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Take a look at a selection of our recent media coverage:

Subpopulations of children with atopic dermatitis linked to cognitive impairment

25th March 2024

Children with atopic dermatitis (AD) and attention-deficit/hyperactivity disorder (ADHD) or a learning disability are at increased risk of cognitive impairment and should be prioritised for assessment, research suggests.

Previous studies had suggested AD was associated with cognitive impairment in children, US researchers wrote in the journal JAMA Dermatology, but it was unknown whether certain subpopulations of children with AD were at greater risk.

To answer this question, lead study author Dr Joy Wan, assistant professor of dermatology at the Johns Hopkins University School of Medicine, and colleagues designed a cross-sectional study using data from the 2021 US National Health Interview Survey (NHIS).

Drawing on a weighted sample of 69,732,807 children (13.2% with AD), researchers found when compared to those without the condition, children with the condition were more likely to experience learning difficulties (10.8% vs 5.9%) and memory difficulties (11.1% vs 5.8%).

In multivariable logistic regression models adjusted for sociodemographic factors, asthma, food and seasonal allergies, AD was associated with increased odds for learning difficulties (adjusted odds ratio: 1.77) and memory difficulties (adjusted odds ratio 1.69).

However, further analysis showed the association was primarily limited to children with neurodevelopmental comorbidities, such as ADHD or learning disabilities, pointing to them being the subgroups of children with AD at highest risk of cognitive impairment.

‘The findings of this study suggest that evaluation for cognitive impairment in children with AD should be prioritised among those with comorbid neurodevelopmental disorders,’ Dr Wan and colleagues wrote.

While the mechanism underlying the interaction between AD and neurodevelopmental disorders was unknown, it was possible that AD-related sleep disturbances might be more likely to negatively impact cognitive functions in children with ADHD or learning disability, the authors continued.

‘Our results also suggest that memory and learning difficulties related to AD may vary by developmental condition,’ Dr Wan and colleagues added.

In children with ADHD, for example, AD was associated with nearly three-times greater risk of memory difficulties but was not associated with learning difficulties.

However, in children with learning disabilities, AD was linked with twice the odds of memory difficulties but half the odds of learning difficulties.

It was possible that children with AD and concomitant learning disabilities were more likely to receive appropriate interventions, perhaps due to greater healthcare use or caregiver awareness, leading to relatively lower odds of reported learning difficulties.

‘Another possibility is that AD affects different areas of cognition to varying degrees, with perhaps a greater impact on memory than on learning,’ Dr Wan and colleagues said.

The study included children aged 17 years and younger without intellectual disability or autism, the researchers said, noting that strengths of the research included its population-based nature and the data adjustment for confounders.

Limitations included the cross-sectional study design and reliance on caregiver-reported symptoms.

‘Finally, we were unable to examine factors, such as AD severity, age at AD diagnosis, and sleep, which were not collected in the NHIS data,’ the researchers wrote.

Cognitive impairment lower after early mobilisation in mechanically ventilated ICU patients

9th March 2023

Longer-term cognitive impairment at 12 months in mechanically ventilated intensive care patients can be reduced through early mobilisation

The potential for long-term cognitive impairment (CP) among mechanically ventilated patients within an intensive care unit can be significantly reduced through early mobilisation according to the findings of a randomised trial by researchers at the University of Chicago, Chicago, USA.

Patients in both medical and surgical intensive care units are at a high risk of long-term cognitive impairment. In fact, after only two days of documented delirium, at 12 months, 71% of survivors had cognitive impairment and of whom, 36% had severe impairment. While delirium commonly occurs in critical illness, whether this causes longer-term cognitive impairment is less clear. Delirium can be reduced through early mobilisation, i.e., whole-body rehabilitation with interruption of sedation and physical and occupational therapy in the earliest days of critical illness. However, no studies have examined whether early mobilisation also positively impacts on the longer-term development of CP.

In the current study, the US team performed a randomised trial of early mobilisation among functionally independent and mechanically ventilated patients admitted to the ICU versus usual care to determine if this reduced cognitive impairment, 12 months after the critical illness. Adult patients admitted to the ICU intensive-care unit (ICU), were randomised 1:1 to either early physical and occupational therapy (i.e., early mobilisation) or usual care. The primary outcome, cognitive impairment 1 year after hospital discharge, was assessed using the Montreal Cognitive Assessment (MoCA) scale and on which, CP is deemed to be present if the score is < 26.

Cognitive impairment and early mobilisation

A total of 198 patients with mean age of 56.2 years (42.5% female) were equally randomised to early mobilisation or usual care.

