This website is intended for healthcare professionals only.
Take a look at a selection of our recent media coverage:
2nd May 2022
Having atopic eczema in older life increases the risk for developing Alzheimer’s disease, according to a study by researchers from UC Berkeley School of Public Health, Berkeley, California, USA.
Alzheimer’s disease (AD) is a neurodegenerative disorder which is progressive and characterised clinically by cognitive decline and physiologically by the presence of two core pathologies; amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs). AD is the most common form of dementia which, according to the World Health Organization (WHO), affected some 55 million people in 2021 with AD accounting for 60-70% of all dementia cases.
Among those with AD, there is a sustained inflammatory response in the brain which is thought to represent a persistent immune response and a factor exacerbating both Aβ and NFTs. Moreover, there is emerging evidence that peripheral inflammation is an early event in the pathogenesis of AD. Atopy, which manifests as either allergic rhinitis, atopic eczema or asthma, represents a set of peripheral inflammatory diseases that have been found to be associated with a modestly increased risk of AD and dementia. To date, only one study has suggested that atopic eczema may be an independent risk factor for new-onset dementia and in particular, AD.
For the present analysis, the team set out to determine whether active atopic eczema among older adults was associated with incident AD and wondered if the strength of this association was dependent upon atopic eczema disease severity. They performed a longitudinal cohort study of patient data collected from the Health Improvement Network, which provides information on a representative sample of patients from UK general practitioners. For their analysis, the researchers included patients aged 60 to 100 years of age without a prior diagnosis of AD or dementia and for whom the primary exposure was the presence of active atopic eczema and for which at least two prescriptions for treatment of the condition had been issued. The severity of atopic eczema during follow-up was categorised as either mild moderate or severe and the primary outcome was a new diagnosis of dementia during the period of follow-up. The researchers also examined the reported disease codes for dementia and excluded those where the condition was drug- or alcohol-related or due to trauma or a rarer form (e.g. Huntington’s). The analysis was adjusted for potential confounders including gender, smoking, alcohol status, etc.
Atopic eczema and risk of Alzheimer’s disease
In a total of 1,767,667 individuals aged 60 to 100 years of age at baseline, 57,263 were diagnosed with dementia over mean of 6.8 years of follow-up. The median age of patients with a dementia diagnosis was 82 years, of whom, two-thirds (65%) were female.
Atopic eczema was diagnosed in 12% of the whole cohort and using mild disease severity as the default, 44% had moderate and 5% disease severity over the follow-up period.
Considering AD, the analysis showed that after adjustment for confounders, mild atopic eczema was associated with a 22% higher risk of AD (HR = 1.22) and this risk was higher still for those with moderate (HR = 1.37) and severe (HR = 1.52) disease.
With AD being the most common form of dementia, the researchers also examined the link between atopic eczema and the risk of developing dementia. The incidence of dementia was 57/10,000 person-years among those with atopic eczema compared to 44/10,000 person-years among those without the condition. Overall, patients with atopic eczema had a 27% higher risk for dementia after adjustment for potential confounders (hazard ratio, HR = 1.27, 95% CI 1.23 – 1.30). Further adjustment for co-morbidities slighted attenuated this risk but it remained significant (HR = 1.19, 95% CI 1.16 – 1.22).
The authors concluded that given the increased risk of AD among adults with atopic eczema, clinicians consider the impact of screening those with eczema for signs of cognitive impairment.
Magyari A et al. Adult atopic eczema and the risk of dementia: A population-based cohort study J Am Acad Dermatol 2022
28th March 2022
Increased physical activity levels in older adults with high serum levels of neurofilament light chain (NFL) leads to a reduction in the rate of cognitive decline. This was the conclusion of a study by researchers from the Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, US.
Neurofilament light chain is a neuronal cytoplasmic protein expressed in large calibre myelinated axons. Furthermore, in both central nervous system and peripheral nervous system diseases associated with axonal injury or degeneration, the concentration of NFL has been found to increase in both cerebrospinal fluid (CSF) and blood. In addition, levels of CSF NFL are associated with cognitive impairments in patients with Alzheimer disease and fronto-temporal dementia. As a result, it has been suggested that NFL could be used to predict the development of sporadic Alzheimer’s disease and cognitive decline. One factor which appears to be associated with a reduced cognitive decline is physical activity and in a 2011 meta-analysis, the authors concluded that there was a significant and consistent protection for all levels of physical activity against the occurrence of cognitive decline.
