Subgenual Cingulate Deep Brain STIMulation for Apathetic Behavioral Variant FRONtotemporal Dementia

Summary

Frontotemporal dementia (FTD), the most common dementia in individuals younger than 60 years of age, has no disease-modifying treatment. Neuroimaging studies have revealed salience and default mode network dysfunction, frontotemporal atrophy and hypometabolism as pathophysiological hallmarks of behavioral variant FTD (bvFTD). A key brain structure affected by bvFTD is the subgenual cingulate (SGC), which serves as a hub for multi-axonal projections to and from the ventromedial prefrontal, dorsal anterior cingulate, orbitofrontal, and dorsolateral frontal cortices, and limbic structures.

The disruption of these SGC projections in bvFTD result in the core clinical features of apathy, disinhibition, loss of empathy, compulsivity, hyperorality and loss of executive function. The central goal of this proposal is to use deep brain stimulation (DBS) for modulation of the SGC downstream projections to treat bvFTD. Investigators hypothesize that SGC DBS will drive activity in the dysfunctional networks, reverse hypometabolism, and potentially improve symptoms. To determine the physiologic effects and mechanisms of SGC DBS, investigators will assess cerebral metabolism by FDG-PET, connectivity by rsfMRI and MEG, atrophy by volumetric MRI, and neurodegenerative and neuroinflammatory biomarkers. The safety and preliminary efficacy data obtained in these patients will inform the possible future role of DBS in apathetic bvFTD.

Conditions

• Frontotemporal Dementia
• Deep Brain Stimulation

Interventions

DEVICE

Bilateral subgenual cingulate deep brain stimulation (SGC DBS)

Deep Brain Stimulation (DBS) is a neurosurgical procedure involving the implantation of deep brain electrodes, connected via a subcutaneous extension wire, to an implantable pulse generator (IPG, or 'battery') that is implanted below the collarbone. All patients will receive deep brain stimulation (DBS) targeting the subgenual cingulate (SGC) bilaterally. No other changes to pre-existing treatment will be made. This is the only arm in this experiment.

Sponsors & Collaborators

• Weston Brain Institute

  collaborator OTHER

• University Health Network, Toronto

  lead OTHER

Principal Investigators

• Andres M Lozano, MD, PhD · University Health Network, Toronto

• Carmela Tartaglia, MD · University Health Network, Toronto

• Cletus Cheyuo, MD, PhD · University Health Network, Toronto

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

40 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-01-12

Primary Completion

2026-01-12

Completion

2026-01-12

Countries

• Canada

Study Locations