rTMS brain magnetic stimulation in Alzheimer’s treatment

Dementia is a debilitating disorder of cognitive functions that affects millions of people worldwide. There are several disorders belonging to the spectrum of dementia, Alzheimer’s being one of them. Magnetic brain stimulation rTMS is a safe and non-invasive form of brain stimulation that is effective for the treatment of various neurological and psychiatric disorders. In this article, the available studies related to rTMS in the treatment of dementia are reviewed. Most of the studies are related to Alzheimer’s and have shown beneficial effects independently or as a supplement to standard drug treatment and cognitive training. Most of the applied protocols seem to be focused on the DLPFC region, but several parameters still need to be defined. In addition, rTMS has also shown potential effects in mild cognitive disorders.

Source: https://doi.org/10.3390/healthcare9080949

Some rTMS treatment protocols in the DLPFC region

Table 1. rTMS over the DLPFC * in Alzheimer’s disease.
Reference Protocol Results
[۱۸] HF ** (20 Hz), bilaterally Improved action naming
[۱۹] HF (20 Hz), bilaterally Improved action naming in milder cognitive decline Improved general naming in moderate to severe cognitive decline
[۲۰] HF (20 Hz), left Improved auditory sentence comprehension, persisted for 2 months
[۲۱] HF (10 Hz), left Improved neuropsychological test scores and daily functioning
[۲۲] HF (20 Hz)/LF *3 (۱ Hz), bilaterally Improved cognitive function and mood in the HF group, persisted for 3 months
[۲۳] HF (20 Hz), bilaterally Improved cognitive function and behaviorImproved word-image association
[۲۴] HF (20 Hz), left Improved cognitive function and behavior
[۲۵] LF (1 Hz), right Improved episodic memory (non-verbal recognition)
* Dorsolateral prefrontal cortex. ** High-frequency rTMS. *3 Low-frequency rTMS.

Some rTMS treatment protocols combined with cognitive training

Table 2. rTMS over 6 areas of interest * combined with respective cognitive training in AD.
Reference Protocol Results
[۲۶] HF (10 Hz) Improved cognitive function, persisted in the maintenance period
[۱۴] HF (10 Hz) Improved cognitive function, persisted in the maintenance period
[۲۷] HF (20 Hz) Improved cognitive function
[۲۸] HF (10 Hz) Improved cognitive function, stronger results for milder cognitive decline
[۲۹] HF (10 Hz) Improved cognitive function, persisted in the maintenance period
[۳۰] HF (10 Hz) Improved cognitive function, persisted at 6 months for those with better baseline scores
[۳۱] HF (10 Hz) Improved cognitive function that persisted, specifically for those with better baseline scores
[۳۲] HF (10 Hz) Improved cognitive function, persisted in follow-up, no differences between groups receiving real or sham cognitive training
* Left inferior frontal gyrus, left superior temporal gyrus, left and right dorsolateral prefrontal cortex, left and right parietal somatosensory association cortices.

