Blood–brain barrier (BBB) disruption, modulated by APOE4 mutation, is implicated in the pathogenesis of cognitive decline. We determined whether BBB permeability differed according to cognitive functioning and APOE4 status in elderly subjects without dementia. In this prospective study, 33 subjects with mild cognitive impairment (MCI) and 33 age-matched controls (normal cognition [NC]) underwent 3 T brain magnetic resonance imaging. The Patlak model was used to calculate tissue permeability (Ktrans). A region-of interest analysis of Ktrans was performed to compare relevant brain regions. Effects of Ktrans on cognitive functioning were evaluated with linear regression analysis adjusted for confounding factors. NC and MCI groups did not differ in terms of vascular risk factors or hippocampal Ktrans, except for hippocampal volume. Hippocampal Ktrans was significantly higher in APOE4 carriers than in non-carriers ( p = 0.007). Factors which predicted cognitive functioning included hippocampal volume (beta=−0.445, standard error [SE]=0.137, p = 0.003) and hippocampal BBB permeability (beta = 0.142, SE = 0.050, p = 0.008) after correcting for age, education, and APOE4 status. This suggests that hippocampal BBB permeability is associated with APOE4 mutation, and may predict cognitive functioning. BBB permeability imaging represents a distinct imaging biomarker for APOE4 mutations in NC and MCI subjects and for determining the degree of APOE4-related pathology.
The role of the blood–brain barrier (BBB) breakdown has been recognized as being important in Alzheimer’s disease pathogenesis. We aimed to evaluate whether regional BBB integrity differed according to sex and whether differences in BBB integrity changed as a consequence of aging or cognitive decline, using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI). In total, 75 participants with normal cognition (NC) or mild cognitive impairment (MCI) underwent cognitive assessments and MRI examination including DCE-MRI. Regional Ktrans was calculated in cortical regions and the Patlak permeability model was used to calculate BBB permeability (Ktrans, min−1). Females had a lower median Ktrans in the cingulate and occipital cortices. In the “older old” group, sex differences in Ktrans were only observed in the occipital cortex. In the MCI group, sex differences in Ktrans were only observed in the occipital cortex. Age was the only predictor of cognitive assessment scores in the male MCI group; however, educational years and Ktrans in the occipital cortex could predict cognitive scores in the female MCI group. Our study revealed that females may have better BBB integrity in cingulate and occipital cortices. We also found that sex-related differences in BBB integrity are attenuated with aging or cognitive decline.
Objective This study aimed to determine whether there are regional differences in the blood-brain barrier (BBB) permeability of cognitively normal elderly participants and to identify factors influencing BBB permeability with a clinically feasible, 10-minute dynamic contrast-enhanced (DCE) MRI protocol. Materials and Methods This IRB-approved prospective study recruited 35 cognitively normal adults (26 women; mean age, 64.5 ± 5.6 years) who underwent DCE T1-weighted imaging. Permeability maps (K trans ) were coregistered with masks to calculate the mean regional values. The paired t test and Friedman test were used to compare Ktrans between different regions. The relationships between K trans and the factors of age, sex, education, cognition score, vascular risk burden, vascular factors on imaging, and medial temporal lobar atrophy were assessed using Pearson correlation and the Spearman rank test. Results The mean permeability rates of the right and left hippocampi, as assessed with automatic segmentation, were 0.529 ± 0.472 and 0.585 ± 0.515 (K trans , × 10 −3 min −1 ), respectively. Concerning the deep gray matter, the K trans of the thalamus was significantly greater than those of the putamen and hippocampus ( p = 0.007, p = 0.041). Regarding the white matter, the K trans value of the occipital white matter was significantly greater than those of the frontal, cingulate, and temporal white matter ( p < 0.0001, p = 0.0007, p = 0.0002). The variations in K trans across brain regions were not related to age, cognitive score, vascular risk burden, vascular risk factors on imaging, or medial temporal lobar atrophy in the study group. Conclusion Our study demonstrated regional differences in BBB permeability (K trans ) in cognitively normal elderly adults using a clinically acceptable 10-minutes DCE imaging protocol. The regional differences suggest that the integrity of the BBB varies across the brains of cognitively normal elderly adults. We recommend considering regional differences in K trans values when evaluating BBB permeability in patients with neurodegenerative diseases.
Background Recent advances in rapid imaging techniques necessitate the reconsideration of the optimal imaging delay time for contrast-enhanced T1-weighted imaging. The aim of our study was to determine the optimal contrast-enhanced T1-weighted imaging delay time from the obtained time-signal intensity curve (TIC) using gadobutrol in patients with brain metastases, primary brain tumors, and meningiomas. Methods This prospective study enrolled 78 patients with brain metastases (n = 39), primary brain tumors (n = 22), or meningiomas (n = 17) who underwent 7-min dynamic contrast-enhanced imaging with single-dose gadobutrol. Based on the time-to-peak (TTP) derived from the TIC, we selected four different time points for analysis. Lesion conspicuity, enhanced rate (ER) and contrast rate (CR) of 116 index lesions were evaluated. Statistical comparisons were made for the four different time points using the Friedman test. Results Maximum TTP (305.20 ± 63.47 s) was similar across all three groups (p = 0.342). Lesion conspicuity, CR and ER increased over time in all index lesions; however, no significant difference between the 5- and 7-min images was observed. The longest diameter in all groups differed significantly among time points (p < 0.001); the perpendicular diameter did not differ between the 5- and 7-min images. Conclusions Maximum contrast enhancement and lesion conspicuity was achieved 5–7 min after a single gadobutrol injection for brain metastases detection and for primary brain tumor/meningioma evaluation. Acquiring images 5 min after gadobutrol injection is the optimal timing for brain tumor detection during MRI work-up.
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