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Research on Superagers Informs Potential Dementia Treatments

In This Article

  • Superagers are older adults who have avoided the normal cognitive decline associated with aging
  • Massachusetts General Hospital investigators have found that superagers have less brain shrinkage, more brain connectivity and greater activity in the visual cortex than their peers
  • Alexandra Touroutoglou, PhD, and her team is pursuing a clinical trial using neurostimulation to treat patients with early Alzheimer's disease

Findings by Massachusetts General Hospital researchers about older adults who don't experience normal brain atrophy associated with aging are informing an ongoing clinical trial of noninvasive electromagnetic stimulation as a treatment for early Alzheimer's disease.

"These so-called 'superagers' have given researchers valuable insights," says Alexandra Touroutoglou, PhD, director of imaging operations at Mass General's Frontotemporal Disorders Unit.

"Superagers are an elite group of older adults. They show remarkable resilience against age-related memory decline," she says. "From them, we can better understand who may be vulnerable to memory decline and who may be more resilient towards it. Studying superagers can also inform our strategies to prevent and develop effective treatments for Alzheimer's disease and other dementias."

Identifying Superagers

In 2016, Dr. Touroutoglou and her fellow researchers discovered a group of adults aged 65 to 80 who performed remarkably well on the California Verbal Learning Long Delay Free Recall Test. Participants are given a list of 16 unrelated words in this test, which they are asked to recall 30 minutes later.

"An average 50-year-old will remember nine words, and the average 80-year-old will remember five. Superagers remember all 16 words, which is as much as the young adults we gave the same memory test to," Dr. Touroutoglou says.

Studying the Brains of Superagers With Neuroimaging

The investigators were interested in pinpointing what was neurologically different about these individuals. This led to their first superagers neuroimaging study, published in The Journal of Neuroscience.

Using a standard MRI, the team discovered superagers had little to no brain atrophy compared to their healthy, age-matched peers. "The cerebral cortex was thicker in superagers than in average older adults. Additionally, superagers had a larger hippocampus, and we know that the hippocampus is important for memory function," says Dr. Touroutoglou.

The researchers also examined the midcingulate cortex, which is associated with motivation, attention, and persistence. They found no difference in this region between superagers and young adults. Additionally, the older adults with a thicker midcingulate cortex performed better on memory tests. "The midcingulate cortex is preserved in superagers, and we think this makes them more willing to exert effort on the task we give them, despite its difficulty," Dr. Touroutoglou explains.

As we age, the brain also suffers declining connectivity and activity in the cerebral cortex, which is essential for memory and recall. In another study published in Cerebral Cortex, Dr. Touroutoglou and colleagues measured participants' brain activity in the visual cortex.

The team studied two groups: 40 adults with a mean age of 67, and 41 young adults with a mean age of 25. They gave the same visual memory test to both groups. Using fMRI, investigators monitored activity in the visual cortex while the participants completed the memory test.

"We know that the selective function of neurons in the visual cortex diminishes with normal aging. But we found that the visual cortex of superagers maintained a youthful activity pattern during this visual memory task. It was almost identical to the young adults who underwent the same test in the fMRI," says Dr. Touroutoglou.

Reversing Age-related Memory Decline With Neurostimulation Intervention

The superagers research laid the foundation for Dr. Touroutoglou and her colleagues to pursue a clinical trial for Alzheimer's disease. In the ongoing study, Mass General investigators treat trial participants in the early stages of Alzheimer's disease with transcranial magnetic stimulation (TMS), which noninvasively induces neuroplasticity, the brain's ability to form and reorganize synaptic connections in response to new information. By inducing neuroplasticity in participants, Dr. Touroutoglou says researchers hope to effectively mimic the brains of superagers—improving connectivity in the brain and reducing Alzheimer's symptoms.

"The study is still ongoing, but preliminary data looks very promising," she says. "I believe the secrets of super-agers are paving the way to develop effective treatments for Alzheimer's disease and other dementias."

Learn more about the Frontotemporal Disorders Unit

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