Tied to the Past, Unprepared for the Future: Meeting the Alzheimer’s Disease Challenge With HEOR

By Beth Fand Incollingo

There has been a lot of fanfare about the first 2 medicines capable of slowing the progress of Alzheimer’s disease, lecanemab and donanemab, but their costs over a typical 1.5- to 2-year course of treatment can easily rival the sticker price for the average new car.

Yet, without the ability to slow the disease during its earlier symptomatic stages, how much more would society pay as these patients required an extra 6 to 8 months of round-the-clock care, in many cases preventing family caregivers from continuing to work and spend time with their children?

At the other extreme, if Alzheimer’s disease (AD) could be prevented or treated before symptoms developed, how much would that burden drop, and what level of investment in public education, research, and medical care would be warranted to make it happen?

As AD cases spiral, experts in health economics and outcomes research (HEOR), health technology assessment, policy, science, and advocacy are at odds about how to respond cost-effectively—and even about the importance of that effort.

Each year, dementia costs the world more than $1.3 trillion US dollars, half funding medical treatment and nursing-home fees and the other half constituting care provided at no charge but often significant sacrifice by loved ones, according to Paola Barbarino, CEO of Alzheimer’s Disease International (ADI), the federation of AD and dementia associations around the world.¹ That investment is likely to grow quickly, as the number of people with AD is expected to nearly double every 20 years.¹

A reluctance to shoulder more of that burden could explain why many governments limit their engagement with AD, the most common form of dementia, Barbarino said.

"Each year, dementia costs the world more than $1.3 trillion US dollars. That investment is likely to grow quickly, as the number of people with Alzheimer’s disease is expected to nearly double every 20 years."

Yet, advocates believe it’s crucial for governments to increase their commitment to raising awareness about AD and its proven preventive measures while supporting more timely diagnosis so that a broader swath of patients will be eligible for the new drugs. Supporters are also calling for increased scientific funding so that research programs can expand to match the scope of the problem. While nearly 40% of the world’s pharmaceutical research and development efforts are centered around the development of cancer treatments, dementia gets a much smaller piece of the pie.²

The bottom line, many advocates agree, is that AD isn’t getting the attention it deserves.

“There are as many people with neurodegeneration as with cancer, but there’s a huge underinvestment in neurodegeneration,” said Bart De Strooper, MD, a group leader at the UK Dementia Research Institute at University College London and a 2018 winner of the Lundbeck Foundation Brain Prize for his research into the mechanisms underlying AD.

“If you go to PubMed, where the world’s scientific publications are compiled, there are 5 million papers about cancer but only 400,000 about neurodegeneration,” De Strooper continued. “Yet, there are equal numbers of cancer patients—55 million in the world versus 58 million people with dementia. So, there’s really something not right here.”

Barbarino believes that imbalance arises, in part, from bias.

“The attitude of payers seems to be that these people are old, and that giving them an extra 6 months won’t mean much,” she said. “Yet, you wouldn’t say that in cancer, would you?”

A Misunderstood and Underrecognized Condition

Globally, 65% of healthcare professionals and 80% of the public wrongly believe that dementia is a part of normal aging,³ Barbarino said, and that view is often coupled with the misconception that meaningful intervention is impossible.

Responsible for 60% to 70% of dementia cases, AD is driven by biological changes that cause otherwise healthy proteins to accumulate in the brain, manifesting as amyloid plaques and neurofibrillary, or “tau,” tangles.⁴ These built-up proteins kill cells and cause the brain to shrink, resulting in progressive memory loss, personality changes and, ultimately, death—unless disease-related infection or aspiration pneumonia become fatal first.⁵

ADI’s goals are to improve risk reduction, timely diagnosis, care, and inclusion while working toward a cure for the disease.⁶

To support prevention, ADI promotes educational campaigns and government interventions focused around
14 risk factors that, if modified, can reduce the risk of AD by 45%: less education in early life; hearing loss, high LDL cholesterol, depression, traumatic brain injury, physical inactivity, diabetes, smoking, hypertension, obesity, and excessive alcohol use in midlife; and social isolation, air pollution, and visual loss in late life.⁷

“I do not see a huge amount of uptake of the kind of campaign that would make the public aware of that—although countries like Canada have done it,” Barbarino said. “Then, there’s still a lot of work needed to understand how to get people to change their behaviors.”

