Potential benefits and concerns of surgical treatment for severe Alzheimer’s disease: a decade of experience

By 2050, over 200 million people worldwide will have dementia, with Alzheimer’s disease (AD) accounting for 75%. Severe AD is associated with profound cognitive decline, neuropsychiatric symptoms (NPS) in 80% of patients, and a high caregiver burden. Current pharmacological and non-pharmacological treatments offer limited efficacy, especially in advanced stages. In line with the TITAN Guideline 2025[1], our study ensures transparent reporting of artificial intelligence usage and declarations. We explored surgical neuromodulation as a novel approach for severe AD, informed by advances in the brain glymphatic system[2]. From 2015 to 2025, we conducted a clinical study at two centers in Beijing, recruiting 44 patients with severe AD (MMSE 0–10, CDR3)[3]. Of these, 24 underwent surgical treatment: 14 received bilateral fornix deep brain stimulation (DBS)[4], 6 bilateral nucleus basalis of Meynert (NBM) DBS[5], and 4 underwent lymphovenous anastomosis (LVA). All procedures were ethically approved, with informed consent obtained through a three-dimensional decision-making model (advance directive + family + ethics committee). Preliminary results showed that both DBS and LVA were safe, with no major adverse events. One month post-surgery, DBS improved cognition, NPS (especially NBM-DBS on NPI scores), and quality of life. LVA also showed early cognitive improvement, though long-term data and larger trials are needed[6–9]. Our decade-long experience suggests that surgical interventions may offer a promising therapeutic avenue for severe AD, complementing existing strategies. These approaches may act through neural circuit modulation (DBS) and glymphatic pathway enhancement (LVA). We advocate for a multicenter alliance for AD surgery (CAST-AD) to refine indications using biomarkers such as APOEε4 and Aβ-PET.