Trending With Impact: Neuromodulation in Alzheimer’s Disease Treatment

Dr. Fabrizio Vecchio wrote about the potential synergistic effects of neuromodulation combined with cognitive training to treat Alzheimer’s disease.

Neuromodulation in Alzheimer’s Disease Treatment

The Trending With Impact series highlights Aging (Aging-US) publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at

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Many neurodegenerative disorders among elderly populations share some common characteristics. In dementias, for example, neurons and glial cells undergo a progressive loss of structure or function in the brain and spinal cord. Alzheimer’s disease (AD) is the most common form of dementia and the main cause of cognitive impairment. Studies have confirmed that cognitive treatments, such as cognitive stimulation, training and rehabilitation, can improve brain function by increasing brain plasticity.

Recently, researcher Fabrizio Vecchio, from IRCCS San Raffaele Roma‘s Brain Connectivity Laboratory, discussed innovative treatment options for Alzheimer’s disease. On April 27, 2022, Dr. Vecchio published his new editorial paper in Volume 14, Issue 9, of Aging (Aging-US), entitled, “Cognitive training and neuromodulation for Alzheimer treatment.”

“Neuromodulation techniques are having a growing consensus as a therapeutic approach of incipient and mild to moderate dementia because of their capability to be modulated both in space, i.e. in different cortical and subcortical areas of the brain, and time.”


Neuromodulation is a considerably recent development in the medical field. This promising treatment option therapeutically alters nerve activity within specific neurological sites of the body using the targeted delivery of electrical stimulation or chemical agents. Neuromodulation can be used not only for patients with dementia but also for those with a number of other disorders, including chronic pain, epilepsy and psychiatric disorders. However, the demonstrated value of cognitive treatments has not been discounted by Dr. Vecchio. In his editorial paper, he discussed the potential synergistic effects of neuromodulation combined with cognitive training (COG). 

“Together with cognitive treatments one of the possible innovative strategies to be undertaken is the neuromodulation that involves non-invasive brain stimulation techniques (NIBS) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS).”

Dr. Vecchio described his recent study on repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training. In this randomized, double-blind, sham-controlled trial, researchers evaluated the efficacy of rTMS-COG treatment in Alzheimer’s patients. Before, immediately after and 40 weeks after rTMS-COG treatment, patients were assessed using neuropsychological and electroencephalography (EEG) examinations. The researchers evaluated six regions of the brain and analyzed neuropsychological and neurophysiological data derived from EEG. After six weeks of intensive daily treatment, immediate results showed an improvement in cognitive scales. At the 40-week follow-up evaluation, improvements in brain connectivity emerged.

“Based on these assumptions and promising results, particularly of rTMS and COG, some researchers hypothesized that a treatment combining rTMS and COG may result in synergic effects more effective [in] respect to applying the two therapies separately.”


Although more research must be conducted to confirm the clinical efficacy of neuromodulation for the treatment of Alzheimer’s disease, initial results are promising. Cognitive treatments should not be discounted either, as they have been shown to improve brain function. Dr. Vecchio suggests a potentially efficacious combination of neuromodulation and cognitive training that may offer significant benefits for patients with Alzheimer’s disease.

“In conclusion, rTMS combined with cognitive training, can be regarded as a potentially useful treatment for AD, not modifying the neuropathological changes, but slowing down their effects on brain networks and providing important groundwork for future studies to build upon. Derived EEG parameters can be awarded the role of diagnostic and predictive biomarkers of AD progression.”

Click here to read the full editorial paper published by Aging (Aging-US).

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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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Risks for Dementia and Mortality: Sleep Disturbance and Deficiency

Researchers used nationally representative data to examine the relationship between sleep disturbance and deficiency and their risk for incident dementia and all-cause mortality among older adults.

