J Clin Neurol.
2023 Mar;19(2):131-137. 10.3988/jcn.2022.0088.
Hypoperfusion Precedes Tau Deposition in the Entorhinal Cortex: A Retrospective Evaluation of ADNI-2 Data
- Kapadia A
1,2 - Billimoria K3
- Desai P4
- Grist JT5,6,7,8
- Heyn C1,2
- Maralani P1,2
- Symons S1,2
- Zaccagna F1
- Affiliations
-
- 1Division of Neuroradiology, Department of Medical Imaging, University of Toronto, Toronto, ON, Canada
- 2Division of Neuroradiology, Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- 3MD Program, Temetry Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- 4Department of Medicine, Maharaja Sayajirao University of Baroda, Vadodara, India
- 5Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK
- 6Oxford Centre for Clinical Magnetic Reso- nance Research, University of Oxford, Oxford, UK
- 7Department of Radiology, Oxford University Hospitals Trust, Oxford, UK
- 8Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
- KMID: 2539610
- DOI: http://doi.org/10.3988/jcn.2022.0088
Abstract
- Background and Purpose
Tau deposition in the entorhinal cortex is the earliest pathological feature of Alzheimer’s disease (AD). However, this feature has also been observed in cognitively normal (CN) individuals and those with mild cognitive impairment (MCI). The precise pathophysiology for the development of tau deposition remains unclear. We hypothesized that reduced cerebral perfusion is associated with the development of tau deposition.
Methods
A subset of the Alzheimer’s Disease Neuroimaging Initiative data set was utilized. Included patients had undergone arterial spin labeling perfusion MRI along with [18F]flortaucipir tau PET at baseline, within 1 year of the MRI, and a follow-up at 6 years. The association between baseline cerebral blood flow (CBF) and the baseline and 6-year tau PET was assessed. Univariate and multivariate linear modeling was performed, with p<0.05 indicating significance.
Results
Significant differences were found in the CBF between patients with AD and MCI, and CN individuals in the left entorhinal cortex (p=0.013), but not in the right entorhinal cortex (p=0.076). The difference in maximum standardized uptake value ratio between 6 years and baseline was significantly and inversely associated with the baseline mean CBF (p=0.042, R2=0.54) in the left entorhinal cortex but not the right entorhinal cortex. Linear modeling demonstrated that CBF predicted 6-year tau deposition (p=0.015, R2=0.11).
Conclusions
The results of this study suggest that a reduction in CBF at the entorhinal cortex precedes tau deposition. Further work is needed to understand the mechanism underlying tau deposition in aging and disease.
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