New Approaches to Treating Alzheimer’s Disease

Alzheimer’s disease is a devastating condition that strips away people’s memory, thinking, and independence. By 2050, it is expected to affect over 100 million people around the world, making it a high priority for scientific and medical research. Researchers are now exploring the potential for mechanical and light-based stimulation of the brain and nervous system to treat Alzheimer’s disease symptoms. At the University of Minho in Portugal, Francisca Monteiro is developing a PhD project supervised by a multidisciplinary set of experienced researchers, who have reviewed the evidence behind these approaches, including whole-body vibration, auditory stimulation, transcranial ultrasound stimulation, and photobiomodulation. The team aims to synthesize the evidence to support these treatments and understand what further work is needed.

Alzheimer’s disease

Alzheimer’s disease is the most common form of dementia and affects approximately 40 million people around the world, but this number is set to triple by 2050 as global populations age. Despite the significant impact on people and health systems, there are currently no effective treatments to stop or reverse symptoms. This makes Alzheimer’s disease one of the biggest current health challenges, requiring scientific and medical research. The disease can affect memory, thinking skills, language, and behaviour. As Alzheimer’s disease is a progressive condition, symptoms gradually worsen over time, often leading to a loss of independence and the need for full-time care. The emotional and financial burden on families and healthcare systems is enormous.

Whilst the likelihood of developing Alzheimer’s disease increases with age, it is not a normal part of aging. This condition is caused by complex changes in the brain that lead to a loss of brain cells and their connections.

Changes in the Alzheimer’s brain

The causes of Alzheimer’s disease are complex and not yet fully understood, but the disease has been linked with two proteins inside the brain called β-amyloid and Tau. These proteins can build up and clump together —leading to structures called plaques and tangles, respectively, which make it harder for the brain to work properly. Alzheimer’s disease can also lead to certain parts of the brain shrinking, and reducing the amount of key chemicals needed for sending signals around the brain. These changes all add up. Eventually, the brain struggles to cope, leading to problems with memory and thinking.

As well as these key substances, factors such as genetics, older age, chronic stress, brain injuries, and cardiovascular disorders are also associated with a higher likelihood of developing Alzheimer’s.

Whilst our understanding of the mechanisms and potential causes of Alzheimer’s disease have improved, there are still no effective treatments to stop or reverse Alzheimer’s disease symptoms and progression. Due to the limited efficacy of drugs for Alzheimer’s, researchers such as Francisca Monteiro and a team of scientists from the University of Minho, in Portugal, have been researching alternative treatment options for Alzheimer’s disease, such as electrical-, magnetic-, optical-, and mechanical-based therapies. The team have conducted several rigorous systematic reviews of evidence published by other research teams to understand these treatment options and how they could help people with Alzheimer’s disease.

Mechanical vibrations

Scientific evidence suggests that mechanical vibrations could be an exciting treatment possibility for Alzheimer’s disease. These are gentle physical movements or waves which can be used to stimulate the body or brain. When used for Alzheimer’s disease treatment, they are typically delivered in one of three main ways. One is whole-body vibrations, where a person sits or stands on a platform that lightly vibrates; this may help improve movement and balance, as well as brain functions by sending signals through the nervous system. Transcranial ultrasound stimulation uses safe, low-level sound waves aimed at the brain from outside the head; these vibrations may help to clear some of the harmful proteins associated with Alzheimer’s and improve brain activity. Transcranial ultrasound stimulation is often used in combination with a technique using microbubble injections – where tiny gas-filled bubbles are injected into the bloodstream to temporarily allow substances to cross the barrier between the brain and the blood system. Auditory stimulation is a sensory-based technology which involves people listening to sounds of certain frequencies; these frequencies have been associated with positive changes in brainwaves, as well as reduced β-amyloid and Tau structures.

