Neuroprotective effects of aortic valve replacement: a propensity score-matched retrospective cohort study

Background Aortic stenosis is associated with cognitive decline and dementia, potentially due to cerebral hypoperfusion and microemboli. Whether aortic valve replacement (AVR) confers long-term neuroprotection compared with medical management remains unclear, particularly comparing transcatheter (TAVR) and surgical (SAVR) approaches. Purpose To evaluate the association between AVR and long-term risks of dementia subtypes and stroke in a large, propensity score-matched cohort. Methods Retrospective cohort study using the TriNetX Global Collaborative Network (167 healthcare organisations). Patients with aortic stenosis undergoing AVR were compared with those managed medically. Propensity score matching balanced baseline characteristics, including frailty indicators, sensory impairment, mental health, cardiovascular medications, and prior stroke/TIA. Hazard ratios (HR) with 95% confidence intervals were estimated using Cox regression for Alzheimer’s disease, vascular dementia, other dementias, unspecified dementia, mild cognitive impairment, senile degeneration, and cerebral infarction. Results In the main matched cohort (159,823 vs 159,823), AVR was associated with reduced risk of Alzheimer’s disease (HR 0.75, 95% CI 0.70-0.82), vascular dementia (HR 0.78, 95% CI 0.71-0.84), other dementias (HR 0.80, 95% CI 0.74-0.85), unspecified dementia (HR 0.81, 95% CI 0.77-0.85), and senile degeneration (HR 0.62, 95% CI 0.43-0.90). No significant differences were observed for mild cognitive impairment (HR 1.02, 95% CI 0.95-1.10) or cerebral infarction (HR 1.01, 95% CI 0.96-1.05). SAVR showed substantially stronger protection than TAVR across dementia subtypes (e.g., Alzheimer’s: SAVR HR 0.49 vs TAVR HR 0.91). Benefits were consistent in both sexes, with slightly stronger Alzheimer’s protection in women (HR 0.70 vs 0.78 in men), and persisted in patients with prior stroke/TIA. Conclusion AVR is associated with significant long-term reductions in dementia risk across multiple subtypes, independent of early peri-procedural effects, with SAVR demonstrating more pronounced neuroprotective benefits than TAVR. These findings support the potential cognitive benefits of valve intervention in aortic stenosis, though residual confounding by disease severity cannot be excluded.