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Choroid plexus volume and permeability are potential MRI imaging markers for Alzheimer’s disease

1st June 2022

A higher choroid plexus volume and permeability could be useful imaging markers for cognitive impairment in patients with Alzheimer’s disease

An increased choroid plexus (CP) volume as well as higher permeability, might represent useful imaging markers for the severity of cognitive impairment along the Alzheimer’s disease spectrum. This was the conclusion of an imaging study by researchers from South Korea.

It is estimated that across the globe, there are some 55 million people living with dementia, of which, Alzheimer’s disease (AD) is the most common, accounting for 60 to 70% of all dementia cases. Alzheimer’s disease pathology is characterised by the build-up amyloid-β (Aβ) and tau neurofibrillary tangles in the brain. Nevertheless, in the last decade, it has become recognised that while accumulation of amyloid-β plaques occurs, this might arise due to a reduced clearance rather than simply over-production. One poorly studied area of the brain is the choroid plexus (CP), which is responsible for the manufacture of blood-cerebrospinal fluid (B-CSF). Moreover, the integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability and the structure is thought to play a role in the development of neurodegenerative diseases such as AD. In fact, use of choroid plexus epithelial cells transplanted into the brain of animal models of AD revealed a significant reduction in brain Aβ deposits, suggesting neuro-protective potential of these cells in AD. In a 2020 study, researchers also identified a negative associations between CP volume and CSF proteins (i.e., as the CP volume increased, CSF proteins decreased), leading the authors to suggest that the CP is involved in both the clearance of CSF proteins and that CP dysfunction is present in AD.

Nevertheless, imaging studies of both CP volume and permeability are lacking and in the present study, the Korean team retrospectively examined the relationship between these two factors and cognitive impairment using MRI. They recruited a cohort of patients with either subjective cognitive impairment (SCI), mild cognitive impairment (MCI), late MCI and AD. A subgroup of these patients underwent both MRI and dynamic contrast-enhanced (DCE) imaging. The effect of CP volume on cognition in the different groups was evaluated using multivariable regression analysis and which was adjusted for several factors including age, sex and education.

Choroid plexus and cognitive symptoms

A total of 532 patients with a mean age of 72 years (73% women) were included in the analysis and a subgroup of 132 underwent DCE MRI assessment.

The CP volume was highest in patients with AD (1.3) compared to those with SCI (0.9) and progressively increased as impairment worsened, i.e., from SCI through to AD and these differences were statistically significant (p < 0.01). In addition, AD patients had the lowest hippocampal volume, which is also consistent with cognitive impairment in AD.

According to the results of the DCE MRI, CP volume was greater in AD patients whereas CP permeability was lowest among those with AD. Furthermore, when comparing CP volume with cognition, the researchers found that the CP volume was negatively associated with memory, executive function and visuospatial function.

The authors concluded that the CP volume was highest in those with the most severe cognitive impairment and that changes in CP permeability were also associated with disease severity. They added that both CP volume and permeability might represent imaging markers for cognitive impairment in AD and which was independent of amyloid abnormalities or neurodegeneration.

Citation
Choi JD et al. Choroid Plexus Volume and Permeability at Brain MRI within the Alzheimer Disease Clinical Spectrum Radiology 2022

Atrial fibrillation appears to be linked to a range of cerebrovascular pathologies

1st October 2021

Atrial fibrillation appears to be associated with several cerebrovascular pathologies including strokes, lacunes and silent brain infarcts.

Atrial fibrillation (AF) is the most common arrhythmia diagnosed in clinical practice and an analysis of an international database in 2017 found that a total of 3.046 million new cases were registered. The presence of AF increases the risk of stroke and thus subsequent cognitive impairment but one study also showed that AF is associated with an almost three-fold increased risk of dementia. Moreover, there is a growing body of literature that supports AF as being a risk factor for both cognitive decline and dementia although the mechanisms responsible for this association are diverse and not solely related to the increased risk of stroke.

In trying to understand these associations, a team from the Institute of Neuroscience and Physiology, Sahlgrenska, Gothenburg, Sweden, set out to determine whether AF was associated with cerebrovascular pathologies. The team obtained data from the Gothenburg H70 Birth Cohort Studies, which included individuals born in 1944 who underwent structural brain MRI scans between 2014 – 2017. Using these scans, the team looked for markers of cerebral small vessel disease such as white matter hyper-intensities (WMHs), lacunes, brain infarcts and cerebral micro-bleeds, with the latter two conditions assessed by a radiologist. The patient’s diagnosis of AF was either self-reported or based on electrocardiogram results or data from Sweden’s National Patient Register (NPR). A control group of patients who did not undergo an MRI scan were included for comparative purposes.

Findings

A total of 776 participants were included of whom 65 (8.4%) had a diagnosis of AF. The presence of AF was associated with a history of symptomatic stroke (odds ratio, OR = 4.5 95% CI 2.1–9.5), large infarcts (OR = 5.0), lacunes (OR = 2.7) and silent brain infarcts (OR = 3.5). Additionally, individuals with AF had larger WMH volumes than controls, especially those currently treated for AF.

The authors concluded that AF was associated with broad range of cerebrovascular pathologies and called for further work to establish whether cerebrovascular MRI markers could help to complement current treatment guidelines for patients with AF.

Citation

Ryden L et al. Atrial Fibrillation, Stroke, and Silent Cerebrovascular Disease: A Population-Based MRI Study. Neurology 2021