2026 American Academy of Neurology Abstract Website

Rashad G. Mohamed¹, Mohamed Zanaty², Amir Hegazi¹, Muataz Kashbour³, Moaz Abouelmagd⁴, Ahmed Negida⁵, Moheb Wadie⁶
¹Mansoura Manchester Program for Medical Education, Faculty of Medicine, Mansoura University, Mansoura, Egypt., ²Faculty of medicine, South valley University, Qena, Egypt, ³Diagnostic Radiology Department, National Cancer Institute, Misrata, Libya, ⁴Faculty of Medicine, Cairo University, Cairo, Egypt., ⁵Virginia Commonwealth University, ⁶Associate professor at cardiology department, Mansoura university, Egypt

Objective:

This study aims to investigate the potential association between sacubitril/valsartan use and dementia risk compared to treatment with ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in heart failure patients.

Background:

Sacubitril/valsartan improves clinical outcomes in heart failure with reduced ejection fraction by inhibiting neprilysin, thereby enhancing natriuresis and vasodilation. However, since neprilysin plays a role in clearing amyloid-β from the brain, there are concerns that it may increase the risk of dementia.

Design/Methods:

A systematic search of PubMed, Scopus, Web of Science, and Embase was conducted to identify studies comparing dementia risk in heart failure patients treated with Sacubitril/valsartan versus ACEIs or ARBs. Both randomized controlled trials and cohort studies were included. The primary outcome was the incidence of all cause dementia, Alzheimer’s disease, vascular dementia, and other dementias. Data was synthesized using RevMan software, and the GRADE system was applied to evaluate evidence quality

Results:

Seven studies, involving 129,265 participants, were included in our analysis. The Sacubitril/valsartan group showed significantly lower odds of developing overall dementia and vascular dementia compared to those receiving ACEIs or ARBs (OR = 0.78; 95% CI: 0.70–0.87; P < 0.00001; I² = 39% and OR = 0.70; 95% CI: 0.56–0.86; P = 0.0007; I² = 0%, respectively). Additionally, Sacubitril/valsartan was associated with reduced incidence of Alzheimer’s disease (OR = 0.76; 95% CI: 0.56–1.00; P = 0.08; I² = 74%) and other dementias (OR = 0.72; 95% CI: 0.53–0.99; P = 0.04; I² = 59%).

Conclusions:

This meta-analysis suggests that sacubitril/valsartan is associated with a lower risk of developing overall dementia, including Alzheimer’s disease, vascular dementia, and other dementias, compared to ACEIs or ARBs in heart failure patients. These findings support the cognitive safety of sacubitril/valsartan, though further high-quality studies are needed to confirm its long-term neurological effects.