Clinical outcomes and anti-inflammatory mechanisms of nucleus basalis of Meynert deep brain stimulation in Alzheimer’s disease

Aim: Deep brain stimulation of the nucleus basalis of Meynert (NBM-DBS) represents an emerging therapeutic strategy for Alzheimer's disease (AD), yet clinical outcomes have been inconsistent and its mechanistic underpinnings are not fully elucidated. This study aimed to assess the cognitive and psychobehavioral effects of NBM-DBS and to explore its potential impact on systemic inflammatory markers. Methods: In this open-label trial, nine individuals with moderate-to-severe AD underwent bilateral NBM-DBS. Six participants (four with moderate and two with severe AD) completed the full 12-month protocol, which included serial neuropsychiatric assessments and serum cytokine profiling. Results: Stratification by baseline disease severity revealed divergent cognitive trajectories. Patients with moderate AD (CDR = 2) maintained their preoperative performance on the Montreal Cognitive Assessment (MoCA) and Boston Naming Test (BNT) over the 12-month follow-up. In contrast, patients with severe AD (CDR = 3) experienced significant decline on these measures. Serum analyses demonstrated a significant immunomodulatory effect, characterized by elevated levels of the anti-inflammatory cytokines IL-10 and IL-27, and reduced levels of the pro-inflammatory chemokines CXCL10 and RANTES at the 12-month timepoint. Conclusion: Our findings indicate that NBM-DBS may be associated with stabilization of cognitive function in patients with moderate AD, potentially through the modulation of inflammation. The therapeutic benefit appears to be more pronounced in the moderate stage of the disease.