Introduction

Alzheimer’s disease came to public attention in 1906 when German physician Alois Alzheimer announced the discovery of amyloid plagues and neurofibrillary tangles in patients with memory loss and other cognitive impairments. Despite the increasing number of people suffering from Alzheimer’s disease over the years, there has been a notable absence of effective drugs and treatments for most of the time since the diseases was named.

That is changing. The theme of the 31st World Alzheimer’s Day, which took place on September 21, 2024, was “Time to act on dementia, Time to act on Alzheimer’s.”[i] This theme serves as a timely reminder that dementia in general, and Alzheimer’s disease in particular, has become a major public health issue worldwide as the global population ages and life expectancy increases.

Encouragingly, in recent years, there have been significant advancements in the management of Alzheimer’s disease. New drugs have entered the market with recognised efficacy, and there have been promising developments in early diagnosis. Importantly, new technologies and recent scientific studies indicate that Alzheimer's disease is both preventable and controllable. Through early detection, intervention and treatment, we can prevent and delay the onset and progression of dementia, thereby improving the quality of life for patients and their families.

Alzheimer's disease

1.       Alzheimer's disease and risk factors

Alzheimer's disease is a degenerative lesion of the central nervous system that typically occurs in old age and pre-geriatric age. It is characterised by progressive cognitive dysfunction and behavioural impairments, which can be manifested as memory impairment, aphasia, dysarthria, anosognosia, impaired visuospatial ability, and impaired abstract thinking and computational ability, as well as personality and behavioural changes.

The disease is among the most common chronic conditions in old age and is the fifth leading cause of death among the elderly in the US.[i] Globally, the World Health Organization (WHO) recognises Alzheimer’s disease and other dementias as the seventh leading cause of death.[ii] The prevalence of Alzheimer’s disease is closely related to age, with the prevalence rate increasing by a factor of one for every 6.1 years of age increase on average. Among elderly individuals aged 85 years and above, the prevalence rate can be as high as 20-30%.  According to the WHO,  more than 55 million people worldwide are living with dementia, with Alzheimer’s disease accounting for 60-70% of cases. By 2050, the number of people with dementia could reach 139 million.[iii]

Numerous risk factors can increase the risk of developing Alzheimer’s disease, including advanced age, female gender, heredity, physical inactivity, smoking, alcoholism, sleep disorders, air pollution, head injuries, obesity, high blood pressure, diabetes, depression, and inadequate socialisation.

2.       Causes and pathogenesis of Alzheimer's disease

Genetically inherited familial Alzheimer’s disease  accounts for around 10% of cases and most often starts before the age of 65. Mutations in the gene encoding amyloid precursor protein (APP) have been identified as a cause of familial Alzheimer’s disease. Sporadic Alzheimer’s disease  accounts for the remaining 90% of cases. Carriers of the APOEε4 mutation gene are at high risk for sporadic Alzheimer’s disease. Studies show that people carrying one APOEε4 allele have a risk of Alzheimer’s disease approximately 3.2 times higher than the general population, while those carrying two APOEε4 alleles have a risk about 8-12 times higher.[iv] Therefore, genetic screening can help identify individuals at potential risk for Alzheimer’s disease, allowing for early prevention and intervention to delay the onset and reduce the costs of medical treatment and care.

3.       Pathologic changes and clinical stages of Alzheimer's disease

The general pathology of Alzheimer’s disease is characterised by a reduction in the size and weight of the brain, deepening and widening of the sulci, and atrophy of the cerebral gyrus. Typical histopathological changes include neuroinflammatory plaques formed by deposition of Aβ-amyloid protein (Aβ) outside the nerve cells and neuroprogenitor fibril tangles formed by the aggregation of hyperphosphorylated tau protein inside the nerve cells.

The pathologic changes of Alzheimer’s disease may precede the onset of cognitive impairment symptoms by 10-20 years, and awareness in the early stages of the disease is very low. This underscores the importance of early screening, diagnosis, and intervention, as these measures are more likely to slow the progression of the disease.

