Neuropsychiatric Symptoms, ApoE4 and the Risk Of Incident Dementia: The Mayo Clinic Study of Aging (P3.215)

OBJECTIVE: To examine neuropsychiatric symptoms (NPS), and their interaction with APOE e4 allele (ApoE4), in predicting the transition from mild cognitive impairment (MCI) to incident dementia. BACKGROUND: There is a need to determine the population-based risk of incident dementia as predicted by baseline neuropsychiatric symptoms(NPS) and APOE4 status. DESIGN/METHODS: We prospectively followed 332 participants with prevalent MCI (aged 70 years and older), enrolled in the Mayo Clinic Study of Aging for a median (inter-quartile range [IQR]) of 3.0 (2.5, 5.3) years. The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria. NPS was determined at baseline using the Neuropsychiatric Inventory Questionnaire (NPIQ). We estimated the risk of incident dementia by calculating hazard ratios (HR) and 95% confidence intervals (95% CI) by using Cox proportional hazards model, with age as a time scale. Models were adjusted for sex, education, and medical comorbidity. We also examined the interactions between each NPS and ApoE4 in predicting risk of dementia. RESULTS: Baseline agitation (HR=1.97; 95% CI, 1.13-3.42), nighttime behaviors (HR=1.68; 95% CI, 1.02-2.78), depression (HR=1.63; 95% CI, 1.10-2.41) and apathy (HR=1.62; 95% CI, 1.03-2.54) significantly predicted incident dementia. We observed synergistic interactions between ApoE4 and depression (joint effect HR=2.21; 95% CI, 1.24-3.91; test for additive interaction, p<0.001); ApoE4 and apathy (joint effect HR=1.93; 95% CI, 0.93-3.98; test for additive interaction, p=0.031). Anxiety (HR=0.93; 95% CI, 0.54-1.61), irritability (HR=1.00; 95% CI, 0.61-1.67), and appetite/eating (HR=1.59; 95% CI, 0.86, 2.95) were not associated with increased risk of incident dementia. CONCLUSIONS: Among prevalent MCI cases, baseline agitation, nighttime behaviors, depression and apathy predicted incident dementia. Risk of dementia was stronger for participants with depression or apathy who were ApoE4 carriers. Study Supported by: NIH (K01 MH068351, U01 AG006786 and K01 AG028573), RWJ Foundation, Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program; European Regional Development Fund: FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123) Disclosure: Dr. Pink has nothing to disclose. Dr. Acosta has nothing to disclose. Dr. Roberts has received research support from Abbott Laboratories and the Driskill Foundation. Dr. Mielke has nothing to disclose. Dr. Christianson has nothing to disclose. Dr. Pankratz has received research support from Abbott Laboratories, Inc. Dr. Stokin has nothing to disclose. Dr. Boeve has received research support from Cephalon, Inc., Allon Therapeutics, and GE Healthcare. Dr. Geda has nothing to disclose.