Longitudinal Cerebral Blood Flow Changes in Normal Aging and the Alzheimer's Disease Continuum Identified by Arterial Spin Labeling MRI

Abstract

Background: Cross-sectional studies have shown lower cerebral blood flow (CBF) in Alzheimer's disease (AD), but longitudinal CBF changes in AD are still unknown.

Objective: To reveal the longitudinal CBF changes in normal control (NC) and the AD continuum using arterial spin labeling perfusion magnetic resonance imaging (ASL MRI).

Methods: CBF was calculated from two longitudinal ASL scans acquired 2.22±1.43 years apart from 140 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). At the baseline scan, the cohort contained 41 NC, 74 mild cognitive impairment patients (MCI), and 25 AD patients. 21 NC converted into MCI and 17 MCI converted into AD at the follow-up. Longitudinal CBF changes were assessed using paired-t test for non-converters and converters separately at each voxel and in the meta-ROI. Age and sex were used as covariates.

Results: CBF reductions were observed in all subjects. Stable NC (n = 20) showed CBF reduction in the hippocampus and precuneus. Stable MCI patients (n = 57) showed spatially more extended CBF reduction patterns in hippocampus, middle temporal lobe, ventral striatum, prefrontal cortex, and cerebellum. NC-MCI converters showed CBF reduction in hippocampus and cerebellum and CBF increase in caudate. MCI-AD converters showed CBF reduction in hippocampus and prefrontal cortex. CBF changes were not related with longitudinal neurocognitive changes.

Conclusion: Normal aging and AD continuum showed common longitudinal CBF reductions in hippocampus independent of disease and its conversion. Disease conversion independent longitudinal CBF reductions escalated in MCI subjects.

Keywords: Aging; Alzheimer’s disease; arterial spin labeling; cerebral blood flow; longitudinal analysis.

Figure 1.

Voxel-wise statistical analysis results of the within-subject CBF changes in patients with no change of disease status at both assessed time points. CBF changes were marked with the red clusters. Figure 1-A is the longitudinal CBF reductions in the 20 non-converter NC subjects; significant CBF reduction was found in the left and right hippocampus and left fusiform gyrus. Figure 1-B shows the longitudinal CBF reductions in the 57 non-converter MCI patients; significant reduction of CBF was found on left and right hippocampus, left and right cerebellum, basal ganglia, and left fusiform gyrus. The number underneath each image slice indicate the slice location in the MNI standard brain space.

Figure 2:

Voxel-wise statistical analysis results for the converter groups. Figure 2-A shows the CBF change patterns in the 21 NC to MCI converters; significant reduction of the CBF was found on the left and right hippocampus, right cerebellum, and an increase in CBF in the right putamen and right caudate nucleus. Figure 2-B shows the CBF change patterns for 17 MCI to AD converters; significant CBF reduction was found in the right hippocampus and right superior orbital gyrus. The number underneath each image slice indicate the slice location in the MNI standard brain space.