Having an agile mind in your 90s might sound like wishful thinking, but some people manage to retain youthful memories until their dying days.
Superagers have the memory and cognition of the average person almost half their age, and manage to avoid Alzheimer's symptoms. To qualify as a superager, someone must be over the age of 80 but perform as well as 55-year-olds in memory tests. When asked to recall a list of 15 words 15 minutes after hearing them, the average 80-year-old remembers about five, while superagers remember around nine.
Aras Rezvanian at Northwestern University in Chicago, Illinois, and his colleagues have been looking at brain samples donated by such people to try to understand what their secret might be.
The amyloid hypothesis has driven drug development strategies for Alzheimer's disease for over 20 years. There are several unresolved issues in the field of Alzheimer's research including the presence of plaque deposition in cognitively normal individuals and the weak correlation between plaque load and cognition.
There are many thousands of papers on Alzheimer’s disease, and many of these papers can be interpreted in alternative ways, while still more are contradictory to, and/or inconsistent with, the amyloid hypothesis.
There are a growing number of Clinicians and Scientists who are convinced that excitotoxins and heavy metals play a critical role in the development of several neurological diseases, including Parkinson's and Alzheimer's disease. As more research comes forward, many are beginning to dismiss the amyloid hypothesis which drug makers depend on.
The group looked at eight brains, all from people who had lived into their 90s, and had memory and cognition scores of the average 50-year-old until their final days. Specifically, the team studied two brain regions -- the hippocampus, which is involved in memory, and the prefrontal cortex, which is key for cognition.
They found that the brain samples of the superagers had plaques and tangles in them to varying degrees. These are sticky clumps and twisted fibres of protein that seem to be linked to the death of neurons, and are usually found in the brains of people with Alzheimer's disease after they die. Of the eight superager samples, two had such a high density and distribution of these proteins that they resembled the most severe cases of Alzheimer's.
sit between the neurons and end up as dense clusters of beta-amyloid molecules, a sticky type of protein that clumps together and forms plaques.
When the team counted the neurons in the brain samples, they found that they had many more neurons than samples from people who had died with Alzheimer's. This is surprising, as it is thought that plaques are toxic and lead to the loss of neurons during Alzheimer's disease.
"The oldest old with superior memory can display the full range of Alzheimer's pathology," says Rezvanian, who presented his findings at the Society for Neuroscience annual meeting on Monday. "It points to some unknown factors that protect some elderly from the plaques and tangles of Alzheimer's," he says.
Imaging studies have revealed that superagers had brains with youthful characteristics. While the cortex -- the outermost sheet of brain cells that is critical for many thinking abilities -- and other parts of the brain typically shrink with aging, in the brains of superagers a number of those regions were comparable in size to those of young adults.
Perhaps superagers just had more neurons to begin with, says Changiz Geula, who led the study. "They may actually be losing cognition and neurons, but start at high levels," he says.
The findings support growing evidence that plaques and tangles might not be a direct cause of Alzheimer's, says Cheasequah Blevins at University of Texas at Austin. "A lot of money was spent on getting rid of plaques, but it didn't help -- it actually made the patients quite sick," she says. The next step is figuring out what the protective factor might be, she says.
It is essential to expand our view of pathogenesis beyond amyloid plaque pathology and suggest several future directions for Alzheimer's research, which will be critical to understanding its pathogenesis.