Some of the earliest signs of Alzheimer's disease have been found in the brain, more than two decades before the first symptoms usually appear.
Treating the disease early is thought to be vital in order to prevent damage to memory and thinking.
A study, published in the Lancet Neurology, found differences in the brains of people destined to develop an early form of Alzheimer's.
Experts said the US study may give doctors more time to treat people.
Alzheimer's disease starts long before anyone would notice; previous studies have shown an effect on the brain 10-15 years before symptoms.
It is only after enough brain cells have died that the signs of dementia begin to appear - some regions of the brain will have lost up to 20% of their brain cells before the disease becomes noticeable.
Dementia signs
- Struggling to remember recent events
- Problems following conversations
- Forgetting the names of friends or objects
- Repeating yourself
- Problems with thinking or reasoning
- Confusion in familiar places
However, doctors fear so much of the brain will have degenerated by this time that it will be too late to treat patients. The failure of recent trials to prevent further cognitive decline in patients with mild to moderate Alzheimer's disease has been partly put down to timing.
Early startA team at the Banner Alzheimer's Institute in Arizona looked at a group of patients who have familial Alzheimer's. A genetic mutation means they nearly always get the disease in their 40s. Alzheimer's normally becomes apparent after the age of 75.
Brain scans of 20 people with the mutation, aged between 18 and 26, already showed differences compared with those from 24 people who were not destined to develop early Alzheimer's.
The fluid which bathes the brain and spinal cord also had higher levels of a protein called beta-amyloid.
The researchers said differences could be detected "more than two decades before" symptoms would appear in these high-risk patients.
"Start Quote
End Quote Prof Nick Fox University College LondonThe key thing this does is open up the window of early intervention before people take a clinical and cognitive hit"
Dr Eric Reiman, one of the scientists involved, said: "These findings suggest that brain changes begin many years before the clinical onset of Alzheimer's disease.
"They raise new questions about the earliest brain changes involved in the predisposition to Alzheimer's and the extent to which they could be targeted by future prevention therapies."
Prof Nick Fox, from the Institute of Neurology at University College London, said some of his patients had lost a fifth of some parts of their brain by the time they arrived at the clinic.
He told the BBC: "I don't think this pushes us forwards in terms of early diagnosis, we already have markers of the disease.
"The key thing this does is open up the window of early intervention before people take a clinical and cognitive hit."
However, he said this raised the question of how early people would need to be treated - if drugs could be found.
Dr Simon Ridley, the head of research at Alzheimer's Research UK, said: "Although early-onset inherited Alzheimer's is rare and may not entirely represent the more common late-onset form, the findings highlight changes can take place in the brain decades before symptoms show.
"Mapping what changes happen early in the brain will help scientists to improve detection of the disease and allow potential new treatments to be tested at the right time.
"New drugs are being developed and tested to stop amyloid from taking hold, but studies like these show that timing could be crucial for whether these drugs are successful."
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