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

Abstract

AbstractBackgroundDementia 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 [18F]flortaucipir PET scan.MethodEighteen 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 [18F]flortaucipir PET scan. Receptor parametric mapping (cerebellar gray matter reference region) was used to extract (regional, Hammers based) binding potential (BPND) and R1, which reflect tau pathology and rCBF, respectively. We performed voxel‐wise comparisons (Puncorrected < 0.001) of [18F]flortaucipir BPND and R1 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 [18F]flortaucipir BPND, R1 and cognition in the following regions‐of‐interest (ROIs); medial and lateral temporal/ parietal, occipital and frontal cortex, adjusted for age, sex and education.ResultAveraged [18F]flortaucipir BPND images across groups showed visually minimal tau uptake in the inferior temporal lobe in DLB (Figure 1). Voxel‐wise comparisons showed lower [18F]flortaucipir R1 in the occipital lobe in DLB compared to AD and controls (Figure 2). Regional [18F]flortaucipir BPND was lower in DLB compared to AD and comparable with tau binding in controls (Figure 3). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p<0.01, Figure 3). R1 but not BPND 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) R1 was related to lower language score (Figure 4).ConclusionIn 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.