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Risk for Alzheimer’s does not differ between sexes

Men and women with apolipoprotein E 3/4 had similar risk for Alzheimer’s disease from ages 55 to 85 years, whereas women had increased risk at younger ages, according to study findings.

“For nearly 20 years, the prevalent view has been that women who carry copies of the 4 allele of the apolipoprotein E (APOE) gene have a greater risk of developing Alzheimer disease than men with the same number of copies,” Scott C. Neu, PhD, of Keck School of Medicine at University of Southern California, Los Angeles, and colleagues wrote. “Among studies of residents in city suburbs and communities, there is general agreement that elderly female 4 carriers have an increased risk of [Alzheimer’s disease], dementia, and cognitive decline vs. male 4 carriers. However, when participants are randomly recruited from hospitals, retirement homes, and aging consortiums, most studies have found no sex-specific difference between men and women in the risks of [Alzheimer’s disease] and dementia associated with the APOE 4 allele.”

To determine the role of sex and APOE genotype in risk for mild cognitive impairment and Alzheimer’s disease, researchers analyzed 27 independent research studies in the Global Alzheimer’s Association Interactive Network for approximately 58,000 participants. The study cohort was aged 55 to 85 years.

Alzheimer’s disease risk did not differ between men (OR = 3.09; 95% CI, 2.79-3.42) and women (OR = 3.31; 95% CI, 3.03-3.61) with the APOE 3/4 genotype from ages 55 to 85 years. However, women had increased risk from ages 65 to 75 years (OR = 4.37; 95% CI, 3.82-5), compared with men (OR = 3.14; 95% CI, 2.68-3.67; P = .002).

Alzheimer’s disease risk was higher in men with APOE 3/4, compared with men with APOE 2/3.

APOE 2/3 had a protective effect among women (OR = 0.51; 95% CI, 0.43-0.61), compared with men (OR = 0.71; 95% CI, 0.6-0.85).

Men (OR = 1.55; 95% CI, 1.36-1.76) and women (OR = 1.6; 95% CI, 1.43-1.81) with APOE 3/4 had similar risk for mild cognitive impairment between ages 55 and 85 years; however, women had increased risk between ages 55 and 70 years (OR = 1.43; 95% CI, 1.19-1.73; P = .05).

Risk for converting from mild cognitive impairment to Alzheimer’s disease did not significantly differ between sexes from ages 55 to 85 years.

Participants with APOE 4/4 had increased risk compared with those with APOE 3/4, but researchers observed no significant differences between men and women with APOE 4/4.

“The study by Neu [and colleagues] importantly adds to our knowledge about APOE4 and [Alzheimer’s disease] risk in women. Their findings are timely, further validate female vulnerability in a large meta-analysis of defined populations, and inspire us to explain how 2 amino acid substitutions in APOE preferentially affect [Alzheimer’s disease] pathogenesis in women long before clinical manifestations,” Dena B. Dubal, MD, PhD, and Camille Rogine, BA, of the University of California, San Francisco, wrote in an accompanying editorial. “What if we could identify young women at high risk for [Alzheimer’s disease] decades before its onset, based on APOE4 status combined with other biomarkers, and offer a treatment derived from newfound, sex biology-based, APOE 4 pathways? And what if the treatment worked in men, too? This would represent monumental progress against [Alzheimer’s disease], a major biomedical challenge with no truly effective medical therapies.” – by Amanda Oldt

Disclosure s : The researchers report no relevant financial disclosures.