Journalist Natalie Morales spreads the word about Alzheimer's disease

Soon after Natalie Morales began dating Joe Rhodes in the mid-1990s, she met Kay Rhodes, her future mother-in-law, and they instantly hit it off. “We had a mutual passion for watching the stock market and investing, so she'd share stock tips with me,” says Morales, a former Today anchor, who now co-hosts the daytime talk show The Talk. “She was so vibrant and smart, and she lived for her kids. Her husband was an insurance executive, and wherever they moved for his career, she'd make sure the kids had a great home and good friends.”

Kay's home for the final years of her life was a memory care facility. She was diagnosed with Alzheimer's when Natalie and Joe were still newlyweds, and she died in 2014 at the age of 70. Even before Natalie and Joe married, the family began noticing something amiss with Kay, who was then in her early fifties. “We were living in New York City, and they were in Colorado, so we didn't see them as much as we would've liked,” Morales says. “But my father-in-law would tell us she was having anxiety attacks and worrying about strange things like running out of food. He'd find food hidden in the linen closet or rotten bananas in between the sheets.”

A bigger warning sign came when Morales and Rhodes flew to Colorado for their wedding in August 1998. “We had shipped our wedding rings to them in Denver ahead of time,” she says. “Kay had become so anxious that someone would break into the house and steal the rings that she hid them—and then she couldn't remember where she had put them. Actually, she didn't even remember receiving them. She tore the house apart looking for them but never found them. Fortunately, the rings were insured and we were able to get replacements, but we knew then that something was very wrong.”

Rhodes' father—also named Joe—took Kay to Mayo Clinic in Rochester, MN, to find out what her worsening symptoms could mean. It would be the first of several visits there. “She was repeating herself, panicking easily, losing things,” Morales says. “She couldn't complete sentences or would forget what she was saying. It seemed to get worse very quickly.”

During her initial visit to Mayo, Kay showed some diminished ability to recognize words but “passed” screening tests for dementia. A year later, however, with her condition continuing to decline, she underwent testing again at Mayo and was diagnosed with dementia from early-onset Alzheimer's disease. She was 55 years old.

Although her mental function deteriorated, Kay remained physically fit. “She was otherwise extraordinarily healthy, so she lived for a very long time with the disease,” Morales says. “My father-in-law cared for her at home for about 10 years, and the burden on him was tremendous. We were living in Connecticut at the time, and my husband's sister lives in St. Louis, where they grew up. While we tried to visit as much as we could, the day-to-day caregiving fell to him.”

Fortunately, Joe was able to connect with a chapter of the Alzheimer's Association near their home in Littleton, CO. “Volunteers would come to the house and care for her,” Morales says. “They'd keep her entertained and preoccupied with things like art projects so my father-in-law could take a break and play golf.”

Eventually the chapter helped Joe find a memory care facility where Kay could receive round-the-clock attention. “We realized it was taking a toll on his health,” Morales says. “He developed Parkinson's disease and also had to have heart surgery. My husband and his sister helped pack up their mother's things, and they all went to the facility so she wouldn't feel afraid. It was a wonderful place, and the staff were so good with her, but it was hard for the family to leave her there.”

One day not long after Kay had moved into the memory care facility, Joe was sorting through his wife's things, and in the back of a drawer, inside a ball of rolled-up socks, he felt something bumpy and heavy—the missing wedding rings that Kay had stashed there a decade before.

During the six years Kay lived at the facility, Morales and her husband would bring their two sons, Josh and Luke, to visit her, but Kay never recognized her grandchildren. And the cost of her care wiped out Joe and Kay's savings. She died in 2014 at age 70. The years of caregiving and worry took their toll on Joe, who died in January 2021 at the age of 79.

Preventive measures

Morales turns 51 this year, so she's just a few years younger than Kay was when she first started showing signs of Alzheimer's disease. “My mother-in-law and I are not biologically related, and any risk that may be in her family wouldn't be the same as in mine,” Morales says, “but we do have a lot of Parkinson's disease in my family, and I know in some people it can affect cognitive function, so I'm very concerned about brain health.”

Her husband and their sons might be at an increased risk of developing Alzheimer's disease if there is a genetic link in the family. (Kay Rhodes never had any testing for Alzheimer's-related gene variants.) “Kay's mother, Vera, lived to be 98 and was a sharp woman who traveled the world until she was in her eighties,” says Morales. “There's nobody that we can identify, but going further back, it's hard to know, because people may not have seen a doctor for memory problems.”