For the present study, the US team wanted to examine whether among individuals with high NFL concentrations, increased physical activity was associated with a slowed rate of cognitive decline over time. They turned to the Chicago Health and Aging Project (CHAP), which is a longitudinal population study of common chronic health problems of older persons and in particular, risk factors for incident Alzheimer’s disease. Blood samples were taken and the concentration of NFL measured at baseline and during each follow-up appointment and dichotomised as low (< 25.5 pg./ml) or high (> 25 pg./ml). Levels of physical activity were self-reported divided into three groups: little activity, medium and high, in which the latter group reported physical activity levels > 150 minutes/week. A number of cognitive tests were used to assess global cognitive function. The main outcome measure was the association of baseline activity and NFL concentrations with changes in global cognitive function over time.
Increased physical activity and NFL in relation to cognitive decline
A total of 1158 participants with a mean age of 77.4 years (63% female) were included in the study. The mean level of physical activity per week was 170.78 minutes and the geometric mean NFL concentration was 26.1 pg/ml.
Among those with a high NFL levels, indicating more axonal injury, individuals engaging in medium physical activity (< 150 minutes/week), had a 12% slower rate of global cognitive decline compared to those in the low physical activity group. Similarly, those with increased physical activity (i.e., the high group), had a 36% slower rate of decline in comparison to the low physical activity group.
Interestingly, the the rates of cognitive decline were also higher among those with lower levels of NFL, i.e., with less neural damage. For example, in comparison to the group who undertook little or no physical activity, those who undertook medium physical activity had a 43% slower decline and the high activity group, at 30% slower decline.
The authors concluded that among older adults with high levels of serum NFL, increased physical activity levels were associated with a slower rate of cognitive decline. They added that future studies should examine the relationship between cognitive decline and different forms of exercise such as aerobics and strength training.
Desai P et al. Examination of Neurofilament Light Chain Serum Concentrations, Physical Activity, and Cognitive Decline in Older Adults JAMA Netw Open 2022
1st February 2022
Relevant vital sign cut off values used for the risk stratification and hence prognosis for patients attending an emergency department do not exist for some signs which has important implications for their use and interpretation. This was the conclusion of a large study by a team from the Emergency Department, Maxima Medical Centre, Veldhoven, The Netherlands.
An emergency department encounters a large number of sick patients who require quick evaluation to detect those who have serious medical problems and which might require hospital admission. This has led to the introduction of various triage tools such as the modified early warning score (MEWS) which serves as a rapid, simple triage method to identify medical patients in need of hospital admission and those at increased risk of in-hospital death. Other tools commonly used such as the quick sequential organ failure assessment (qSOFA) rely on the use of vital sign measurements and specify a cut-off for each vital sign to discriminate between a better or worse prognosis. However, the use of disease severity assessment tools may not be appropriate, particularly for elderly patients as revealed in one study of sepsis, which concluded that ‘prognostic and discriminative performance of the five most commonly used disease severity scores was poor and less useful for risk stratification of older ED sepsis patients.’
For the present study, the Dutch team looked to assess the association between vital signs and relevant clinical outcomes such as mortality and admission to an intensive care unit. In addition, they wanted to determine whether a single cut-off or threshold existed for each vital sign and the extent to which these were influenced by advancing age. They undertook an observational study at three EDs in the Netherlands and examined consecutive adult patients (18 years and older) where one or more of the following vital signs were measured: respiratory rate (RR), peripheral oxygen saturation (SpO2), systolic (SBP) and diastolic (DBP) blood pressure, mean arterial blood pressure (MAP), heart rate (HR) and temperature. Patients were stratified by age into three categories; 18 – 65, 66 – 80 and > 80 years and the primary outcome was whether there was a vital sign category that could be used as a cut-off to predict the outcome of in-hospital mortality or ICU admission.
A total of 101,416 patients with a mean age of 59.6 years (49.6% female) were included in their analysis. In many cases the vital sign values were outside of the usual range. For example, 23.4%, 79.1% and 14.2% of the total cohort had a RR, SBP and SP02 respectively, outside of the normal range. This proportion was also higher in older patients as seen for example with SBP for which 83.3% of patients aged > 80 had a reading outside of the normal range compared to 76.3% of those aged 18 to 65 years.
