Carregant...
Fitxers
Tipus de document
ArticleData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/200903
Association of biological sex with clinical outcomes and biomarkers of Alzheimer’s disease in adults with Down syndrome
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer's disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-beta 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein.4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein.4, female.4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein.4 and biomarkers showed that female.4 carriers tended to exhibit lower CSF amyloid-beta 42/amyloid-beta 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer's disease in adults with Down syndrome. Consideration of apolipoprotein.4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.
Matèries (anglès)
Citació
Citació
IULITA, M. florencia, BEJANIN, Alexandre, VILAPLANA, Eduard, CARMONA IRAGUI, María, BENEJAM, Bessy, VIDELA, Laura, BARROETA, Isabel, FERNÁNDEZ, Susana, ALTUNA, Miren, PEGUEROLES, Jordi, MONTAL, Victor, VALLDENEU, Silvia, GIMÉNEZ, Sandra, GONZÁLEZ ORTIZ, Sofía, TORRES, Soraya, EL BOUNASRI EL BENNADI, Shaimaa, PADILLA, Concepción, ROZALEM ARANHA, Mateus, ESTELLÉS, Teresa, ILLÁN GALA, Ignacio, BELBIN, Olivia, VALLE TAMAYO, Natalia, CAMACHO, Valle, BLESSING, Esther, OSORIO, Ricardo s., VIDELA, Sebastià, LEHMANN, Sylvain, HOLLAND, Anthony j., ZETTERBERG, Henrik, BLENNOW, Kaj, ALCOLEA, Daniel, CLARIMÓN, Jordi, ZAMAN, Shahid h., BLESA, Rafael, LLEÓ, Alberto, FORTEA, Juan. Association of biological sex with clinical outcomes and biomarkers of Alzheimer’s disease in adults with Down syndrome. _Brain Communications_. 2023. Vol. 5, núm. 2, pàgs. fcad074. [consulta: 23 de gener de 2026]. ISSN: 2632-1297. [Disponible a: https://hdl.handle.net/2445/200903]