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Alpha tACS in Dementia With Lewy Bodies

Not Applicable
Completed
Conditions
Dementia With Lewy Bodies
Lewy Body Disease
Interventions
Device: Alpha tACS (12 Hz) over the occipital cortex
Registration Number
NCT05188105
Lead Sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
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".

Dementia with Lewy bodies (DLB), which is the second most frequent cause of neurodegenerative dementia, is characterized by an important alteration of brain oscillations. The restoration of oscillations by neuronal entrainment in animal models of neurodegenerative disease has shown a significant reduction in the neuropathological load of toxic proteins, with a consequent significant increase in cognitive performance.

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 alpha tACS is proposed in patients with DLB.

In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether a single stimulation with alpha tACS on the occipital lobes can improve symptoms in patients with DLB.

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".

Dementia with Lewy bodies (DLB), which is the second most frequent cause of neurodegenerative dementia, is characterized by an important alteration of brain oscillations. The restoration of oscillations by neuronal entrainment in animal models of neurodegenerative disease has shown a significant reduction in the neuropathological load of toxic proteins, with a consequent significant increase in cognitive performance.

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 alpha tACS is proposed in patients with DLB.

In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether a single stimulation with alpha tACS on the occipital lobes can improve symptoms in patients with DLB.

Subjects will be randomized in two groups, one receiving a single treatment with alpha tACS (12 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
15
Inclusion Criteria
  • Dementia with Lewy bodies (criteria according to McKeith, Neurology 2017).
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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 DLB
  • History of seizures
  • Pregnancy
  • Metal implants in the head (except dental fillings)
  • Electronic implants (i.e. pace-maker, implanted medical pump)
  • Age <18 years
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
real tACSAlpha tACS (12 Hz) over the occipital cortexSingle session of alpha tACS (12 Hz) at 3 mA over the occipital cortex.
sham tACSAlpha tACS (12 Hz) over the occipital cortexSingle session of sham tACS over the occipital cortex.
Primary Outcome Measures
NameTimeMethod
Changes in Visual Search Task Test scores40 minutes after the start of the intervention

The visual search task requires participants to determine whether a target (such as a particular letter, shape, or image) is present in an array of other stimuli. The task consists of two parts, each with 64 stimuli, for a total of 128 stimuli. Participants are asked to look at the screen and press a button if the target stimulus is present or another button if the target stimulus is absent. After pressing the chosen button, a feedback will appear on the screen that will tell the subject if his answer is correct or incorrect. Subjects must respond as quickly as possible, otherwise the answer will be considered missed and they will proceed to the next screen.

The score ranges from 0 (worse performance) to 128 (best performance).

Secondary Outcome Measures
NameTimeMethod
Change in ICF measurementsBaseline (immediately before the intervention) - Immediately after the intervention

By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of alpha tACS on intracortical facilitation (ICF), which is a marker of glutamatergic transmission.

Changes in Trail Making Test Part ABaseline (immediately before the intervention) - Immediately after the intervention

The Trail Making Test Part A consists of 25 circles on a piece of paper with the numbers 1-25 written randomly in the circles. The test taker's task is to start with number one and draw a line from that circle to the circle with the number two in it to the circle with the three in it, etc. The person continues to connect the circles in numerical order until they reach number 25.

Scoring is based on time taken to complete the test with lower scores being better.

Changes in Rey Auditory Verbal Learning Test scoresBaseline (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 relative alpha power in occipital EEG leadsBaseline (immediately before the intervention) - Immediately after the intervention

By using electroencephalography (EEG), the investigators will evaluate the effects of alpha tACS on relative alpha power in occipital EEG leads.

Change in SICI measurementsBaseline (immediately before the intervention) - Immediately after the intervention

By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of alpha tACS on short interval intracortical inhibition (SICI), which is a marker of GABAergic transmission.

Changes in Trail Making Test Part BBaseline (immediately before the intervention) - Immediately after the intervention

The Trail Making Test Part B consists of 24 circles on a piece of paper, but rather than all of the circles containing numbers, half of the circles have the numbers 1-12 in them and the other half (12) contain the letters A-L. The person taking the test has to draw a line from one circle to the next in ascending order; however, he must alternate the circles with numbers in them (1-13) with circles with letters in them (A-L). In other words, he is to connect the circles in order like this: 1-A-2-B-3-C-4-D-5-E and so on.

Scoring is based on time taken to complete the test with lower scores being better.

Change in SAI measurementsBaseline (immediately before the intervention) - Immediately after the intervention

By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of alpha tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic transmission.

Trial Locations

Locations (1)

ASST Spedali Civili di Brescia

🇮🇹

Brescia, BS, Italy

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