltens P ，van der Flier WM ，Ossenkoppele R ，van Berckel BNM ... -  《-》

Differential associations between neocortical tau pathology and blood flow with cognitive deficits in early-onset vs late-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) differ in neuropathological burden and type of cognitive deficits. Assessing tau pathology and relative cerebral blood flow (rCBF) measured with [18F]flortaucipir PET in relation to cognition may help explain these differences between EOAD and LOAD. Seventy-nine amyloid-positive individuals with a clinical diagnosis of AD (EOAD: n = 35, age-at-PET = 59 ± 5, MMSE = 23 ± 4; LOAD: n = 44, age-at-PET = 71 ± 5, MMSE = 23 ± 4) underwent a 130-min dynamic [18F]flortaucipir PET scan and extensive neuropsychological assessment. We extracted binding potentials (BPND) and R1 (proxy of rCBF) from parametric images using receptor parametric mapping, in medial and lateral temporal, parietal, occipital, and frontal regions-of-interest and used nine neuropsychological tests covering memory, attention, language, and executive functioning. We first examined differences between EOAD and LOAD in BPND or R1 using ANOVA (region-of-interest analysis) and voxel-wise contrasts. Next, we performed linear regression models to test for potential interaction effects between age-at-onset and BPND/R1 on cognition. Both region-of-interest and voxel-wise contrasts showed higher [18F]flortaucipir BPND values across all neocortical regions in EOAD. By contrast, LOAD patients had lower R1 values (indicative of more reduced rCBF) in medial temporal regions. For both tau and flow in lateral temporal, and occipitoparietal regions, associations with cognitive impairment were stronger in EOAD than in LOAD (EOAD BPND - 0.76 ≤ stβ ≤  - 0.48 vs LOAD - 0.18 ≤ stβ ≤  - 0.02; EOAD R1 0.37 ≤ stβ ≤ 0.84 vs LOAD - 0.25 ≤ stβ ≤ 0.16). Compared to LOAD, the degree of lateral temporal and occipitoparietal tau pathology and relative cerebral blood-flow is more strongly associated with cognition in EOAD.

Visser D ，Verfaillie SCJ ，Wolters EE ，Coomans EM ，Timmers T ，Tuncel H ，Boellaard R ，Golla SSV ，Windhorst AD ，Scheltens P ，van der Flier WM ，van Berckel BNM ，Ossenkoppele R ... -  《-》

Regional [(18)F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer's disease.

Wolters EE ，Ossenkoppele R ，Verfaillie SCJ ，Coomans EM ，Timmers T ，Visser D ，Tuncel H ，Golla SSV ，Windhorst AD ，Boellaard R ，van der Flier WM ，Teunissen CE ，Scheltens P ，van Berckel BNM ... -  《-》

Associations between quantitative [(18)F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum.

Timmers T ，Ossenkoppele R ，Wolters EE ，Verfaillie SCJ ，Visser D ，Golla SSV ，Barkhof F ，Scheltens P ，Boellaard R ，van der Flier WM ，van Berckel BNM ... -  《Alzheimers Research & Therapy》