Megan Brooks

July 21, 2015

WASHINGTON ― Women with mild cognitive impairment (MCI) decline twice as fast as men with MCI, and they also have a much higher risk for cognitive problems after surgery and general anesthesia, new research suggests.

"Two thirds of Americans with Alzheimer's are women, and two thirds of caregivers are women, so this is a problem. These findings tell us that we may want to look at biological differences in men and women and vulnerability to Alzheimer's," Maria Carrillo, PhD, chief science officer of the Alzheimer's Association, told Medscape Medical News.

The studies were presented here at the Alzheimer's Association International Conference (AAIC) 2015.

Long-term Results

Katherine Amy Lin, of the Duke Institute for Brain Sciences, in Durham, North Carolina, and colleagues examined 8-year rates of cognitive decline in 257 men and 141 women with MCI from the Alzheimer's Disease Neuroimaging Initiative.

The annual rate of decline in the Alzheimer's Disease Assessment Scale–cognitive subscale was 2.7 points in women vs 1.5 points in men. The effect of female sex remained highly significant in adjusted analysis (P < .001).

The annual rate of change in the Clinical Dementia Rating–sum of boxes (CDR-SB) was also greater in women than men (0.91 points vs 0.59 points). The effect of female sex on CDR-SB score worsening over time was also significant (P = .003).

"We also noted acceleration of decline that was almost twice as fast in women, which was not evident in shorter studies," Lin told Medscape Medical News. "We also found greater variability in rates of decline in women. The effect of gender was above and beyond the effects of age, Alzheimer's risk gene [APOE ε4] status, and education," she noted.

"Our findings do suggest greater vulnerability in women at MCI stage. Higher vulnerability of women to amyloid plaques may be a potential contributor. The greater variability in rates of decline in women suggests unknown genetic links," Lin said.

She believes sex-specific research in AD "needs to be made a priority. Potentially, Alzheimer's prevention trials could test treatment effects separately by gender. Gender-specific clinical trials appear warranted."

Older women also appear more vulnerable after surgery and general anesthesia (GA), according to a study by Katie Schenning, MD, MPH, and colleagues from Oregon Health and Science University, in Portland.

Urgent Research Need

The investigators conducted a retrospective analysis of 527 elderly individuals enrolled in two natural history studies of cognitive aging. Of these, 182 underwent a total of 331 procedures under GA.

They found that older men exposed to surgery/GA declined in standard measures of cognition, functional status, and brain volume significantly faster than their peers without this exposure. Women exposed to surgery/GA also declined on those measures, and at a significantly faster rate than men. The difference was even more pronounced for women who underwent multiple surgeries with general anesthesia.

"The role of gender in postoperative cognitive dysfunction is unknown. These data suggest that clinically, older women might be at a higher risk for deleterious postoperative neurocognitive outcomes than older men," Dr Schenning told Medscape Medical News.

"More studies are needed to confirm this observation and to identify ways to minimize the effects of surgery and general anesthesia on older adults. Future research should focus on whether certain people are more susceptible to postoperative cognitive decline by virtue of sex or genetic risk factors," she added in a statement.

"Women are disproportionately affected by Alzheimer's, and there is an urgent need to understand if differences in brain structure, disease progression, and biological characteristics contribute to higher prevalence and rates of cognitive decline," Dr Carrillo added in the statement.

"The Alzheimer's Association is launching a $2 million grant program in the fall that will have a call for applications for researchers to study biological, genetic, and hormonal underpinnings of sex differences in Alzheimer's disease," said Dr Carrillo.

The studies had no commercial funding. The authors report no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2015. Posters P4-108 and P1-264. Presented July 21, 2015.

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