Early strike on dementia

Researchers say they may now be able to predict memory problems far in advance – and begin treatment earlier – by identifying particular brain activity patterns.

In a new study out of independent non-profit US biomedical research organisation Gladstone Institutes, scientists tested a new method with the goal of identifying Alzheimer’s memory loss sooner so that interventions could be established as quickly as possible.

“Being able to predict [memory] deficits long before they appear could open up new opportunities to design and test interventions that prevent Alzheimer’s in people,” said Yadong Huang, Gladstone senior investigator and an author of the study.

The study, published in Cell Reports, relied on research from a previous study on the APOE4 gene. The APOE4, or apolipoprotein E4, gene has been the subject of numerous recent investigations to better understand its role in neurodegenerative diseases. If someone carries the APOE4 gene, they have a much higher chance of developing Alzheimer’s disease.

In the most recent development on APOE4, scientists discovered that a woman carrying the APOE4 gene also had a genetic mutation that delayed development of the disease. While the gene she carried greatly increased her risk of developing Alzheimer’s in her 30s, she did not develop it until her 70s.

In an earlier Gladstone study, the researchers examined sharp-wave ripples (SRWs), a type of brain pattern involved in spatial learning and memory in mammals. In ageing mice that carried the APOE4 gene, the researchers noticed SRWs were weaker compared to healthy ageing mice. Impaired SRWs are associated with worsened memory and spatial learning.

In the latest study, researchers decided to test whether identifying weak SRWs in advance could help predict Alzheimer’s disease.

“We actually successfully replicated this experiment two years later with different mice,” Dr Huang said. “What was striking is that we were able to use the results from the first cohort to predict with high accuracy the extent of learning and memory deficits in the second cohort, based on their SWR activity.”

The researchers also wanted to test whether it was possible to predict memory problems, based on SRW activity, at a young age.

They found that impaired SRWs at an early age could predict whether mice would have memory problems later on.

“We were not betting on these results, the idea that young mice with no memory problems already have the seed of what’s going to lead to deficits in old age,” said Emily Jones, lead author of the study. “Although we would love to, but we thought it would be ridiculous to be able to predict so far in advance.”

Dr Huang said he would now work to determine the predictive powers of SWRs in Alzheimer’s patients.

The researchers hypothesise that testing SRW activity in humans at an early age could predict memory loss from Alzheimer’s years down the road.

“A major advantage of this approach is that researchers have recently developed a non-invasive technique for measuring SWRs in people, without implanting electrodes in the brain,” he said.

If SWRs can predict Alzheimer’s in humans, measuring them could boost research and drug development efforts in two important ways, Dr Huang said.

First, they could be used to select participants for clinical trials testing new drugs to stave off Alzheimer’s. “Enrolling patients who already show SWR deficits would enhance the trials’ statistical power,” he said.

Second, SWR measurements could be taken repeatedly and non-invasively, enabling researchers to test drug effects over time, even before memory deficits appear.

“I feel strongly that Alzheimer’s research should not just focus on pathology, but use functional alterations like SWR deficits to guide research and drug development,” he said.

Memory and neurological tests can help identify people who are likely to develop dementia, but these are often carried out long after a person begins showing symptoms.

Researchers say that being able to detect Alzheimer’s risk far in advance, whether through the APOE gene or SRW patterns, could help doctors start treatment or preventive approaches much earlier.

Does current research spark hope that dementia will soon be better understood and able to be treated at an early age?

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Written by Janelle Ward

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