Immune Changes in Pregnancy May Protect Against Alzheimer's

CHICAGO — Pregnancy-related changes in the immune system may help protect women from developing Alzheimer's disease (AD) later in life, new research shows.

Depleted immunoregulatory mechanisms have been implicated in AD etiology. Pregnancy is associated with improvement in immunoregulation — benefits that may persist into the geriatric phase of life, Molly Fox, PhD, of the Department of Behavioral and Biobehavioral Sciences, University of California, Los Angeles, explained during a press briefing.

"This is the first study to suggest pregnancy affects Alzheimer's risk through alterations in the immune system," she said.

The findings were presented here at the Alzheimer's Association International Conference (AAIC) 2018.

More Months Pregnant, Lower Risk

The investigators collected information on reproductive and medical history for 133 women aged 70 years and older living in Southern England. About half had AD, and half did not. The researchers determined for each woman the total number of months the woman was pregnant in her lifetime, as well as the number of childbirths, miscarriages, and abortions.

"Consistently and reliably, we found that more months pregnant was associated with lower risk of AD," said Fox.

Specifically, the researchers observed a 5.5% decrease in AD risk (P = .02) for each additional month pregnant. After adjusting for parity, they saw a 4.7% decrease in AD risk for each additional month pregnant (P = .03).

To determine whether the protection against AD might be related to the effects of estrogen or to immunologic changes, they assessed the protection conferred by first and third trimesters.

They found that the cumulative number of first trimesters was associated with a lower risk for AD after adjusting for the number of third trimesters (P < .01), whereas the number of third trimesters was not a significant predictor of AD risk after adjusting for first trimesters (P = .31).

Fox said the finding that more first trimesters (but not third trimesters) conferred protection against AD is more consistent with pregnancy's persisting immunologic effects, which are driven by early gestational physiology, than the estrogen exposures associated with pregnancy, which are greatest in late gestation.

"Estrogen is still probably neuroprotective, but it might not explain how pregnancy affects Alzheimer's risk," she told the briefing.

Provocative Data

Briefing moderator Suzanne Craft, PhD, Wake Forest School of Medicine, Winston-Salem, North Carolina, who is a member of the Alzheimer's Association Medical and Scientific Advisory Council, said these are "provocative" data that show that the decreased risk with pregnancy might be "preferentially associated with the first trimester of pregnancy and in fact to immunological changes that are happening in pregnancy."

AD disproportionately affects women, and "we are now just beginning to uncover reasons for that association," said Craft.

"Initially it was thought that this was because women live longer, but now we know that that is not the case and that there are important biological factors which can render women more vulnerable Alzheimer's," she added.

"It's critical that we understand what those factors might be. To do so, I think, will help get us to the root causes of Alzheimer's disease. I think it's also going to be necessary to develop sex-specific therapies and prevention strategies," she said.

The study was funded by the Gates Cambridge Trust. The authors have disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2018. Abstract 25107, presented July 23, 2018.

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