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 (BP_ND) and R₁, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [¹⁸F]flortaucipir BP_ND and R₁ between diagnostic groups. In DLB patients only, we performed regression analyses between regional [¹⁸F]flortaucipir BP_ND, R₁ and performance on ten neuropsychological tests.

Regional [¹⁸F]flortaucipir BP_ND 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.