Abstract
<h3>Introduction</h3> Cognitive decline is prevalent in older adults, and predicting onset of cognitive decline in patients is a significant challenge for physicians. Studies have shown a relationship between neuroticism and the onset of cognitive decline in a ten-year time span, and have identified one aspect of neuroticism (N6 – vulnerability to stress) to be specifically elevated in those who later develop cognitive impairment. However, little is known about the onset of cognitive decline in a shorter time span, or if other aspects of neuroticism might be predictors. In addition, the effects of depression in this relationship have yet to be determined. The purpose of this study is to evaluate the relationship between the various facets of neuroticism and the onset of cognitive decline in a 1 to 3 year time span in the presence and absence of depression in a cohort of elderly subjects. <h3>Methods</h3> This is a retrospective cohort study. Subjects participated in "Neurobiology of Late-life Depression" (NBOLD) study at the University of Connecticut Health Center (UCHC) and Olin Neuropsychiatry Research Center at the Institute of Living in Hartford Hospital. Participants were screened for depression using the Center for Epidemiologic Studies – Depression (CES-D) scale, with a score of 16 or greater as a cut-off for depression. The NEO PI-R was used to screen for neuroticism. CERAD neurophysiological tests were used to screen for cognitive decline, and were administered annually. Statistical analysis of the data involved linear regression and correlation analysis was done to assess the significance of the predictive value of various facets of neuroticism in future cognitive decline development. Mixed model analysis was done to examine how changes in neuroticism score can moderate the rate of cognitive decline. Analysis was done by using baseline neuroticism scores and cognition scores after one, two, and three years. <h3>Results</h3> 163 subjects were enrolled. 28.8% of subjects identified as male, and 71.2% identified as female. The mean age was 72.27 ± 7.44 years. 89.6% identified as White, 7.7% identified as Black or African American, 1.8% identified as Asian, and 0.61% identified as mixed race. 1.8% had completed 9<sup>th</sup> grade, 14.1% had graduated high school, 22.7% had completed some college, 20.9% had a college degree, and 40.5% had completed post-graduate education124 subjects had depression at the time of baseline measurement, and 39 comparison subjects did not have depression at baseline. Two facets of neuroticism were shown to be statistically significant predictors of cognitive decline in the non-depressed patients. High baseline N6 (vulnerability of stress) was a predictor of a lower CERAD score at 1 year (p=0.08) and 3 years (p=0.09). High baseline N4 (self-consciousness) was also found to be a predictor of lower CERAD score at 1 year (p=0.01), 2 years (p=0.03), and 3 years (p=0.08). In addition, improvement in N4 over time was shown to cause a lower rate of progression of cognitive decline in non-depressed patients. The findings for depressed patients were not found to be statistically significant. <h3>Conclusions</h3> Both N6 and N4 are statistically significant predictors of cognitive decline 1 to 3 years after baseline neuroticism measurement. Improvement in N4 is associated with a lower rate of cognitive decline. These results were found in non-depressed patients but not depressed patients. These findings raise the possibility that longer periods of follow-up are needed to illustrate the association between neuroticism, cognitive decline, and depression. Investigating predictive factors of cognitive decline is key to foreseeing the development of the disease early on, allowing patients to prepare and access care that may be difficult to obtain as cognitive conditions progress. <h3>This research was funded by</h3> All subjects in the study were enrolled in NBOLD, a NIMH R01 grant entitled "Neurobiology and Adverse Outcomes of Neuroticism in Late-Life Depression".
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