Cerebral Perfusion Insufficiency and Relationships with Cognitive Deficits in Alzheimer\u2019s Disease: A Multiparametric Neuroimaging Study

Chi-Wei Huang,Chun-Chung Lui,Chen-Chang Lee,Yung-Cheng Huang,Wen-Neng Chang,Na-Ching Chen,Ya-Ting Chang,Shu-Hua Huang,Chiung-Chih Chang,Shih-Wei Hsu

doi:10.1038/s41598-018-19387-x

Abstract

Micro- or macro-circulatory insufficiency has a negative impact in patients with Alzheimer’s disease (AD). This study used arterial spin-labeled magnetic resonance imaging (ASL-MRI) and ethylcysteinate dimer single-photon emission computed tomography (ECD-SPECT) in 50 patients with AD and 30 age-matched controls to investigate how hypoperfusion patterns were associated with gray matter atrophy and clinical data. All participants completed 3DT1-MRI, ECD-SPECT and ASL-MRI examinations. Medial temporal cortex (MTC) volumes were correlated with regional signals showing significantly lower relative cerebral blood flow (rCBF) in ASL-MRI or perfusion index (PI) in ECD-SPECT. Neurobehavioral scores served as the outcome measures. Regions with lower PI showed spatial similarities with atrophy in the medial, anterior and superior temporal lobes, posterior cingulate cortex and angular gyrus, while regions showing lower rCBF were localized to the distal branches of posterior cerebral artery territories (posterior parietal and inferior temporal lobe) and watershed areas (angular gyrus, precuneus, posterior cingulate gyrus and middle frontal cortex). rCBF values in watershed areas correlated with MTC volumes and language composite scores. Precuneus and angular gyrus hypoperfusion were associated with the corresponding cortical atrophy. Macro- or micro-vasculature perfusion integrities and cortical atrophy determined the overall perfusion imaging topography and contributed differently to the clinical outcomes.

Highlights

Arterial spin labeling-magnetic resonance imaging (ASL-MRI)[5] and ethyl cysteinate dimer single-photon emission computed tomography (ECD-SPECT)[6] both measure cerebral perfusion
One theory supports upstream hippocampal atrophy and downstream posterior parietal cortical hypoperfusion[17], whereas another postulates that vascular damage and reduced perfusion in the parietal association cortex, posterior cingulate cortex (PCC) and precuneus lead to the initiation and aggravation of Alzheimer’s disease (AD) pathology in the MTC18
We evaluated the relationships between regional perfusion index (PI) and their corresponding gray matter (GM) volume by simple Pearson’s correlation, followed by multivariate linear regression analysis to test the independent effect of PI

Summary

Introduction

Arterial spin labeling-magnetic resonance imaging (ASL-MRI)[5] and ethyl cysteinate dimer single-photon emission computed tomography (ECD-SPECT)[6] both measure cerebral perfusion. A recent report suggested that the default mode network may be comprised of multiple, spatially dissociated but interactive components, of which two subsystems are relevant: the “medial temporal lobe subsystem”, and the “dorsal medial prefrontal cortex subsystem” (or the midline core subsystem)[10]. Both PCC and precuneus areas have been reported to represent important cortical hubs of the midline core subsystem[11]. The metabolic changes of default mode network and medial temporal atrophy are well known, multi-parametric modalities using ECD-SPECT and ASL-MRI with structural comparisons to delineate the top-down modulation theory in patients with AD are still lacking. The impact of reduced CBF and cognitive scores were used to validate the clinical significance of vascular risk factors

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Conclusion