Dementia is a group of diseases associated with an ongoing decline of brain functioning that can result in loss of thinking ability, memory, attention, logical reasoning, and other mental abilities. Dementia imposes substantial health, social, and economic burdens on individuals, families, and communities. Globally, approximately 50 million individuals are currently living with dementia. With the ageing population, this figure is anticipated to surge to 152 million by the year 2050.
Cognitive decline is one of major manifestations of dementia. Current treatments for dementia are limited, and most of the available treatment options for dementia primarily address its symptoms. There is a need to explore new treatment options. Leukotriene receptor antagonists (LTRAs) are a class of medicines used to prevent the symptoms of asthma and seasonal allergies. There is evidence from animal studies that LTRA use may delay the progress of dementia and maintain cognitive function. However, the effects of LTRA in preventing dementia in humans have not been well studied.
This study aims to assess the effect of LTRAs in reducing the risk of dementia at the population level. The results of this study will allow us to better understand the potential of developing LTRAs for preventing and treating dementia.
With the aging of the global population, the prevalence of dementia is becoming a significant public health concern. Currently, there is no cure for dementia. Leukotriene receptor antagonists (LTRAs) are currently being used for the treatment of asthma and seasonal allergies. Preclinical animal studies suggested that LTRAs may alleviate the dementia pathology, restore the cognitive function in aged rats and may be effective in treating dementia.
This study aims to evaluate the association between LTRA use and dementia among patients with asthma, using data from CPRD. The Hospital Episode Statistics (HES) data will be used for capturing hospital diagnosis of dementia and potential confounding factors. The Office of National Statistics (ONS) data will be used to determine death. Linkage to Index of Multiple Deprivation will be used to control for the confounding from socioeconomic status.
This study will follow the target trial emulation framework to compare the effect of LTRAs with long-acting beta-agonists (LABAs, another class of medicines for asthma). Patients with asthma who initiated LTRA and LABA between 1 January 2005 and 31 December 2021 will be included. First, the new users of LTRAs will be compared with the new users of LABAs. Then, among those who initiated LABA, subsequent target trials will be emulated based on the time since LABA initiation to compare those who remained on LABA to those who added or switched to LTRA. Both intention-to-treat and per-protocol analyses will be conducted. Hazards ratios (HRs) will be approximated using pooled logistic regression models. Inverse probability treatment weighting (IPTW) will be used to account for the baseline confounding. Inverse probability of censoring weighting (IPCW) will be used to address the selection bias induced by artificial censoring in the per-protocol analysis. A pooled logistic regression model will be used to pool data over all emulated trials.
The hazard ratio (HR) and absolute risk difference of dementia for LTRA treatment vs. LABA treatment.
Wallis Lau - Chief Investigator - University College London ( UCL )
Boqing Chen - Corresponding Applicant - University College London ( UCL )
Chengsheng Ju - Collaborator - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
Yogini Jani - Collaborator - University College London ( UCL )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation