Interaction effect of sex and onset of Alzheimer’s disease—rates of progression and prognosis.

Objectives: To investigate the interaction effect of sex and early vs. late onset of Alzheimer’s disease (AD) on long-term cognitive and functional outcomes and survival. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study of clinical practice involving 1,017 participants diagnosed with mild-to-moderate AD at the start of cholinesterase inhibitor treatment. The patients were evaluated using cognitive and functional assessment scales at baseline and semi-annually over 3 years. The date of death was recorded for 20 years. Results: Women with late-onset AD (LOAD) showed a higher frequency of apolipoprotein E (APOE) ε4-carriers than did men with LOAD (71% vs. 58%, p<0.001). This sex difference was not detected in early-onset AD (EOAD). The annual decline in Alzheimer’s Disease Assessment Scale–cognitive subscale was faster in women with EOAD compared with women with LOAD (mean, 95% confidence interval) (5.8, 3.9–7.8 vs. 3.0, 2.3–3.7 points; p=0.013), but this difference was not observed in men. Functional deterioration rates did not differ between the groups. The survival time after AD diagnosis was longer in women with LOAD than in men with LOAD (7.0, 6.7–7.3 vs. 5.4, 5.1–5.8 years; p<0.001), but this sex difference was not found in EOAD. Conclusions: Women, but not men, with EOAD demonstrated almost twice as fast long-term cognitive decline compared with the LOAD groups. Women with LOAD had a lower education, exhibited a high proportion of APOE ε4-carriers and approximately 50% lived alone. Men with LOAD had a shorter lifespan after diagnosis than did all other patients.