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13th January 2023
A brain-derived tau biomarker which can be easily measured in blood samples, represents an important step in the specific identification of Alzheimer’s disease-type neuro-degeneration according to a study by an international research group.
Biomarkers for the identification of Alzheimer’s disease (AD) are based on the A/T/N” system where ‘A’ refers to the value of a β-amyloid biomarker, ‘T’ the value of a tau biomarker and ‘N’, biomarkers of neuro-degeneration or neuronal injury. To date, at least two of these markers are satisfactory. For example, plasma β-amyloid marker measurement (A), accurately determines amyloid positron emission tomography status in cognitively normal research participants. In addition, blood-based tau markers (T) could be used as a simple, accessible, and scalable test for screening and diagnosis of Alzheimer’s disease. Nevertheless, neuro-degeneration (N) markers such as plasma neurofilament light chain (NfL), which measures axonal injury, showed no discriminatory power for AD compared to other neurological diseases.
Rather than focusing on developing a more specific ‘N’, researchers recognised that since tau measurements can be contaminated by peripherally generated (i.e., from liver, kidney or heart), it might be better to focus to identifying a specific brain-derived tau. In the present study, researchers created an anti-tau antibody which was designed to selectively bind with only brain-derived tau and which would hopefully be specific for patients with Alzheimer’s disease. The team then set out to validate the biomarker in five independent cohorts, including autopsy samples.
Brain-derived tau and Alzheimer’s disease
Using paired cerebrospinal fluid (CSF) and serum samples from AD patients and controls, there was a strong correlation (Spearman’s rho = 0.85, p < 0.0001) between the brain-derived (BD) tau levels in serum and CSF samples. In contrast, serum and total tau measurements were no significantly correlated (Spearman’s rho = 0.23, p = 0.3364). In addition, plasma brain-derived tau accurately distinguished autopsy-confirmed Alzheimer’s disease from other neurodegenerative diseases, with an area under the curve (AUC) value of 86.4%. Furthermore, using samples from patients in two memory clinic cohorts, serum brain-derived tau differentiated Alzheimer’s disease from a range of other neurodegenerative disorders (AUC = 99.6%). In another cohort, BD-tau levels were significantly increased in AD patient serum and CSF samples compared to controls (p < 0.0001). Finally, BD-tau levels were inversely correlated with clinical dementia rating global scores (Spearman’s rho = -0.30, p = 0.0352).
Taken together, the authors wrote ‘across cohorts, plasma/serum brain-derived tau was associated with CSF and plasma AT(N) biomarkers and cognitive function. Brain-derived tau is a new blood-based biomarker that outperforms plasma total-tau and, unlike neurofilament light, shows specificity to Alzheimer’s disease-type neuro-degeneration.’
They concluded that the brain-derived tau demonstrates potential to complete the AT(N) scheme in blood, and will be useful to evaluate Alzheimer’s disease-dependent neurodegenerative processes for clinical and research purposes.
Citation
Gonzalez-Ortis F et al. Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration. Brain 2022
19th December 2022
According to a press release by drug manufacturer Lilly, donanemab provides a greater level of brain amyloid clearance compared to aducanumab at 6 months.
Brain amyloid-β deposition is a hallmark used to define Alzheimer’s disease. Moreover, in March 2022, the Food and Drug administration (FDA) in the US, approved the first in vitro diagnostic test for early detection of amyloid plaques associated with Alzheimer’s disease. The FDA added that a positive test was consistent with the presence of amyloid plaques, similar to what would be seen in a PET scan and that a negative result is consistent with a negative amyloid PET scan result, reducing the likelihood that a patient’s cognitive impairment was due to Alzheimer’s disease, enabling physicians to pursue other causes of cognitive decline and dementia.
The current data announced by Lilly, comes from the TRAILBLAZER-ALZ 4 trial, which was a randomised, open-label phase 3 study designed to compare donanemab (DM) with aducanumab (AM) on amyloid plaque clearance in participants with early, symptomatic Alzheimer’s Disease. In the trial, donanemab and aducanumab were administered via intravenous infusions every four weeks for up to 18 months.
Donanemab efficacy
In the co-primary outcomes, brain amyloid plaque clearance, defined as achieving brain amyloid plaque levels of <24.1 Centiloids, was achieved in 37.9% of DM-treated participants compared with 1.6% of AM-treated patients at 6 months. In the intermediate tau subpopulation, 38.5% of DM-treated participants reached brain amyloid clearance compared with 3.8% of AM-treated participants by 6 months. In a key secondary outcome, DM reduced brain amyloid levels vs. baseline by 65.2% compared with 17.0% for AM at 6 months. In an exploratory outcome, donanemab, but not aducanumab treatment significantly reduced plasma P-tau217 at 6 months compared to baseline.
