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Background: The Angiotensin-Converting Enzyme (ACE) gene has drawn attention for its possible role in regulating the degradation of β-amyloid (Aβ), yet its role in affecting the cognitive and psychiatric symptoms of Alzheimer's Disease (AD) patients has yet to be elucidated. Objective: This study aimed to investigate whether the ACE gene acts as a risk factor of Behavioral and Psychological Symptoms of Dementia (BPSD) in the AD population. Methods: The genotyping of ACE and Apolipoprotein E gene with allele ε4(APOEε4) was determined among 360s clinically diagnosed AD patients. Symptoms and severity of BPSD were evaluated annually via Neuropsychiatric Inventory (NPI). Results: At the base measurement of the first year of patient recruitment, there were no significant contributory risk factors to NPI score. In the two-year follow-up, ACE insertion polymorphism showed a significant risk (adjusted odds ratio=1.65, 95% CI=1.1- 2.5, p=0.019) of progression of NPI total score. Conclusion: ACE gene is involved in aggravating BPSD among AD patients.