This article was originally published on Medical News Today
Dutch researchers have discovered a subgroup of individuals in a national brain bank whose brains showed signs of Alzheimer’s disease but who never had it during their lifetime.
It’s a rare phenomenon, some experts say, but it can happen since it can take decades between the first amyloid deposits in the brain that characterize the disease and the appearance of symptoms.
So-called resilience to Alzheimer’s symptoms may develop through genetics or lifestyle choices, but some studies have shown that activities that boost cognitive function can help offset these symptoms.
Dutch researchers, after studying data from more than 2,000 brains from the Dutch Brain Bank, recently made a surprising discovery.
Their study — which appears in Acta Neuropathology Communications — found that a subgroup of people had clear indications of Alzheimer’s disease in their brain tissue, but they had no symptoms while alive.
Certainly, they only identified 12 of these individuals from available brain tissue with the necessary clinical information recorded. But it raised a number of questions about the disease itself and what makes a person resilient.
Dementia directly affects more than 55 million people worldwide, and up to 70% of them suffer from Alzheimer’s disease, characterized by a loss of brain cells associated with the toxic accumulation of two proteins, l amyloid and tau protein.
The most common symptoms of Alzheimer’s disease are: memory loss, cognitive deficits, problems with expression, recognition, spatial awareness, reading or writing, and significant changes in personality and behavior.
Because Alzheimer’s disease is progressive, these symptoms are usually mild at first and tend to get worse over time.
What could cause Alzheimer’s disease to progress without symptoms?
The phenomenon of Alzheimer’s disease without symptoms is called “resilience.”
In the resilient group, the researchers observed that a type of brain cell called astrocytes — which they described in a press release as “garbage collectors” that play a protective role in the brain — appeared to produce more of an antioxidant called metallothionein.
Astrocytes can increase inflammation when they interact with microglia in the brain, but these Alzheimer’s-related pathways appear less active in the resilient group.
The researchers also found that a brain cell response meant to eliminate all misfolded toxic proteins was relatively normal in the resilient group.
This “unfolded protein response” is usually affected in patients with Alzheimer’s disease. And there were signs that the brain cells of the resilient individuals contained more mitochondria than the cells of other Alzheimer’s patients, meaning that energy production would have been stronger in the resilient group.
Cognitive reserve and the phenomenon of “resilience”
Genetics and lifestyle may play a role in this type of resilience, David Merrill, MD, PhD, a geriatric psychiatrist and director of the Pacific Brain Health Center at the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California, who was not involved in the study, said Medical News Today.
“Cognitive reserve, which corresponds to the brain’s resilience to damage, plays an important role. Additionally, genetic factors, lifestyle, and environmental influences can modulate the onset and severity of symptoms despite the underlying pathology,” Merrill said.
“The authors talk about changes in the function of neuronal supporting cells like astrocytes and microglia, or in neuron components like energy-producing mitochondria,” he added.
Yuko Hara, PhD, director of aging and Alzheimer’s prevention at the Alzheimer’s Drug Discovery Foundation (ADDF), who was also not involved in the study, said MNT that there can be a lag of 20 to 30 years between the first signs of amyloid deposits in the brain and the appearance of symptoms.
Hara explained that there are ways people can build up their cognitive reserve over time:
“Cognitive reserve is the brain’s ability to resist the effects of age-related changes or disease-related pathology, such as amyloid beta, which typically leads to a decline in cognitive function. Based on this phenomenon, the knowledge and experiences that people acquire throughout their lives allow them to better cope with pathologies like beta-amyloid and maintain their cognitive functions for longer. There are many things you can do to increase your cognitive reserve: take a class to learn something new, read books, learn a new language, learn to play a musical instrument, or stimulate and engage your brain. challenge in another way.
How common is Alzheimer’s disease without symptoms?
Merrill said adult children or spouses of people with Alzheimer’s disease can come in for testing without symptoms, but in general, most clinic patients seek care when symptoms appear.
He explained: “It’s not common to have patients without symptoms, whether it’s Alzheimer’s disease or otherwise. That said, the early symptoms of (Alzheimer’s disease) can mimic normal aging, which is why many people find themselves answering this question: Is what is happening normal or is this the beginning of (Alzheimer’s disease) ?
“We’re seeing more of a continuum of symptoms rather than a categorical phenomenon between symptomatic and non-symptomatic. In this way, it makes sense that brain donors without any symptoms were rarely observed in the study,” Merrill added.
“Alzheimer’s pathology is observed in asymptomatic individuals, although this is the exception and not the rule in clinical practice. This is consistent with emerging research that suggests Alzheimer’s disease can exist without overt cognitive symptoms, likely due to the brain’s cognitive reserve or compensatory mechanisms, which were reported in the study.
–David Merrill, MD, PhD
Hara said markers for Alzheimer’s disease can appear quite early in life without the presence of typical symptoms. She highlighted a number of interesting studies on the phenomenon.
“Many people have pathological markers of Alzheimer’s disease without having symptoms of Alzheimer’s disease. Beta-amyloid, a pathological marker of Alzheimer’s disease, can begin to accumulate in the brain as early as the twenties,” she emphasizes.
“Amyloid deposition in the brain begins decades before symptoms of Alzheimer’s disease appear. One study found that 44% of 90-year-olds with good cognitive function had amyloid pathology,” Hara said.
“There are also examples of genetic mutations that confer protection against a genetic form of Alzheimer’s disease,” she added.
However, she noted that these events appear rare:
“A 2019 study reported that a woman with the presenilin 1 (PSEN1) mutation, a genetic cause of early-onset Alzheimer’s disease, did not develop dementia in her 40s like other people with the mutation. Instead, she had only mild memory problems at age 70. Researchers discovered that the woman had two copies of a rare mutation called APOE3 Christchurch mutation, which likely made her resistant to the onset of Alzheimer’s symptoms within 30 years, despite very high levels of beta-amyloid in the brain.
Strategies for preventing Alzheimer’s disease
Although there are genetic factors that can determine a person’s vulnerability to developing Alzheimer’s disease, a 2020 report published in The Lancet indicated that alcohol consumption, smoking, poor diet, lack of education, lack of social interaction and lack of exercise can all contribute to the progression of the disease.
At the same time, research suggests that certain lifestyle interventions that stimulate brain activity may help either strengthen cognitive reserve or alleviate certain symptoms.
For example, a study published in Neurology in 2021 revealed that high levels of cognitive activity, such as reading, playing checkers and puzzles, and writing letters, can delay the onset of Alzheimer’s disease by 5 years in people aged 80 years and over.
Another study, published in 2022 in PNASfound that more time spent on passive cognitive activities, such as watching television, is linked to an increased risk of dementia, while more time spent on cognitively active tasks, such as using a computer, is linked to a reduced risk of dementia.
And a study of Open JAMA Networkpublished in July 2023, found that frequent participation in brain-stimulating activities, including journaling, playing chess and solving crosswords, was associated with a lower risk of developing dementia in older adults.
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