In terms of safety, amyloid-related imaging abnormalities were the most common treatment emergent adverse event in both groups and occurred with a similar frequency (25.4% vs 26.1%, DM vs AM).
Although only 6-month data is currently, available, the press release describes how TRAILBLAZER-ALZ 4 is an on-going study and results from 12 or 18 months will be presented once available.
23rd November 2022
Gantenerumab which is a fully human monoclonal IgG1 antibody failed to meet the primary endpoint of slowing clinical decline in people with early Alzheimer’s disease (AD) in two randomised, double-blind, placebo-controlled trials according to a release by the manufacturer Roche.
It has been estimated that currently, an estimated 6.2 million Americans aged 65 and older are living with Alzheimer’s dementia. Moreover, the World Health Organisation has estimated that there are more than 55 million people with dementia worldwide and nearly 10 million new cases every year, with Alzheimer’s disease accounting for between 60 – 70% dementia cases. The amyloid cascade hypothesis of AD proposes that deposition of the amyloid-β peptide in the brain is a central event in disease pathology and several drugs have been developed, including gantenerumab which binds with high affinity to aggregated amyloid-β species and removes amyloid-β plaques.
The potential value of gantenerumab came from a small trial in 2012, which revealed that it resulted in a dose-dependent reduction in brain amyloid levels. However, these early findings were called into question after a 2017 randomised trial with the drug in patients with prodromal AD, i.e., mild cognitive impairment, over a 2-year period, was halted early for futility. Despite this, the manufacturer Roche embarked to two global phase III trials, GRADUATE I and II designed to evaluate the safety and efficacy of gantenerumab in people with mild cognitive impairment due to Alzheimer’s and mild Alzheimer’s dementia over 27 months. The primary endpoint of both trials was the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 116 weeks, a tool that measures cognitive and functional change across six areas including memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care.
Gantenerumab and Alzheimer’s disease outcomes
According to the press release, 1,965 participants across 30 countries were randomised 1:1 to receive gantenerumab or placebo by subcutaneous injection and titrated to reach a target dose of 510 mg which was administered every two weeks. The results showed that while there was a slowing of clinical decline in GRADUATE I of -0.31 (p = 0.095) and -0.19 (p = 0.29) in GRADUATE II of -0.31 (p=0.0954) from baseline on CDR-SB, neither decrease was statistically significant. Additionally, the level of beta-amyloid removal was also lower than expected.
Commenting on the findings, Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development said, ‘While the GRADUATE results are not what we hoped, we are proud to have delivered a high quality, clear and comprehensive Alzheimer’s dataset to the field, and we look forward to sharing our learnings with the community as we continue to search for new treatments for this complex disease.’
Nevertheless, the press release reports that Roche remains committed to Alzheimer’s disease and is continuing to develop and deliver tests to enable early and accurate Alzheimer’s diagnosis and has a pipeline of investigational medicines for different targets, types and stages of the disease.
6th October 2022
Lecanemab use in patients with mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD) demonstrated an improvement in cognitive function compared to placebo after 18 months of treatment according to a press release by the joint manufacturers Eisai Co., Ltd and Biogen Inc.
Alzheimer’s disease is a progressive neurodegenerative disease that slowly impairs cognition and function and is the most common form of dementia. The discoveries of amyloid β (Aβ) and tau, the main components of plaques and tangles respectively, has provided detailed information about the molecular pathogenetic events of the disease. Given the build-up of soluble Aβ aggregates, it is possible that a reduction of such aggregates could represent an effective treatment approach in the early stages of AD. Lecanemab is a humanised IgG1 monoclonal antibody that binds to soluble Aβ aggregates and in a phase 1 dose ranging study in patients with mild to moderate AD, the drug (known as BAN 2401) was well-tolerated across all doses. Based on these findings, a randomised, double-blind, placebo-controlled, phase 2 trial was undertaken in 854 subjects with early Alzheimer’s disease and observed a reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints.
Clarity AD was a phase 3 trial to evaluate the efficacy of lecanemab in patients with early Alzheimer’s disease. Participants were administered lecanemab at a dosage of 10 mg/kg bi-weekly and randomised 1:1 to either placebo or lecanemab. The primary endpoint was the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) after 18 months of treatment. The CDR-SB is a numeric scale used to quantify the various severity of symptoms of dementia and is an appropriate item for evaluating the effectiveness of therapeutic drugs targeting the early stages of AD. Based on interviews of people living with AD and family/caregivers, qualified healthcare professionals assess cognitive and functional performance in six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The total score of the six areas is the score of CDR-SB. Key secondary endpoints for the trial were the change from baseline at 18 months compared with placebo of treatment in amyloid levels in the brain measured by amyloid positron emission tomography (PET), the AD Assessment Scale-cognitive sub-scale14 (ADAS-cog14), AD Composite Score (ADCOMS) and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).
