Modulators of Gamma tACS in Alzheimer's Disease (Mod-GammAD)

Conditions

Alzheimer Disease

Keywords

Alzheimer's disease, transcranial Alternating Current Stimulation, Gamma stimulation, tACS

Brief summary

Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as oscillopathies. Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances. Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory. On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease. In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate the modulators of response on cognitive measure to a single stimulation with gamma tACS on the posterior parietal cortex in patients with Mild Cognitive Impairment due to Alzheimer's disease.

Detailed description

Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as oscillopathies. Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances. Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory. On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease. In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate the modulators of response on cognitive measure to a single stimulation with gamma tACS on the posterior parietal cortex in patients with Mild Cognitive Impairment due to Alzheimer's disease. Subjects will be randomized in two groups, one receiving a single treatment with gamma tACS (40 Hz) first and the other receiving sham stimulation. After one week the treatments will be exchanged. Patients will be evaluated with neuropsychological tests and neurophysiological measures of cholinergic transmission. Modulators of response, including cognitive reserve, baseline impairment, apo-E genotype, MRI measures of atrophy and connectivity, electric field modelling, will be considered.

Related papers

No related papers found yet.

Interventions

DEVICEGamma tACS (40 Hz) over the superior parietal cortex

Single session of gamma tACS (40 Hz) over the superior parietal cortex

DEVICESham tACS over the superior parietal cortex

Single session of sham tACS over the superior parietal cortex

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

\- Mild Cognitive Impairment due to Alzheimer's disease (according to Albert et al., Alzheimers Dement 2011).

Exclusion criteria

* Cerebrovascular disorders, previous stroke, hydrocephalus, and intra-cranial mass documented by MRI. * History of traumatic brain injury or other neurological diseases. * Serious medical illness other than AD * History of seizures * Pregnancy * Metal implants in the head (except dental fillings) * Electronic implants (i.e. pace-maker, implanted medical pump) * Age \<18 years

Design outcomes

Primary

Measure	Time frame	Description
Changes in Rey Auditory Verbal Learning Test scores	Baseline (immediately before the intervention) - Immediately after the intervention	Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the patient must again repeat the original list of 15 words and then again after 30 minutes. The score ranges from 0 (worse performance) to 15 (best performance).
Changes in Face-Name Associative Memory Test scores	During the intervention compared to sham comparator	The Face-Name Associative Memory Test is a cross-modal associative memory test, it includes 20 face-name pairs. The administration procedure starts with the presentation of 20 faces with each name and participants should read the name underneath the faces and try to learn each face-name pair. After 5 minutes, the faces are shown one by one and participants are asked to recall the associated names from 4 different names. The correct number of pairs recalled is recorded. The score ranges from 0 (worse performance) to 20 (best performance).

Secondary

Measure	Time frame	Description
Change in SAI measurements	Baseline (immediately before the intervention) - Immediately after the intervention	By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic transmission.

Countries

Italy

Outcome results

None listed