Multiple Births Associated With Greater Late-Life Risk for Alzheimer Disease

large family sitting outside
large family sitting outside
Grand multiparity was associated with significantly worse Mini-Mental State Examination scores compared with those with 1 to 4 completed pregnancies.

In a study published in Neurology, a multi-international team of researchers reports that grand multiparity, or women who have ≥5 live births in their lifetime, is associated with an increased risk for Alzheimer disease (AD). In addition, the researchers also found a low late-life risk for AD in women who had experienced incomplete pregnancies compared with women who had never experienced an incomplete pregnancy.

The Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were pooled to obtain a cohort of 3549 women with a full reproductive history available for analysis. Study investigators retrospectively assessed the association between complete and incomplete pregnancies with mild cognitive impairment and AD.

In the cohorts, researchers used the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale Short Form to assess mental status. For dementia-free women, analyses of covariance of the pooled analysis were used to evaluate associations of both complete and incomplete pregnancies with the MMSE score.

Compared with women who had 1 to 4 completed pregnancies, women with ≥5 complete pregnancies had an approximately 1.7-fold increased AD risk (odds ratio [OR] 1.68; 95% CI, 1.04-2.72; P =.036). Conversely, 1 incomplete pregnancy (OR 0.43; 95% CI, 0.24-0.76; P =.004) and ≥2 incomplete pregnancies (OR 0.56; 95% CI, 0.34-0.92; P =.022) were associated with a significantly lower risk for AD compared with those who had never had an incomplete pregnancy.

In the separate analysis of dementia-free women, grand multiparity was associated with significantly worse MMSE scores compared with those with 1 to 4 completed pregnancies (P <.001). In addition, those who had ≥1 incomplete pregnancies scored significantly better on the MMSE vs women with no prior incomplete pregnancy (P =.008).

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The retrospective assessment of self-reported reproductive histories, which may have introduced recall bias, represented a primary study limitation.

These findings hold possible clinical implications, including its potential to “lead to the development of hormone-based preventive strategies aimed at reducing AD risk in women, particularly those who are grand multipara,” the authors write.


Jang H, Bae JB, Dardiotis E, et al. Differential effects of completed and incomplete pregnancies on the risk of Alzheimer disease. Neurology. 2018;91(7):e643-e651.