The burden of Alzheimer's disease

1.       Accelerated aging leads to a significant increase in Alzheimer’s disease patients

The prevalence of Alzheimer’s disease is increasing rapidly in countries with aging populations. For instance, Mainland China reported that by the end of 2021, 9.83 million individuals aged 60 and older were living with Alzheimer’s disease.[i] Similarly, a study conducted in Kuyama, Japan, showed that from the 1980s to 2005, the prevalence of Alzheimer’s disease increased 3.28-fold over a 20-year period, from 1.4% to 6.1%.[ii]

2.       The economic burden of Alzheimer’s disease and related dementia is severe

The economic burden of Alzheimer’s disease and related dementias continues to escalate globally. In 2019, the “value of a statistical life” (VSL)-based estimate of the global burden of Alzheimer’s disease and related dementias was USD2.8 trillion.[iii] This burden is projected to increase to USD4.7 trillion by 2030, USD8.5 trillion by 2040, and USD16.9 trillion by 2050.

3.       The other burdens of the Alzheimer’s disease

In addition to increasing the burden of living and mortality, Alzheimer’s disease  significantly raises the incidence of falls and fractures.[iv] It is also positively associated with an increased risk of stroke, particularly hemorrhagic stroke.[v] Furthermore, Alzheimer’s disease is linked to the occurrence of suicidal behaviours,[vi] and patients with Alzheimer’s disease often suffer from a high prevalence of co-morbidities and a high medication burden.[vii]

Alzheimer's disease is highly prevalent, poorly prognosed, and imposes a significant burden on families, society, and the healthcare system. The insidious onset of the disease, low awareness, the risk associated with invasive tests, and the lack of consistent blood markers over the years make diagnosis challenging. At the same time, there has been no breakthrough in the therapeutic field of Alzheimer’s disease for a long time. Almost no new Alzheimer's disease drug has been launched globally for the past 30 years. Data indicate that between 2000 and 2017, more than 300 clinical drugs for Alzheimer's disease were developed and failed globally, with a failure rate of 99.6% (compared with a 19% success rate for cancer drugs). Major pharmaceutical companies have spent tens of billions of dollars on repeated failures, and some have even permanently abandoned research in this area.

The dawn of a new era

The turnaround began around 2020. In 2019, the commercialisation of a potent Alzheimer's disease drug, GV-971 (sodium oligomannate), was approved in Mainland China, followed by the approval of two Aβ monoclonal antibody drugs in 2022 and 2023. Almost at the same time, significant innovations emerged in the early diagnosis, screening and intervention of Alzheimer’s disease. These include AI in MRI, Aβ-PET, intelligent questionnaire assessment, digital intervention therapy and other products that have been approved and launched. This marks the beginning of an era with a comprehensive value chain for the management of Alzheimer’s disease, encompassing screening, diagnosis, intervention and treatment.

1.       New therapies are mainly used for early Alzheimer's disease

So far, three new drugs have shown effectiveness in slowing the progression of Alzheimer's disease in patients: GV-971, Aducanumab (an Aβ monoclonal antibody) and Lecanemab (another Aβ monoclonal antibody). A fourth drug, Donanemab (an Aβ monoclonal antibody), is approved to be used in the US while awaiting approval in Europe. Available clinical data indicate that these new drugs are primarily effective for early-stage patients. Consequently, these drugs are mostly introduced to patients with mild cognitive impairment or mild dementia who have been shown to have amyloid plaques. This underscores the renewed importance of identifying patients with early Alzheimer’s disease.

2.       New screening techniques make non-invasive early diagnosis possible

Similar to other diseases that benefit from early screening, Alzheimer’s disease, as a neurodegenerative disease, progresses slowing. It often takes more than 10 years from the appearance of abnormalities in relevant brain biomarkers to the onset of significant cognitive impairment. Because of this, new technologies for early diagnosis and screening that emerged in recent years, such as Aβ kits, Aβ-PET visualizers, and AI in MRI diagnostic technology, can advance the first diagnosis of Alzheimer’s disease by 2-10 years, buying valuable time for intervention and treatment.

