Deep Brain Stimulation of Frontal Lobe Networks to Treat Alzheimer’s Disease

Abstract

The study objective was to evaluate the safety and efficacy of deep brain stimulation (DBS) at the ventral capsule/ventral striatum (VC/VS) region to specifically modulate frontal lobe behavioral and cognitive networks as a novel treatment approach for Alzheimer's disease (AD) patients. This is a non-randomized phase I prospective open label interventional trial of three subjects with matched comparison groups. AD participants given DBS for at least 18 months at the VC/VS target were compared on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), our primary outcome clinical measure, to matched groups without DBS from the AD Neuroimaging Initiative (ADNI) cohort. Serial 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) images of AD participants were also compared longitudinally over time. Three AD DBS participants were matched to subjects from the ADNI cohort. All participants tolerated DBS well without significant adverse events. All three AD DBS participants had less performance decline and two of them meaningfully less decline over time on our primary outcome measure, CDR-SB, relative to matched comparison groups from the ADNI using score trajectory slopes. Minimal changes or increased metabolism on FDG-PET were seen in frontal cortical regions after chronic DBS at the VC/VS target. The first use of DBS in AD at a frontal lobe behavior regulation target (VC/VS) was well-tolerated and revealed less performance decline in CDR-SB. Frontal network modulation to improve executive and behavioral deficits should be furthered studied in AD.

Current and future directions of deep brain stimulation for neurological and psychiatric disorders

“…Furthermore, VC/VS DBS resulted in frontal cortical activation. 79 Both nbM and VC/VS DBS offer a safe and potentially efficacious treatment strategy, but require more supportive evidence.…”

Current Status of Deep Brain Stimulation for Alzheimer's Disease: From Chance Observation to Clinical Trials

“…As such, VC/VS DBS was performed in three AD patients with less cognitive decline than age-matched controls over at least an 18-mo period. FDG-PET imaging was consistent with frontal cortical engagement (Scharre et al 2018).…”

Call of Duty at the Frontier of Research: Normative Epistemology for High-Risk/High-Gain Studies of Deep Brain Stimulation

“…This information would have been valuable to inform "first-in-human" studies, which were explored using three competing brain targets. 23,24,25 However, directly relevant studies in mice came only after the "first-in-human" studies. 26 The lack of prior probabilities derived from animal models has some very serious methodological repercussions that are difficult to spot for scientists themselves, and are all the more perplexing for research participants in the situation of Ms. Metis.…”