Category: Blog Post

A new study describes the first human trials of an experimental cure for Alzheimer’s that uses sound and light. The preliminary findings are intriguing, with the novel treatment resulting in some neurological and cognitive improvements. However, the small trial size implies further research is needed before anyone can claim that this therapy works.

According to the results of two recent small trials published in the journal PLoS One, an Alzheimer’s treatment is under development at MIT that alters patients’ brain waves using light and sound may be a safe approach to boost memory while preventing brain abnormalities associated with the disease.

These investigations are far too small to demonstrate the efficacy of the therapy. However, a much larger study is already underway to test this treatment option and might be completed by May 2025.

Brain Waves 101

About 86 billion neurons make up our brains, and these cells interact with one another using brief electrical pulses. When several neurons are activated, the pulses can synchronize and repeat in a systematic pattern, resulting in a rhythm known as a brain wave.

The brain generates five types of brain waves, classified based on their frequencies or how many times the cycle repeats every second. The frequency of delta waves is the lowest (0.5-4 Hertz), while the frequency of gamma waves is the highest (32–100 Hz).

Although our brains can produce more than one form of brain wave at a time, the dominant type is typically associated with alertness. For example, delta waves may predominate when you sleep, while gamma waves may predominate when you concentrate very hard.

What’s the idea behind the research?

Researchers have previously noted that those who have Alzheimer’s may have weaker and less synchronized gamma waves than those who do not. In a series of earlier investigations, scientists from MIT showed that exposing animals to 40 Hz clicking sounds or flickering lights could boost the strength and synchronization of these waves in Alzheimer’s mice models.

Together with their boosted gamma waves, the mice also appeared to have a range of benefits, such as memory enhancements, delayed neuronal degeneration, and decreased levels of proteins linked to Alzheimer’s in the brain compared to controls.

The researchers think this is because more powerful and in-sync gamma waves strengthen the neural connection, enlarge waste-clearing arteries, and improve immune cell responsiveness in the brain.

Evaluating the Safety and Effectiveness

The MIT researchers have completed two short clinical trials to see how the 40-Hz light and sound treatment, known as “Gamma ENtrainment Using Sensory stimuli” (GENUS), impacts people.

Two early-stage clinical studies evaluating the safety and effectiveness of 40-hertz sensory stimulation for Alzheimer’s treatment have found that the potential therapy was well-tolerated, had no notable adverse effects, and was associated with some considerable neurological and behavioral advantages in a small cohort of patients.

In a phase 1 trial, 43 participants, including 16 people with early-stage Alzheimer’s and two persons with epilepsy who were about to have brain surgery, received the 40-Hz GENUS treatment for a few minutes.

The team used scalp electrodes to track the activity of the participants’ frontal and occipital lobes before, during, and after the sensory stimulation. Activity in deeper brain areas that were reachable during surgery was evaluated in epilepsy patients.

According to the results, the strength of gamma waves in all brain areas seemed to rise throughout therapy, and gamma wave synchronization in the frontal and occipital lobes also increased. Sleepiness was the most often reported adverse event, and no other serious adverse events.

Home Therapy

In a phase 2a trial, the team provided GENUS devices to 15 individuals with early-stage Alzheimer’s to be used at home for an hour each day for at least three months. Each comprised a light panel linked to a speaker and video cameras to watch device usage.

They then randomly divided the participants into two groups and exposed eight of them to sound and light of 40 Hz frequency via the GENUS apparatus. White noise and steady light served as a sham treatment for the other seven.
At the start and end of the study, the subjects underwent cognitive testing, EEG recordings, and MRIs to quantify brain volume. Both groups’ users utilized the gadget around 90% of the time as instructed and reported no severe adverse effects.

The treatment group had a much greater connection between the areas of the brain associated with cognition and visual processing than the control group. They also fared much better on a memory assessment that challenged them to match faces with names.

Two metrics linked to Alzheimer’s progression — reduced hippocampal volume and raised ventricle volume — worsened in control participants but did not alter significantly in the treatment group. Yet, with only a few individuals in each group, it is hard to be confident in these results.

What’s Next?

While these trials imply that 40-Hz GENUS is safe and beneficial for Alzheimer’s patients, the sample sizes are far too limited to prove that sensory stimulation works.