3.       New interventions can slow progression in early-stage patients

The famous ACTIVE study on cognitive disorders in the US reported that early intervention with cognitive training can effectively avoid about 33% of dementia cases. In January 2022, cognitive function assessment software and training software, along with other related products, were approved as Class II medical devices for digital therapy. These products offer comprehensive, clinical-grade non-pharmacological interventions targeting various aspects of health, including sleep, exercise, nutrition, mood, posture, trajectory, voice, and vision. This can help the middle-aged and elderly population enhance cognitive function, combat risk factors of cognitive decline, avoid or delay the development of Alzheimer’s disease, and improve patients' ability to live independently.

Space for innovation in new technologies and commercial insurance

In 2015, the annual per capita cost of Alzheimer’s disease patients in China was estimated at around CNY130,000, with the total socio-economic burden due to the disease amounting to CNY1,140.6 billion. By 2030, the economic burden of Alzheimer’s disease is expected to reach a staggering CNY17 trillion per annum. Given the significant financial burden on individuals and societies, the insurance industry has previously tried to include Alzheimer’s disease in its coverage, but with limited success.

Alzheimer’s disease has a long latent development period (about 5-10 years). Early diagnosis and timely intervention and treatment can potentially slow the progression of Alzheimer’s disease from mild to moderate or severe stages thereby reducing overall cost. Both screening and intervention can lead to a longer life expectancy and an extended period of milder disease stages in patients with Alzheimer’s disease. This can reduce the risk of claims for commercial insurance customers, whether they are in life insurance, critical illness insurance, or long-term care insurance, as the claim event will be delayed.

However, screening and intervention also extend the overall window of time for the disease to be managed, potentially increasing societal health costs. For countries where social health care covers Alzheimer’s disease, payment risk will likely increase. As social health insurance is less flexible than commercial insurance for policy adjustments, and given the risk of high future costs, it is reasonable to leverage commercial insurance to supplement social insurance.

The introduction of new technologies, such as early screening interventions, to commercial insurance customers to improve their health and enhance the experience of life, critical illness, and long-term care insurance. This can foster risk reduction in existing policies and create space for innovation in these products. Since social health insurance has not yet included new Alzheimer’s disease prevention and screening technologies in its reimbursable scope, commercial insurers can take advantage of this window of opportunity to upgrade their health insurance products. They can add Alzheimer’s disease -related coverage and provide health management services while ensuring flexibility for adjustment.

[i] World Alzheimer's Day is September 21, 2024 | alz.org

[ii] Alzheimer's Association 2024 Alzheimer's Disease Facts and Figures. Figures refer to 2021.

[iii] Alzheimer's Association 2024 Alzheimer's Disease Facts and Figures. Figures refer to 2021.

[iv] World-Alzheimer-Report-2024.pdf, Alzheimer’s Disease International, 2024.

[v] Sienski G., et al. APOE4 disrupts intracellular lipid homeostasis in human iPSC-derived glia. Sci Transl Med. 2021 Mar 3;13(583):eaaz4564. doi: 10.1126/scitranslmed.aaz4564.

[vi] Jia L, Du Y, Chu L, et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study[J]. The Lancet Public Health, 2020, 5(12): e661-e671.

[vii] An overview of the Alzheimer's disease (AD) diagnostic industry in China by 2021[J].

[viii] Nandi A, Counts N, Chen S, et al. Global and regional projections of the economic burden of Alzheimer's disease and related dementias from 2019 to 2050. A value of statistical life approach[J]. EClinicalMedicine, 2022, 51: 101580.

[ix] Dev K, Javed A, Bai P, et al. Prevalence of Falls and Fractures in Alzheimer's Patients Compared to General Population[J]. Cureus, 2021, 13(1): e12923.

[x] Pinho J, Quintas-Neves M, Dogan I, et al. Incident stroke in patients with Alzheimer's disease: systematic review and meta-analysis[J]. Sci Rep, 2021, 11(1): 16385.

[xi] Alipour-Haris G, Armstrong MJ, Sullivan JL, et al. Suicidal Ideation and Suicide-Attempt-Related Hospitalizations among People with Alzheimer's Disease (AD) and AD-Related Dementias in the United States during 2016-2018[J]. J Clin Med, 2022, 11(4).

[xii] Wang JH, Wu YJ, Tee BL, et al. Medical Comorbidity in Alzheimer's Disease: a Nested Case-Control Study[J]. J Alzheimers Dis, 2018, 63(2): 773-781.