The team’s research into evidence in the literature has found that these therapies are showing exciting potential to support brain health and reduce symptoms in patients. They appear to do this in several ways. Firstly, they may help to reduce the build-up of the harmful amyloid and Tau proteins, which can damage cells in the brains of people with Alzheimer’s disease. The team found that auditory stimulation and transcranial ultrasound clear these proteins effectively in animal studies, sometimes by helping the brain’s natural cleaning and immune systems to work more efficiently. These therapies also appear to boost brain activity — for example, auditory stimulation can encourage healthier brainwave patterns and improve how the cells in the brain communicate with each other. There is evidence that these mechanical stimulation therapies may also be able to reduce inflammation, which is a big problem in Alzheimer’s disease. Both transcranial ultrasound and auditory stimulation calm the pathological overactive immune response, protecting the brain tissue from further damage. They may also help new brain cells grow and strengthen the connection between cells, which is essential for memory and certain types of thinking.

Additionally, all of these therapies are low-cost, non-invasive (they don’t involve needles or surgery), and easily customisable to each patient.

Photobiomodulation

The team also investigated another potential avenue of treatment for Alzheimer’s disease called light-based brain stimulation, including photobiomodulation and visual stimulation. Photobiomodulation uses red or near-infrared light, which has already proven useful in accelerating wound healing, destroying cancerous tumours, and stimulating hair growth. Thus, their potential value in Alzheimer’s disease has been suggested via their tissue-repairing properties and ability to enhance synaptic function. Photobiomodulation therapy can be given through LED lights placed on the scalp, or technologies which combine transcranial and intranasal (through the nose) light delivery, to reach deeper brain regions. These approaches are non-invasive and generally well tolerated, with very few reported side effects. Visual stimulation involves exposure to flashing light, often at 40 times per second. This helps train the brain to produce healthier electrical activity, reducing amyloid levels and improving memory in mouse studies.

Photobiomodulation can help in combating Alzheimer’s disease by stimulating the tiny structures inside our cells called mitochondria, which act like batteries providing energy. This boost in energy production helps brain cells function better, reduces harmful stress, and activates protective responses. Research in animals shows that, apart from reducing the build-up of β-amyloid and Tau proteins, photobiomodulation can also improve blood flow in the brain, bringing in more oxygen and nutrients to the brain cells. It reduces inflammation, supports the growth of new brain cells called neurons, and strengthens the connections between brain cells, all important factors for improving thinking, memory, and mood.

Following promising results for photobiomodulation in laboratory animals, some small human trials have also been conducted, and these reported improved brain function, attention, and sleep in people with mild cognitive impairment or early Alzheimer’s. However, while initial findings are exciting, the team warns that larger and longer-term trials are still needed to confirm the benefits and refine the treatment protocols for people with Alzheimer’s disease.

Optimising and Standardising Treatments for Alzheimer’s Disease

The team found that while light- and vibration-based therapies (like photobiomodulation and transcranial ultrasound stimulation) show great promise for treating Alzheimer’s disease, one of the biggest challenges is optimising and standardising how they are used. Currently, there is no universal agreement on the best treatment settings, such as the best wavelength of light, or ultrasound frequency, intensity, or duration to use. This lack of consistency makes it hard to compare studies or confidently apply these therapies in the clinic.

The need for optimisation was highlighted in a recent study using genetically modified brain cells that mimic Alzheimer’s disease. Researchers tested a wide range of photobiomodulation and transcranial ultrasound stimulation settings, such as varying light wavelengths, pulsing patterns, power levels, and treatment timings, to identify the most effective combinations. They focused on outcomes like neuron activity and reduction of toxic β-amyloid and Tau proteins. The goal was to find the settings where stimulation is both safe and effective. This type of systematic testing is essential for designing therapies that are not just promising in theory, but reliable and reproducible in practice.

Standardisation is also critical for tailoring treatments to different stages of Alzheimer’s disease or to meet the specific needs of individual patients. What works for early cognitive decline might not be effective in later stages. By developing disease-specific protocols and sharing clear guidelines, researchers hope to bridge the gap between experimental success and real-world use. Ultimately, fine-tuning these therapies could unlock their full potential, offering safer, more targeted, and more effective options for people living with Alzheimer’s.

Francisca Monteiro and the team’s work is providing valuable evidence and critical insight to help understand and develop accessible, safe, and scientifically rigorous treatment options, offering real hope for improve the lives of the millions of people affected by Alzheimer’s disease.