Lecanemab and treatment outcome
Clarity AD included 1,795 people with early AD and according to the press release, lecanemab met the primary endpoint and reduced clinical decline on the CDR-SB, compared with placebo at 18 months by 27%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat (ITT) population. Starting as early as six months, across all time points, the treatment showed highly statistically significant changes in CDR-SB from baseline compared to placebo (all p-values are less than 0.01). All key secondary endpoints were also met with highly statistically significant results compared with placebo (p<0.01).
The incidence of amyloid-related imaging abnormalities-oedema/effusion (ARIA-E), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. The ARIA-H (ARIA cerebral micro-haemorrhages, cerebral macro-haemorrhages, and superficial siderosis) rate was 17.0% in the lecanemab group and 8.7% in the placebo group. The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group. Overall, lecanemab’s ARIA incidence profile was within expectations.
Commenting on these early findings, Dr Susan Kohlhaas, director of research at Alzheimer’s Research UK, said: “this is a historic moment for dementia research, as this is the first phase 3 trial of an Alzheimer’s drug in a generation to successfully slow cognitive decline. These results show that lecanemab slows the progression of memory and thinking problems in people with early Alzheimer’s, demonstrating a major breakthrough in dementia research. This is the first drug that’s been shown to not only remove the build-up of a protein called amyloid in the brain, but to have a small but statistically significant impact on cognitive decline in people with early-stage disease.’
27th September 2022
A new diagnosis of Alzheimer’s disease appears to be significantly associated with a COVID-19 infection suggesting that the virus might play a causative role in the development of the dementia according to the findings of a retrospective study by a team of US researchers.
It has been speculated for many years that infectious agents in the brain have a role in the pathogenesis of Alzheimer disease (AD) and while discarded in the past, several recent discoveries have reignited interest in the infectious theory. For instance, in a retrospective study of the electronic health records of 61.9 million adult and senior patients, it was found that those with dementia were at an increased risk for COVID-19 compared to those without it and that the risk was also significantly elevated among those with Alzheimer’s disease. Moreover, genome-wide association studies indicate that a large percentage of AD risk genes are associated with innate immunity and inflammation, suggesting that the immune system plays a critical, and previously unappreciated, role in AD pathology. In addition, follow-up studies of patients infected with COVID-19 have demonstrated the presence of neuropsychiatric symptoms which would suggest that the virus is able to enter the brain. Taken together, these findings imply that inflammatory changes, particularly if these occur within the brain, could increase Alzheimer’s disease risk but this topic has not been studied in any detail. For the present study, the US researchers retrospectively examined the de-identified electronic health records of older adults ( > 65 years of age) without a prior diagnosis of AD. The cohort were then divided into two groups: those with and without a documented infection of COVID-19. The team then examined the subsequent development of AD between the two groups and propensity-matched individuals for demographics, occupational exposure, physical and social and psychosocial environments and known risk factors for AD.
Alzheimer’s disease risk and COVID-19
After propensity matching, the COVID-19 cohort contained 410,478 individuals with a mean age of 73.7 years (53.6% female), the majority of whom (75.3%) were of White ethnicity. Co-morbidities included hypertension (59.4%), overweight and obesity (23%) and type 2 diabetes (30.4%).
After matching, the COVID-19 cohort had a significantly higher Alzheimer’s disease risk (hazard ratio, HR = 1.69, 95% CI 1.53 – 1.72). This risk was elevated in all groups when stratified by age although the highest risk occurred in those aged 85 years and older (HR = 1.89, 95% CI 1.73 – 2.07). Individuals of Black and White ethnicity had a similar level of increased risk (HR = 1.62 and 1.61, for Black and White ethnicities respectively).
The authors concluded that older adults with COVID-19 had an increased Alzheimer’s disease risk although they accepted the limitation of using a retrospective analysis and called for research to better understand the underlying mechanisms and for continuous surveillance of the long-term impact of COVID-19 on Alzheimer’s disease.
Citation
Wang L et al. Association of COVID-19 with New-Onset Alzheimer’s Disease J Alzheimers Dis 2022
23rd August 2022
Increased amounts of all types of leisure activities e.g., cognitive, physical and social reduce the risk of developing all-cause dementia (ACD) including Alzheimer’s disease (AD) and vascular dementia (VD) according to a systematic review and meta-analysis by a team of Chinese researchers.
