Study Provides New Details on How Brain Ages

A population-based study carried out by Mayo Clinic researchers has painted a more complete picture of how three key brain metrics—memory, hippocampal volume, and beta amyloid levels—change and interact during aging.

The results, published in JAMA Neurology, revealed some interesting insight into how gender influences an aging brain while also indicating that amyloid accumulation may not be the driving force in the onset of Alzheimer’s disease (AD).

Mayo Clinic

The team, led by Clifford Jack Jr., M.D., a professor of radiology, developed its portrait of aging by examining positron emission tomography (PET) images of over 1,200 cognitively normal people between the ages of 30 and 95.

Researchers saw that both memory and hippocampal volume declined continuously from age 30 onward, with the hippocampus showing a more steep decline after age 60.

“Memory loss is a general trend that everyone obeys,” Jack said. “The rate of decline varies from person to person, but it happens to everybody.”

While it may seem intuitive, Jack noted that many people see memory loss as a marker for some problems, assuming that in the absence of an underlying disease, the brain should work as well as it did a few years ago.

“Consider how well your heart pumps at 90 compared to 30 or the elasticity of your skin over time,” Jack said. “All other organs decline over time; why should we think the brain is magically different?”

But while passage of time is linked to memory loss, the buildup of amyloid may not be so significant. The PET scans also showed that amyloid levels were fairly low until age 70, even in people who had the ApoE4 biomarker, considered a major AD risk factor. ApoE4 also showed no profound influence over memory or hippocampal volume, as carriers did not fare worse in either category at any given age.

“It’s a remarkable contrast, as amyloid plaques are the big indicator of an Alzheimer’s diagnosis in brain samples, yet they don’t reach abnormal levels until late in life,” Jack told Psychiatric News.

“Our data suggest that midlife memory problems and brain shrinkage, which have been attributed to preclinical Alzheimer’s, is likely due to something else, as memory loss precedes any biological evidence of AD,” Jack said.

Besides age, Jack believes vascular problems like stroke, high blood pressure, and diabetes—which often become health issues in middle age—contribute to memory problems and AD risk.

Another big risk is being male. Though it’s been known for a while that men have worse memory scores than women, this study emphasized how strong these gender effects are, as men showed lower memory scores than women at every age, especially after age 40. Jack believes these trends line up well with the emphasis on vascular issues, as such vascular risks as smoking and high blood pressure are more common in men.

“We hope this study might be a wake-up call to the Alzheimer’s research community,” Jack said. “A lot of work has been done comparing Alzheimer’s patients with cognitively normal individuals at specific age groups, but that doesn’t provide insight into that epoch between a normal and diseased brain.”

Charles DeCarli, M.D., a professor of neurology at the University of California, Davis, agreed with that assessment in an editorial accompanying the study. “Understanding the basic biology of early [aging] processes is likely to substantially inform us about ways in which we can maintain cognitive health and optimize resistance to late-life dementia. Establishing what is normal creates avenues for new research and increasing the likelihood of discovering novel therapeutics for late-life disease states, which is a laudable goal indeed,” he wrote.

The study was supported by grants from the National Institute on Aging and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Foundation. ■