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by claude@2026-07, 2026-07-04
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This paper used diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI in 186 cognitively normal participants aged 8 to 92 years to measure age- and sex-dependent trajectories of blood-brain barrier function via BBB water exchange rate (kw) and perfusion across brain regions. The authors found that BBB kw declines with aging in a region-specific pattern, with a decline beginning in the early 60s and being more pronounced in males, alongside observed sex differences particularly in parietal and temporal regions. A key caveat noted is that the work is observational and provides in vivo associations in healthy participants, framed as a foundation for future investigations rather than testing downstream clinical outcomes. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders. Significance statement The blood-brain barrier (BBB) serves as a critical protection mechanism for the CNS. A natural decline of BBB function with aging has been reported in both animal and human studies, with possible differences in BBB function by sex. Using our MRI technique, DP-pCASL that measures water exchange rate (kw) without contrast in 186 participants from diverse race and age groups, we identified age and sex-specific patterns in BBB kw especially in parietal and temporal regions. We observed of a decline in kw beginning in the early 60s, especially in males. Our study unveils the dynamic spatiotemporal pattern of kw differences with age and sex, which serve as a foundation for understanding aberrations of BBB function in neurodegenerative and other brain disorders.
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Abstract
The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.
Significance statement The blood-brain barrier (BBB) serves as a critical protection mechanism for the CNS. A natural decline of BBB function with aging has been reported in both animal and human studies, with possible differences in BBB function by sex. Using our MRI technique, DP-pCASL that measures water exchange rate (kw) without contrast in 186 participants from diverse race and age groups, we identified age and sex-specific patterns in BBB kw especially in parietal and temporal regions. We observed of a decline in kw beginning in the early 60s, especially in males. Our study unveils the dynamic spatiotemporal pattern of kw differences with age and sex, which serve as a foundation for understanding aberrations of BBB function in neurodegenerative and other brain disorders.
- Blood-brain barrier
- Ageing
- Sex difference
- Arterial spin labeling
- Water exchange rate
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
This revision is in accordance with our revised submission to eLife journal: https://elifesciences.org/reviewed-preprints/96155
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