Cognito Therapeutics, an MIT spinoff formed by senior author Li-Huei Tsai and co-author Ed Boyden, has already initiated a phase 3 trial in which they will randomly assign 500 persons with Alzheimer’s to receive daily 40-Hz auditory and visual stimulation or placebo treatment for 9 to 12 months.

If this more extensive experiment, dubbed HOPE, can demonstrate the treatment’s success, it could one day provide individuals with Alzheimer’s with a safer strategy to tackle the illness that does not put them in danger of grave side effects that some medications can cause.

References

1. Chan, D., Suk, H.J., Jackson, B.L., Milman, N.P., Stark, D., Klerman, E.B., Kitchener, E., Fernandez Avalos, V.S., de Weck, G., Banerjee, A. and Beach, S.D., 2022. Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies. PloS one, 17(12), p.e0278412.
2. A Pivotal Study of Sensory Stimulation in Alzheimer’s Disease (Hope Study, CA-0011) (Hope). ClinicalTrials.gov. U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/show/NCT05637801. Accessed: 5th April, 2023.
3. 40HZz Rhythms Fight Alzheimer’s at the Cellular and Molecular Level. The Picower Institute for Learning and Memory. https://picower.mit.edu/discoveries/40hz-rhythms-fight-alzheimers-cellular-and-molecular-level. Accessed: 5th April, 2023.
4. MIT is testing light and sound to combat Alzheimer’s. Freethink. https://www.freethink.com/health/gamma-waves-alzheimers. Published online: 23rd Dec, 2023. Accessed: 5th April, 2023.
5. First human trials test light & sound therapy for Alzheimer’s disease. New Atlas. https://newatlas.com/medical/light-sound-therapy-alzheimers-disease-human-trials/. Published online: 14th Dec, 2023. Accessed: 5th April, 2023.

Scientists have understood for a long time that exercise is beneficial to the body. They are demonstrating in recent years how good it is for the brain, too.

Regular physical activity seems to be one of the most effective things you can do to lower your chance of developing dementia out of all the lifestyle changes the researchers have evaluated.

A decrease in cerebral blood flow is one of the causes of Alzheimer’s [1]. However, improving blood flow can prevent cognitive loss. Aerobic exercise (an activity that raises your heart rate) enhances blood flow in the brain, and studies have indicated that it can help prevent and slow the onset of Alzheimer’s.

Several research studies examining the impact of aerobic exercise on middle-aged or older adults have demonstrated improvements in thinking and memory, as well as lower rates of dementia.

Exercising & Physical Activity in Mid-Life

Prospective studies track the health and behavior of a group of people through time. Many prospective studies have examined the impact of physical activity on middle-aged people’s thinking and memory in later life. The Alzheimer’s Society in the UK combined the findings of 11 studies, revealing that regular exercise can dramatically lower dementia risk by roughly 30%. In the case of Alzheimer’s, the risk decreased by 45% [2].

According to a 44-year longitudinal population study in women, stamina has a connection with the risk of dementia. An article in the medical journal Neurology found that women with superior cardiovascular health had an 88% lower risk of developing dementia than other women [3].

Similarly, one study tracked over 2,000 men in Wales for 35 years while examining their health-related behaviors. Exercise had the most significant impact on lowering the risk of dementia of the five behaviors evaluated (regular exercise, avoiding smoking, moderate alcohol use, healthy body weight, and good food). Those who engaged in four or five of the mentioned behaviors were generally up to 60% less likely to develop dementia [4].

Adults in good health can do better on thinking tests over the short term when they engage in aerobic activity. Combining the findings of 29 clinical trials demonstrated that regular aerobic exercise, as opposed to regular non-aerobic exercise like stretching and toning, improved memory, attention, and processing speed after a month or more [2].

Exercising & Physical Activity in Later Life

Although there have been fewer studies done with healthy older individuals, there is some indication that regular exercise can help older adults minimize their risk of dementia. In one study of 716 persons with an average age of 82 years, those in the bottom 10% of regular physical activity were more than twice as likely to acquire Alzheimer’s as those in the top 10% [5].

A literature review revealed 27 studies that investigated the influence of physical activity on brain function in individuals over 60 years. There was a definite correlation between physical activity levels and cognitive performance in 26 trials, indicating that exercise may effectively decrease the cognitive decline in later life [2].

