Carrying the APOE ε4 gene is a known risk factor for the onset of Alzheimer's disease.
The study, published in JAMA Neurology, measured memory performance, brain structure according to lower hippocampal volume and the presence of amyloid - brain plaques associated with Alzheimer's disease.
"Our objectives were to compare age, sex and APOE ε4 effects on memory performance, hippocampal volume and amyloid positron emission tomography (PET) across the adult lifespan," write the authors.
APOE ε4 is a gene that is consistently identified as a risk factor for late-onset Alzheimer's disease and has been found to significantly lower the age of onset for this condition. It is also recognized as a risk factor for early-onset Alzheimer's disease as well.
Due to the associations between APOE ε4, amyloid accumulation and Alzheimer's disease, many experts have also associated the presence of the former two factors with cognitive decline and poorer memory performance.
For the study, 1,246 cognitively normal participants between the ages of 30 and 95 underwent PET, magnetic resonance imaging (MRI) and memory testing. The participants were categorized into four groups by their sex and whether they carried the APOE ε4 gene or not.
Dr. Clifford R. Jack Jr. of the Mayo Clinic and Foundation, Rochester, MN, and his co-authors found that overall memory appeared to worsen from the age of 30 through to the 90s. Alongside this, lower hippocampal volume also worsened from the age of 30, with this decline steepening from the age of 70.
The average amount of amyloid accumulation observed by the researchers on PET scans was low until the age of 70, but in older participants amyloid accumulation was much higher.
APOE ε4 carriers had greater average amyloid accumulation than non-carriers from the age of 70 onwards. The researchers found that the age at which 10% of the participants had amyloid accumulation showing on their PET scans was 57 years for APOE ε4 carriers and 64 years for non-carriers.
Memory performance and brain structure changes unaffected by APOE ε4 carrier status
Overall, men had worse memory than women at 40 and lower hippocampal volume than women at 60. However, these measurements were not affected by APOE ε4 carrier status at any age.
The researchers believe that the study reveals interesting sex and APOE ε4 effects on age-related trends in brain structure, function and amyloid accumulation.
They state that their findings are consistent with a model of late-onset Alzheimer's disease in which amyloid accumulation occurs later on in life alongside pre-existing structural and cognitive decline associated not with amyloid accumulation but general aging.
The study is limited in that it is a cross-sectional observation, so its findings cannot prove causation. Additionally, only examining data for individuals deemed to be cognitively normal meant that the participants only represented a subset of people who shared their age.
Despite the limitations, the authors believe that the study reveals interesting sex and APOE ε4 effects on age-related trends in brain structure, function and amyloid accumulation.
In a related editorial, Dr. Charles DeCarli of the University of California at Davis, Sacramento, states that the study presents new information to challenge the notion that amyloid accumulation explains memory performance across the entire age range:
"Importantly, this work does not only address the likely highly significant impact of cerebral amyloid accumulation on dementia risk, but also extends current knowledge relating to the impact of the aging process across the spectrum of ages 30 to 95 years to brain structure, amyloid accumulation and memory performance among cognitively normal individuals."
According to Dr. DeCarli, the findings of the study help to explain the basic biology of effects of the aging process. "Establishing what is normal creates avenues for new research, increasing the likelihood of discovering novel therapeutics for late-life disease states, which is a laudable goal indeed," he concludes.
Recently, Medical News Today reported on the results of the first ever randomized controlled trial investigating an intervention designed to slow cognitive decline among older people.