Changes in hippocampal volume during a preceding 10-year period do not correlate with cognitive performance and hippocampal blood‒brain barrier permeability in cognitively normal late-middle-aged men

Abstract

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.

Blood–Brain Barrier Disruption and Perivascular Spaces in Small Vessel Disease and Neurodegenerative Diseases: A Review on MRI Methods and Insights

“…74 Contrarily, hippocampal BBB leakage did not relate to hippocampal volume in a memory clinic sample 84 and hippocampal atrophy during a 10-year period in a birth cohort. 85 These studies also did not find a relation between hippocampal BBB leakage and cognition. 84,85 Similar negative results were obtained by Moon et al, who found no difference in hippocampal leakage rate between MCI patients and controls, while they did find a higher leakage rate in the caudate nucleus of the MCI group.…”

“…85 These studies also did not find a relation between hippocampal BBB leakage and cognition. 84,85 Similar negative results were obtained by Moon et al, who found no difference in hippocampal leakage rate between MCI patients and controls, while they did find a higher leakage rate in the caudate nucleus of the MCI group. 83 The water transport across the BBB is also thought to be affected in the pathophysiological processes in AD.…”

“…Hippocampal BBB breakdown was also demonstrated in APOE‐ε4 carriers, 74,83 but no relation was found between the BBB leakage rate in the hippocampus and CSF or PET‐derived Aβ or tau concentrations 74 . Contrarily, hippocampal BBB leakage did not relate to hippocampal volume in a memory clinic sample 84 and hippocampal atrophy during a 10‐year period in a birth cohort 85 . These studies also did not find a relation between hippocampal BBB leakage and cognition 84,85 .…”

Early cerebral amyloid-β accumulation and hypermetabolism are associated with subtle cognitive deficits before accelerated cerebral atrophy

“…These longitudinal assessments make the cohort optimal for assessing age-related changes in brain function from a life course perspective. From the same subset of participants, we have previously found that compromised blood–brain barrier permeability is associated with increased vascular risk factors [ 19 ] and associations between cognitive dysfunction and electrophysiological changes [ 20 ]. Previously published work on the cohort has also reported associations between cognitive dysfunction and cerebrovascular functions [ 21 ].…”

Imaging the neurovascular unit in health and neurodegeneration: a scoping review of interdependencies between MRI measures

“…In this sample, BBB permeability was positively correlated with mean free water levels. Regarding literature investigating WMH, studies generally suggested a positive relationship between BBB permeability and WMH [105][106][107][108][109][110]. One longitudinal study showed that increased BBB permeability preceded some WMH lesions [111].…”