To make matters worse, she said, on average, 75% of the world’s dementia cases are never diagnosed, and that proportion rises to 90% in some low- and middle-income countries, where stigma is more pronounced.⁸

As a result, Barbarino said, “85% of people living with dementia are not accessing any form of post-diagnostic support,”⁹ which could otherwise include:

• Nonpharmaceutical rehabilitative strategies like brain and physical exercises, wearable health monitors, home modifications, and skill building for family caregivers¹⁰
• Medical treatment in the disease’s early symptomatic stages with 1 of the 2 drugs on the market or therapy at various stages with more than 125 compounds being tested in clinical trials¹¹
  
• Treatment at more advanced symptomatic stages with drugs like memantine hydrochloride, which slow the processes that damage neurons and are often paired with cholinesterase inhibitors, which improve nerve cell communication to ease memory loss

As most patients live 3 to 11 years after diagnosis,¹² an unmitigated battle with the disease can be not only grueling but expensive, De Strooper noted.

"To make matters worse, 75% of the world’s dementia cases are never diagnosed, and that proportion rises to 90% in some low- and middle-income countries, where stigma is more pronounced."

The Potential of Alzheimer’s Treatments

Also misunderstood is the promise of lecanemab and donanemab, said De Strooper, whose prize-winning research contributed to the development of the drugs by shedding light on a trigger of the disease cascade—the abnormal production of amyloid due to genetic mutations. The infused drugs work by clearing the brain of amyloid plaques.

As of March 2025, lecanemab (Lequembi; Eisai and Biogen) had been approved in the United States, South Korea, China, Japan, Israel, Hong Kong, the United Arab Emirates, Macau, and Mexico, but was largely unavailable in Europe. Meanwhile, donanemab (Kisunla; Eli Lilly) had received the green light in the United States, China, and Japan.¹²

Many decision makers complain that the medications don’t delay AD for long, are expensive, and come with side effects, including a 35% rate of ARIA — a brain edema or bleed that can cause headaches or dizziness but typically no other symptoms, De Strooper said.¹³ Severe brain bleeds occur in less than 1% of patients and cause death in 0.2% to 0.3%, he said.^14,15

In a 2023 report, the Institute for Clinical and Economic Review—an independent, nonprofit US organization that compares the value of proposed interventions against that of existing alternatives—found that lecanemab was not cost-effective at its list price of $26,500 per year, citing its mild slowing of cognitive loss versus the risks of ARIA.¹⁶

Nevertheless, De Strooper believes regulators should support the use of such drugs and offer fast-track approvals—as they often do when reviewing cancer treatments—because anti-amyloids have the potential to radically change the trajectory of AD. The goal, he said, should be to offer them to affected patients as long as 2 decades before symptoms appear,¹⁷ while also refining eligibility requirements.

Early treatment could become more feasible, he said, as clinics gain access to diagnostics like Lumipulse, which recently became the first blood test for AD to be approved by the US Food & Drug Administration.¹⁸ In the United Kingdom, a clinical trial is assessing diagnostic blood tests for dementia with the hope of eventually administering them before patients develop symptoms.¹⁹

“If you treated patients before they had already lost neurons, you could make the amyloid disappear before it triggered the other steps and have a much bigger effect,” De Strooper said. “There are already some preliminary data in patients suggesting that.”

Stopping the formation of amyloid plaques and tau tangles before irreversible brain damage occurred, he said, could make it possible to transplant memory-restoring neurons into the hippocampus of affected patients; that technique is already evolving as a treatment for Parkinson’s disease.²⁰

He added that the ability to stop the disease presymptomatically could open the door to additional novel therapies that could be used in concert with anti-amyloid drugs. His ongoing research on the role of genetics in AD could help make that possible.

“If we don’t get rid of the taboo atmosphere and fatalism surrounding AD and allow these anti-amyloid drugs to enter the market, doctors won’t be able to do clinical trials testing them in earlier treatment,” De Strooper said. “Also, by approving these drugs, we’ll create a market around them that will be in place when better antibodies come out, such as small-compound formulations that can be taken as pills, and that will enable competition.”

While scientists at Harvard University are using artificial intelligence to determine whether existing drugs might work against AD,^21,22 De Strooper said he doesn’t expect that research to produce miracles.

“These efforts should not take away from the hardcore basic research, screening, and testing that has been successful in any other field,” he said.

Considering Investment

Despite those arguments, many governments remain reluctant to invest, which is why the World Health Organization’s global action plan on the public health response to dementia has not been fully executed, Barbarino said.