Among the cohort, a total of 2374 (2.3%) patients died. The adjusted odds ratios (aOR) for predicted mortality increased gradually with worsening values of SBP and SpO2 although there was no clear cut-off point for SBP, DBP, Sp02 and HR and mortality. In addition, for all vital signs, older adults had a larger increase in absolute mortality. For ICU admission, SBP had a relevant cut-off at 70mmHg and for MAP there was a threshold of < 60 mmHg.
In summarising their findings, the authors noted how in-hospital mortality increased gradually with decreasing SBP and SpO2 and there was no evidence of a specific cut-off for either vital sign. For DPB, MAP and HR, there was a quasi-U-shaped association with in-hospital mortality and while there was a single cut-off for MAP, RR and temperature, the authors argued that using a single cut-off value would ignore further increase of risk with more extreme values for these vital signs.
They concluded that the use of a single cut-off for each vital sign in acute care deserves scrutiny and that age-adjusted numerical scores would improve risk stratification since older patients have a larger increase in mortality with changing vital signs even after adjustment for confounds.
Candel BGJ et al. The association between vital signs and clinical outcomes in emergency department patients of different age categories Emerg Med J 2022
25th October 2021
Supplementing with high calcium and protein dairy foods resulted in a 33% lower fracture incidence in the elderly according to research by a team from the Departments of Medicine and Endocrinology, University of Melbourne, Australia. The study was a cluster randomised controlled trial undertaken across 60 residential care facilities in predominately ambulatory patients. Falls in older patients are an important public health issue and data from 2017 showed that among adults aged 70 and older who sought medical attention due to an injury, 8.4 million were due to a fall-related injury. Moreover, in an analysis of malnutrition in the elderly, it was found that 68 % of individuals were considered malnourished or at risk of malnutrition. In addition, the study identified that mean protein intakes in residents were below recommended levels, exacerbating aged-related loss of muscle mass and function. Furthermore, ensuring appropriate nutrition in the elderly by supplementing with a protein, calcium and vitamin D, reduced the incidence of falls among malnourished elderly patients. There is also evidence that calcium supplementation with vitamin D can reduce the incidence of hip fractures. Other work has found that consumption of food sources containing calcium can positively affect skeletal metabolism that is beneficial for bone health in older adults.
With the potential to correct malnutrition in the elderly, the Australian researchers set out to test whether the achievement of adequate calcium and protein intake could reduce the fracture incidence among institutionalised adults who were already vitamin D replete. For their trial, participants were randomised, at facility rather than the individual level, to receive additional milk, yoghurt and cheese whereas the control group continued to receive their normal diet. The primary outcome of interest was the difference in fractures, falls and all-cause mortality between the two groups, whereas secondary outcomes were the time to fall and changes in bone morphology and biochemistry.
A total of 7195 individuals were randomised to either the intervention (3301) or control arm. Among those allocated to the intervention arm, the mean age was 86 years (70% female). Diary intake increased from 2 to 3.5 servings per day, achieving a calcium intake of 1142 mg daily and 12 gm protein/day. During a mean follow-up of 12.6 months, the overall fracture incidence was 324 with 121 occurring in the intervention group and 203 in the control arm, a 33% risk reduction (Hazard ratio, HR = 0.67, 96% CI 0.48 – 0.93, p = 0.02). Post hoc analysis showed that the incidence of hip fractures was 1.3% in the intervention group and 2.4% in controls *(HR = 0.54, 95% CI 0.35 – 0.83, P = 0.005). Overall, there was an 11% lower risk of having a fall (HR = 0.89, 95% CI 0.78 – 0.98, p = 0.04) and there were 1974 deaths although this did not differ between the groups.
Data for biochemistry and bone morphology showed that at 12 months, there was a 20.4% difference between groups in serum C terminal telopeptide of type 1 collagen (p = 0.002). For bone morphology, there was a significant difference in lumbar spin bone mineral density (p = 0.04).
The authors concluded that their nutritional intervention was widespread implications as a public health measure for fracture prevention in the elderly.