Alzheimer’s disease (AD) (McKhann et al., 2011), the most common neurodegenerative cause of dementia, is characterized by progressive memory decline and pathologic accumulations of amyloid-β plaques and tau neurofibrillary tangles. Previous autopsy studies showed concomitant Lewy body (LB) pathology in approximately 40% of patients with AD (Hamilton, 2000, Leverenz et al., 2006) and frequent AD pathology in LB disease (LBD). (Walker et al., 2019) Further, clinical presentations of AD and LBD overlap. Cognitive fluctuation, (Escandon et al., 2010) rapid eye movement sleep behavior disorder (RBD), (Gagnon et al., 2006) and visual hallucination, (Sinclair et al., 2019) the core clinical features of dementia with LB (DLB), were frequently reported to occur in AD. Parkinsonism, such as rigidity, bradykinesia, and postural impairment, is also common in patients with AD, with the prevalence ranging from 12% to 92%. (Attems et al., 2007, Sasaki, 2018) Clinicopathological studies indicated that LB pathology was related to parkinsonism in patients with AD. (Attems et al., 2007, Burns et al., 2005, Hamilton, 2000)

Although reduced striatal dopamine transporter (DAT) uptakes on DAT PET are useful imaging biomarkers for Parkinson’s disease (PD), their sensitivities to diagnose DLB (McKeith et al., 2007) and AD with parkinsonism are suboptimal. (Chung et al., 2019) With improved high-resolution DAT PET, previous studies have shown that DAT uptake in the substantia nigra (SN) is reduced in early LBD including idiopathic RBD (Lee et al., 2019) and early PD. (Delva et al., 2020, Fazio et al., 2018) In addition, reduced DAT uptake has an inverse relationship with relative glucose hypermetabolism in the striatum of patients with DLB (Huber et al., 2020) and early PD. (Kim et al., 2022), suggesting that the identification of metabolic perturbations at early stages of dopaminergic dysfunction could serve as a potential biomarker of LBD for early diagnosis and monitoring disease severity. Considering that early-phase imaging with 18F-N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) PET is a potential substitute for metabolic PET (Jin et al., 2017) and that dual-phase FP-CIT PET has clear advantages over a combination of metabolic PET and delayed-phase FP-CIT PET in terms of radiation exposure, total cost, and time, combining early- and delayed-phase FP-CIT PET could provide information of use in identifying patients in early stages of LBD.

The aim of the present study was to examine the implication of DAT uptake and early-to-delayed DAT uptake ratios (E/Ds) on FP-CIT PET in the basal ganglia for AD patients with concomitant clinical features of LBD. We hypothesized that the SN DAT uptake and E/D ratio in the striatum have advantages over conventional striatal DAT uptake in differentiating AD patients with concomitant clinical features of LBD from normal controls (NCs) and in explaining the severities of cognitive dysfunction and parkinsonism. Our findings could provide a useful clinical clue to find concomitant LBD in patients with AD.