While Japan and South Korea have put together large budgets to help cope with AD, she said, the United Kingdom—where dementia is the biggest killer in absolute terms—has continually postponed plans to boost its dementia care resources.

Government leaders often tell Barbarino they can’t afford to devote additional funding to AD, and one country’s representatives falsely claimed the disease didn’t exist there.

That lack of commitment often results in loved ones providing care, which takes them away from their jobs, schools, and families and tends to leave them more isolated, which can negatively affect their mental health. In higher-income countries, inadequate support drives up emergency department visits and nursing-home stays. Alternatively, in low- and middle-income countries, where migration is widespread, Barbarino said, people with dementia often have no family or pensions to help them and end up dying alone, sometimes sadly in the street.

Barbarino also said, “Currently many countries experience a loss of workforce in the crucial years, in which caregivers are caring for parents with dementia and for children,” Barbarino said. “Better respite care and support provision would enable people in this situation to continue working and providing for their families.”

Policy makers can consider how proposed investments in AD care would play out by using HEOR-based algorithms that predict outcomes, said Eric Jutkowitz, PhD, an associate professor of health services, policy, and practice at Brown University. His team has created a microsimulation that predicts dementia progression and associated costs at the population level, available as a tool for leaders in government, health plans, and hospital systems.

Another strategy for cost-effectiveness is to strategically coordinate existing AD resources, and the United States is one of several countries to have introduced such an effort. On July 1, 2024, the United States launched an 8-year pilot test of its Guiding an Improved Dementia Experience (GUIDE) Model, which uses standardization to support quality of life for eligible Part A or B Medicare recipients who don’t participate in Medicare Advantage, along with their unpaid caregivers.²³

Being offered by 390 longstanding providers and a growing spate of new physician groups, all of which receive value-based payments for their efforts, the program is intended to help patients stay in their homes and communities while reducing strain on unpaid caregivers through education, access to a 24-hour support line, assistance in finding community-based providers, and up to $2500 per year in respite care services.²⁴

“Coordinating these services instead of providing them individually represents a huge shift in how healthcare systems are thinking about providing care to people with dementia,” Jutkowitz said. “There’s an increased emphasis on using evidence-based models.”

Still, because global AD support remains a patchwork, 120 groups affiliated with ADI are working to fill unmet needs by providing care and support groups, funding or participating in research, urging policy makers to boost services, and monitoring governments as they roll out their plans.

Unfortunately, Barbarino said, “There are many countries where we cannot work because of a conflict or mistrust of civil society, and a denial of the existence of dementia.”

A Global Commitment

As the world’s decision makers grapple with the cost of AD, Jutkowitz said, HEOR experts can provide guidance on the allocation of resources.

Of course, De Strooper would like to see a significant portion of that funding go to medical research, and he believes supporters can help by mobilizing a grassroots approach, as did advocates for the AIDS community in the 1980s.

“AIDS was also a terrible disorder that was seen as taboo, and patients were too occupied to do anything about it,” he said. “But after initial drugs had little effect, friends and colleagues of those patients went to industry and the government and successfully pushed for more research.”

Continued support for AD research will remain just as crucial, he said, especially as the United States, which historically led this effort, considers cutting the budget of its National Institutes of Health by 40%, among other policy changes restricting scientific investigation.^25-27

"As the world’s decision makers grapple with the cost of Alzheimer’s, HEOR experts can guide them by determining where the bulk of funding should be directed to produce the best outcomes."

“In the richer countries, we need to develop and use Alzheimer’s drugs and give industry an appetite to make more,” De Strooper said. “Then, governments, social networks, and patients need to demand treatment for everybody so we can think about how to bring these medications to the rest of the world.”

While Barbarino agrees that investment in research is essential, she would like to see decision makers diversifying their focus in an effort to execute all 7 areas outlined in the WHO’s Global Action Plan. In addition to research and innovation, those action areas are: dementia as a public health priority; dementia awareness and friendliness; dementia risk reduction; dementia diagnosis, treatment, care, and support; support for dementia carers; and information systems for dementia. “Dementia is an all-of-society issue, and without funding in each of those areas, we will not achieve true progress toward dementia action,” Barbarino said.

References

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Beth Fand Incollingo is a freelance writer who reports on scientific, medical, and university issues.

Further Reading:
The April 2025 issue of Value in Health featured a special collection of papers on The Health Economics of Alzheimer’s Disease and Related Dementia. The themed section includes an introductory editorial by the Guest Editors, Thomas Rapp and Pei-Jung Lin, and 8 full-length articles. You can read the themed section here.