Researchers uncover factors responsible for onset of Alzheimer's symptoms

  • The risk of dementia is influenced by a person's family history and conditions like cardiovascular disease and diabetes. But little is known about what affects the appearance of first symptoms of forgetfulness.
  • Researchers in a new study have revealed that people with dementia – whose parents also had dementia – develop symptoms six years earlier than their parents, on average.

The study from Washington University School of Medicine in St. Louis, published in the journal JAMA Network Open states that factors such as education, blood pressure and carrying the genetic variant APOE4, which increases the risk of dementia, accounted for less than a third of the variation in the age at onset.

“It’s important to know who is going to get dementia, but it’s also important to know when symptoms will develop,” said first author Gregory Day, MD, an assistant professor of neurology and an investigator at the Charles F. and Joanne Knight Alzheimer’s Disease Research Center (ADRC).

Researchers studied people with dementia who were participating in research studies at the Knight ADRC. They identified 164 people with dementia who had at least one parent who had been diagnosed with dementia.

Using medical records and interviews with participants and knowledgeable friends or family members, researchers determined the age at onset of dementia for each participant and their parent(s).
Researchers analyzed a large set of known risk factors for Alzheimer’s disease. They studied heritable factors such as ethnicity, race, genetic variants and which parent had the disease.

People who had one parent with dementia developed symptoms 6.1 years earlier than the parent had, on average. If both parents had dementia, the age at onset was 13 years earlier than the average of the parents’ ages at diagnosis.

Changes over the past few decades in diagnostic criteria and social attitudes toward cognitive decline in later life partially explain why the study participants were diagnosed at younger ages than their parents, the researchers said. But other factors were likely at play as well.

“What’s most interesting, I think, is that people with two parents with dementia developed the disease much younger than people with one parent. That suggests that it’s more than just changes in diagnostic criteria or social attitudes. People with two parents with dementia may have a double dose of genetic or other risk factors that pushes them toward a younger age at onset,” said Day.

They also looked at education, body mass index, diabetes, cardiovascular disease, blood pressure, blood cholesterol level, depression, tobacco use, excessive alcohol use, and histories of traumatic brain injury.

All of the factors together only accounted for 29 per cent of the variability, meaning that most of what influences the age of dementia onset remains to be identified.

Intriguingly, researchers also found that people who were diagnosed with Alzheimer’s disease at younger or older ages than their parents were more likely to have certain mutations in Alzheimer’s genes than people diagnosed at the expected age.

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