Deep brain stimulation in Alzheimer's disease

Deep brain stimulation (DBS) is a well-established treatment for neurological disorders, but its efficacy and safety in Alzheimer's disease (AD) remain uncertain. This narrative review synthesizes nine clinical trials in patients with mild to severe AD, focusing on stimulation of the fornix, nucleus basalis of Meynert (NBM), and ventral capsule/ventral striatum. Literature was identified through PubMed using the terms "deep brain stimulation" and "Alzheimer's disease," and the results were restricted to clinical trials and case reports in English, with additional references identified through Google Scholar. Across studies, DBS was safe and well tolerated, with few adverse events. Stimulation produced short-term cognitive improvements, most commonly measured by Alzheimer's Disease Assessment Scale cognitive subscale, along with transient reversal of glucose hypometabolism and activation of memory-related networks. One study reported slowed hippocampal atrophy, suggesting neuroplastic effects. In severe AD, DBS targeting both the fornix and NBM yielded transient cognitive gains, with NBM-DBS showing greater benefit for neuropsychiatric symptoms and caregiver burden. Patients with higher baseline cognition and glucose metabolism responded more favorably to DBS. Age-related differences emerged: younger patients (<65 years old), with earlier onset and more aggressive progression, showed less favorable responses to DBS targeting the fornix, whereas older patients (≥65 years old) had comparatively better outcomes. Despite these benefits, DBS does not halt disease progression or reverse AD pathology. Larger, biomarker-stratified, sham-controlled trials with extended follow-up are needed to clarify durability, identify optimal patient subgroups, and determine the most effective stimulation targets.