Antipsychotic Use Is Not Associated with an Increased Burden of Cerebrovascular Pathology at Autopsy (S04.004)

Abstract

Objective: Assess the correlations between antipsychotic medication use in elderly dementia persons with neuropathological outcomes data, including cerebrovascular disease (CVD) pathology. Background A 2006 FDA-issued black box indicated that elderly patients with dementia treated with antipsychotics are at an increased risk of death, primarily from vascular complications (myocardial infarction and stroke) and infections (pneumonia). Despite the profound impact this warning has had on the field, the cerebrovascular consequences of antipsychotic use in dementia remain poorly understood. Design/Methods: We identified all subjects with a history of dementia related psychosis treated with antipsychotic agents (DPAP; n=32) in the University of Kentucky Alzheimer9s Disease Center Brain Bank. Control subjects were placed in two cohorts matched for age, gender, apoe, education and MMSE including subjects with dementia but no psychosis or antipsychotic medication (DNPNAP group; n=32), and subjects with dementia and psychosis but no antipsychotic medication (DPNAP group; n=32). Demographic, clinical, genetic, and neuropathological features were compared between groups. Results: Comparative analysis of vascular risk factors (hypertension, hyperlipidemia, myocardial infarction, smoking, diabetes mellitus, cardiac arrhythmia, and Hachinski scores) revealed no significant between group differences. Clinical diagnoses including Alzheimer9s, Lewy-Body, frontotemporal, and vascular dementia did not differ between groups. Cause of death including myocardial infarction, stroke, and pneumonia did not differ between groups (p=0.73, χ2 test). Braak, CERAD, amyloid angiopathy, and Lewy body scores supported the diagnoses of moderate to severe dementia in the majority of cases (86%), but did not differ between groups. No statistically significant differences were found between the 3 groups for degree of atherosclerosis (p=0.25) or lacunar (p=0.34), micro- (p= 0.67), hemorrhagic (p= 0.81), or macro (p= 0.90) infarcts. Conclusions: Antipsychotic medication use is not associated with increased burden of cerebrovascular disease on neuropathological examination. Future studies investigating causal relationship between antipsychotic use and increased risk of death in dementia patients is warranted. Disclosure: Dr. Singhal has nothing to disclose. Dr. Abner has nothing to disclose. Dr. Schmitt has nothing to disclose. Dr. Nelson has nothing to disclose. Dr. Jicha has received personal compensation for activities with Pfizer Inc, Janssen Immunotherapy, and Eli Lilly & Company. Dr. Jicha has received research support from Baxter, Janssen, Pfizer Inc, Medivation, and Danone.