A small study on elderly participants with above average memory has shown evidence that some people could be protected against the cognitive decline associated with Alzheimer’s disease.
Researchers examined the brains of eight participants who had displayed excellent memory capacity and cognitive ability at the time of their death, and found that three of them contained the telltale signs of Alzheimer’s disease. So how could they have the disease, but not the debilitating symptoms?
The study, led by neurologist Changiz Geula from Northwestern University, selected eight participants aged 95 to 100 years who had scored above average performance on memory tests and displayed preserved cognitive function for their age.
Once these eight people had passed, Geula and his team examined their brains for signs of Alzheimer’s or other types of chronic brain disease.
After examining four regions of the brain related to memory, emotion, and language, they found that five of the brains looked normal, but three contained "high densities and widespread distributions" of amyloid plaques and neurofibrillary tangles - considered to be the two telltale signs of Alzheimer’s disease.
The results suggest that there can be high densities of plaques and tangles in the brains of some elderly individuals, but they can somehow remain cognitively normal or even superior to people of the same age.
"It tells us there are some factors that are protecting their brains and memories against the Alzheimer’s pathology of plaques and tangles. Now we have to find out what those are."
While studies in the past have shown evidence of people with Alzheimer’s disease being able to hold onto their cognitive abilities, this could be the clearest example of the phenomenon so far, owing to the fact that the participants were all so elderly.
As George Perry, a neuroscientist from the University of Texas at San Antonio who was not involved in the research, told STAT, by the age of 90-something, those amyloid plaques and neurofibrillary tangles should have wreaked havoc on the participants’ brains at the time of their death.
This is because, in the brains of people with Alzheimer’s disease, amyloid proteins clump up into toxic plaques, and together with neurofibrillary tangles, they cause severe disruptions to the transportation of essential nutrients around the brain.
This process is thought to bring on the cognitive decline and memory loss associated with Alzheimer’s disease.
But when Geula and his team examined the three participants’ brains, they found that the neurons in key language and memory-forming regions had remained relatively intact.
When they examined the brains of a separate group of five patients who had been diagnosed with Alzheimer’s disease and had displayed severe cognitive decline at the time of their death, they found significant neuron death in the same regions.
To be clear, these results are preliminary and have yet to be peer-reviewed. They need to be replicated using a much larger sample size by an independent team before we can read too much into them.
There’s also the possibility that the three patients who had developed the physical signs of Alzheimer’s disease had died before the symptoms had a chance to take hold, rather than being naturally protected from them.
But, as Sharon Begley reports for STAT, the results could be important, because researchers have increasingly been seeing signs that some brains could exhibit the physical signs of Alzheimer’s without the symptoms bearing out.
There are two main hypotheses for why this could be the case.
The first is known as 'cognitive reserve', and suggests that if you keep your brain active throughout your older years, your brain might be able to withstand the loss of neurons that comes with Alzheimer’s.
"What you do in your life somehow protects against these otherwise toxic molecules, allowing you to lose cells and synapses and still function," Dean Hartley, director of science initiatives at the Alzheimer’s Association, who was not involved in the study, told Begley.
Another possibility is that there's something going on in the brains of these apparently 'resistant' patients that render the amyloid plaques and neurofibrillary tangles less damaging than usual.
"[S]ome people might produce molecules that make amyloid nontoxic, in which case even if plaques build up they don’t destroy synapses," says Begley. "Or, some genetic or other factor might make synapses strong enough to endure even the toxicity of amyloid."
Right now, it's anyone's guess as to what's actually going on here, but if scientists can confirm that certain people respond to Alzheimer's disease in milder ways than others, it could point the way to better treatments.
Geula and his team are now going to continue their research, trying to find the factors that could mitigate the deleterious effects of Alzheimer's disease on neurons.
"We will look at genetic, dietary and environmental influences that could confer protection for neurons against Alzheimer’s pathology," he told The Telegraph.