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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

Cognitive impairment remains 6 months post-COVID-19 infection

13th April 2022

Only cognitive impairment and not new-onset psychiatric diagnoses differ between COVID-19 and control patients 6 months post-infection

Cognitive impairment persists 6 months after an acute COVID-19 infection but there are no differences in the level of new-onset psychiatric diagnoses when compared to a group of non-COVID-19, hospitalised patients. This was the main and important conclusion of a study by researchers from the Mental Health Center Copenhagen, Denmark.

Survivors of COVID-19 appear to be at increased risk of psychiatric sequelae and in one Italian study which followed-up on patients 8 weeks after being discharged from hospital with COVID-19, the most frequent symptoms were fatigue (46%), dyspnea (30%), insomnia (26%), anosmia (20%), and dysgeusia and palpitation (15%). However, the development of cognitive impairment is not unique to COVID-19 with research showing that hospitalised patients in medical and surgical intensive care units are also known to be at a high risk for long-term cognitive impairment. Consequently, while there is much current interest in the cognitive sequelae of COVID-19, it is important to put this impairment into some context by comparing the incidence in relation to other hospitalised patients.

For the present study, the Danish team therefore undertook a prospective study of all patients hospitalised with COVID-19 and who were then matched for age, sex and intensive care unit status with non-COVID-19 patients. Cognitive impairment was assessed using the Montreal Cognitive Assessment (MoCA) which was dichotomised into normal or abnormal using pre-specified cut-off scores of 26 or lower and 24 or lower. The MoCA score ranges from 0 to 30 with a score of 26 or more considered to be normal. The team also examined the incidence of new-onset psychiatric diagnoses and together with the MoCA scores, both measures were set as the co-primary outcome and which were assessed at 6 months post-infection. In addition, secondary outcomes included the presence of a specific psychiatric diagnosis such as depression and self-reported symptoms as described in a supplement to the article (Table 1).

Cognitive impairment in both groups

A total of 85 individuals with a mean age of 56.8 years (42% women) hospitalised with COVID-19 were matched with 61 non-COVID-19 patients and included in the analysis. Among the COVID-19 cohort, 51% were admitted to an intensive care unit and the median follow-up time after COVID-19 was 165 days.

The total MoCA score at 6 months was 26.7 in the COVID-19 cohort and 27.5 in the control group (p = 0.01). When using the cut-off score of 24 or less, an abnormal test result was more frequent among those with COVID-19 (14% vs 2%, p = 0.03, COVID-19 vs controls). However, in a subset of COVID-19 patients who underwent cognitive assessment at hospital prior to discharge (rather than at 6 months) and were subsequently followed up, while the mean MoCA score at discharge was 19.2, this improved to 26.1 (P = 0.004) at follow-up.

In total, 19% of COVID-19 survivors and 20% of controls developed a new-onset psychiatric diagnosis including panic anxiety, depression, at the 6-month follow-up assessment which was not statistically different (p = 0.87). Furthermore, when the data were adjusted for several factors including levels of intubation, disease severity and co-morbidities, the result remained unchanged.

The authors concluded that while cognitive impairment was more prevalent among COVID-19 survivors 6-months post-infection, the overall neuropsychiatric burden was similar to matched, hospitalised control patients.

Citation
Nersesjan V et al. Neuropsychiatric and Cognitive Outcomes in Patients 6 Months After COVID-19 Requiring Hospitalization Compared With Matched Control Patients Hospitalized for Non–COVID-19 Illness JAMA Psychiatry 2022