The Relationship Between Antipsychotics, Cognitive Enhancers, and Major Adverse Cardiovascular/Cerebrovascular Events (MACCE) in Older Adults with Behavioral and Psychological Symptoms of Dementia

Abstract

Background and objectives: Antipsychotics and cognitive enhancers are often used to treat psychosis and behavioral disturbances in individuals with dementia; however, these drugs have been linked with various adverse events including both metabolic and cerebro/cardiovascular events. Thus, this study sought to estimate the risk of major adverse cardiovascular/cerebrovascular events (MACCE) across four behavioral and psychological symptoms of dementia (BPSD) treatment models by exploring potential associations between antipsychotics (APs), cognitive-enhancing medications, dosage, and earlier MACCE onset.

Methods: Patients were obtained from the Loma Linda University Medical Center database who were age ≥ 50 or older and who were diagnosed with dementia and BPSD symptoms. Treatment group and drug dosing were analyzed using Cox regression analyses to predict time until MACCE onset. Patient age at dementia diagnosis, sex, smoking status, race/ethnicity, and previous MACCE diagnoses were included as covariate variables.

Results: The final study population consisted of 1162 individuals. Results indicated a significant effect of medication type on duration until MACCE, (p < 0.001), with the odds of experiencing a MACCE being 96.3% higher for individuals treated with both APs and cognitive enhancers (p < 0.001). There was also a significant effect of AP dosage on duration until MACCE (p < 0.001) and a significant effect of cognitive enhancer dosage on duration until a MACCE, (p < 0.001). The odds of experiencing a MACCE sooner were 238% higher for those on high doses of APs (p < 0.001) and 76% higher for individuals on high doses of cognitive enhancers (p < 0.010).

Conclusion: The use of APs at high doses was associated with the greatest risk of an adverse medical outcome in older adults with dementia with concurrent behavioral symptoms. Use of AP medications in this population should include close monitoring for cardiovascular/cerebrovascular events.

Fig. 1

MACCE survival according to group by cox proportional hazards regression. BPSD behavioral and psychological symptoms of dementia, MACCE major adverse cardiovascular/cerebrovascular events. Survival curve plotting the probability that a MACCE has not occurred by (and including) each time point (2.5-year intervals). Solid red line, no drugs; solid blue line, cognitive enhancers; solid green line, antipsychotic drugs only; solid yellow line, both cognitive enhancers and antipsychotics

Fig. 2

MACCE survival curves by drug dosage using Cox proportional hazards regression. BPSD behavioral and psychological symptoms of dementia, MACCE major adverse cardiovascular/cerebrovascular events. A A survival curve plotting the probability that a MACCE has not occurred by (and including) each time point (2.5-year intervals) for cognitive enhancer dosing. Solid blue line, low doses of cognitive enhancers; solid green line, medium doses of cognitive enhancers; solid red line, high doses of cognitive enhancers. B A survival curve plotting the probability that a MACCE has not occurred by (and including) each time point (2.5-year intervals) for antipsychotic dosing. Solid blue line, low doses of antipsychotics; solid green line, medium doses of antipsychotics; solid red line, high doses of antipsychotics