Healthy older adults who engage in aerobic activity have their brains affected, too. In a small-scale controlled trial, aerobic exercise showed a slight increase in the size of the hippocampus (the crucial brain region involved in memory), similar to restoring one to two years of age-related shrinkage [6]. Another study of 638 individuals discovered that those who were healthy and active at age 70 had less brain shrinkage in three years than those who were not [7].

What exactly is “physical activity”?

The term “physical activity” or “exercise” is not used uniformly throughout all of the research studies in this field. Generally speaking, they are about an aerobic activity done for a long time—maybe 20 to 30 minutes. Most of the research discusses the benefits of aerobic exercise that are performed several times per week and continued for at least a year.

Physical activity, however, is not limited to jogging or participating in sports. It can also refer to a regular activity like cleaning, gardening, or brisk walking. According to one study, even performing physical activities like cooking and cleaning up after yourself can lower your risk of developing Alzheimer’s [5].

Strength exercise is also linked with improved moods, deeper sleep, and cognitive wellness. Any physical activity will increase blood flow to the brain, which is critical. Some physical activities, such as dancing and boxing, enhance the brain because they require mental effort to learn and repeat steps [8]. According to a paper published in the Journal of the International Neuropsychological Society, just one exercise session can boost your brain’s functioning and the component of memory that allows us to remember standard information [9].

More Research is Required!

Further research is required to determine the best type and amount of exercise, which will probably change over a person’s lifetime. More research is also needed to fully comprehend the role of physical activity in lowering the risk of various types of dementia.

References

1. Goldsmith, H.S., 2022. Alzheimer’s Disease: A Decreased Cerebral Blood Flow to Critical Intraneuronal Elements Is the Cause. Journal of Alzheimer’s Disease, (Preprint), pp.1-4.
2. Physical Exercise and Dementia. https://www.alzheimers.org.uk/about-dementia/risk-factors-and-prevention/physical-exercise. Accessed: 31st March, 2023.
3. Hörder, H., Johansson, L., Guo, X., Grimby, G., Kern, S., Östling, S. and Skoog, I., 2018. Midlife cardiovascular fitness and dementia: a 44-year longitudinal population study in women. Neurology, 90(15), pp.e1298-e1305.
4. Elwood, P., Galante, J., Pickering, J., Palmer, S., Bayer, A., Ben-Shlomo, Y., Longley, M. and Gallacher, J., 2013. Healthy lifestyles reduce the incidence of chronic diseases and dementia: evidence from the Caerphilly cohort study. PloS one, 8(12), p.e81877.
5. Buchman, A.S., Boyle, P.A., Yu, L., Shah, R.C., Wilson, R.S. and Bennett, D.A., 2012. Total daily physical activity and the risk of AD and cognitive decline in older adults. Neurology, 78(17), pp.1323-1329.
6. Tarumi, T., Rossetti, H., Thomas, B.P., Harris, T., Tseng, B.Y., Turner, M., Wang, C., German, Z., Martin-Cook, K., Stowe, A.M. and Womack, K.B., 2019. Exercise training in amnestic mild cognitive impairment: a one-year randomized controlled trial. Journal of Alzheimer’s Disease, 71(2), pp.421-433.
7. Gow, A.J., Bastin, M.E., Maniega, S.M., Hernández, M.C.V., Morris, Z., Murray, C., Royle, N.A., Starr, J.M., Deary, I.J. and Wardlaw, J.M., 2012. Neuroprotective lifestyles and the aging brain: activity, atrophy, and white matter integrity. Neurology, 79(17), pp.1802-1808.
8. Croft, J. Why Exercise Can Help Alzheimer’s. WebMD. https://www.webmd.com/fitness-exercise/news/20210720/why-exercise-can-help-prevent-alzheimers. Published online: 21st Jan, 2021. Accessed: 31st March, 2023.

Although both frontotemporal dementia (FTD) and Alzheimer’s can result in dementia, the affected brain regions and, as a result, the symptoms differ significantly between the two. Knowing the differences between frontotemporal dementia and Alzheimer’s might assist in lowering the incidence of misdiagnosis, which may promote early treatment, better health outcomes, and improved life quality.

