Research and Funding

Increased brain activity may compensate for amyloid pathology in older brains

September 15, 2014


Researchers have long wondered why some older people remain cognitively normal despite having abnormal levels of beta-amyloid in their brains, a hallmark of Alzheimer’s disease. While research has shown that older adults with Mild Cognitive Impairment (MCI), which often leads to Alzheimer’s, frequently have increased activity in the hippocampus compared to their cognitively healthy peers, scientists questioned what the hyperactivity represented. Was it helping to compensate for declining brain function or signaling onset of the disease? New NIA-supported brain imaging research has deepened our understanding of this complex puzzle by showing increased activity in several cortical regions of the brain may help compensate for amyloid build-up and help prevent onset of dementia or slow rate of progression.

Dr. Jeremy Elman, of the Life Sciences Division of the U.S. Department of Energy's Lawrence Berkeley National Laboratory, and colleagues at the Helen Willis Neuroscience Institute, University of California, Berkeley, reported the findings online Sept. 14, 2014 in Nature Neuroscience. The work was funded by NIA and the McKnight Brain Research Foundation, through the Foundation for the National Institutes of Health (FNIH), under a joint effort since 2007 to identify age-related changes in the brain and cognition.

The researchers used functional magnetic resonance imaging (fMRI) to assess the brain activity of volunteers tasked with memorizing pictures of scenery and then asked the group questions about the images. The volunteers included 22 young adults and 49 cognitively normal older people; among the latter, positron emission tomography (PET) brain imaging showed 16 with abnormal levels of beta-amyloid and 33 free of deposits. While both groups of older volunteers did equally well in remembering the images, those with beta-amyloid in their brains had greater brain activity while performing the memorization task. The researchers also noted that in both young adults and in older volunteers with abnormal levels of beta-amyloid, greater activity in the visual and memory areas of the brain correlated directly with success in recalling picture details. In contrast, for older adults free of amyloid, lower brain activity in areas not generally associated with vision and memory predicted how well they remembered details.

The researchers concluded increased brain activity in older people with amyloid deposits may help compensate for the neurodegeneration wrought by Alzheimer’s disease. Interestingly, the study adds a new piece to the complex puzzle of Alzheimer’s with the finding that older brains with amyloid function more like younger brains than do older brains free of amyloid. More research is needed to explore this dynamic as well as the various and complex mechanisms involved in Alzheimer’s and healthy cognitive aging.

Reference: Elman J.A., et al. Neural compensation in older people with brain amyloid-β deposition. Nature Neuroscience. Published online Sept. 14, 2014. doi:10.1038/nn.3806

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