Year: 2013
Type: article
Study design: Observational Study
Abstract: Substantial work in preclinical Alzheimer's disease (AD) has been focused on understanding the relationships between amyloid, cognition, atrophy and neural activity; however, there have been limited investigations of cerebral blood flow (CBF) to date. Recently, CBF, as measured with pulsed arterial spinning labeling (pASL), has been shown to be a reliable marker of blood flow in cognitively normal older adults (CN) and may have potential as an early AD biomarker. The objective of the present study is to assess the effect of amyloid burden, APOE ε4 carrier status and age on CBF using pASL. 84 CN participants (CDR=0) in the Harvard Aging Brain Study had a pASL scan that passed quality control, a PiB-PET scan, and APOE genotyping. pASL images were motion corrected and entered into the UPenn ASL Toolbox to compute CBF maps. The CBF maps were then normalized to MNI space and additionally smoothed (Fig1). Mean cortical (mc) DVR PiB values were obtained from the PiB-PET scans. Regional CBF from fcMRI networks derived using a factor analysis were analyzed with general linear models with PiB status (mcPiB+ defined as mcPiB>1.4), APOE genotype (ε 3/ε 3 vs ε 3/ε 4), age and their interactions as predictors. Forward and backward model selection methods were used to select the final model for each region. Amyloid positive CN had significantly higher CBF in the DMN (p=0.0315, Fig2), lateral visual network (p=0.045), medial visual network (p=0.011), and dorsal attention network (p=0.002). Significant decreases with age were found in the both visual networks (p<0.001) and the dorsal attention network (p=0.002). Interestingly, we found that ε 4 carriers had greater age-related decreases in the DMN (p=0.008, Fig3) and association network (p=0.007). Consistent with reports from longitudinal studies, we found that amyloid burden is associated with increased cerebral blood flow cross-sectionally in our sample. The amyloid-related increases might represent the brains response to initial stages of neuronal damage. Furthermore, the increased age-related decline in ε4 carriers extends previous work comparing young and old ε 4 carriers. These results support the potential of CBF as a biomarker to detect early functional change in the DMN, specifically related to amyloid deposition.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2064503749