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Alzheimer's Timeline Starts 25 Years Before Severe Dementia

By Daniel J. DeNoon
WebMD Health News

Reviewed by Brunilda Nazario, MD

July 11, 2012 -- Data from people with a rare form of early-onset Alzheimer's disease offer a detailed look at each ominous step of the descent into severe Alzheimer's dementia.

Only 1% of people with Alzheimer's disease get the early-onset form. But the new findings strongly suggest that the relentless progression of Alzheimer's disease is the same in patients with the much more common "sporadic" form of the illness.

"A series of changes begins in the brain decades before the symptoms of Alzheimer's disease are noticed by patients or families," study leader Randall Bateman, MD, of Washington University, said in a news release. "This cascade of events may provide a timeline for symptom onset."

To get this timeline, Bateman and colleagues in the Dominantly Inherited Alzheimer's Network (DIAN) studied 128 people who inherited one of the three gene mutations that doom a person to early Alzheimer's disease.

Each generation carrying the mutation gets full-blown Alzheimer's dementia at about the same age. So the DIAN team used the age of symptom onset in participants' parents to estimate when they, too, would have full-blown Alzheimer's. In this study that was about age 46, give or take seven years.

Timeline of Alzheimer's Disease

The findings reveal the dramatic timeline of Alzheimer's disease:

• 25 years before severe dementia, beta-amyloid protein levels in the spinal fluid begin to drop, suggesting that amyloid has begun to accumulate in the brain.
• 15 years before severe dementia, beta-amyloid can be detected in the brain. As this does not seem to occur in people without Alzheimer's, it may be the earliest sure sign of the disease.
• 15 years before severe dementia, tau protein begins to accumulate in the spinal fluid. Many researchers believe that tau is more important than amyloid in Alzheimer's disease.
• 15 years before severe dementia, the brain begins to shrink.
• 10 years before severe dementia, brain metabolism slows down.
• 10 years before severe dementia, episodic memory is impaired. Episodic memories are like snapshots or video footage of a person's experience.
• 5 years before severe dementia, cognitive impairment sets in.

"These exciting findings are the first to confirm what we have long suspected -- that disease onset begins years before the first sign of cognitive decline or memory loss," Laurie Ryan, PhD, of the National Institute on Aging, says in a news release. The DIAN study is largely funded by the National Institutes of Health.

The new data suggest that even in age-related Alzheimer's disease, the disease timeline depends less on a person's age than on the time when the disease process begins.

The findings also suggest that targeting beta-amyloid early in the disease process may be more helpful than waiting until a patient starts to develop symptoms of mental decline.

Bateman and colleagues report the findings in the July 11 online issue of the New England Journal of Medicine.

SOURCES: Bateman, R.J. The New England Journal of Medicine, published online July 11, 2012. News release, Washington University School of Medicine.

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