A family history of Alzheimer's can be a risk factor for the disease but is not a guarantee that subsequent generations will develop it. The likelihood of developing the condition or passing the risk on to children depends on several factors, including how many and which relatives have had it and how early they were diagnosed.

“Having a first-degree relative—meaning a parent or sibling—with the condition definitely increases your risk, even for developing late-onset Alzheimer's disease, although it's not clear how much,” says Liana Apostolova, MD, FAAN, professor of neurology at the Indiana University School of Medicine in Indianapolis. “And if you have several generations of family members with early cognitive decline, the risk increases even more.”

The term “early-onset” is applied when people are diagnosed before the age of 65, as Kay Rhodes was. People with early-onset Alzheimer's disease represent less than 10 percent of all diagnosed cases, according to the National Institutes of Health.

But in some families, the prevalence is higher. “In families where about half of each generation seems to develop early-onset dementia, we are often able to identify pathogenic changes in three specific genes,” says James Noble, MD, FAAN, associate professor of neurology at the Columbia University Irving Medical Center in New York City.

People with changes in any of these genes—amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2)—are almost certain to develop the disease before age 60 and have a 50 percent chance of passing the variation on to their children, says Dr. Noble. “On the other hand, many people with early-onset Alzheimer's and a strong family history do not have mutations in any of these genes,” notes Dr. Apostolova.

Genetic testing for Alzheimer's markers would begin with the family member who is affected. “If, for example, your grandmother has Alzheimer's disease, finding out whether she has a known genetic mutation will tell you if anyone else in the family could potentially benefit from testing,” Dr. Noble says. “If no genetic change is identified, there isn't much point in testing other family members.”

Before undergoing genetic testing, he says, it's important to meet with a genetic counselor who can discuss the risks and benefits of these tests and the questions that testing can and can't answer. “Some people with a strong genetic predisposition choose not to test, while others want to know,” Dr. Apostolova says. “Even if you choose not to be tested yourself, but your parent or sibling tests positive, you will always carry the knowledge that you might have that risk.”

“People should think carefully: What would I do differently if I had this information?” says Jason H. Karlawish, MD, professor of medicine, medical ethics and health policy, and neurology at the University of Pennsylvania's Perelman School of Medicine in Philadelphia. “Knowing that you have one of these dominant genes may inform decisions about family planning, career choice, or where to live or retire.”

Morales says she and her family have decided not to do genetic testing for now. “But we try to keep our brains sharp and build resilience.” For her, that means being physically active. “I do different workouts to challenge my brain by changing things up,” she says. “I do yoga and love to run, but I can get stuck in a running rut, so I also do Pilates and boxing and learn new dance choreography.”

As an investment consultant, Morales' husband deals with numbers and math—and that type of mental engagement, especially if it involves learning something new and challenging, is believed to be good for brain health. “He can do complicated equations in his head faster than you could write them down,” she says. “And we play games to challenge our brains. He has a serious chess rivalry with our younger son and plays daily. But I still worry anytime he forgets his keys. And he's notorious for leaving things at hotels. Whenever something like that happens, you think, ‘Oh gosh, is this something to worry about?'”

The couple are also aware that having an active social life such as theirs could be beneficial, having read that maintaining supportive social connections can protect brain health. “We're lucky to have a wonderful group of neighbors,” Morales says. “Even at the height of the pandemic, we'd have weekly, safely distanced get-togethers to check up on each other. As for my own parents, my mom has her mahjong crew. It's important to have community.”

Morales says she and her family have decided not to do genetic testing for now. “But we try to keep our brains sharp and build resilience.” For her, that means being physically active. “I do different workouts to challenge my brain by changing things up,” she says. “I do yoga and love to run, but I can get stuck in a running rut, so I also do Pilates and boxing and learn new dance choreography.”

As an investment consultant, Morales' husband deals with numbers and math—and that type of mental engagement, especially if it involves learning something new and challenging, is believed to be good for brain health. “He can do complicated equations in his head faster than you could write them down,” she says. “And we play games to challenge our brains. He has a serious chess rivalry with our younger son and plays daily. But I still worry anytime he forgets his keys. And he's notorious for leaving things at hotels. Whenever something like that happens, you think, ‘Oh gosh, is this something to worry about?'”

The couple are also aware that having an active social life such as theirs could be beneficial, having read that maintaining supportive social connections can protect brain health. “We're lucky to have a wonderful group of neighbors,” Morales says. “Even at the height of the pandemic, we'd have weekly, safely distanced get-togethers to check up on each other. As for my own parents, my mom has her mahjong crew. It's important to have community.”

