Memory declines with age, but it starts deteriorating long before you become old
Researchers have studied the development of the brains of people aged 30 to 89 years. Brain atrophy leading to memory loss is completely normal, and it starts earlier than you might think.
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Age is the primary risk factor for developing Alzheimer's.
Perhaps it's not so surprising, then, that much of the research on this topic has compared the brains of older individuals who have developed the disease with the brains of healthy older individuals.
"One of the problems with this is that if you're always looking for differences, you fail to see the similarities," says James Michael Roe.
Increased brain atrophy in everyone over 50 years old
He is a researcher at the Centre for Lifespan Changes in Brain and Cognition at the University of Oslo, where the goal is to understand how the brain develops throughout life, from beginning to end.
In a new study from the centre published in Nature Communications, the researchers examined brain atrophy and memory in healthy individuals aged 30 to 89 years.
They found increased brain atrophy – the loss of brain cells and nerve fibers – in everyone over 50 years old. The brain atrophy is also most pronounced in the same areas of the brain that are affected in individuals with Alzheimer's.
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"The memory loss that we all experience is linked to this gradual brain atrophy that occurs throughout life, in the same areas as in Alzheimer's brains," says Roe.
"And this also occurs in completely healthy adults, even in the age range of 30 to 65 years," he says.
Overlap between normal development and Alzheimer's
Roe points out that brain atrophy in these parts of the brain naturally progresses more rapidly in those who develop Alzheimer's.
People who fall ill lose memory and brain tissue faster than would be expected for their age.
"However, the study shows there is an overlap between normal brain changes and those seen in Alzheimer's disease. We need to keep this in mind when trying to understand Alzheimer's," says Roe.
He believes it is important to normalise memory loss in general.
"Memory loss as we age is a normal process. It also doesn't occur only with ageing. Even early in adulthood, many of us notice that it can take longer to remember things than before," says Roe.
"Our findings show that the loss of brain cells is a continuous process throughout life. It begins early and accelerates after we turn 50," he says.
Saw risk of Alzheimer's in completely healthy people
The study also indicates that we need to consider Alzheimer's throughout life, not just towards the end of life, according to Roe.
"We can detect signs of Alzheimer's risk even in healthy and fit adults," he says.
The researchers applied artificial intelligence trained to recognise brains with Alzheimer's on the healthy brains in the study, which had been monitored over time.
"We saw that the AI could indeed reveal genetic risk for Alzheimer's even in healthy individuals who often perform very well on memory and cognitive tests," he explains.
However, the study also revealed that genetic risk alone does not appear sufficient to trigger Alzheimer’s.
"Those with the highest brain atrophy and genetic risk for Alzheimer's also had the fastest memory loss. But not all with genetic risk exhibited high levels of brain atrophy and memory loss," Roe clarifies.
"It seems, therefore, that you can be genetically predisposed to Alzheimer's without it affecting the brain more negatively than others of the same age," he says.
Changes over time
Roe is part of a centre where brain diseases like Alzheimer's are studied from a lifespan perspective.
"If you want to understand brain development, you need to know where it started. That's what makes our study unique. We measure changes over time in a sample of very healthy people of all ages," says Roe.
In the recently published study, participants have had their brains scanned up to seven times and were followed up with MRIs and cognitive tests. The study is ongoing, and the sample – which also includes children – continues to be tested and scanned at regular intervals.
The researchers have repeatedly argued that events early in life, as early as during foetal development, have a greater impact on the development of Alzheimer's than events later in life and in old age.
"This study did not specifically examine that, but it appears that interventions early in life matter more than those we implement later," says Roe.
Controversial conclusion
"This is a very interesting study that seems to be well thought out," says Asgeir Kobro-Flatmoen.
Kobro-Flatmoen is a researcher at the K.G. Jebsen Center for Alzheimer's Disease at NTNU's Kavli Institute for Systems Neuroscience. He has read the article from the lifespan researchers.
"The results are important as part of the knowledge we need to uncover the ageing processes at multiple levels," says Kobro-Flatmoen.
However, he is not convinced that this is related to Alzheimer's.
"Many previous findings suggest that normal ageing and Alzheimer's disease are two separate processes," says Kobro-Flatmoen.
The researchers behind the new study challenge this view with analyses based on large datasets, but the interpretation that normal ageing and Alzheimer's disease are two aspects of the same process is somewhat controversial, he believes.
Specific to Alzheimer's
Kobro-Flatmoen refers to a study showing that the brain's energy consumption in specific areas of the brain differs between normal ageing and Alzheimer's disease.
Several other studies, including one by Kobro-Flatmoen himself, have also documented significant loss of neurons in specific parts of the brain in Alzheimer's disease, which does not occur during normal ageing.
Kobro-Flatmoen is working to identify exactly which groups of neurons are the first to become affected in Alzheimer's and what makes them particularly vulnerable.
"I hope to contribute to getting closer to understanding what goes wrong in the brain when we transition from being healthy to developing the first changes underlying the disease," he says.
Believes lifestyle plays a role
Kobro-Flatmoen believes there is solid evidence that various lifestyle choices significantly influence the risk of developing Alzheimer's disease or delaying its onset.
"We know with high certainty that factors such as diet, physical activity, alcohol consumption, smoking or not, social participation, and the extent to which one actively uses their brain collectively account for between 30 and 50 per cent of the risk for the disease," he says.
"This does not mean an individual can be guaranteed protection, but the risk can be significantly reduced through healthy choices," he says.
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Translated by Alette Bjordal Gjellesvik
Read the Norwegian version of this article on forskning.no
References:
Kobro-Flatmoen et al. Re-emphasizing early Alzheimer's disease pathology starting in select entorhinal neurons, with a special focus on mitophagy, Ageing Research Reviews, vol. 67, 2021. DOI: 10.1016/j.arr.2021.101307
Roe et al. Brain change trajectories in healthy adults correlate with Alzheimer’s related genetic variation and memory decline across life, Nature Communications, vol. 15, 2024. DOI: 10.1038/s41467-024-53548-z
Small et al. 'Imaging hippocampal function across the human life span: is memory decline normal or not?' Annuals of Neurology, vol. 51, 2002. DOI: 10.1002/ana.10105 (Abstract)
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