Non-invasive Stimulation of Brain Networks and Cognition in Alzheimer's Disease and Frontotemporal Dementia

NCT03422250 | Completed Results

• 1 other identifier: GR-2011-02349787
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study aims to test clinical and connectivity changes following non-invasive stimulation of disease-specific networks in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Brain network stimulation will be carried out with transcranial direct current stimulation (tDCS). Target networks will be the default mode network (DMN) and salience network (SN). Twenty AD and 20 bvFTD patients will be recruited and assessed with a comprehensive clinical, behavioral and cognitive battery, and 3 Tesla MRI scan (including resting-state functional MRI, arterial spin labeling, diffusion tensor imaging, structural MRI) at three time-points: baseline, after tDCS, and after 6 months. Patients will be randomized to 2 arms: anodal stimulation of the disease-specific network (DMN in AD, SN in bvFTD) or cathodal stimulation of the anti-correlated network (SN in AD, DMN in bvFTD). The intervention will consist of 10 tDCS sessions over two weeks. Cerebrospinal fluid (CSF) samples will be collected at baseline for biomarker's assessment; blood samples will be collected at each time-point to assess changes in peripheral inflammatory markers. Blood and CSF collection will be optional. A sample of 20 elderly controls will be included for baseline comparisons.

Conditions

Alzheimer's Disease; Frontotemporal Dementia, Behavioral Variant

Outcome Measures

Primary Outcomes (5)

• Change in Clinical Disease Severity (CDR)

  CDR - Clinical Dementia Rating score The clinical dementia rating (CDR) is a clinical global rating scale administered to both the participant and the caregiver, assessing 6 domains of participant function: memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care. Each domain is based on a 5-point scale ranging from no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 to severe impairment=3. The global CDR score is computed via a memory-weighted averaging algorithm of the six domain scores and ranges from 0 to 5. The CDR-sum of boxes (CDR-SB) is the sum of the individual domain scores and ranges from 0 to 18. Higher scores indicate more clinical impairment. Negative changes at post tDCS compared to baseline represent an improvement on the scale.

  Baseline, post tDCS (week 3)

• Change in Behavioral Symptom Severity (NPI)

  The Neuropsychiatric Inventory (NPI) is a behavioral scale administered to the caregiver assessing 12 dimensions: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, nighttime behaviors, and appetite/eating. Each dimension has multiple screening questions relating to symptoms. If the answer to the screening questions is "Yes", the dimensional-score is the product of frequency (1=occasionally to 4=very frequently) and severity (1=Mild to 3=Severe) of symptoms. Dimensional-scores are summed (from 0 to 144). Higher scores indicate greater behavioral disturbances. Negative changes at post tDCS compared to baseline represent an improvement on the scale.

  Baseline, post tDCS (week 3)

• Change in Behavioral Symptom Severity (FBI)

  The Frontal Behavioral Inventory (FBI) is a 24-item inventory designed to assess behavior and personality changes via caregiver. Item-level scores range from 0=none, 1=mild/occasional, 2=moderate, 3=severe/most of the time. Item-scores are summed (from 0 to 72). Higher scores indicate greater behavioral/personality disturbances. Negative changes at post tDCS compared to baseline represent an improvement on the scale.

  Baseline, post tDCS (week 3)

• Change in Functional Connectivity

  Default mode network (DMN) and salience network (SN) mean functional connectivity is assessed on resting state functional MRI. Functional connectivity is standardized to Z scores and thresholded at Z\>2. Higher values denote greater functional connectivity. A positive change at post tDCS compared to baseline represents an increase in resting-state functional connectivity.

  Baseline, post tDCS (week 3)

• Change in Cerebral Blood Flow

  Default mode network (DMN) and salience network (SN) mean cerebral blood flow is assessed on arterial spin labeling. Cerebral blood flow is computed by averaging values across the DMN and SN regions of interest. Cerebral blood flow is a measure of brain perfusion, higher values denoting higher perfusion. A positive change at post tDCS compared to baseline represents an increase in perfusion.

  Baseline, post tDCS (week 3)

Secondary Outcomes (7)

• Change in Cognition: Memory

  Baseline, post tDCS (week 3)

• Change in Cognition: Language

  Baseline, post tDCS (week 3)

• Change in Cognition: Executive Function

  Baseline, post tDCS (week 3)

• Change in Cognition: Visuospatial Function

  Baseline, post tDCS (week 3)

• Change in Cognition: Emotion Recognition

  Baseline, post tDCS (week 3)

Study Arms (4)

Arm 1

EXPERIMENTAL

Alzheimer's disease (AD): anodal tDCS of the default mode network (DMN)

Device: transcranial direct current stimulation (tDCS)

Arm 2

EXPERIMENTAL

Alzheimer's disease (AD): cathodal tDCS of the salience network (SN)

Device: transcranial direct current stimulation (tDCS)

Arm 3

EXPERIMENTAL

Behavioral-variant frontotemporal dementia (bvFTD): anodal tDCS of the salience network (SN)

Device: transcranial direct current stimulation (tDCS)

Arm 4

EXPERIMENTAL

Behavioral-variant frontotemporal dementia (bvFTD): cathodal tDCS of the default mode network (DMN)

Device: transcranial direct current stimulation (tDCS)

Interventions

transcranial direct current stimulation (tDCS) DEVICE

10 daily 25-minutes tDCS sessions over two weeks.

Arm 1; Arm 2; Arm 3; Arm 4

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AD or bvFTD according to current clinical criteria (Albert et al., 2011; Rascovsky et al., 2011)
• Ability to provide written informed consent
• Availability of a collateral source

You may not qualify if:

• Moderate/severe dementia
• Presence of any medical or psychiatric illness that could interfere in completing assessments
• metal implants, pace-makers, prosthetic heart valves
• claustrophobia
• history of epilepsy
• pregnancy
• Current or past history of clinical, neurological, or psychiatric conditions that could interfere with the assessment (e.g., transient ischemic attack, ictus, head trauma, epilepsy, multiple sclerosis, neuropathy, mood disorders, substance abuse)

Sponsors & Collaborators

• IRCCS Centro San Giovanni di Dio Fatebenefratelli: lead

Study Sites (1)

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Brescia, 25125, Italy

Location

Related Publications (2)

• Pievani M, Pini L, Cappa SF, Frisoni GB. Brain networks stimulation in dementia: insights from functional imaging. Curr Opin Neurol. 2016 Dec;29(6):756-762. doi: 10.1097/WCO.0000000000000387.

  PMID: 27661207 BACKGROUND

• Pini L, Pizzini FB, Boscolo-Galazzo I, Ferrari C, Galluzzi S, Cotelli M, Gobbi E, Cattaneo A, Cotelli MS, Geroldi C, Zanetti O, Corbetta M, van den Heuvel M, Frisoni GB, Manenti R, Pievani M. Brain network modulation in Alzheimer's and frontotemporal dementia with transcranial electrical stimulation. Neurobiol Aging. 2022 Mar;111:24-34. doi: 10.1016/j.neurobiolaging.2021.11.005. Epub 2021 Nov 20.

  PMID: 34942516 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Pick Disease of the Brain

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Dementia; Frontotemporal Lobar Degeneration

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Results Point of Contact

• Title: Michela Pievani
• Organization: IRCCS Centro San Giovanni di Dio Fatebenefratelli

mpievani@fatebenefratelli.eu

+39 030 35011

Study Officials

• Michela Pievani, PhD

  IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: February 5, 2018
• Study Start: June 8, 2015
• Primary Completion: November 3, 2018
• Study Completion: November 3, 2018
• Last Updated: May 19, 2021
• Results First Posted: April 29, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)