And Morales believes making the move from Today to The Talk has greatly reduced her stress levels. “I was in a very high-pressure, high-stress job where I'd have to be up before dawn sometimes. It wasn't good for my marriage, my family, or my health, and I knew I had to make a change,” she says. “You have to be willing to take risks and shake things up.”

Morales isn't focused just on her own and her family's brain health. She's made it her mission to educate others about Alzheimer's disease and other types of dementia and has been an active supporter of the Alzheimer's Association for more than 15 years, speaking at events and running the New York City Half Marathon with the Athletes to End Alzheimer's team. She also appears regularly in the association's #EndAlzheimers social media campaigns and interviews experts on air about advances in Alzheimer's disease treatment and how the condition affects women.

“So many of us start researching these things only when they hit close to home. Well, they're going to be hitting close to home more and more as the boomers age,” says Morales. “By 2025, it's expected that more than 7 million Americans will be living with Alzheimer's disease, so we all may be caregivers at some point in our lives. Having places to go and organizations like the Alzheimer's Association to reach out to are so important.”

Ongoing research on early-onset Alzheimer's disease

Two separate studies on early-onset Alzheimer's disease are recruiting participants, and the doctors working on the studies encourage anyone with a family history of the disease and those who develop cognitive changes before age 65 to inquire about signing up.

The Dominantly Inherited Alzheimer Network (DIAN) trial is an international observational study led by Randall J. Bateman, MD, at Washington University in St. Louis that focuses on people who have one of the gene mutations (amyloid precursor protein, presenilin 1, or presenilin 2) that cause early-onset Alzheimer's. For more information, visit the Dominantly Inherited Alzheimer Network.

The Longitudinal Early-Onset Alzheimer's Disease Study, or LEADS, is enrolling people whose disease is not traceable to any currently known genetic mutation. It is being conducted by the Indiana University School of Medicine, with Liana Apostolova, MD, FAAN, professor of neurology, radiology, and medical and molecular genetics, as a lead investigator. Go to LEADS study for further details.

“As much as we think of Alzheimer's as being one disease, we are learning that even in the rare cases of families with the early-onset form, it is variable, and treatment may need to be more specific than we originally thought,” says James Noble, MD, FAAN, associate professor of neurology at the Columbia University Irving Medical Center, who's working on the DIAN trial. “Just as we learned with cancer, it may be that Alzheimer's treatment is not one-size-fits-all.”

New hope for Alzheimer's treatment

In January 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to lecanemab (Leqembi), the second in a new category of medications designed to treat the pathophysiology of Alzheimer's disease. In clinical trials, the drug—which targets accumulation of beta-amyloid plaques in the brain—offered a modest but significant benefit in slowing cognitive decline in people with mild cognitive impairment or mild dementia due to Alzheimer's disease.

Also this year, the ongoing trial of donanemab, another anti-amyloid drug, found that more people with early symptomatic Alzheimer's disease had amyloid cleared and plaque reduced after six months of treatment with donanemab versus aducanumab (Aduhelm), the first anti-amyloid drug to be approved. In May 2023, pharmaceutical company Eli Lilly announced the results of the donanemab phase 3 trial, which showed a 35 percent slowing of cognitive decline and a 40 percent reduction of decline in ability to perform daily activities. The FDA will likely review the application for approval of donanemab before the end of 2023.

These developments represent real hope for people at risk for Alzheimer's disease, especially in the aftermath of disappointing results for two other anti-amyloid drugs, gantenerumab and crenezumab. In June 2022, the National Institutes of Health announced that crenezumab did not demonstrate a significant clinical benefit in a phase 3 trial. “This was a big letdown, particularly for people who are at heightened risk for developing early-onset Alzheimer's disease because of a dominant gene, since that was exactly the population being studied,” says Jason H. Karlawish, MD, professor of medicine, medical ethics and health policy, and neurology at the University of Pennsylvania's Perelman School of Medicine in Philadelphia.

Crenezumab did not slow or prevent decline in cognitive function, according to the results of a 10-year study that tested a group of 252 people in Colombia, two-thirds of whom carry a mutation in the presenilin 1 gene that makes them almost certain to develop early-onset Alzheimer's.

And in November 2022, Roche announced negative results for the clinical trials testing its anti-amyloid drug gantenerumab in people with mild cognitive impairment due to early-stage Alzheimer's disease. In two trials, participants randomized to receive gantenerumab did not show a statistically significant slowing in progression compared with those who received a placebo.