PAVE: Global research study on epidemiology of Alzheimer’s disease

The epidemiology of Alzheimer’s - MRI brian of Dementia patient
© Atthapon Raksthaput

To improve understanding of the impact and epidemiology of Alzheimer’s disease, Project Alzheimer’s Value Europe (PAVE) demonstrates the prevalence of Alzheimer’s across the stages of the disease, including prodromal and preclinical – which aren’t recognised by previous studies

Project Alzheimer’s Value Europe (PAVE) has published findings from its recent study “Global estimates on the number of persons across the Alzheimer’s continuum,” which suggests a window of opportunity for preventive measures and disease modifying treatments and a better understanding of the epidemiology of Alzheimer’s.

The need for accurate data in defining and treating Alzheimer’s

Accurately defining Alzheimer’s disease (AD) and quantifying its effect on global populations and healthcare systems has proven difficult. While available studies suggest that the estimated number of patients with dementia exceeds 50 million, comprehensive data on the burden of AD does not account for prodromal or preclinical stages of AD, where a majority of patients have no measurable symptoms and present a diagnostic challenge. With the potential opportunity for interventions that could prevent the disease from progressing, health care planners and policymakers require a better under- standing of the size and demographics of the AD population to accurately assess the value of preventive interventions and potential disease-modifying therapies (DMTs) for people living with Alzheimer’s and their families.

PAVE – a collaborative, multi-stake-holder forum committed to Alzheimer’s disease (AD) research, value assessment and funding in Europe – recently published research aiming to fill this data gap by evaluating the global prevalence of disease across the Alzheimer’s disease continuum. The study considered all stages of AD and found that the number of people affected by AD is significantly higher than previous published estimates. By shedding light on the size of the AD population and including those in the earliest stages before symptoms appear, the study provides a starting point for the assessment of non-pharmaceutical interventions aimed at preventing this disease, as well as candidate DMTs aimed at slowing progression.

The approach to measuring the global prevalence of AD To measure the global prevalence of AD, a review of published evidence from the last ten years reporting prevalence estimates of any AD stage was conducted, with preference given to those reporting data from multiple cohorts stratified by sex, age, and country/region. Researchers compiled evidence into three pre-defined stages of the AD continuum – preclinical AD, prodromal AD and AD dementia – and analyzed patient demographics at each stage of disease, relying on the presence of a predictive biomarker which can appear many years prior to the onset of clinical signs and symptoms of disease.

What the results tell us about the prevalence of Alzheimer’s

First and foremost, disease prevalence across the Alzheimer’s continuum was found to be significantly higher than current estimates suggest. The present estimate of 50 million persons living with AD globally does not capture those in the earliest stages of disease. The study’s co-authors found that 416 million people, or 22% of all persons aged 50 and above, are on the Alzheimer’s continuum. Within the overall AD continuum, AD dementia, prodromal AD and preclinical AD stage populations were estimated to be 32, 69 and 315 million, respectively.

The results suggest that the proportion of people with early-stage prodromal or preclinical AD is significant, with as many as 86 million people potentially qualifying for emerging candidate therapies that slow Alzheimer’s disease progression. Within this subgroup, women and those with a lower degree of education present with AD at a higher rate than other demographic groups, though additional research and evidence is needed to confirm these findings. Evaluation of biomarkers further bolstered under- standing around early-stage AD populations. The study’s co-authors evaluated the presence of the APOE ε4 allele – a biomarker predictive of Alzheimer’s disease – among subjects, and identified the allele in 55% and 57% of those with preclinical AD and prodromal AD, respectively. Additional research on biomarker-confirmed populations is needed to further the understanding of risk associated with various demographic factors as well as to support a precision-medicine approach to the treatment of AD. Most importantly, however, these findings suggest that available epidemiological estimates underestimate the prevalence of AD, especially amongst pre-dementia-stage populations where there is the greatest opportunity for effective prevention measures aimed at reducing the risk of developing the disease.

The paradigm shift towards prevention and early treatment of Alzheimer’s

Current Alzheimer’s treatments focus on addressing the symptoms of those people in later stages of disease. The science around the benefit of disease prevention, risk reduction and disease modification suggests there is a significant opportunity to expand upon the current research and increase healthcare systems’ focus to populations at the earliest stages of the disease. Evaluating the overall investment needed and the socioeconomic value of a paradigm shift from merely treating symptoms to slowing the progression of and preventing the disease requires a better understand- ing of the overall patient population size and target populations for DMTs. The findings of this study can offer a starting point for the future assessment of AD burden and disease distribution across subgroups. PAVE hopes these estimates will inform prevalence-based approaches to value assessment of new innovations in AD. Without accurate definitions for, and numbers for the subgroups of the AD patient population or a full understanding of the broader socioeconomic burden of AD, health care systems and payers will remain ill-equipped to effectively assess the full value of expected new diagnostic tools and therapies for Alzheimer’s disease.

Looking ahead to ensure access

PAVE’s goal is to educate, develop evidence and provide solutions to support the value assessment of and funding for future Alzheimer’s disease therapies and diagnostics. With this new evidence on the global prevalence of AD and greater insight on the scale of potential benefit of prevention measures and emerging DMTs, we aim to contribute to the expanding research on AD and work towards holistic approaches to value assessment, health system planning and policymaking.

Follow PAVE on LinkedIn and visit PAVEurope.com for more information on our work and how to become a part of our effort.

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