Why is memory affected by age? Is it actual cell loss?

Marc Coutanche
PhD student
University of Pennsylvania

Michael, CA, US

Why is memory affected by age? Is it actual cell loss?

Marc Coutanche
HHMI predoctoral fellow,
PhD student,
Center for Cognitive Neuroscience,
University of Pennsylvania
Most of us are familiar with the idea that memory difficulties can come with aging, perhaps from personal experience, through someone we know or from media portrayals. Although the brain does shrink with age, the specific neural changes underlying memory decline are complex and are still being studied by numerous research labs.

An aging human brain can change in a host of ways, including a thinning cortex, white matter disruption, and alterations in neurotransmitter activity. That being said, the brain’s diverse systems are not all affected equally. Certain regions, such as the frontal lobes, are particularly susceptible to age-related shrinkage, while others are relatively spared. The frontal lobes are responsible for executive functions, such as planning, attention, and manipulating the content of working memory. If these functions deteriorate, our ability to use and manipulate the information that we are keeping in mind suffers. Middle-aged and older adults with less prefrontal cortex volume tend to have reduced executive functioning, which in turn influences learning and memory.

A brain structure more closely linked to long-term memory, the hippocampus, also seems to be subject to atrophy. Although exact estimates vary, researchers typically find between 1% and 2% hippocampal cell loss per year. However, not all studies have found a link between hippocampus size and age-related memory performance. This might be because changes that are unrelated to region size, including deteriorations in cell repair and regeneration capabilities, are more directly related to memory decline. Recent work has also pointed to age-related structural changes in the neighboring entorhinal cortex. This area provides direct input to the hippocampus and these changes have been linked to memory function in the very old. The selective disruption of some regions, but not others, likely explains why long-term and working memory functions can decline, while other forms of memory, such as our verbal knowledge (i.e., vocabulary), tend to be spared.

The changes described so far concern the brain’s structure, but neuroimaging techniques have also given us access to how brain functioning shifts with age. Older adults show differing patterns of brain activation compared with younger people. When young adults recall memories, they tend to engage one side of the prefrontal cortex more than the other, but older people have bilateral activation. This difference might reflect a compensatory response by the aging brain: Alternative neural systems step in as typical memory networks start to degrade. Fitting with this, greater bilateral activation is correlated with better cognitive performance in older adults. This compensation is likely less efficient than our normal memory machinery, but it may help our memories function as other systems become less effective.

Another key change with aging is a reduction in white matter integrity. White matter allows brain regions to share information and communicate effectively. Aging is accompanied by greater numbers of white matter “hyperintensities,” named after the bright signals found in magnetic resonance brain images. These white matter lesions are caused by vascular damage or demyelination (the removal of the insulating layer that promotes fast transmission in white matter axons) and are more likely to occur in people with hypertension or high systolic blood pressure. As these pathways break down, the communication within and between brain systems is disrupted and less efficient. Aging-related deficits also affect the dopamine neurotransmitter system, particularly receptor and transport protein binding mechanisms. Striatal brain areas are particularly vulnerable to this dopamine disruption and are heavily connected to the frontal regions discussed above. Reduced dopamine functioning with age has been linked to worse episodic memory performance.

It is important to remember that there is great individual variation in the extent to which people experience these changes. Some of this variation, already coded in our genes, is out of our hands, but experiments linking low blood pressure and exercise to protection from age-related changes suggest that our behavior also has an influence.