Sex Differences of Longitudinal Brain Changes in Cognitively Unimpaired Adults

Article type: Research Article

Authors: Falcon, Carles^{a; b; c} | Grau-Rivera, Oriol^{a; c; d; e} | Suárez-Calvet, Marc^{a; c; d; e} | Bosch, Beatriz^f | Sánchez-Valle, Raquel^f | Arenaza-Urquijo, Eider M.^{a; c; d} | González-de-Echavarri, José María^{a; c} | Gispert, Juan Domingo^{a; b; c; g} | Rami, Lorena^{f; *} | Molinuevo, José Luis^{a; c; d; g; *}

Affiliations: [a] Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain | [b] Centro de Investigación Biomédicaen Red Bioingeniería, Biomateriales y Nanomedicina (CIBERBBN), Madrid, Spain | [c] IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain | [d] CIBERFragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain | [e] Servei de Neurologia, Hospital del Mar, Barcelona, Spain | [f] Alzheimer’s disease and other cognitive disorders Unit, Neurology Service, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain | [g] Universitat Pompeu Fabra, Barcelona, Spain

Correspondence: [*] Correspondence to: José L. Molinuevo, Barcelonaβeta Brain Research Center, Wellington 30, 08005 Barcelona, Spain. Tel.: +34 933263190; E-mail: [email protected]; Lorena Rami, Alzheimer’s disease and other cognitive disorders Unit, Neurology Service, Hospital Clínic, Institutd’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. Tel.: +34 932275414; E-mail: [email protected].

Abstract: Background:There is increasing evidence that AD progression differs by sex. Objective:The aim of this work was to determine sex differences in the association of baseline levels of cerebrospinal fluid (CSF) biomarkers (Aβ42, p-tau, YKL-40, sTREM2) with longitudinal brain changes in cognitively unimpaired (CU) older adults. Methods:This pilot study included 36 CU subjects (age 66.5±5.5, 12 male) scanned twice, two years apart. Using a voxel-wise analysis, we determined the sex differences in the association maps between CSF biomarkers and atrophy rates. Results:We did not find differences related to Aβ42. We found a greater impact of the rest of CSF biomarkers in areas of the Papez circuit in women versus men. Men showed greater involvement in lateral parietal and paracentral areas. Discussion:Results suggest an early differential progression of brain atrophy between sexes. Further research will elucidate whether the mechanisms responsible for sex-specific atrophy patterns are biological and/or environmental.

Keywords: Cerebrospinal fluid biomarkers, cognitively unimpaired older adults, longitudinal VBM, sex differences, sTREM2, YKL-40

DOI: 10.3233/JAD-200293

Journal: Journal of Alzheimer's Disease, vol. 76, no. 4, pp. 1413-1422, 2020