Dementia linked to problems with brain’s waste clearance system

Recommendable! More evidence how the cerebrospinal fluid is involved.

"A study ... found that impaired movement of cerebrospinal fluid (CSF) – the clear liquid that cushions and cleans the brain – predicted risk of dementia later in life among 40,000 adults recruited to UK Biobank. ...

In the healthy brain, the so-called glymphatic system serves to clear out toxins and waste materials, keeping the brain healthy. Only discovered as recently as 2012, this system functions by flushing CSF through the brain along tiny channels around blood vessels known as perivascular spaces. It collects waste then drains out of the brain, helping keep it clean and healthy. ...

Until recently, it has only been possible to study glymphatic function in mice, but recent advances in MRI scanning have made it possible to study it indirectly in humans. Even so, it was only possible to do this practically in relatively small numbers, but ... developed machine learning algorithms capable of assessing glymphatic functions from MRI scans at scale.

The team applied the algorithm to MRI scans taken from around 40,000 adults in UK Biobank. They found three biomarkers – biological signatures – associated with impaired glymphatic function assessed at baseline, predicted the risk of dementia occurring over the subsequent decade. 

One of these was DTI-ALPS, a measure of the diffusion of water molecules along the perivascular spaces.

Another was the size of the choroid plexus, where the CSF is produced.

The third measure reflected the flow velocity of CSF into the brain. ...

Further analysis showed that several cardiovascular risk factors impaired glymphatic function – and hence increased dementia risk, and that this was partly via causing cerebral small vessel disease, which is visible in the MRI scans. ..."

From the highlights and abstract:

"Highlights

• We developed fully automated methods for quantifying diffusion tensor image analysis along the perivascular space (DTI-ALPS) and blood oxygen level–dependent cerebrospinal fluid (BOLD-CSF) coupling.
• Three CSF dynamics markers—BOLD-CSF coupling, DTI-ALPS, and choroid plexus (CP) volume—were predictive of incident dementia, whereas PVS volume was not.
• Magnetic resonance imaging proxies of CSF dynamics markers were associated with cardiovascular injury. CP volume and DTI-ALPS mediated the associations of both white matter hyperintensities and diabetes with dementia.

INTRODUCTION

Impaired cerebrospinal fluid (CSF) dynamics may contribute to dementia, but human evidence is limited. We examined associations between magnetic resonance imaging–based proxies of CSF dynamics and incident dementia, and whether CSF dysfunction mediates links between cardiovascular risk and dementia.

METHODS

Using the UK Biobank, we measured CSF dynamics:

perivascular space (PVS) volume, diffusion tensor image analysis along the

PVS (DTI-ALPS), blood oxygen level–dependent CSF (BOLD-CSF) coupling, and

choroid plexus (CP) volume.

We assessed cardiovascular risk factors and their associations with CSF dynamics and dementia based on general practitioner, mortality, and hospital records. Mediation analysis evaluated CSF dysfunction in cardiovascular risk–dementia relationships.

RESULTS

Lower DTI-ALPS, lower BOLD-CSF coupling, and higher CP volume predicted dementia, but PVS volume did not. DTI-ALPS and CP volume mediated the effect of white matter hyperintensities and diabetes duration on dementia.

DISCUSSION

Impaired CSF dynamics may lead to dementia and partially mediate cardiovascular risk–dementia associations."

Dementia linked to problems with brain’s waste clearance system | University of Cambridge "Problems with the brain’s waste clearance system could underlie many cases of dementia and help explain why poor sleep patterns and cardiovascular risk factors such as high blood pressure increase the risk of dementia."

MRI markers of cerebrospinal fluid dynamics predict dementia and mediate the impact of cardiovascular risk (open access)

Fig. 1 The illustration of non-invasive MRI proxies of CSF dynamics markers.

Fig. 2 The association of MRI proxies of CSF dynamics with demographics and risk factors.