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.