Gene variant linked to faster decline in planning after 90
The statistical estimate of the difference in decline in planning and task-management skills was minus 0.07 for variant carriers versus noncarriers.
Limit: Survivor selection may favor unusually resilient ɛ4 carriers, distorting the link with cognitive decline
An observational cohort study followed 445 adults aged 90–104; their average age was 93, and 59% were female. Researchers identified variants of APOE, a gene associated with Alzheimer’s disease risk, using saliva DNA. They tested thinking skills every six months over an average follow-up of 3.9 years.
Carrying the ε4 variant was linked to faster decline in planning and task-management skills compared with noncarriers. The analysis accounted for deaths during follow-up and adjusted for age and sex. Decline in memory for facts and meanings and in recall of verbal information was similar between ε4 carriers and noncarriers. Carriers of ε2 had slower decline in recall of verbal information, but similar decline in the other two measures. Neither variant was associated with a substantially different risk of death.
Why it matters
APOE ε4 is the strongest genetic risk factor for late-onset Alzheimer’s disease. Studying people aged 90 and older addresses whether that genetic risk also relates to thinking changes at exceptionally old ages.
Caveats
This observational study cannot establish causation, and its findings concern adults aged 90–104. The range of likely values for the ε2 memory result included no difference.
