Study Shows How Early-Onset Alzheimer’s Spreads Differently In The Brain

Alzheimer's disease is technically considered early-onset when symptoms start before age 65, but the disease also looks and moves differently than it does in older adults. Now, researchers are finally figuring out why.

Researchers compared 390 people with early-onset Alzheimer's (average age 59) to 211 people with late-onset Alzheimer's (average age 78).

Everyone in the study had mild cognitive impairment or mild dementia and had tested positive for amyloid on brain scans. A portion of participants underwent repeat tau PET scans over an average of two to three years so researchers could track how tau changed over time.

In this study, people with early-onset Alzheimer's showed higher levels of tau in their brains at the outset, and that tau was spread across more areas of the brain, compared to people with late-onset disease. Researchers found tau accumulated twice as fast in the early-onset group than in the late-onset group.

Regardless of amyloid levels or how advanced the disease already was, tau accumulation and spread was particularly aggressive in patients with early-onset disease and was more strongly related to progression in memory loss.

This research also revealed that early-onset Alzheimer's doesn't always look like classic memory loss. One in five people with early-onset disease had what's called a "non-memory-dominant" presentation, compared to less than 1% of late-onset patients.

Instead of traditional memory loss, patients with early-onset Alzheimer's might have difficulty interpreting what they're seeing despite a normal eye exam, or struggle with judging distances and reading, said co-senior author of the study Renaud La Joie, PhD, in a press release.

He said some patients may experience a decline in language abilities in which they have difficulty retrieving words and following long sentences, even while speech remains fluent, while others may struggle with executive functioning, such as attention, problem-solving, planning, and adapting to changing situations.

Why does Alzheimer's hit some people so much earlier, and so much harder? That part is still unclear.

The two drugs currently approved to slow Alzheimer's progression target amyloid. But this study found the gap between early- and late-onset disease was far bigger for tau than for amyloid. While the study didn't test any treatments directly, the findings raise real questions about how early-onset patients might respond to amyloid-only therapies.

The authors of the study suggest that treatments targeting tau may be particularly important in early-onset Alzheimer's, and that younger patients may be good candidates for clinical trials combining treatments that target both amyloid and tau.

There are also many lifestyle changes that can support brain health as you age. We spoke with one woman who has the highest genetic risk for Alzheimer's, but has taken action to prevent the disease from taking hold of her brain as best she can. The habits she mentions, including a diversity of exercise, reduction of alcohol, and following a mediterranean diet, are things anyone can do.

Early-onset Alzheimer's isn't just "regular" Alzheimer's that happens to show up early. It behaves differently in the brain, and often looks different in real life, too.