Understanding the distinction between Alzheimer’s and Frontotemporal Dementia

Dementia is an umbrella word used to represent a range of symptoms linked to a decline in memory, thinking, reasoning, or other cognitive skills rather than a specific disease. Frontotemporal dementia and Alzheimer’s are two of the several causes of dementia.

The Brain Regions They Affect

The fundamental distinction between frontotemporal dementia and Alzheimer’s is the brain regions they impact. Frontotemporal dementia, as its name suggests, predominantly affects the frontal and temporal lobes of the brain. The frontal and temporal lobes are typically related to personality, language, and behavior and are crucial for some cognitive processes. The frontal lobe is essential for performing higher-level executive functions, including judgment, reasoning, emotional regulation, and problem-solving. On the other hand, the temporal lobe plays a role in processing auditory data and encoding memories.

Contrarily, Alzheimer’s typically affects multiple brain regions with the disease progression. In the early stages, the disease affects the entorhinal cortex and hippocampus, which are critical for memory and learning. Later in the disease’s progression, it may deteriorate the cerebral cortex, which includes the frontal, parietal, temporal, and occipital lobes and is involved in memory, personality, behavior, language, speech, sensorimotor planning, spatial recognition, and visual perception and processing, among other things.

The Age of Onset

The timing of onset is another chief distinction between Alzheimer’s and frontotemporal dementia. Alzheimer’s affects adults aged 65 and over. The most significant risk indicator for acquiring Alzheimer’s is advancing age, but it is not a normal part of healthy aging. Contrarily, most patients with FTD are diagnosed between 40 and 60 years.

The Difference in Symptoms

Frontotemporal dementia and Alzheimer’s differ significantly; however, it can be difficult to distinguish between the two in clinical settings. Although early symptoms of FTD and Alzheimer’s can resemble one another in later stages, early stages are critical for getting an early, correct diagnosis since early stages symptoms are frequently quite different.

There are several differences between the symptoms of both disorders.

• Memory loss is more prevalent in early Alzheimer’s than in early Frontotemporal dementia. However, advanced FTD frequently induces memory loss in addition to its more typical impact on language and behavior.
• Behavioral changes are frequently the initial indications of bvFTD, the most prevalent type of FTD. Changes in behavior are frequent as Alzheimer’s advances, but they tend to appear later in the disease.
• The occurrence of spatial orientation problems, such as becoming lost in familiar surroundings, is higher in Alzheimer’s than in FTD.
• Although individuals with Alzheimer’s may struggle to find the proper word or remember names, they may experience less difficulty making sense when speaking, following others’ speech, or reading than those with FTD.
• When Alzheimer’s disease worsens, delusions and hallucinations become more frequent; however, they are less common in FTD.

Memory loss is a common early indication of Alzheimer’s, whereas personality changes, behavioral problems, and linguistic difficulties are typical early signs of frontotemporal dementia. Also, it is crucial to remember that there are two main categories of FTD, each having a unique set of symptoms. Primary progressive aphasia (PPA) is related to a decline in speaking, language, writing, and comprehension, whereas behavioral variant frontotemporal dementia (bvFTD) is associated with behavior and personality changes.

The best likelihood of a successful therapeutic outcome, especially for Alzheimer’s, is thought to come from early diagnosis and intervention. The key to decreasing the rate of misdiagnosis and improving patient outcomes can be early and regular neurocognitive testing, employing highly-sensitive neurocognitive evaluations.

References

1. How Is Frontotemporal Dementia Different From Alzheimer’s?. Altoida. https://altoida.com/blog/frontotemporal-dementia-different-from-alzheimers/. Published online: 8th Dec, 2022. Accessed: 27th March, 2023.
2. Frontotemporal Dementia. Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/frontotemporal-dementia. Accessed: 27th March, 2023.
3. The Difference Between Alzheimer’s Disease and Frontotemporal Dementia. Assisted Hands. https://www.assistinghands-il-wi.com/blog/alzheimers-disease-vs-frontotemporal-dementia/.  Accessed: 27th March, 2023.

According to a recent study from the University of Colorado Anschutz Medical Campus, increased fructose intake may be a chief cause of Alzheimer’s.

An ancient human foraging drive, fueled by fructose synthesis in the brain, may provide insights into Alzheimer’s development and potential treatment. The study1, published in The American Journal of Clinical Nutrition, provides a fresh perspective on a fatal condition distinguished by aberrant protein accumulations in the brain that gradually degrade memory and cognition.