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Are serious health consequences looming for those with trouble sleeping? Based on a large sum of available research, the answer appears to be yes—poor sleep poses an increased risk of dementia and all-cause mortality. But what defines poor sleep? Conflicting results have been reported by researchers regarding the characteristics of sleep when examining incident dementia and all-cause mortality. For instance, one meta-analysis suggests that sleeping fewer than five hours (short sleep) and longer than nine hours (long sleep) per night is associated with greater risk of mortality. Another meta-analysis finds that only longer than nine hours is associated with greater risk of mortality.

“Research on sleep disturbance and deficiency and all-cause mortality therefore has shown conflicting results. Further, few studies have included a comprehensive set of sleep characteristics in a single examination of incident dementia and all-cause mortality.” 

From Brigham and Women’s Hospital, Harvard Medical School, and Boston College, based out of Massachusetts, United States, a team of researchers saw the need to address the gaps in this research and developed a new study. They organized a single examination of the relationships between a comprehensive set of sleep characteristics and incident dementia and all-cause mortality. This paper was entitled, “Examining sleep deficiency and disturbance and their risk for incident dementia and all-cause mortality in older adults across 5 years in the United States,” and published in Aging’s Volume 13, Issue 3 in February 2021.

The Study

The researchers collected baseline data from the National Health and Aging Trends Study (NHATS). The NHATS is a nationally-representative longitudinal study of Medicare beneficiaries (65 years and older) in the United States. The data were collected from a randomly selected subset of 2,812 participants from the NHATS population that were administered sleep questionnaires in 2013 and 2014.

“Participants with dementia at baseline (year 2013) were excluded (n = 202) for a sample of 2,812 with sleep data in either 2013 or 2014.”

The sleep characteristics measured from the questionnaire were: sleep duration, sleep latency, difficulty maintaining alertness, sleep quality, napping frequency, and snoring. First, participants rated their memory and performed a memory-related activity to assess their cognitive capacity and screen for incident dementia. Body weight was reported by participants annually, and diagnosis of heart attack, heart disease, hypertension, arthritis, diabetes, stroke, and cancer were also self-reported. Annual interviews were conducted to record instances of participant mortality. The researchers used Cox proportional hazards modeling and controlled for confounders to examine each sleep characteristic and outcome.


“Overall, our findings show a strong relationship between several sleep disturbance and deficiency variables and incident dementia over time.”

In the results adjusted for confounders, the team found that longer time to fall asleep and shorter sleep duration predicted incident dementia. They also found that short sleep duration, difficulty maintaining alertness, napping, and poor sleep quality predicted all-cause mortality. Given that short sleep duration was a strong predictor for both incident dementia and all-cause mortality, the researchers suggest that this may be the most important sleep characteristic related to adverse outcomes among older adults. 

“The association observed in our study between short sleep (5 hours or less) and incident dementia screening may be understood via the research drawing upon animal models to demonstrate brain toxin removal during sleep [24].”

Another fascinating finding from this study was the difference between unadjusted and adjusted results for long sleep. As mentioned, previous studies have shown that long sleep is associated with both incident dementia and all-cause mortality. However, after the researchers adjusted for confounders, such as age and chronic conditions, the association between long sleep and incident dementia and all-cause mortality disappeared. The relationship between short sleep and both incident dementia and all-cause mortality remained significant even after full adjustment. These findings stand in contrast to the meta-analyses initially mentioned that have found associations between both short and long sleep and all-cause mortality in adults. The researchers suggest the cause may be that long sleep is a reflection of underlying disease.

“The most parsimonious explanation for the disappearance of the effect of long sleep on dementia and mortality in adjusted models is that the deleterious impact of long sleep is a reflection of underlying disease.”


The researchers confirm that addressing the sleep disturbance and deficiency variables in this study may have a positive impact on risk for incident dementia and all-cause mortality among older adults.

“Also, future research may consider the development of novel behavioral interventions to improve sleep among older adults.”

Click here to read the full study, published on

Aging is an online open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

For media inquiries, please contact [email protected].

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