• Bryce Picton, Joey Wong, Alexander M Lopez, Sean S Solomon, Saman Andalib, Nolan J Brown, Rajeev R Dutta, Michelle R Paff, Frank P Hsu, and Michael Y Oh.
• Department of Neurological Surgery, University of California, Irvine, Orange, California, USA. Electronic address: bpicton@hs.uci.edu.
• World Neurosurg. 2024 Apr 1; 184: 253266.e2253-266.e2.

ObjectiveWith no cure for Alzheimer disease (AD), current efforts involve therapeutics that prevent further cognitive impairment. Deep brain stimulation (DBS) has been studied for its potential to mitigate AD symptoms. This systematic review investigates the efficacy of current and previous targets for their ability to slow cognitive decline in treating AD.MethodsA systematic review of the literature was performed through a search of the PubMed, Scopus, and Web of Science databases. Human studies between 1994 and 2023 were included. Sample size, cognitive outcomes, and complications were recorded for each study.ResultsFourteen human studies were included: 7 studies with 6 distinct cohorts (n = 56) targeted the fornix, 6 studies with 3 distinct cohorts (n = 17) targeted the nucleus basalis of Meynert (NBM), and 1 study (n = 3) investigated DBS of the ventral striatum (VS). The Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental State Examination, and Clinical Dementia Rating Scale Sum of Boxes were used as the primary outcomes. In 5 of 6 cohorts where DBS targeted the fornix, cognitive decline was slowed based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale or Mini-Mental State Examination scores. In 2 of 3 NBM cohorts, a similar reduction was reported. When DBS targeted the VS, the patients' Clinical Dementia Rating Scale Sum of Boxes scores indicated a slowed decline.ConclusionsThis review summarizes current evidence and addresses variability in study designs regarding the therapeutic benefit of DBS of the fornix, NBM, and VS. Because of varying study parameters, varying outcome measures, varying study durations, and limited cohort sizes, definitive conclusions regarding the utility of DBS for AD cannot be made. Further investigation is needed to determine the safety and efficacy of DBS for AD.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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