WASHINGTON -- Australian researchers say that a genotype that heightens the risk for Alzheimer's disease does not contribute to cognitive change during most of adulthood. The largest study of its kind has found that carriers and non-carriers show the same type and extent of normal age-related cognitive declines, decades before carriers start to more often develop symptoms of dementia. The findings suggest that the higher-risk genotype acts only in later years to layer disease on top of normal aging.
The findings appear in the January issue of Neuropsychology, which is published by the American Psychological Association (APA).
The study may help rule out the possibility of very early Alzheimer's as the cause of the declines among carriers before they reach old age. Write the authors, "[Alzheimer's disease] processes may occur later in the lifespan and add to normal cognitive aging to produce a dementia syndrome."
The study confirmed that carriers of the APOE4 gene type (allele), which confers higher risk for Alzheimer's, are just like other people their age throughout most of adult life in terms of core mental functions. Previous findings had been unclear. Lead author Anthony Jorm, PhD, DSc, explains, "Although some areas of cognitive decline begin from early adulthood onwards, this is not due - as some have speculated -- to very early Alzheimer's changes in the brain."
The APOE gene helps to transport cholesterol through the production of apolipoprotein E. People carry two copies of APOE, each being one of four APOE alleles. APOE4 raises Alzheimer's risk. In this study, researchers at the University of Melbourne and Australian National University assessed whether the small percentage (varying by ethnicity) of the population that carries at least one copy of APOE4 are cognitively different from non-carriers long before anyone shows signs of dementia.
The authors studied 6,560 people living in Canberra or neighboring Queanbeyan enrolled in the PATH Through Life Project, a long-term study of aging that assesses people in the age groups of 20-24, 40-44, and 60-64 years every four years for a period of 20 years. Jorm and his colleagues evaluated whether, in each age group, carriers of APOE4 (27 percent in their sample) were significantly different from non-carriers on tests of functions affected by Alzheimer's: episodic memory, working memory, mental speed, reaction time, and reading vocabulary.
Performance on all tests (except for reading vocabulary, which tends to hold up with age) declined across age groups, a sign of normal cognitive aging. However, APOE4 did not affect performance at any age. Thus the researchers conclude that at least between ages 20 and 64, people with APOE4 age normally in those central cognitive functions.
This finding suggests that APOE4 heightens the risk for Alzheimer's in old age through an additional, as-yet-unknown process that accelerates or intensifies normal changes, pushing them into the range of disease. Jorm provides an analogy. "In general, hair becomes thinner with age," he says. "However, there are some people who have an additional hereditary factor that makes them bald at an early age."
Article: "APOE Genotype and Cognitive Functioning in a Large Age-Stratified Population Sample;" Anthony F. Jorm, PhD, DSc, University of Melbourne and Australian National University, and Karen A. Mather, PhD, Peter Butterworth, PhD, Kaarin J. Ansley, PhD, Helen Christensen, PhD, and Simon Easteal, PhD, Australian National University; Neuropsychology, Vol 21. No. 1.
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