Cerebral Blood Flow is an Earlier Indicator of Perfusion Abnormalities than Cerebral Blood Volume in Alzheimer's Disease

Abstract

The purpose of this study was to elucidate whether cerebral blood flow (CBF) can better characterize perfusion abnormalities in predementia stages of Alzheimer's disease (AD) than cerebral blood volume (CBV) and whether cortical atrophy is more associated with decreased CBV or with decreased CBF. We compared measurements of CBV, CBF, and mean cortical thickness obtained from magnetic resonance images in a group of healthy controls, patients with mild cognitive impairment (MCI) who converted to AD after 2 years of clinical follow-up (MCI-c), and patients with mild AD. A significant decrease in perfusion was detected in the parietal lobes of the MCI-c patients with CBF parametric maps but not with CBV maps. In the MCI-c group, a negative correlation between CBF values and cortical thickness in the right parahippocampal gyrus suggests an increase in CBF that depends on cortical atrophy in predementia stages of AD. Our study also suggests that CBF deficits appear before CBV deficits in the progression of AD, as CBV abnormalities were only detected at the AD stage, whereas CBF changes were already detected in the MCI stage. These results confirm the hypothesis that CBF is a more sensitive parameter than CBV for perfusion abnormalities in MCI-c patients.

Divergent regional patterns of cerebral hypoperfusion and gray matter atrophy in mild cognitive impairment patients

“…Both blood flow and volume abnormalities were previously found in AD converters, 11,49 highlighting their mutual sensitivity to pathogenic mechanisms. However, rCBF may be more affected by early ADrelated pathological mechanisms than rCBV.…”

“…6,8,9 By contrast, gray matter atrophy is predominant in medial-temporal regions. [10][11][12] Hence, there appears to be an early dissociation between temporo-parietal hypoperfusion and medial-temporal atrophy. 13 Yet, the possibility that magnetic resonance imaging (MRI)-based biomarkers of gray matter structure and cerebral perfusion may provide complementary information in early disease detection remains unclear.…”

“…15 The DSC-MRI relies on the passage of a gadoliniumbased contrast agent injected intravenously that will flow through the brain vasculature. Applied to MCI patients, a previous study reported changes in CBF prior to CBV in AD progression, 11 proposing the former as a more sensitive indicator of perfusion abnormalities.…”

“…The AD-related regions-of-interest (ROIs) were selected based on previous neuroimaging studies using amyloid, metabolic, structural, and perfusion biomarkers. 11,[16][17][18] The MRI-based measures were extracted in the ROIs and compared between MCI patients and healthy control (HC) older adults. Specifically, our first aim was to assess divergence and convergence of regional patterns of hypoperfusion and gray matter atrophy in AD-related regions.…”

Development and validation of an open source quantification tool for DSC-MRI studies

“…The correct quantification of these parameters has several clinical applications, such as detection and assessment of ischemic stroke prior to treatment [3], characterization of multiple sclerosis lesions [7], tumor diagnosis [1,13,4,12,9,6] or as indicators on the progress of Alzheimer's disease [8]. As this technique is also widely used in preclinical studies [20,25,26,15], it is therefore interesting to have a tool that performs the quantification process in a fast and reliable way for research purposes.…”