Acute Effect of Low-intensity Gamma rTMS on Cognitive and EEG Parameters in Adults With Mild Dementia by Alzheimer's Disease

Neurocognitive disorders have a growing prevalence and impact on public health; their main etiology corresponds to Alzheimer's disease. To date, there is no treatment that can reverse neuronal damage in these pathologies. However, several non-invasive neuromodulation techniques, including transcranial magnetic stimulation, have been proposed as a viable option to halt the progression of the disease.

Transcranial magnetic stimulation (TMS) is a noninvasive, nonpainful neurostimulation technique with a high safety profile that has been successfully used to improve cognitive function in subjects with mild cognitive impairment. Our research group conducted a study that showed that the use of low-intensity TMS at gamma frequencies is a safe, non-invasive method with minimal adverse effects.

The present protocol proposes a new randomized, double-blind, crossover trial to be conducted in memory clinic patients over 65 years of age who meet the diagnosis of mild dementia due to Alzheimer's disease. The main objective is to evaluate the short-term cognitive and electroencephalographic changes produced by low-intensity, gamma-frequency transcranial magnetic stimulation.

A TMS device that emits a pulsed magnetic field at a frequency of 40 Hz, with a maximum magnitude of 150 gauss for 45 minutes will be used as an intervention. The intervention will be of two types, real or simulated, and will be applied twice to each patient, that is, in one session they will receive the real stimulation and in another the simulated one. In addition, during the sessions, cognitive and electroencephalographic measurements will be taken before, during and after each intervention. Each of these stimulation sessions should be separated by at least one week.


Eligibility Criteria:
Inclusion Criteria:

* Both sexes
* Age over 65 years old
* Who give written informed consent
* Patients with a diagnosis compatible with mild dementia according to NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, 1984) criteria.
* CDR 1
* Preserved or corrected ability to see and hear
* Have a formal or informal caregiver

Exclusion Criteria:

* Clinical diagnosis of a neurodegenerative disease other than mild dementia due to Alzheimer's disease
* Present an uncontrolled medical condition at the time of the assessment for admission to the protocol (diabetes, heart disease, hypertension, hypothyroidism, uncontrolled renal or hepatic insufficiency).
* Diagnosis of major depression and/or some other untreated psychiatric illness (calculated with GDS)
* Excessive alcohol use
* Current or recent (6 months) use of any neurostimulation methods
* Metal implants excluding dental
* Signs or symptoms of increased intracranial pressure
* History of having received electroconvulsive therapy.
* Suffering from epilepsy.
* Having a deep brain stimulator implanted.
* Having any metallic prosthesis in the head.
* Having a pacemaker
* Extensive tattoos
* Taking any of the following medications:
* Tricyclic antidepressants such as: imipramine, amitriptyline, doxepin, nostriptyline, matroptyline.
* Antivirals such as: foscarnet, ganciclovir, ritonavir, dissociative anesthetics such as: phencyclidine, ketamine, γ-hydroxybutyrate
* Other stimulant drugs such as: amphetamines, cocaine, MDMA (ecstasy)