The study’s lead author Richard Johnson, MD, a professor at the University of Colorado School of Medicine specializing in renal disease and hypertension, made the case that the diet drives Alzheimer’s. According to Johnson and his team, AD is a detrimental adaptation of a survival route that evolved in animals and our ancient ancestors to help them survive in times of scarcity.

Fructose: A Trigger For The Foraging Survival Response

Early humans had a survival reflex that sent them foraging for food when threatened with the risk of starvation. Yet, foraging is only productive if metabolism is suppressed in different brain regions. Focus, quick judgment, impulsivity, risk-taking, and exploratory behavior are necessary for foraging. It improves by obstructing anything that gets in the way, such as recent memories and time awareness. A type of sugar called fructose aids in calming these areas so that acquiring food can be the main focus.

The researchers discovered that fructose metabolism—whether it was consumed or created by the body—set the entire foraging response in action. It was essential for both humans and animals to metabolize fructose and its byproduct, intracellular uric acid.

The hippocampus, thalamus, and cerebral cortex of the brain that are involved in self-control all experience decreased blood flow as a result of fructose, according to the study’s authors. In the meantime, blood flow across the visual cortex related to food reward increased. Everything triggered the foraging response.

Researchers believed that initially, the fructose-dependent decrease in brain metabolism in these areas was reversible and intended to be advantageous. Yet, recurring fructose metabolism-driven chronic and permanent decline in cerebral metabolism causes progressive brain atrophy and cell death, symptoms of Alzheimer’s.

“Survival Switch” Remained In The “On” Position

Johnson hypothesizes that in an era of relative abundance, the survival reflex, or “survival switch,” that enabled prehistoric people to survive times of scarcity, is currently stuck in the “on” position. This results in excessive consumption of foods high in fat, sugar, and salt, which increases the creation of fructose.

According to the study, fructose generated in the brain may eventually cause inflammation and Alzheimer’s disease. When administered fructose, animals exhibit memory loss, decreased maze navigation skills, and neuroinflammation.

Johnson further stated that laboratory rats fed fructose for an extended period in a study developed the tau and amyloid beta proteins implicated in Alzheimer’s in their brains and that high fructose levels are also present in the brains of Alzheimer’s patients.

Johnson hypothesizes that certain AD patients’ propensity to wander off may be a trace of the primate foraging reflex.

The researchers proposed that both dietary and pharmaceutical trials to minimize fructose consumption or inhibit fructose metabolism be conducted to assess if there is potential benefit in the prevention, management, or treatment of this condition.

References

• Johnson, R.J., Tolan, D.R., Bredesen, D., Nagel, M., Sánchez-Lozada, L.G., Fini, M., Burtis, S., Lanaspa, M.A. and Perlmutter, D., 2023. Could Alzheimer’s Disease Be a Maladaptation of an Evolutionary Survival Pathway Mediated by Intracerebral Fructose and Uric acid Metabolism?. The American Journal of Clinical Nutrition. https://www.sciencedirect.com/science/article/abs/pii/S0002916523000047.
• Kelly, D. Study Suggests Fructose Could Drive Alzheimer’s Disease. University of Colorado Anschutz Medical Campus. https://news.cuanschutz.edu/news-stories/study-suggests-fructose-could-drive-alzheimers-disease. Published online: 13th Feb, 2013, Accessed: 6th March, 2023.
• Fructose could drive Alzheimer’s disease. Science Daily. https://www.sciencedaily.com/releases/2023/02/230213113345.htm. Published online: 13th Feb, 2013, Accessed: 6th March, 2023.
• Group of Scientists Propose a New Driver of Alzheimer’s Disease: Fructose. Science Alert. https://www.sciencealert.com/group-of-scientists-propose-a-new-driver-of-alzheimers-disease-fructose. Published online: 20th Feb, 2023. Accessed: 6th March, 2023.
• Sugary Foods May Be Driving Alzheimer’s, Study Suggests. Psychiatrist.com. https://www.psychiatrist.com/news/sugary-foods-may-be-driving-alzheimers-study-suggests/. Published online: 20th Feb, 2023. Accessed: 6th March, 2023.