Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021;81(4):1727-1735.
doi: 10.3233/JAD-210116.

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

Aldo Camargo  1   2 , Ze Wang  1 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

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

Aldo Camargo et al. J Alzheimers Dis. 2021.

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.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST/DISCLOSURE STATEMENT

The authors have no conflict of interest to report.

Figures

Figure 1.
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:
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.
See this image and copyright information in PMC

References

    1. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH (2011) Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7, 280–292. - PMC - PubMed
    1. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors (2018) NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14, 535–562. - PMC - PubMed
    1. Alsop DC, Detre JA, Grossman M (2000) Assessment of cerebral blood flow in Alzheimer’s disease by spin-labeled magnetic resonance imaging. Ann Neurol 47, 93–100. - PubMed
    1. Wolk DA, Detre JA (2012) Arterial spin labeling MRI: an emerging biomarker for Alzheimer’s disease and other neurodegenerative conditions. Curr Opin Neurol 25, 421–428. - PMC - PubMed
    1. Zlokovic BV, Deane R, Sallstrom J, Chow N, Miano JM (2005) Neurovascular pathways and Alzheimer amyloid beta-peptide. Brain Pathol 15, 78–83. - PMC - PubMed

Publication types

LinkOut - more resources