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Alzheimer's brains that never got dementia
The finding comes from postmortem studies in which people were followed as they aged and donated their brains. Under the microscope, those brains had plaques made of the protein amyloid and tangles made of the protein tau, and some of their neurons had died. The person never developed dementia. Alzheimer's disease is the leading cause of dementia, though not the only one, and its pathology can build with age without leading to dementia.
What lets some people carry that burden and stay cognitively intact is an open question. Physical habits can matter: exercise, blood pressure kept down, no diabetes or pre-diabetes, controlled cholesterol, little alcohol, and no smoking. Other factors turn out to be almost as important. People who maintain or increase their number of social relationships have a far lower risk of dementia, even after correcting for other confounders. Curious, open-minded people who take up new pursuits do too, and so do people who wake up with a sense of purpose.
What is cognitive reserve?
Neurologist Yaakov Stern developed the term for the brain's ability to cope with damage by using its networks more flexibly or efficiently. It was prompted by a 1988 report by Robert Katzman and colleagues in the Annals of Neurology. They found that some women with plaques at autopsy had never shown dementia and had more neurons and heavier brains than expected. Education, occupation, and mentally active leisure have since been linked with higher reserve.
Why do plaques not always cause dementia?
Amyloid plaques and tau tangles do not do equal damage. In 1991, Heiko Braak and Eva Braak described a staging of tau tangles that spread through the brain in a regular pattern. Tangle spread tracks the loss of neurons and the symptoms more closely than plaque load does. Plaques can build for years in a brain where tangles stay confined to a small area.
What did the Nun Study find about this?
David Snowdon at the University of Kentucky followed 678 members of the School Sisters of Notre Dame, who agreed to donate their brains. Some sisters whose brains showed extensive Alzheimer's pathology at autopsy had performed normally on cognitive tests while alive. Their convent records of writing, teaching, and daily routine gave unusually complete life histories to compare with the autopsies.
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