Tau pathology, relative cerebral flow and cognition in dementia with Lewy bodies

Background Dementia with Lewy Bodies (DLB) is characterized by the presence of neuronal inclusions containing alpha‐synuclein proteins, and often co‐occurs with Alzheimer’s disease (AD) pathology. We aimed to determine the pattern of tau pathology and relative cerebral blood flow (rCBF) in DLB, compared to AD and controls, and their association with cognitive impairment using a single dynamic [ 18 F]flortaucipir PET scan. Method Eighteen patients with DLB (66 ± 8 years, MMSE 25 ± 4, 44% amyloid positive (abnormal CSF (Aβ42 <813 pg/mL)/visual read amyloid‐PET), 100% FP‐CIT SPECT abnormal, Table 1), 65 amyloid positive cognitively impaired patients (MCI‐AD (n = 13), AD (n = 52)) and 50 controls underwent a dynamic 130‐minute [ 18 F]flortaucipir PET scan. Receptor parametric mapping (cerebellar gray matter reference region) was used to extract (regional, Hammers based) binding potential (BP ND ) and R 1 , which reflect tau pathology and rCBF, respectively. We performed voxel‐wise comparisons (P uncorrected  < 0.001) of [ 18 F]flortaucipir BP ND and R 1 between diagnostic groups using SPM, adjusted for age and sex. DLB patients underwent extensive neuropsychological assessment covering memory, executive functioning, language, attention and visuospatial domains. For DLB only, we performed linear regression analyses between [ 18 F]flortaucipir BP ND , R 1 and cognition in the following regions‐of‐interest (ROIs); medial and lateral temporal/ parietal, occipital and frontal cortex, adjusted for age, sex and education. Result Averaged [ 18 F]flortaucipir BP ND images across groups showed visually minimal tau uptake in the inferior temporal lobe in DLB (Figure 1). Voxel‐wise comparisons showed lower [ 18 F]flortaucipir R 1 in the occipital lobe in DLB compared to AD and controls (Figure 2). Regional [ 18 F]flortaucipir BP ND was lower in DLB compared to AD and comparable with tau binding in controls (Figure 3). Occipital and lateral parietal R 1 was lower in DLB compared to AD and controls (all p<0.01, Figure 3). R 1 but not BP ND was related to cognition (language only); lower medial temporal (stß = 0.76, p = 0.001), medial parietal (stß = 0.64, p = 0.02) and frontal (stß = 0.64, p = 0.02) R 1 was related to lower language score (Figure 4). Conclusion In our sample, tau load in patients with DLB did not differ from controls, but there were DLB‐specific occipital and lateral parietal flow reductions compared to both controls and AD patients. Our results indicate that rCBF may be of more clinical relevance than tau pathology in DLB.