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

Article type: Research Article

Authors: Scharre, Douglas W.^{a; *} | Weichart, Emily^b | Nielson, Dylan^c | Zhang, Jun^d | Agrawal, Punit^e | Sederberg, Per B.^b | Knopp, Michael V.^d | Rezai, Ali R.^c | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Neurology, Cognitive Neurology Division, The Ohio State University Wexner Medical Center, OH, USA | [b] Department of Psychology, The Ohio State University, Columbus, OH, USA | [c] Department of Neurosurgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA | [d] Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA | [e] Department of Neurology, Movement Disorder Division, The Ohio State University Wexner Medical Center, OH, USA

Correspondence: [*] Correspondence to: Douglas W. Scharre, MD, 395W. 12th Ave., 7th Floor, Columbus, OH 43210, USA. Tel.: +1 614 293 4969; Fax: +1 614 293 1891; E-mail: Scharre.1@osu.edu.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pd

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.

Keywords: Alzheimer’s disease, deep brain stimulation, executive function, positron-emission tomography, ventral striatum

DOI: 10.3233/JAD-170082

Journal: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 621-633, 2018