Neuroticism Is Associated with Tau Pathology in Cognitively Unimpaired Individuals with Autosomal Dominant Alzheimer’s Disease

Article type: Research Article

Authors: Baena, Ana^a | Bocanegra, Yamile^a | Torres, Valeria^b | Vila-Castelar, Clara^b | Guzmán-Vélez, Edmarie^{b; d} | Fox-Fuller, Joshua T.^{b; c} | Gatchel, Jennifer R.^b | Sánchez, Justin^e | Pluim, Celina F.^b | Ramirez-Gómez, Liliana^d | Martínez, Jairo^b | Pineda, David^a | Lopera, Francisco^a | Quiroz, Yakeel T.^{a; b; d; *}

Affiliations: [a] Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia | [b] Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA | [c] Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA | [d] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [e] Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Yakeel T. Quiroz, PhD, Associate Professor, Harvard Medical School, Departments of Psychiatry and Neurology, Massachusetts General Hospital, 39 1st Ave, Building 39, Suite 101, Charlestown, MA 02129, USA. Tel.: +1 617 643 5944; Fax: +1 617 726 5760; E-mail: yquiroz@mgh.harvard.edu.

Abstract: Background:Greater neuroticism has been associated with higher risk for Alzheimer’s disease (AD) dementia. However, the directionality of this association is unclear. We examined whether personality traits differ between cognitively-unimpaired carriers of autosomal-dominant AD (ADAD) and non-carriers, and are associated with in vivo AD pathology. Objective:To determine whether personality traits differ between cognitively unimpaired ADAD mutation carriers and non-carriers, and whether the traits are related to age and AD biomarkers. Methods:A total of 33 cognitively-unimpaired Presenilin-1 E280A mutation carriers and 41 non-carriers (ages 27–46) completed neuropsychological testing and the NEO Five-Factor Personality Inventory. A subsample (n = 46; 20 carriers) also underwent tau and amyloid PET imaging. Results:Carriers reported higher neuroticism relative to non-carriers, although this difference was not significant after controlling for sex. Neuroticism was positively correlated with entorhinal tau levels only in carriers, but not with amyloid levels. Conclusion:The finding of higher neuroticism in carriers and the association of this trait with tau pathology in preclinical stages of AD highlights the importance of including personality measures in the evaluation of individuals at increased risk for cognitive impairment and dementia. Further research is needed to characterize the mechanisms of these relationships.

Keywords: Alzheimer’s disease, biomarkers, neuroticism, personality, preclinical, presenilin-1

DOI: 10.3233/JAD-210185

Journal: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1809-1822, 2021