Researchers finds a link between blood supply to the hippocampus and cognitive performance


Memory performance and other cognitive abilities benefit from a good blood supply to the brain.

This applies in particular to people affected by a condition known as “sporadic cerebral small vessel disease”.

Researchers of the German Center for Neurodegenerative Diseases (DZNE) and the University Medicine Magdeburg report on this in the journal “BRAIN”. 

Their study suggests that blood perfusion of the so-called hippocampus could play a key role in age- and disease-related memory problems.

Inside the human brain there is a small structure, just a few cubic centimeters in size, which is called the “hippocampus” because its shape resembles a seahorse. Strictly speaking, the hippocampus exists twice: once in each brain hemisphere.

It is considered the control center of memory. Damage to the hippocampus, such as it occurs in Alzheimer’s and other brain diseases, is known to impair memory. But what role does blood supply in particular play?

A team of scientists headed by Prof. Stefanie Schreiber and Prof. Emrah Duezel, both affiliated to the DZNE and the University Medicine Magdeburg, investigated this question.

The researchers used high-resolution magnetic resonance imaging (MRI) to examine the blood supply to the hippocampus of 47 women and men aged 45 to 89 years.

The study participants also underwent a neuropsychological test battery, which assessed, in particular, memory performance, speech comprehension and the abilty to concentrate.

A double supply line

“It has been known for some time that the hippocampus is supplied by either one or two arteries. It also happens that only one of the two hippocampi, which occur in every brain, is supplied by two vessels. This varies between individuals.

The reasons are unknown,” explained Schreiber. “Maybe there is a genetic predisposition. However, it is also possible that the individual structure of the blood supply develops due to life circumstances.

Then the personal lifestyle would influence the blood supply to the hippocampus.” In the cognition tests, those study participants in whom at least one hippocampus was doubly supplied generally scored better.

“The fact that the blood supply is fundamentally important for the brain is certainly trivial and has been extensively documented.

We were therefore particularly focused on the hippocampus and the situation of a disease of the brain vessels. Little is actually known about this.”

The researchers used high-resolution magnetic resonance imaging (MRI) to examine the blood supply to the hippocampus of 47 women and men aged 45 to 89 years.

Patients benefited in particular

Of the study subjects, 27 did not manifest signs of brain diseases. The remaining twenty participants showed pathological alterations in brain blood vessels, which were associated with microbleeding.

“In these individuals, sporadic cerebral small vessel disease had been diagnosed prior to our investigations,” said Dr. Valentina Perosa, lead author of the current study, who is currently doing postdoctoral research in Boston, USA.

These individuals exhibited a broad spectrum of neurological anomalies, including mild cognitive impairment. “The healthy subjects generally scored better on cognitive tests than the study participants with small vessel disease.

Among the participants with disease, those with at least one hippocampus supplied by two arteries reached better scores in cognition.

They particularly benefited from the double supply. This may be due to a better supply not only of blood but also of oxygen. However, this is just a guess,” said Perosa.

Starting point for therapies?

“Our study shows a clear link between blood supply to the hippocampus and cognitive performance,” Schreiber summarised the results.

“This suggests that brain blood flow might play a key role in the declining of memory performance, whether caused by age or disease.”

Such findings help to understand disease mechanisms and can also be useful for the development of novel treatment options, she indicates:

“At present we can only speculate, because we don’t know, but it is possible that lifestyle has an influence on the formation of the blood vessels that supply the hippocampus. This would then be a factor that can be influenced and thus a potential approach for therapies and also for prevention. This is a topic we intend to investigate.”

The hippocampus is critical for episodic memory (Zola-Morgan, 1986Düzel et al., 2001), spatial navigation (O’Keefe and Nadel, 1979Suthana et al., 2009), consolidation of long-term memory (Frey and Frey, 2008Düzel et al., 2010) and contributes to many other cognitive faculties. Moreover, a wide range of diseases is related to hippocampal dysfunction (for a review see Small et al., 2012).

A sufficient blood supply is a decisive factor to preserve function of any brain region. In fact, a positive relation between resting cerebral blood flow and cognition has recently been observed in older adults for global (Rabbitt et al., 2006Ogoh, 2017) and hippocampal cerebral blood flow (Heo et al., 2010). Differences in perfusion might also lead to differences in structural integrity (Maass et al., 2015Boraxbekk et al., 2016). This aspect is especially relevant for the hippocampus, which is particularly sensitive to hypoxia (Duvernoy, 2013). The latter probably relates to both the conformation of the intrahippocampal vessels (Duvernoy, 2013) and the relative lack of capillary anastomoses between them (Klosovskii, 1963).

