Rick is helping to answer a question central to the future of Alzheimer’s care: Can the disease be stopped, or delayed, before it has noticeable effects?
Doctors now believe the seeds of Alzheimer’s are planted decades before symptoms emerge, and the best hope for combating the illness will be treating people when they’re feeling just fine.
Rick is participating in the AHEAD study, one of two nationwide studies in which people with no symptoms are given a drug that is otherwise provided only to those already experiencing signs of Alzheimer’s disease. (Rick doesn’t know whether he’s receiving the drug or an inactive placebo.)
Within a few years, the study may show whether the drugs can prevent the disease from developing in the first place.
If the answer is yes, “that would be revolutionary,” said Dr. Daniel Z. Press, chief of the Division of Cognitive Neurology at Beth Israel Deaconess Medical Center, who is not involved with that research. “We would then be for the first time trying to prevent Alzheimer’s disease rather than treating it.”
That’s only one piece of the sprawling puzzle of Alzheimer’s research. Also under study are dozens of other drugs that work on different aspects of the biology of the disease. At the same time, there’s growing evidence people can lower their risk of dementia with a healthy lifestyle. And a new emphasis on learning how to live with dementia is shifting the grim paradigm that for so long has defined the illness.
“I’m feeling quite optimistic,” said Susan Antkowiak, vice president of programs and services at the Alzheimer’s Association of Massachusetts and New Hampshire.
Such optimism marks a shift in the fraught and often disappointing history of Alzheimer’s research, which critics say had focused too narrowly on the role of amyloid and has been tainted by allegations of fraud. The drug Aduhelm, which could slightly slow the progress of Alzheimer’s but had major risks, was pulled off the market in 2024 after skeptical doctors shunned it and insurers and Medicare restricted coverage.
The enthusiasm is also tempered by fears that reductions in federal research funding could stall the most promising work. President Trump has asked Congress to cut the National Institutes of Health budget by 40 percent. But appropriations committees in both the Senate and the House have voted to increase funding for Alzheimer’s research.
“As we’re making this progress, we cannot back up,” Antkowiak said.
The current leading hypothesis is that Alzheimer’s disease is driven by two types of malformed proteins — amyloid plaques and tau tangles — which interfere with brain function, gradually diminishing the ability to think and remember.
Tau helps the neurons in healthy brains function. But it becomes a problem when it twists into sticky tangles that accumulate in the brain. How tau and amyloid interact is not fully understood, but tau tangles seem to play a greater role in imminent cognitive decline, said Dr. Reisa Sperling, director of the Center for Alzheimer’s Research and Treatment at Mass General Brigham and a leader of the AHEAD study that Rick is participating in. When tau tangles start spreading, it “almost always occurs in the setting of pretty high amyloid,” she said.
Participants in the AHEAD study receive infusions of Leqembi (lecanemab), one of two drugs that have been approved to treat people who already have symptoms. Leqembi and the other drug, Kisunla (donanemab), remove amyloid and slow the illness, but do not stop it.
A new study showed that many symptomatic participants who had low levels of malformed tau when they started taking Leqembi either got better or maintained the same level of function after four years. This has bolstered hopes that providing the medication even earlier in the process, to people at risk but still without symptoms, can prevent tau tangles from spreading.
These drugs have serious downsides, however. They require trips to the hospital, or a visit from a home nurse, to get infusions, although a new injectable version that can be self-administered may soon be available. Also, up to 14 percent of patients experience inflammation or bleeding in the brain, necessitating regular brain scans to check for this side effect.
A Massachusetts General Hospital research team has identified a substance that, instead of clearing out amyloid, may short-circuit its formation in the first place, based on laboratory results. Rudolph E. Tanzi, director of Mass. General’s Henry and Allison McCance Center for Brain Health, said this drug, known as GSM, for gamma secretase modulator, would come in the form of a pill and would be less expensive. He hopes to start testing its safety in humans in the fall.
If it’s proven safe and effective, Tanzi envisions GSM someday being offered to people at risk of Alzheimer’s in the same way statins are prescribed for people at risk of heart disease. “We’re going to nip it in the bud,” he said.
All told, said Antkowiak, of the Alzheimer’s Association, more than 140 unique therapies are being tested in clinical trials, targeting amyloid and tau but also inflammation and the health of blood vessels — all believed to be involved in the development of Alzheimer’s.
One study published in August stirred excitement when it showed that the metal lithium, used to treat psychiatric illnesses, plays a role in brain function and might protect against Alzheimer’s. The study found lithium was depleted in the brains of people in the earliest stages of memory loss during aging, as amyloid began forming. Amyloid bound to the lithium, apparently depriving cells of its protective function. The study also found that feeding tiny amounts of lithium to mice with signs of dementia restored their memory.
But those who are worried about Alzheimer’s don’t need to wait for new drugs to improve their prospects. Ample and growing evidence shows that lifestyle changes can reduce the risk of developing dementia. In the largest such randomized trial, published in July, older people at risk of cognitive decline who followed a program of diet, exercise, and brain training saw, on average, their performance on cognitive tests improve. Another study of people with a strong genetic risk for Alzheimer’s found those following a Mediterranean diet full of fruits, vegetables, nuts, whole grains, fish, and olive oil were significantly less likely to develop dementia.
For guidance on where to start on lifestyle changes, the McCance Brain Care Score helps pinpoint which aspects are most important to tackle. Tanzi, of the MGH brain center, has developed a regime called SHIELD, for Sleep, Handling stress, Interaction with friends, Exercise (150 minutes per week), Learning new things, and Diet (lots of vegetables, fruits, whole grains, nuts and seeds).
Meanwhile, another, quieter revolution may be occurring: the notion of living well with dementia.
That might seem inconceivable. But Kerry Dennis said a rewarding life is possible even when the diagnosis comes at an early age. Dennis, who is 60 and lives in Auburn, N.H., spent three years trying to find out why, in her mid-50s, she could no longer perform routine tasks at her high-powered job with a financial services company. Eventually a Mass. General neurologist diagnosed her with mild cognitive impairment, likely due to brain changes that typically lead to Alzheimer’s.
Her “overwhelming relief” at learning what was wrong quickly gave way to dark thoughts. Her mother and grandmother had died of Alzheimer’s, and her uncle is living with the disease. “All I could think about was what I was going to put my family through,” Dennis said.
With time, though, she accepted her diagnosis and realized she had plenty more life to live.
Through the Alzheimer’s Association, she joined a support group and got engaged with advocacy, which gave her a sense of purpose. Dennis speaks about the importance of early diagnosis at association events.
Of course there are losses. She left her job, can no longer knit or quilt, and relies on AI to compose her emails. But with her husband, Dennis stays active and eats healthfully. “I am living a beautiful life,” she said, “that I am more appreciative of because of my diagnosis.”
