Medical Bulletin 10/ March/ 2025 - Video

For more than three decades, scientists have been racing to stop Alzheimer’s disease by removing amyloid beta plaques — sticky clumps of toxic protein that accumulate in the brain. Now, a new Northwestern Medicine study suggests a promising alternative: enhancing the brain’s own immune cells to clear these plaques more effectively.

The findings could reshape the future of Alzheimer’s treatments, shifting the focus from simply removing plaques to harnessing the brain’s natural defenses. The paper is published in Nature Medicine. By analyzing donated brain tissue from deceased people with Alzheimer’s disease who received amyloid-beta immunization and comparing it to those who did not, the scientists found that when these treatments work, the brain’s immune cells (called microglia) don’t just clear plaques — they also help restore a healthier brain environment.

The study included six control brains that had no neurologic disease; six brains with Alzheimer’s disease that had not been treated with any immunization drug; and 13 brains that had been vaccinated with amyloid beta. Of those 13, seven had high levels of amyloid-plaque clearance in the brain while the other six had limited amounts of clearance.The scientists then compared the immune cells in the brains between those two groups.

"Our study is highly novel because we had the rare opportunity to analyze one of the largest post-mortem brain cohorts of Alzheimer's patients treated with amyloid-targeting drugs — similar to those now approved by the FDA for Alzheimer's disease," said lead author Lynn van Olst.

"This allowed us to investigate the brain mechanisms that determine why some individuals respond well to these treatments and successfully clear toxic amyloid-beta, while others do not. We found that brain immune cells play a crucial role in this process and identified the molecular genetic factors that drive these differences."

Ref: van Olst, L., Simonton, B., Edwards, A.J. et al. Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease. Nat Med (2025). https://doi.org/10.1038/s41591-025-03574-1

A new Cochrane review has found evidence that music-based therapy may benefit people living with dementia, particularly by improving symptoms of depression. Dementia is a collective term for progressive degenerative brain syndromes that affect memory, thinking, behaviour and emotion.

The work has been published in Cochrane Database of Systematic Reviews. Alzheimer’s Disease International reported that there were 55 million people with dementia worldwide in 2019, a figure predicted to increase to 139 million by 2050. While some medicines are available, the therapeutic use of music is considered a relatively simple and inexpensive approach that remains accessible even in the later stages of dementia.

The research team from several institutions in the Netherlands examined evidence from 30 studies involving 1,720 people. The studies investigated the effects of music-based therapeutic interventions on emotional well-being including quality of life, mood disturbance, behavioural problems, social behaviour, and cognition.

"This review increases our understanding of the effects of music therapy and strengthens the case for incorporating music in dementia care, particularly in care home settings,” says lead author Jenny van der Steen from Leiden University Medical Center and Radboudumc Alzheimer Center. “Music therapy offers benefits beyond those of other group activities, helping to support mood and behaviour in a way that is engaging and accessible, even in later stages of dementia. Care home managers should consider integrating structured musical sessions as part of a person-centred approach to dementia care.”

The findings suggest that music-based therapy probably improves depressive symptoms and may improve overall behavioural problems by the end of treatment. Music therapy is unlikely to significantly impact agitation, aggression, emotional well-being, or cognition but, when compared to other interventions, there is some evidence that it may improve social behaviour and could decrease anxiety.

The review underscores the need for further research into the long-term effects of music-based therapy particularly in community settings.

Ref: Music-based therapy may improve depressive symptoms in people with dementia, Cochrane Database of Systematic Reviews (2025). DOI: 10.1002/14651858.CD003477.pub5/full

A growing body of research indicates that older adults in assisted living facilities can delay or even prevent cognitive decline through interventions that combine multiple activities, such as improving diet, solving puzzles and increasing social interactions.

Multidomain interventions, including games and exercises delivered through smartphone-based apps, have also proven effective in slowing cognitive decline in this population. One such intervention is the Silvia Program, a free, cognitive health care lifestyle app that offers one-on-one coaching from a clinical psychologist, cognitive exercises and activities, personalized routine suggestions and a voice analysis tool that can detect symptoms of dementia.

The study was published recently in Public Health and Practice. The researchers recruited 20 residents experiencing mild cognitive impairment and conducted a randomized clinical trial with 10 participants receiving the Silvia intervention and 10 in a control group that had no interventions. The average participant age was 78 years, and the male-to-female ratios were similar. Educational levels differed, however, with seven control group participants and three intervention group participants reporting less than a high school education or only a high school education.

The Silvia Program intervention included daily goal setting, cognitive training through 15 personalized programs and monitoring of nutrition, activity and sleep patterns. It also featured a home-based aerobic and resistance exercise program with visual step-by-step guides. Cognitive training sessions were held three times a week, lasting 15 to 30 minutes each, for 12 weeks. Physical exercises were conducted twice a week, with each session lasting 30 minutes. Meanwhile, the control group maintained their usual routines without using the app.

“Participants in the Silvia Program also engaged in individualized, AI-generated conversations about their activities, including the difficulty of tasks, time spent and cognitive exercise scores,” explains Junhyoung “Paul” Kim, one of the representatives from Silvia Health, Inc., who pilot tested the Silvia Program with residents at an assisted living facility in Indiana.

The intervention group exhibited improvements in visuospatial/executive function (the ability to successfully complete a task), language, delayed recall and orientation scores. The control group displayed nonsignificant increases in visuospatial/executive function, naming and abstraction scores, with declines in language and delayed recall scores and no changes in attention and orientation scores.

“Our study demonstrates that customized, mobile multidomain programs can benefit older adults experiencing mild cognitive decline,” Kim said. “The potential for even greater outcomes as these programs are further refined and expanded is immense.” Researchers concluded.

Ref: Kim Y, Kim J et al. The efficacy of a mobile-based multidomain program on cognitive functioning of residents in assisted living facilities: Public Health in Practice, Volume 8,2024. https://doi.org/10.1016/j.puhip.2024.100528.