Objective:

This study aims to explore the effect of neurosurgical interventions on outcomes of Alzheimer’s patients, focusing on cognitive, neuropsychiatric, and clinical outcomes.

Background:

Alzheimer’s disease remains one of the leading causes of death worldwide, with rising global prevalence and limited effective treatments. Thus, neurosurgical interventions such as Deep Brain Stimulation (DBS), Ventriculoperitoneal Shunting, Focused Ultrasound (FUS), and targeted nerve growth factor delivery are being explored as innovative therapeutic options. However, data on outcomes and safety in this population are still limited.

Design/Methods:

A systematic review was conducted using PubMed and Cochrane databases in accordance with PRISMA guidelines. Studies were included if they involved adults diagnosed with Alzheimer’s disease who underwent a neurosurgical intervention with reported postoperative or longitudinal outcomes. Two reviewers independently extracted and verified data, focusing on cognition, neuropsychiatric symptoms, complications, and survival. Publications involving non-human data, in vitro studies, non-English language, and systematic reviews were excluded. Discrepancies between reviewers were resolved through discussion or consultation with a third reviewer.

Results:

Eleven peer-reviewed studies, including over 10,000 participants, met the inclusion criteria. DBS, particularly targeting the fornix and nucleus basalis of Meynert, demonstrated the most consistent benefits. Patients receiving DBS showed short-term cognitive improvement, and reductions in anxiety, depression, and caregiver burden with increased cerebral glucose metabolism following stimulation. Other approaches, such as low-flow shunting and FUS, were feasible and safe, showing early biological signals of benefit, including reductions in β-amyloid and tau levels. Major complications were rare, reversible, and mortality was low.

Conclusions:

This study helps advance our understanding of neurological approaches, particularly DBS, and their potential to improve cognitive and neuropsychiatric outcomes in patients with Alzheimer’s disease. While the current evidence remains preliminary, these findings point toward a promising future for neuromodulation-based therapies in supporting patients living with Alzheimer’s disease.