Exploring sex differences in Alzheimer's disease: a comprehensive analysis of a large patient cohort from a memory unit.

Background: Alzheimer's disease (AD) stands as the leading cause of dementia worldwide, and projections estimate over 150 million patients by 2050. AD prevalence is notably higher in women, nearly twice that of men, with discernible sex differences in certain risk factors. To enhance our understanding of how sex influences the characteristics of AD patients and its potential impact on the disease trajectory, we conducted a comprehensive analysis of demographic, clinical, cognitive, and genetic data from a sizable and well-characterized cohort of AD dementia patients at a memory clinic in Barcelona, Spain.
Methods: The study cohort comprised individuals with probable and possible AD dementia with a Clinical Dementia Rating (CDR) score between 1 and 3 diagnosed at the Memory Unit from Ace Alzheimer Center Barcelona, Spain, between 2008 and 2018. We obtained cognitive baseline data and follow up scores for the Mini-Mental State Examination (MMSE), the CDR scale, and the neuropsychological battery used in our center (NBACE). We employed various statistical techniques to assess the impact of sex on cognitive evolution in these dementia patients, accounting for other sex-related risk factors identified through Machine Learning methods.
Results: The study cohort comprised a total of 6108 individuals diagnosed with AD dementia during the study period (28.4% males and 71.6% females). MMSE scores exhibited an average decline of approximately two units per year, unaffected by sex. Similarly, the decline in most neuropsychological functions assessed by NBACE did not exhibit significant differences between males and females. However, we observed that women diagnosed with mild AD dementia progressed more rapidly based on their CDR score (HR = 2.57, 95%CI:2.33-2.84) than men (HR = 2.03, 95%CI: 1.71-2.41) (p-interaction = 0.01).
Conclusions: Our findings do not strongly support the notion that sex significantly modifies the clinical progression of AD dementia based on cognitive data. Further research is essential to validate whether women with mild AD dementia indeed progress more rapidly than men at a similar stage and to delve into the potential underlying reasons for this finding.
Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed with dissociated data, therefore Ethics approval and consent were not applicable. Consent for publication: Not applicable. Competing interests: IdR has received funding support from the Instituto de Salud Carlos III (ISCIII) grant FI20/00215. MA has received funding support from the Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER - Una manera de hacer Europa) grant PI22/01403. AR has received funding support from the Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER - Una manera de hacer Europa) grants AC17/00100, PI19/01301, PI22/01403 and PMP22/00022, and from the European Union Joint Programme – Neurodegenerative Disease Research (JPND) Multinational research projects on Personalized Medicine for Neurodegenerative Diseases/Instituto de Salud Carlos III grant AC19/00097. AR is member of scientific advisory board of Landsteiner Genmed and Grifols SA and has stocks of Landsteiner Genmed. MB has received funding support from Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER - Una manera de hacer Europa) grant grant PI17/01474; has received consulting fees from Grifols, Araclon Biotech, Roche, Biogen, Lilly, Merck, Zambon and Novo-Nordisk; and has participated on Advisory Boards from Grifols, Roche, Lilly, Araclon Biotech, Merck, Zambon, Biogen, Novo-Nordisk, Bioiberica, Eisai, Servier, Schwabe Pharma, Lighthouse Pharma. MM has received funding support from Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER - Una manera de hacer Europa) grant PI19/00335; has received travel support to attend scientific meeting from F. Hoffmann-La Roche Ltd, and has participated in the Spanish Scientific Advisory Board of Biomarkers of Araclon Biotech-Grífols.All other authors declare no potential competing interests.
(© 2024. The Author(s).)