When assessed after 12 months, the rate of CP among those assigned to early mobilisation was 24% (mean MoCA score = 26) compared with 43% (mean MoCA score = 23) with usual care and this difference was statistically significant (p = 0.0043). In fact, CP was also significantly lower upon hospital discharge, (54% vs 69%, p = 0.029). The early mobilisation group also had significantly fewer ICU-acquired weaknesses (p = 0.0001) and higher physical component quality-of-life scores (p < 0.0001). However, there were no significant differences in the rates of functional independence or mental component scores between groups after 12 months.

The authors concluded that early mobilisation could be the first known intervention to improve long-term cognitive impairment among ICU patients following mechanical ventilation.

Patel BK et al. Effect of early mobilisation on long-term cognitive impairment in critical illness in the USA: a randomised controlled trial. Lancet Respir Med 2023

Higher acetylcholinesterase activity associated with delirium during critical illness

12th December 2022

A higher cholinesterase activity in critically ill patients increases the risk of delirium but does not lead to cognitive impairment over time

Increased acetylcholinesterase activity in critically ill patients is associated with an increased risk of being delirious but this does lead to subsequent cognitive impairment following discharge from hospital according to the findings of a prospective study by US researchers.

Delirium is defined as a disturbance of consciousness and cognition that develops over a short period of time (hours to days) and fluctuates over time. Furthermore, it is a common manifestation of acute brain dysfunction in critically ill patients with prevalence as high as 75%. However, more troublesome is the finding from a meta-analysis of 24 studies, which showed how delirium was significantly associated with long-term cognitive decline in both surgical and nonsurgical patients. The causes of delirium remain uncertain although several pro-inflammatory markers have been found to be elevated in critical ill patients with delirium. A widely held hypothesis has proposed that this inflammatory response seen in critically ill patients is regulated by the cholinergic system, resulting from a deficit of acetylcholine (ACh). The cholinesterase enzyme, acetylcholinesterase (AChE), is found primarily found in synapses and red blood cell membranes and cleaves ACh in the synaptic cleft, terminating the transmission of a stimulus. Although the primary neurotransmitter of the cholinergic system is acetylcholine, this cannot be measured directly in clinical settings but the activity of two enzymes, AChE and butyrylcholinesterase (BChE) can be assessed with a decreased activity of the latter, seen in patients with systemic inflammation.

Researchers therefore set out to establish whether there was an association between acute brain dysfunction (i.e., delirium and coma) during critical illness and the activity of these two enzymes as well as if enzyme activity levels were predictive of long-term cognitive impairment, disability, and health-related quality of life in survivors of critical illness. Blood samples were taken on days 1 (study enrolment), 3, 5 and 7 while in the hospital to measure the activity of both enzymes. In addition, patients were assessed for delirium and/or coma twice daily until discharged from the intensive care unit IICU) and then once daily after ICU discharge.

Cholinesterase activity, delirium and cognitive impairment

A total of 272 patients with a median age of 56 (56% male) and a median Sequential Organ Failure Assessment score at enrolment of 8, were included in the analysis. Overall, 15% of the cohort died within the hospital and 23% within 90 days of enrolment.

Measurement showed that a higher AChE enzyme activity level was associated with a higher odd of delirious status on the same day (p = 0.045), but not comatose mental status (p = 0.13). When examining delirium, patients with AChE activity at the 75th percentile compared to those with values at the 25th percentile example, had 64% increased odds of developing delirium (odds ratio, OR = 1.64, 95% CI 1.11 – 2.43, p = 0.045). However, when AChE levels were normalised per gram of haemoglobin (since AChE is found in synapses and on red blood cell membranes), this relationship was no longer significant (OR = 1.20, 95% CI 0.95 – 1.52, P = 0.21).

A further finding was how patients in the 75th percentile of BChE activity, had 44% higher odds of having more days alive without delirium or coma, i.e., indicating less brain dysfunction (OR = 1.44, 95% CI 1.06 – 1.94, p = 0.05). Finally, there was no significant association between any of the cholinesterase enzymes with cognitive impairment, disability, or quality of life after discharge.

The authors concluded that plasma cholinesterase activity was predictive of acute brain dysfunction during critical illness but not long-term impairments. They suggested that future studies need to examine whether cholinergic modulation in selected patients identified by plasma cholinesterase activity, could reduce acute brain dysfunction.

Hughes CG et al. Association between cholinesterase activity and critical illness brain dysfunction. Crit Care 202

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.

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.

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