Initial Alzheimer’s Symptoms Predict rate of progression

Memory loss is the most common symptom associated with Alzheimer’s disease – the terrifying prospect of slowly forgetting yourself and everything around you.

But people who show amnesia early in their dementia actually have a slower rate of decline than those who develop other symptoms earlier, a new study reports.

Difficulty forming sentences, making plans, solving problems or judging space and distance — these symptoms all herald a steeper and more rapid decline for Alzheimer’s and dementia patients than early memory problems, researchers have found.

“In fact, people with memory changes have a slightly slower rate of disease progression than people with other symptoms, such as language or judgment problems, in terms of their ability to function independently and care for themselves,” said lead researcher Dr. Jagan Pillai, a neurologist at the Cleveland Clinic Center for Brain Health in Ohio.

If these early symptoms prove to be a reliable clue, they could help patients and their families better prepare for what’s to come, he said.

Future Alzheimer’s drug trials could also avoid potential bias by noting people’s early symptoms and sorting those that are expected to subside faster, Pillai added.

“In clinical trials, everyone with Alzheimer’s is lumped together,” Pillai said. “You can imagine bias if the drug arm of the study has more people with non-memory problems than the placebo arm. That could skew the results.”

For the study, his team analyzed data from more than 2,400 people with dementia, drawn from a database maintained by the National Alzheimer’s Coordinating Center.

Many Alzheimer’s treatment centers in the United States regularly feed information into the federal database, which since its inception in 1984 has grown into a major repository of patient data for research.

Memory problems are the most common early symptoms of Alzheimer’s and dementia. In nearly 80% of cases, memory loss is the first sign that something is wrong, the results show.

“When someone thinks of Alzheimer’s, they think of someone with memory loss and how it has evolved over time to affect other areas of their function or their thinking,” Pillai said. “It is less known to the general public that Alzheimer’s disease may initially present with other symptoms.”

But nearly 10% of dementia patients initially have symptoms related to their executive function, the researchers found.

“They can have trouble making judgments,” Pillai said. “They can’t plan their day or perform a task like logging into a computer.”

Another 10% present for the first time with symptoms related to language.

“They just can’t speak in complete sentences and struggle with expressing themselves,” Pillai said.

People with those rarer early symptoms had a faster decline in their brain function and their ability to maintain their quality of life, study results showed.

“That really means that a good clinician really has a lot of opportunities to understand what’s going to happen to a patient over time,” said Mary Sano, director of the Alzheimer’s Disease Research Center at Mount Sinai, in New York. City.

“I think that’s really important because there’s always some hesitation about whether or not to diagnose Alzheimer’s disease,” Sano said. “And what you can see is that it’s important to get the evaluation. It will tell you something about your prognosis and what to expect over time.”

There’s no way to know why these differences in decline exist, but it could be based on how Alzheimer’s or dementia affects specific brain regions, Pillai said.

An area of ​​the brain affected by dementia may produce specific early symptoms, and that area may also be prone to rapid deterioration.

Another possible explanation could be how these early symptoms affect a person’s daily life, Pillai said.

“Let’s say someone has a memory problem, but he can still function independently in his daily routine because his routine has been pretty consistent for him over a period of time, so he can function within that particular constraint,” he said. .

“Whereas if you have changes, like language issues, that limits your ability to go out and make things happen in society. Your social life changes quite significantly. Or if you have a spatial issue, it’s hard to navigate outdoors, outside your comfort zone. If you have judgment problems, you can’t take on new projects quickly,” Pillai continued.

So those things start to affect day-to-day functioning much earlier than memory problems, which people can probably compensate for longer, he suggested.

Claire Sexton, senior director of scientific programs and outreach for the Alzheimer’s Association, agreed with Pillai.

“If language skills and executive functioning are somewhat preserved, this may limit the decline in overall cognition and functioning,” she said.

Researchers said the difference in the rate of decline is enough to influence the clinical trials that led to the approval of the Alzheimer’s drugs Aduhelm (aducanumab) and Leqembi (lecanemab).

“Future clinical trials may need to be more careful to ensure that people with memory or non-memory problems are equally balanced in both the drug and placebo arms, so there is no bias in measuring effectiveness,” said Pillai.

He doubts that these symptoms can be used to determine who might benefit from the new Alzheimer’s drugs.

“If future studies show that the disease itself is very different for memory problems than for other non-memory changes, then this could have future implications for therapies,” Pillai said. “But we’re not there yet.

But Sano said the symptoms could give doctors an idea of ​​what to expect from the drug in specific patients.

“If you knew that a person’s first symptom was one of these others and you would expect them to worsen faster, your expectation from the treatment might be that it could still have an effect, but it might not be effective as it is if someone doesn’t have those additional symptoms,” Sano said.

The findings were recently published online in the journal Alzheimer’s & Dementia.

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