Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 41, Issue 5, Pages 1001-1012Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X20935171
Keywords
Alzheimer's disease; cerebral blood flow; early detection; mild cognitive impairment; subtle cognitive decline
Categories
Funding
- U.S. Department of Veterans Affairs Clinical Sciences Research and Development Service [2 1IK2CX001865, 1IK2CX000938, 1IK2CX001415, 1I01CX001842, 5I01CX000565]
- NIH [R01 AG049810, R01 AG054049]
- Alzheimer's Association [AARF-17-528918, AARG-18-566254, AARG-17-500358]
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-20012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
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The study examined patterns of regional cerebral blood flow across different stages of Alzheimer's disease, revealing increased blood flow in specific brain regions in participants with subtle cognitive decline, potentially reflecting early neurovascular dysregulation and cognitive inefficiencies.
Although cerebral blood flow (CBF) alterations are associated with Alzheimer's disease (AD), CBF patterns across prodromal stages of AD remain unclear. Therefore, we investigated patterns of regional CBF in 162 Alzheimer's Disease Neuroimaging Initiative participants characterized as cognitively unimpaired (CU;n = 80), objectively-defined subtle cognitive decline (Obj-SCD;n = 31), or mild cognitive impairment (MCI;n = 51). Arterial spin labeling MRI quantified regional CBF in a priori regions of interest: hippocampus, inferior temporal gyrus, inferior parietal lobe, medial orbitofrontal cortex, and rostral middle frontal gyrus. Obj-SCD participants had increased hippocampal and inferior parietal CBF relative to CU and MCI participants and increased inferior temporal CBF relative to MCI participants. CU and MCI groups did not differ in hippocampal or inferior parietal CBF, but CU participants had increased inferior temporal CBF relative to MCI participants. There were no CBF group differences in the two frontal regions. Thus, we found an inverted-U pattern of CBF signal across prodromal AD stages in regions susceptible to early AD pathology. Hippocampal and inferior parietal hyperperfusion in Obj-SCD may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain cognitive functioning relative to MCI participants, yet is also reflective of early cognitive inefficiencies that distinguish Obj-SCD from CU participants.
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