Dementia is a syndrome characterised by a deterioration in cognitive function beyond that which might be expected from the usual consequences of biological ageing and currently, across the globe, affects some 55 million people. Although there are several types of dementia, the most common is Alzheimer’s disease, followed by vascular dementia. There is currently no cure for dementia and recommendations to reduce risk factors include switching to a healthy diet and staying mentally and socially active. Indeed, there is some evidence that cognitively stimulating leisure activities may delay the onset of dementia in community-dwelling elders although the value of such activities are uncertain. For example, one study found that neither intellectual or physical activity lifestyle factors were associated with AD biomarkers with another concluding that physical inactivity was not associated with all-cause dementia or Alzheimer’s disease.
With some uncertainty over whether any of these leisure activities impact on ACD, for the present study, the Chinese team undertook a systematic review and meta-analysis. They set out to assess the effect of three different forms of leisure activities: physical (PA), cognitive (CA) and social (SA). For the purposes of the study, PA was defined to include walking, playing sports etc, CA, reading books, writing for pleasure or solving crossword puzzles and SA anything that involved communication with others, e.g. attendance at social centres, volunteer work etc. The researchers used regression analysis to determine the relationship between the different leisure activities and ACD and both subtypes, adjusting their results for covariates such as age, gender, education and apolipoprotein E.
Leisure activities and all-cause dementia
The literature review identified a total of 38 eligible studies with 215, 818 participants and a mean age of 45 years at baseline.
Overall, 36 studies were used to investigate the relationship between the different activities and all-cause dementia. The analysis revealed that participation in leisure activities, compared to no participation, was associated with a 17% lower risk of developing ACD (relative risk, RR = 0.83, 95% CI 0.80 – 0.87, p < 0.001). In subgroup analysis, there was also a significant reduction for each of the different forms of activity, e.g., the relative risk for CA was 0.77 (95% CI 0.68 – 0.87).
For AD, there was an 18% lower risk for participation in leisure activities (RR = 0.82, 95% CI 0.74 – 0.90, p < 0.001) and again, while the lower risk was similar for PA and CA, it was non-significant for SA (RR = 0.89, 95% CI 0.63 – 1.26) although the latter activity assessment was based on only a single study.
For vascular dementia, the reduction was even greater at 32% (RR = 0.68, 95% CI 0.54 – 0.86, p = 0.007). However, this association was only significant for PA and not for CA although there were no studies which examined the relationship with SA.
The authors concluded that leisure activities including physical, cognitive and social, were all significantly associated with a reduced risk of incident dementia and that both PA and CA were linked to a lower risk of AD.
Citation
Su S et al. Leisure Activities and the Risk of Dementia: A Systematic Review and Meta-Analysis Neurology 2022
19th July 2022
Noradrenergic drugs produce a small but significant improvement in global cognition and apathy in patients with Alzheimer’s disease(AD) with no important effects on any other measures according to the findings of a meta-analysis by UK researchers.
The World Health Organisation (WHO) defines dementia as a syndrome in which there is deterioration in cognitive function beyond what might be expected from the usual consequences of biological ageing. WHO also estimates that worldwide in 2021, there were approximately 55 million people living with dementia and that AD, which is the most common form of dementia, may contribute to 60-70% of all cases. The neurotransmitter noradrenaline is released by the locus coeruleus and has become recognised as a contributor to various aspects of cognition, including attention, behavioural flexibility, working memory, and long-term mnemonic processes. Furthermore, the locus coeruleus is one of the first sites of tau deposition in AD and with noradrenergic dysfunction being an early sign in patients with AD, it would seem logical to use noradrenergic drugs as a treatment for the disease. Nevertheless, trials examining the value of noradrenergic drugs in AD have generally proved to be unsuccessful. Despite this, there has been no attempt to assess the overall impact of this drug class in AD which was the purpose of the present study. The UK team performed a systemic review and meta-analysis to assess the degree to which drugs, whose principle action is as a noradrenergic agent, could improve the cognition and behavioural aspects of AD.
They searched for trials that included patients with AD in which noradrenergic drugs, that increased levels of noradrenaline, were compared against placebo and where the studies reported on cognitive and neuropsychiatric (e.g., agitation, apathy) changes. The outcomes of interest were changes in measure of both global cognition and neuropsychiatric symptoms.
