Stanford Study Spots Brain Signals That Flag Alzheimer's Years Early

Stanford Medicine researchers say they can spot Alzheimer's risk years before memory trouble shows up — by reading how different parts of the brain talk to each other. The team built a scoring system from brain activity patterns that separated super agers from Alzheimer's patients with roughly 85% accuracy, according to the study published November 4 in Science Advances. When they ran those scores on healthy adults aged 55 to 70, the results forecast who would decline — and who wouldn't.

The researchers started at the extremes of cognitive aging. They analyzed resting-state functional MRI scans from 180 super agers — people at least 75 who scored on memory tests like a typical 45-year-old — and 110 people diagnosed with Alzheimer's disease of similar age. The differences in activity across brain regions became a measurement they call the Alzheimer's resilience-vulnerability connectome, or ARC score. Imaging data came from several large initiatives, including the Open Access Series of Imaging Studies, the Harvard Aging Brain Study, and the Alzheimer's Disease Neuroimaging Initiative.

Then came the test. The team applied the ARC score to more than 1,300 cognitively healthy adults between 55 and 70. At the start, high and low scorers looked the same on cognitive tests. Over follow-up — some records stretched as long as 12 years, though most ran about five to six years — people with Alzheimer's-like patterns declined faster on memory, attention and executive function, and were likelier to accumulate amyloid-beta plaques or get diagnosed. Those with super-ager patterns held up best.

The new score outperformed several established predictors of future decline, including demographic traits, genetic risk factors, and amyloid-beta and tau biomarkers, the study says. Senior author Yu Zhang, an assistant professor of psychiatry and behavioral sciences, said the field's usual biomarkers only show up relatively late. 'What we really care about is defining early markers that can detect earlier signs of cognitive decline and potentially help us deliver timely interventions to people,' he said.

Zhang floats the idea of someday nudging a person's brain activity toward resilience patterns — possibly through cognitive training or transcranial magnetic stimulation, which has already shown it can shift brain activity in people treated for depression. Neither approach has been tested for preventing cognitive decline, and researchers don't yet know whether changing brain activity would alter the disease's course. Lead author Kanhao (Alex) Zhao, a postdoctoral scholar in psychiatry, said the score predicts 'how likely this patient will convert into mild cognitive impairment or Alzheimer's disease.'

About 10% of older adults may qualify as super agers depending on the definition. Zhang argued that older studies comparing them with general older adults miss key biology, since two people can post the same memory scores with very different brains. 'Simply comparing super agers with such a heterogeneous population makes it challenging to define what is critical in terms of resilient or vulnerable brain patterns,' he said.