Background: Alzheimer disease (AD) is a progressive neurodegenerative disorder affecting the elderly with a prevalence of 7.1% in women and 3.3% in men aged 55 or older. Sex-related patterns have been reported in prognosis, biomarker status and risk factors. Despite this, the interaction of sex has received limited attention, with AD trials persistently recruiting lower numbers of women than the population distribution and a lack of information on the sex-disaggregated effects of anti-dementia therapies. This is the first study aiming to identify the role of sex in the selection for screening in AD clinical trials.
Methods: This cross-sectional study provides a comprehensive analysis of screening eligibility according to a set of pre-selection criteria currently applied at Fundació ACE memory clinic for a more efficient trial screening process. A cohort of 6,667 women and 2,926 men diagnosed with AD dementia (55%) or mild cognitive impairment (45%) was analyzed. We also assessed the frequencies of men and women effectively screened for trial enrolment over a period of 10 years.
Results: Women showed a significantly lower chance of being eligible for screening than men (OR=1.26; p<0.01). This imbalance was confirmed by a lower frequency of women screened for enrolment compared to the study population (63.0% vs 69.5%). Education was revealed as the key criterion contributing to this unbalance, with men showing over twice the chance of being screened compared with women (OR=2.25, p<0.01). Education-based differences were greater in earlier born patients, but the gap narrowed and achieved balance with increasing year of birth. Comorbidity was the most limiting criterion with sex differences in frequencies and significant discrimination against the selection of men (OR=0.86, p<0.01).
Conclusions: The large number of low-educated elderly women with AD demands for a sex-focused approach in clinical research. New assessment tools insensitive to education level should be develop to enable a proportional representation of women. Although this gender education gap is mostly inexistent in developed countries, economic or cultural factors may lead to different scenarios in other regions. Overlooking the impact of sex may lead to a handicap in AD research with a direct adverse impact on women’s health.