Noradrenergic drugs and Alzheimer’s disease outcomes
The search identified a total of 19 trials with 1811 patients and all of the studies were prospective, randomised trials and with a treatment duration of between 2 and 52 weeks. The most commonly used noradrenergic drugs were noradrenalin re-uptake inhibitors, alpha1 adrenergic receptor antagonists, alpha2 receptor agonists, alpha2 receptor antagonists and beta adrenergic receptor blockers.
For global cognition, the overall pooled effect size was small but statistically significant in comparison to placebo (standardised mean difference, SMD = 0.14, 95% CI 0.03 – 0.25, p = 0.01). To provide some perspective for this effect, the authors included the SMD for cholinesterase inhibitors from studies in AD which was 0.38. Although noradrenergic drugs had a positive effect on semantic memory (SMD = 0.20), the drugs had no significant effect on any of the other cognitive measures.
For neuropsychiatric measures the only measure for which there was a significant effect was apathy with a pooled SMD of 0.45 (95% CI 0.16 – 0.73, p = 0.002).
The authors concluded that pharmacotherapies targeting the noradrenergic system appeared to improve both cognition and apathy. In addition, they suggested these data provided a strong case for further trials to examine the value of these drugs in AD and other neurodegenerative diseases.
Citation
David MCB et al. Cognitive and neuropsychiatric effects of noradrenergic treatment in Alzheimer’s disease: systematic review and meta-analysis J Neurol Neurosurg Psychiatry 2022
1st June 2022
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
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.
Citation
Magyari A et al. Adult atopic eczema and the risk of dementia: A population-based cohort study J Am Acad Dermatol 2022
22nd April 2022
People who adopt a healthy lifestyle are not only more likely to live longer but also have a reduced risk of developing Alzheimer’s disease compared with those who lead a less healthy lifestyle. This was the finding of an analysis of data from the Chicago Health and Ageing Project (CHAP) by a team from the Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, USA.
Alzheimer’s disease is the most common form of dementia with a high level of inheritability which is thought to be between 60% and 80%. Nevertheless, while genetic factors are associated with a higher risk of developing AD, the extent to which lifestyle modification can off-set this risk is unclear, although some data shows that a favourable lifestyle was associated with a lower dementia risk even among participants with high genetic risk. In fact, evidence suggests that when compared to those with no to only one healthy lifestyle factor, the risk of Alzheimer dementia was 60% lower in those with 4 to 5 healthy lifestyle factors. Since the greatest risk factor for Alzheimer’s disease is advanced age, for the present study, the US team wanted to explore the impact of a healthy lifestyle on both life expectancy lived with and without AD.
The researchers turned to the CHAP, which is a prospective study designed to assess risk factors for AD. To explore the impact of a healthy lifestyle, they created a scoring system which included five recognised and modifiable lifestyle factors: diet, cognitive activities (e.g., reading, doing crosswords, puzzles etc), physical activity, smoking and alcohol consumption. For each of these five factors, researchers assigned individuals a score of 1 (if they met the threshold for a healthy or low risk score) or 0 (where they did not meet the criteria). An individual’s score was then summed, ranging from 0 to 5. The main outcome of interest was life expectancy with and without AD in both sexes.
Healthy lifestyle and life expectancy
A total of 2449 individuals with a mean age of 76.2 years were included in the analysis and the mean lifestyle score was 2.3.
During 13,047 person years of follow-up, 20.8% of participants developed incident AD. Among women with between 4 and 5 healthy lifestyle factors, the risk of AD compared to those with 0 or 1 factors was significantly reduced (hazard ratio, HR = 0.44, 95% CI 0.32 – 0.59). A similar reduction was also evident for me (HR = 0.30, 95% CI 0.19 – 0.47).
The benefits of a healthy lifestyle also led to a reduced mortality risk compared to those with 0 to 1 factors in both women (HR = 0.56, 95% CI 0.49 – 0.65) and men (HR = 0.47, 95% CI 0.39 – 0.57).
The authors calculated that the life expectancy of women aged 65 but without Alzheimer’s dementia and four or five healthy factors was 21.5 years compared to 17 years for those with either 0 or 1 healthy factors. Similar benefits were also seen for men.
The impact of a high healthy lifestyle score also affected the number of years spent with AD. For example, of the total life expectancy of women aged 65, those with four or five healthy factors spent 2.6 years (10.8%) with Alzheimer’s dementia. In contrast, women with 0 or one healthy factor, spent 4.1 years (19.3%) with the disease. Again, similar benefits were seen for men.
The authors concluded that a healthy lifestyle not only increased life expectancy but it was likely to reduce the proportion of remaining years lived with AD.
Citation
Dhana K et al. Healthy lifestyle and life expectancy with and without Alzheimer’s dementia: population based cohort study BMJ 2022
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