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. 2021 Feb 24:13:625511.
doi: 10.3389/fnagi.2021.625511. eCollection 2021.

Blood Hemoglobin, in-vivo Alzheimer Pathologies, and Cognitive Impairment: A Cross-Sectional Study

Jee Wook Kim  1   2 , Min Soo Byun  3 , Dahyun Yi  4 , Jun Ho Lee  5 , So Yeon Jeon  6 , Kang Ko  5 , Haejung Joung  7 , Gijung Jung  7 , Jun-Young Lee  8 , Chul-Ho Sohn  9 , Yun-Sang Lee  10 , Yu Kyeong Kim  11 , Dong Young Lee  3   7   12
Affiliations

Blood Hemoglobin, in-vivo Alzheimer Pathologies, and Cognitive Impairment: A Cross-Sectional Study

Jee Wook Kim et al. Front Aging Neurosci. .

Abstract

Background: Despite known associations between low blood hemoglobin level and Alzheimer's disease (AD) or cognitive impairment, the underlying neuropathological links are poorly understood. We aimed to examine the relationships of blood hemoglobin levels with in vivo AD pathologies (i.e., cerebral beta-amyloid [Aβ] deposition, tau deposition, and AD-signature degeneration) and white matter hyperintensities (WMHs), which are a measure of cerebrovascular injury. We also investigated the association between hemoglobin level and cognitive performance, and then assessed whether such an association is mediated by brain pathologies. Methods: A total of 428 non-demented older adults underwent comprehensive clinical assessments, hemoglobin level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Episodic memory score and global cognition scores were also measured. Results: A lower hemoglobin level was significantly associated with reduced AD-signature cerebral glucose metabolism (AD-CM), but not Aβ deposition, tau deposition, or WMH volume. A lower hemoglobin level was also significantly associated with poorer episodic memory and global cognition scores, but such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a moderating effect. Conclusion: The present findings suggest that low blood hemoglobin in older adults is associated with cognitive decline via reduced brain metabolism, which seems to be independent of those aspects of AD-specific protein pathologies and cerebrovascular injury that are reflected in PET and MRI measures.

Keywords: Alzheimer's disease; anemia; cerebral hypometabolism; cognitive impairment; hemoglobin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Partial regression plot showing the relationship between hemoglobin level and AD-signature cerebral glucose metabolism (AD-CM) in (A) non-demented and (B) cognitive normal older participants. Multiple linear regression analyses were performed after adjusting for age and sex.
Figure 2
Figure 2
Error bar charts displaying AD-signature cerebral glucose metabolism and stratified hemoglobin level in (A) non-demented and (B) cognitive normal older participants. Error bars indicate standard error. Multiple linear regression analyses were performed after adjusting for age and sex.
Figure 3
Figure 3
Error bar charts displaying (A) episodic memory score (EMS) and (B) CERAD total score (TS) according to stratified hemoglobin levels in non-demented older participants. Error bars indicate standard error.
See this image and copyright information in PMC

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