Spatiotemporal Characteristics of Regional Brain Perfusion Associated with Neuropsychiatric Symptoms in Patients with Alzheimer's Disease

Background: Current technology for exploring neuroimaging markers and neural circuits of neuropsychiatric symptoms (NPS) in patients with Alzheimer's disease (AD) is expensive and usually invasive, limiting its use in clinical practice. Objective: To investigate the cerebral morphology and perfusion characteristics of NPS and identify the spatiotemporal perfusion circuits of NPS sub-symptoms. Methods: This nested case-control study included 102 AD patients with NPS and 51 age- and sex-matched AD patients without NPS. Gray matter volume, cerebral blood flow (CBF), and arterial transit time (ATT) were measured and generated using time-encoded 7-delay pseudo-continuous arterial spin labeling (pCASL). Multiple conditional logistic regression analysis was used to identify neuroimaging markers of NPS. The associations between the CBF or ATT of affected brain areas and NPS sub-symptoms were evaluated after adjusting for confounding factors. The neural circuits of sub-symptoms were identified based on spatiotemporal perfusion sequencing. Results: Lower Mini-Mental State Examination scores (p < 0.001), higher Caregiver Burden Inventory scores (p < 0.001), and higher CBF (p = 0.001) andATT values (p < 0.003) of the right anteroventral thalamic nucleus (ATN) were risk factors for NPS in patients with AD. Six spatiotemporal perfusion circuits were found from 12 sub-symptoms, including the anterior cingulate gyri-temporal pole/subcortical thalamus-cerebellum circuit, insula-limbic-cortex circuit, subcortical thalamus-temporal polecortex circuit, subcortical thalamus-cerebellum circuit, frontal cortex-cerebellum-occipital cortex circuit, and subcortical thalamus-hippocampus-dorsal raphe nucleus circuit. Conclusions: Prolonged ATT and increased CBF of the right ATN may be neuroimaging markers for detecting NPS in patients with AD. Time-encoded pCASL could be a reliable technique to explore the neural perfusional circuits of NPS.