Hippocampal vessels are small (average diameter 0.5 mm), restricting their visualization and examination so far to post-mortem studies. Autopsy studies (Marinković et al., 1992Erdem et al., 1993) have highlighted that the hippocampus is vascularized by the posterior cerebral artery (PCA) and the anterior choroidal artery (AchA), from which the hippocampal arteries, directly or indirectly, arise. The exact origin of the hippocampal arteries anatomically varies across individuals and includes PCA branches, such as the inferior temporal arteries, the posterolateral choroideal artery and the splenial artery (Lang, 1981Marinković et al., 1992). Most importantly, the contribution of the AchA to hippocampal vascularization is variable, and when existent, pertains to the hippocampal head, which is in these cases partially vascularized by the uncal branch of the AchA (Gastaut and Lammers, 1961Erdem et al., 1993). A dedicated post-mortem study (Erdem et al., 1993) classified five different hippocampal vascularization patterns (A–E) according to the origin of the hippocampal arteries. In two of them (A and E) the AchA contributes to the hippocampal supply (mixed supply), while in the remaining three (B–D), it does not (single supply). Recently, the same classification was demonstrated in vivo adopting high-resolution time-of-flight (ToF) angiography at 7 T MRI and showing a comparable frequency of the hippocampal patterns to post-mortem studies (Spallazzi et al., 2018).

Sporadic cerebral small vessel disease (CSVD) denotes the pathological alteration of the cerebral small vessels (<1 mm in diameter), such as arterioles, venules and capillaries. It mainly relates to age and vascular risk factors, and comprises hypertensive arteriopathy and cerebral amyloid angiopathy (CAA), which occur independently or together in the ageing brain (Pantoni, 2010Charidimou et al., 20162017). Hippocampal vessels, which present an average diameter of 0.5 mm, are also affected (Hecht et al., 2018). In fact, hippocampal atrophy and neuronal loss (Kril et al., 2002Small et al., 2012), hippocampal microinfarcts (Hecht et al., 2018), as well as decreased regional cerebral blood volume (Wu et al., 2008) have been observed in patients with CSVD. Nonetheless, the extent of the structural harm in the medial temporal lobe (MTL) in CSVD patients is still a matter of debate and some studies report a sparing of this brain region (Lambert et al., 20152016). The cognitive profile of the CSVD cohort is, however, consistent with a concomitant deleterious effect on the MTL and also includes deficits in episodic memory (Xiong et al., 2016van Leijsen et al., 2019), a cognitive domain strongly related to hippocampal function. Recently, stronger focus has been directed towards the interplay between CSVD, MTL degeneration and cognitive decline (O’Sullivan et al., 2009Jokinen et al., 2016van Leijsen et al., 2019), as well as on the mediating role of CSVD on the cognitive trajectories in Alzheimer’s disease (Kril et al., 2002Boyle et al., 2018). Converging evidence indicates that microvascular pathology independently contributes to both structural degeneration of the MTL, and MTL-related cognitive decline (Zhang et al., 2013Iturria-Medina et al., 2016Boyle et al., 2018).

In light of this evidence, we aimed to investigate in vivo the link between hippocampal vascularization and cognition, in a cohort that included older adults with and without CSVD.

So far, it remains unexplored whether differences in the hippocampal vascularization influence: (i) MTL-related and global cognition; (ii) hippocampal structure; and (iii) MTL-related and global cognition, as well as hippocampal structure in face of CSVD. Hippocampal vascularization patterns were characterized using 7 T ToF-angiography, while cognition was evaluated adopting neuropsychological tests that assess cognitive domains related to the hippocampal function [such as memory and learning in the California Verbal Memory Test – II (CVLT-II) (Delis et al., 2000)], and more comprehensive cognitive measures assessing global cognition [such as Mini Mental State Examination (MMSE), and Montreal cognitive Assessment (MoCA)]. Furthermore, we used high-resolution voxel-based morphometry (VBM) at 7 T structural MRI to investigate whether hippocampal vascularization patterns are accompanied by variations in hippocampal volume. We hypothesized that the presence of a mixed hippocampal supply through both the PCA and AchA, may increase the reliability of blood supply to the hippocampus. This increased vascular reserve may be a protective factor for hippocampal structural integrity and cognitive function in normal ageing but particularly in older adults with small vessel disease.



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