A Three-Factor Structure of Cognitive Functioning Among Unimpaired Carriers and Non-Carriers of Autosomal-Dominant Alzheimer’s Disease

Article type: Research Article

Authors: Guzmán-Vélez, Edmarie^{a; 1} | Jaimes, Sehily^{a; 1} | Aguirre-Acevedo, Daniel C.^{b; c} | Norton, Daniel J.^a | Papp, Kathryn V.^{d; e} | Amariglio, Rebecca^{d; e} | Rentz, Dorene^{d; e} | Baena, Ana^c | Henao, Eliana^c | Tirado, Victoria^c | Muñoz, Claudia^c | Giraldo, Margarita^c | Sperling, Reisa A.^{d; e} | Lopera, Francisco^{c; *} | Quiroz, Yakeel T.^{a; c; e; *}

Affiliations: [a] Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA | [b] Grupo Académico de Epidemiología Clínica, School of Medicine, University of Antioquia, Medellín, Colombia | [c] Grupo de Neurociencias de Antioquia, School of Medicine, University of Antioquia, Medellín, Colombia | [d] Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Boston, MA, USA | [e] Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Correspondence: [*] Correspondence to: Yakeel T. Quiroz, PhD, Assistant Professor, Harvard Medical School, Departments of Psychiatry and Neurology, Massachusetts General Hospital, 149 13th Street, Suite 10.014, Boston, MA 02129, USA. Tel.: +1 617 643 5944; Fax: +1 617 726 5760; E-mail: [email protected] and Francisco Lopera, MD, Director, Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Sede de Investigaciones Universitarias, Medellin, Colombia. E-mail: [email protected].

Note: [1] These authors contributed equally to this manuscript.

Abstract: Background:There is a need to find cognitive markers that can help identify individuals at risk for Alzheimer’s disease (AD), and that can be used to reliably measure cognitive decline. Objective:We tested whether a theoretically driven three-factor structure would characterize cognitive functioning in individuals who are genetically-determined to develop AD due to a mutation in Presenilin-1 (PSEN1) gene. We also examined whether these factors could distinguish cognitively unimpaired PSEN1 mutation carriers from age-matched non-carrier family members. Methods:1,395 cognitively unimpaired members of a Colombian kindred with the PSEN1 E280A mutation were included in the study. A confirmatory factor analysis examined the fit of the three-factor model comprising episodic memory (MMSE memory recall, CERAD-COL Word list recall, and Constructional praxis recall), executive function (Phonemic fluency and WCST perseverative errors), and psychomotor processing speed (TMT-A and WAIS-III Digit Symbol). Results:The three-factor model provided an excellent fit for all participants (p = 0.24; RMSEA = 0.01). Further, the episodic memory (p = 0.0004, d = 0.25) and executive functioning (p = 0.001, d = 0.18) factors distinguished cognitively unimpaired carriers from non-carriers. The episodic memory factor provided the earliest indication of preclinical cognitive decline at 35 years of age, nine years before individuals’ estimated age of clinical onset. Conclusions:The three theoretically derived cognitive factors provide a reliable measure of cognition and may be useful for the early detection of AD, as well as for measuring disease progression. However, longitudinal studies are needed to confirm that these factors can be used to track the progression of cognitive decline in preclinical AD.

Keywords: Confirmatory factor analysis, cognitive factors, episodic memory, executive function, preclinical Alzheimer’s disease, processing speed, contstartabstract

DOI: 10.3233/JAD-180078

Journal: Journal of Alzheimer's Disease, vol. 65, no. 1, pp. 107-115, 2018