شخصیت و انعطاف پذیری برای نوروپاتولوژی بیماری آلزایمر: یک مطالعه آینده نگر کالبد شکافی

Alzheimer’s disease (AD) neuropathology is found at autopsy in approximately 30% of cognitively normal older individuals. We examined whether personality traits are associated with such resilience to clinical dementia in individuals with AD neuropathology. Broad factors and specific facets of personality were assessed up to 28 years (mean 11 ± 7 years) before onset of dementia and up to 30 years (mean 15 ± 7 years) before death in a cohort (n = 111) evaluated for AD neuropathology at autopsy. Individuals with higher baseline scores on vulnerability to stress, anxiety, and depression (neuroticism: odds ratio, 2.0; 95% confidence interval, 1.2–3.5), or lower scores on order and competence (conscientiousness: odds ratio, 0.4; 95% confidence interval, 0.2–0.9) were less likely to remain asymptomatic in the presence of AD neuropathology. Neuroticism (r = 0.26), low agreeableness (r = −0.34), and some facets were also significantly associated with advanced stages of neurofibrillary tangles, but the associations between personality traits and risk of clinical dementia were mostly unchanged by controlling for the extent of neurofibrillary tangles and Aβ neuritic plaques. In sum, a resilient personality profile is associated with lower risk or delay of clinical dementia even in persons with AD neuropathology.

Among cognitively normal individuals older than 75 years, approximately a third have sufficient Aβ neuritic plaques and neurofibrillary tangles at autopsy to meet criteria for Alzheimer’s disease (AD) (Arriagada et al., 1992; Bennett et al., 2006a; Driscoll and Troncoso 2011). These cases, referred to as asymptomatic AD (ASYMAD) or high pathology controls, can be informative to understand the progression of the disease and to help identify factors that promote cognitive resilience, or cognitive reserve (Bennett et al., 2006b; Craik et al., 2010; Fratiglioni et al., 2004; Iacono et al., 2009; Tucker and Stern 2011). In this study, we investigate whether personality traits contribute to the cognitive resilience of ASYMAD compared with those with both clinical dementia and corresponding AD pathology at autopsy. A number of studies indicate that those who score higher on conscientiousness and lower on neuroticism engage in fewer health-risk behaviors and have healthier metabolic, cardiovascular, and inflammatory risk profiles (Chapman et al., 2011; Courneya and Hellsten 1998; Deary et al., 2010; Sutin et al., 2010a, 2010b, 2011; Terracciano and Costa 2004; Terracciano et al., 2008; Wilson et al., 2004). Prospective studies indicate that cognitively normal older adults who score higher on conscientiousness or lower on neuroticism have a lower risk of developing clinical symptoms of AD (Duberstein et al., 2011; Wilson et al., 2003, 2005, 2007). These traits were unrelated to the extent of neuropathologic damage at autopsy (Wilson et al., 2003, 2007), which suggests that personality traits may offset the effects of AD-like brain pathology. We test this hypothesis by examining whether personality traits predict who is cognitively resilient (ASYMAD) and who is not (AD) in the face of AD neuropathology found at autopsy. Thus, we specifically compare the preclinical personality traits of those who subsequently developed clinical dementia with those who subsequently died cognitively normal, but with AD neuropathology at autopsy. We also examine whether personality traits are associated with semiquantitative measures of neuritic plaques and neurofibrillary tangles.