Disrupted Regional Cerebral Blood Flow, Functional Activity and Connectivity in Alzheimer’s Disease: A Combined ASL Perfusion and Resting State fMRI Study

Abstract

Recent studies have demonstrated a close relationship between regional cerebral blood flow (rCBF) and resting state functional connectivity changes in normal healthy people. However, little is known about the parameter changes in the most vulnerable regions in Alzheimer’s disease (AD). Forty AD patients and 30 healthy controls participated in this study. The data of resting-state perfusion and functional magnetic resonance imaging (fMRI) was collected. By using voxel-wise arterial spin labeling (ASL) perfusion, we identified several regions of altered rCBF in AD patients. Then, by using resting state fMRI analysis, including amplitude low frequency fluctuation (ALFF) and seed-based functional connectivity, we investigated the changes of functional activity and connectivity among the identified rCBF regions. We extracted cognition-related parameters and searched for a sensitive biomarker to differentiate the AD patients from the normal controls (NC). Compared with controls, AD patients showed special disruptions in rCBF, which were mainly located in the left posterior cingulate cortex (PCC), the left and right dorsolateral prefrontal cortex (DLPFC), the left inferior parietal lobule (IPL), the right middle temporal gyrus (MTG), the left middle occipital gyrus (MOG), and the left precuneus (PCu). ALFF was performed based on the seven regions identified by the ASL method, and AD patients presented significantly decreased ALFF in the left PCC, left IPL, right MTG, left MOG, and left PCu and increased ALFF in the bilateral DLPFC. We constituted the network based on the seven regions and found that there was decreased connectivity among the identified regions in the AD patients, which predicted a disruption in the default mode network (DMN), executive control network (ECN) and visual network (VN). Furthermore, these abnormal parameters are closely associated with cognitive performances in AD patients. We combined the rCBF and ALFF value of PCC/PCu as a biomarker to differentiate the two groups and reached a sensitivity of 85.3% and a specificity of 88.5%. Our findings suggested that there was disrupted rCBF, functional activity and connectivity in specific cognition-related regions in Alzheimer’s disease, which can be used as a valuable imaging biomarker for the diagnosis of AD.

Functional MRI-Specific Alterations in Executive Control Network in Mild Cognitive Impairment: An ALE Meta-Analysis

“…ECN plays an important role in the integration of sensory and memory information, the regulation of cognition and behavior, and the working memory process with the prefrontal lobe as its core (Petersen et al, 2019). A combined arterial spin labeling (ASL), perfusion, and rsfMRI study confirms that the brain regions in AD where cerebral blood flow and ALFF decrease predict a disruption in the ECN (Zheng et al, 2019). However, the lack of consistent results for specific alterations in ECN fail to provide specific imaging markers in predicting the transition from MCI to AD.…”

High-Frequency Repetitive Transcranial Magnetic Stimulation Could Improve Impaired Working Memory Induced by Sleep Deprivation

“…Fourth, in this study, ALFF was employed to estimate the spontaneous activity changes induced by SD and rTMS. The ALFF approach showed higher sensitivity and specificity in detecting spontaneous brain activity and distinguishes some diseases from the normal control than the other fMRI indices [60,61]. However, network analysis including functional connectivity and effective functional connectivity analysis could better reflect the path of modulation of rTMS on working memory.…”

A Neurovisceral Integrative Study on Cognition, Heart Rate Variability, and Fitness in the Elderly

“…Jandackova et al (2016) showed a marked decline in HRV in middle-aged individuals which seems to be secondary to other pathological conditions. Cognitive dementia is the result of multiple age-related neuropathies (Power et al, 2018) associated with cardiovascular risk factors (Oishi et al, 2017), such as chronic brain hypoperfusion (Zheng et al, 2019), which particularly affects the frontal cortex (Sherwood et al, 2011).…”