Relationship between nucleus basalis of Meynert resting state functional connectivity and brain 18F-FDG metabolism in Alzheimer’s disease: a hybrid PET/MR study

1529 Objectives: The nucleus basalis of Meynert (NbM), primary cholinergic source of neurons, is hypothesized to be the origin of Alzheimer’s disease (AD) pathology. The impact of functional nucleus basalis of Meynert (NbM) of NBM mechanisms in AD remains to be identified. Clarifying the role of in vivo 18F-FDG metabolism in relation to cholinergic functional connectivity is crucial to understand the pathophysiologic link between 18F-FDG metabolism and cholinergic dysfunction in the stages of AD. The objective of the study was to determine whether in vivo 18F-FDG metabolism is associated with cholinergic functional connectivity in patients with AD. Methods: This retrospective study was approved by the local ethics committee and written informed consent was obtained from all participants. Twenty-one participants of AD and 42 older normal cognitively (NC) were scanned with a GE Signa PET/MRI scanner with time-of-flight. Resting-state functional connectivity (RSFC) of NBM seed was investigated using DPARSF toolbox based on SPM12. Brain glucose metabolism was measured by 10-min (40-50 min post tracer injection) 18F-FDG PET. Standardized uptake value ratio (SUVR) relative to cerebellum was generated from partial volume corrected FDG PET. The NbM networks were calculated both in AD and NC groups. Two sample t test was used to compare the group difference between AD and NC group with age, gender and education level as covariates. The relationships between SUVR and the SUVR of altered NbM RSFC regions were assessed. Results: Visual inspection revealed that NbM network was diminished in AD group compared with the NC group (Figure 1). The AD group showed reduced functional connectivity to the NbM include thalamus and putamen, and increased connectivity include precentral, postcentral and middle temporal (voxels level with P < 0.001, cluster level with P < 0.05, GRF corrected). Moreover, in AD group, glucose metabolism was reduced in the thalamus while unchanged in the NbM and putamen. The glucose metabolism of NbM was positively associated with putamen and thalamus in AD group, while not in NC group (Figure 2). Conclusions: Data indicate a distinct in vivo association between NbM functional connectivity and 18F-FDG metabolism in AD. The unreduced glucose metabolism in basal forebrain and putamen, as well as their positive association in AD patients consistent with a secondary compensation against functional connectivity at target areas, and may provide brain reserve against functional impairments. Hybrid 18F-FDG PET/MR provided imaging data in the same physiological state to better understand basal forebrain network. Figure 1. Nucleus basalis of Meynert functional connectivity network map in the NC (A) and AD (B) groups. Visual inspection reveals that NbM network was diminished in AD group compared with the NC group. Voxels level with P < 0.01 and cluster level with P < 0.05 with GRF correction.Figure 2. Relationships between nucleus basalis of Meynert 18F-FDG PET SUVR and the SUVR of altered NbM functional connectivity (FC) regions in AD subjects. Regions that had decreased FC to the NbM include thalamus and putamen in the AD group (A, cool color), and increased FC include middle temporal and precentral (B, hot color). NbM SUVR was positively associated with putamen (C) and thalamus (D) in AD group rather than NC group. The SUVR was reduced in the thalamus while unchanged in the NbM and putamen (E).