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A new test that combines the effects of over two dozen gene mutations – which individually lead to only a small increased threat of Alzheimer’s disease – can better predict who’ll have problems with dementia or cognitive decline, scientists say.

The method is preferable to testing limited to the well-known genetic variant APOE E4, according to researchers.

APOE E4 is definitely considered the most powerful genetic predictor of whether someone will probably develop Alzheimer’s, though it is only transported by 10 – 15 % of the population and recent research suggests its results have been overstated.

The polygenic hazard score (PHS), a test developed by the extensive research team that carried out the new study, provides risk estimates for the rest of the 85 – 90 % people who do not carry at least one copy of APOE E4 but nonetheless have some mixture of other genetic variants that put them vulnerable to Alzheimer’s.

“Beyond APOE E4 alone, our polygenic risk rating can identify cognitively normal and mildly impaired older individuals who are at best risk for developing Alzheimer’s-associated clinical decrease as time passes,” said Chin-Hong Tan, a postdoctoral scholar at the University or college of California, SAN FRANCISCO BAY AREA in America.

The researchers viewed five years of data on 1,081 topics who did not have dementia and found the PHS test could predict how long it could take to allow them to progress to Alzheimer’s dementia, as well as how steep their cognitive drop would be, even after considering if they were carriers of APOE E4.

Autopsies of those who did develop Alzheimer’s showed that, even among those who didn’t carry a duplicate of the APOE E4 version, a higher PHS was associated with an increased degree of amyloid plaque – a protein aggregate that is clearly a hallmark of Alzheimer’s – in the mind.

These patients showed steeper declines on cognitive checks throughout their lifetimes also.

Old individuals in the highest PHS percentiles showed the best incidence of Alzheimer’s also, which is identified as having cognitive brain and testing pathology, of their APOE E4 status regardless.

Many scientists think that rather than being a disease of aging now, Alzheimer’s may be the total result of a disease process that starts years, decades perhaps, before symptoms of dementia appear.

That is thought by many to be one reason so many Alzheimer’s drugs examined on the elderly with dementia have failed in medical trials.

 

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