Deep Brain Stimulation as an Emerging Therapy for Cognitive Decline in Alzheimer Disease: Systematic Review of Evidence and Current Targets

With no cure for Alzheimer's Disease, 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 investigated for their ability to slow cognitive decline in treating AD. A systematic review of the literature was performed through a search of the PubMed, Scopus, and Web of Science databases. Human studies between 1994-2023 were included. Sample size, cognitive outcomes, and complications were recorded for each study. Fourteen human studies were included. Seven studies with six distinct cohorts (N=56) targeted the fornix, six studies with three distinct cohorts (N=17) targeted the nucleus basalis of Meynert (NBM) was targeted, and one study (N=3) investigated DBS of the ventral striatum (VS). The ADAS-Cog, MMSE, and CDR-SB tests were used as the primary outcomes. In 5/6 cohorts where DBS targeted the fornix, cognitive decline was slowed based on ADAS-Cog or MMSE scores. In 2/3 NBM cohorts, a similar reduction was reported. When DBS targeted the VS, the patients' CDR-SB scores indicated a slowed decline as well. This review summarizes current evidence and addresses variability in study designs regarding the therapeutic benefit of DBS of the fornix, NBM, and VS. Due to varying study parameters, outcome measures, study durations, and limited cohort sizes, definitive conclusions regarding the utility of DBS for Alzheimer's cannot be made. Further investigation is needed to determine the safety and efficacy of DBS for AD.