Some ongoing clinical trials of rTMS in Alzheimer’s

Table 3. Ongoing studies on the use of repetitive transcranial magnetic stimulation in dementia.
NCT Number Dementia Type Details
NCT02621424 MCI */AD **
  • Last update: May 2021, active—not recruiting
  • Randomized, crossover, sham-controlled
  • Target: DLPFC *5
  • Outcome: Cognitive score improvement and CSF *6 BDNF *7 levels
NCT01894620 AD
  • Last update: February 2021, completed, preliminary results listed
  • Randomized, crossover, sham-controlled
  • Outcome: Cognitive score and sleep improvement
NCT02537496 AD
  • Last update: February 2019, completed, no results listed
  • Randomized, sham-controlled
  • Target: Left DLPFC
  • Outcome: Executive function/working memory improvement
NCT04562506 AD
  • Last update: September 2020, completed
  • Randomized, sham-controlled, double-blinded
  • Target: Bilateral DLPFC
  • Outcome:Cognitivefunctions
NCT03665831 MCT/AD with comorbid MDD *3
  • Last update: October 2019, recruiting
  • Open-label trial
  • Target: Left DLPFC
  • Outcome: Emotional/cognitive symptoms
NCT02908815 AD
  • Last update: February 2021, recruiting
  • Randomized, sham-controlled
  • Target: DLPFC
  • Outcome: Cognitive functions
NCT01885806 AD-related apathy
  • Last update: June 2013, unknown
  • Randomized, sham-controlled
  • Target: Left DLPFC
  • Outcome: Apathy symptoms
NCT04754152 MCI/AD
  • Last update: May 2021, recruiting
  • Randomized, sham-controlled
  • Outcome: Cognitive functions
NCT04012346 MCI/AD
  • Last update: July 2019, unknown
  • Randomized, double-blinded, sham-controlled
  • Outcome: Cognitive functions
NCT04042532 Early onset AD
  • Last update: April 2021, enrolling by invitation
  • Randomized, double-blinded, sham-controlled
  • Target: Left DLPFC
  • Outcome: Cognitive functions
NCT04555941 MCI/AD
  • Last update: October 2020, recruiting
  • Randomized, triple-blinded, sham-controlled
  • Outcome: Cognitive functions
NCT01481961 Early AD
  • Last update: March 2015, completed
  • Open-label trial
  • Target: Left DLPFC
  • Outcome: Cognitive functions
NCT03612622 MCI/Early AD
  • Last update: February 2021, completed
  • Randomized, triple-blinded, sham-controlled
  • Outcome: Associative memory/cognitive and psychological symptoms
NCT04440891 AD
  • Last update: April 2021, recruiting
  • Randomized, double-blinded, sham-controlled
  • Outcome: Cognitive functions
NCT03270137 AD
  • Last update: September2017, unknown
  • Randomized, single-blinded
  • Target: Left DLPFC/six region protocol
  • Outcome: Cognitive functions
NCT04263194 Mild AD
  • Last update: August 2020, recruiting
  • Randomized, triple-blinded, sham-controlled
  • Target: DMN *8
  • Outcome: Cognitive symptoms
NCT03778151 Mild AD
  • Last update: February 2021, completed
  • Randomized, double-blinded, sham-controlled
  • Target: DMN
  • Outcome: Cognitive symptoms
NCT04294888 Prodromal and Preclinical AD
  • Last update: March 2020, recruiting
  • Randomized, cross-over, single-blinded, sham-controlled
  • Target: DMN
  • Outcome: Associative memory/functional connectivity
NCT04045990 Amnestic MCI/Logopenic PPA *4
  • Last update: November 2020, recruiting
  • Cross-over, single-blinded, sham-controlled
  • Target: DMN
  • Outcome: Language/memory
NCT03406429 Agrammatic Non-Fluent PPA/Logopenic PPA
  • Last update: March 2021, recruiting
  • Open-label, cross-over, sham-controlled
  • Target: Left DLPFC
  • Outcome: Language/functional connectivity and cortical thickness
NCT04188067 PPA
  • Last update: February 2021, recruiting
  • Open-label, cross-over, sham-controlled
  • Target: Left DLPFC
  • Outcome: Language/functional connectivity
NCT04193267 Logopenic PPA
  • Last update: March 2021, recruiting
  • Open-label trial
  • Target: Left superior temporal gyrus
  • Outcome: Language
NCT04431401 PPA
  • Last update: June 2020, not yet recruiting
  • Randomized, triple-blinded, sham-controlled
  • Outcome: Language/functional connectivity
NCT03153540 Agrammatic Non-Fluent PPA
  • Last update: January 2021, recruiting
  • Randomized, cross-over, quadruple-blinded, sham-controlled
  • Target: Dominant inferior frontal gyrus
  • Outcome: Safety, tolerability/language/brain function
NCT03448133 PPA
  • Last update: June 2020, withdrawn
* Mild Cognitive Impairment. ** Alzheimer’s Disease. *3 Major Depressive Disorder *4 Primary Progressive Aphasia. *5 Dorsolateral Prefrontal Cortex. *6 Cerebrospinal Fluid. *7 Brain-Derived Neurotrophic Factor. *8 Default Mode Network.

Repetitive Transcranial Magnetic Stimulation in the Treatment of Alzheimer’s Disease and Other Dementias

Dementia is a debilitating impairment of cognitive functions that affects millions of people worldwide. There are several diseases belonging to the dementia spectrum, most prominently Alzheimer’s disease (AD), vascular dementia (VD), Lewy body dementia (LBD) and frontotemporal dementia (FTD). Repetitive transcranial magnetic stimulation (rTMS) is a safe, non-invasive form of brain stimulation that utilizes a magnetic coil to generate an electrical field and induce numerous changes in the brain. It is considered efficacious for the treatment of various neuropsychiatric disorders. In this paper, we review the available studies involving rTMS in the treatment of these dementia types. The majority of studies have involved AD and shown beneficial effects, either as a standalone, or as an add-on to standard-of-care pharmacological treatment and cognitive training. The dorsolateral prefrontal cortex seems to hold a central position in the applied protocols, but several parameters still need to be defined. In addition, rTMS has shown potential in mild cognitive impairment as well. Regarding the remaining dementias, research is still at preliminary phases, and large, randomized studies are currently lacking.

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