Hippocampal blood–brain barrier (BBB) permeability may increase in normal healthy ageing and contribute to neurodegenerative disease. To examine this hypothesis, we investigated the correlation between blood–brain barrier (BBB) permeability, regional brain volume, memory functions and health and lifestyle factors in The Metropolit 1953 Danish Male Birth Cohort. We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a gadolinium-based contrast agent to assess BBB permeability in 77 participants in the cohort. BBB permeability was measured as Ki values in the hippocampus, thalamus and white matter. Over a 10-year period, we observed progressive atrophy of both the left and right hippocampus (p = 0.001). There was no significant correlation between current BBB permeability and hippocampal volume, prior atrophy or cognition. The hippocampus volume ratio was associated with better visual and verbal memory scores (p < 0.01). Regional BBB differences revealed higher Ki values in the hippocampus and white matter than in the thalamus (p < 0.001). Participants diagnosed with type II diabetes had significantly higher BBB permeability in the white matter (p = 0.015) and thalamus (p = 0.016), which was associated with a higher Fazekas score (p = 0.024). We do not find evidence that BBB integrity is correlated with age-related hippocampal atrophy or cognitive functions. The association between diabetes, white matter hyperintensities and increased BBB permeability is consistent with the idea that cerebrovascular disease compromises BBB integrity. Our findings suggest that the hippocampus is particularly prone to age-related atrophy, which may explain some of the cognitive changes that accompany older age, but this prior atrophy is not correlated with current BBB permeability.

Reduced cerebrovascular response to neuronal activation is observed in patients with neurodegenerative disease. In the present study, we examined the correlation between reduced cerebrovascular response to visual activation (ΔCBFVis.Act) and subclinical cognitive deficits in a human population of mid-sixties individuals without neurodegenerative disease. Such a correlation would suggest that impaired cerebrovascular function occurs before overt neurodegenerative disease. A total of 187 subjects (age 64–67 years) of the Metropolit Danish Male Birth Cohort participated in the study. ΔCBFVis.Act was measured using arterial spin labelling (ASL) MRI. ΔCBFVis.Act correlated positively with cognitive performance in: Global cognition (p = 0.046), paired associative memory (p = 0.025), spatial recognition (p = 0.026), planning (p = 0.016), simple processing speed (p < 0.01), and with highly significant correlations with current intelligence (p < 10−5), and more complex processing speed (p < 10−3), the latter two explaining approximately 11–13% of the variance. Reduced ΔCBFVis.Act was independent of brain atrophy. Our findings suggest that inhibited cerebrovascular response to neuronal activation is an early deficit in the ageing brain and associated with subclinical cognitive deficits. Cerebrovascular dysfunction could be an early sign of a trajectory pointing towards the development of neurodegenerative disease. Future efforts should elucidate if maintenance of a healthy cerebrovascular function can protect against the development of dementia.