Title: Moderate reproductive history may protect against certain dementia subtypes in both sexes

Sotiria Moza1a, Nikolaos Scarmeas2, 3, Georgios M. Hadjigeorgiou4, Efthimios Dardiotis5, Mary Yannakoulia6, Paraskevi Sakka7, & Mary H. Kosmidis1b*

1 Lab of Neuropsychology & Behavioral Neuroscience, School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece, asotimoza@psy.auth.gr, bkosmidis@psy.auth.gr

2 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

3 Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, the Gertrude H. Sergievsky Center, Department of Neurology, Columbia University, New York, USA, ns257@columbia.edu 

4 School of Medicine, University of Cyprus, Nicosia, Cyprus, hadjigeorgiou.georgios@ucy.ac.cy 

5 Department of Neurology, Faculty of Medicine, University of Thessaly, Thessaly, Greece, edar@med.uth.gr

6 Department of Nutrition Science-Dietetics, Harokopio University, Athens, Greece, myiannak@hua.gr

7 Athens Alzheimer Association, Athens, Greece, info@psakka.gr

Background:

Parental status (one’s number of children) has been associated with Neurocognitive Disorder (NCD) in late-life, yet evidence on sex-specific associations with the prevalence and sub-types of NCD remains limited. In the present study, we examined associations between parental status and the prevalence and subtypes of NCD in both sexes.

Methods:
The sample included 914 naturally menopausal women (MeanAGE=72.65±5.57 years, meanEDUCATION=7.57±4.89 years) and 811 men (MeanAGE=74.43±5.37 years, meanEDUCATION=8.92±5.28 years) from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD; Dardiotis et al., 2014). Neuropsychological assessments and neurological exams were included in diagnostic consensus meetings to determine MCI and dementia diagnoses and their subtypes. Participants were categorized per their self-reported number of children as childless, with one child, 2–4 children, or ≥5 children (parental status). Associations between parental status and NCD diagnostic subtypes were examined using chi-square tests.

Results:
Among men, parental status was not significantly associated with MCI subtype (χ²(18, n=797)=17.53, p>.05). However, childless men were more likely to develop frontotemporal, alcohol-related, or Alzheimer’s disease dementia, and less likely to have no dementia. Also, men with 2–4 children were underrepresented in frontotemporal dementia (χ²(18)=31.54, p=.025). Likewise, childless women more often presented with unclassified MCI, women with one child more frequently showed MCI with hydrocephalic features, women with ≥5 children more often exhibited MCI with psychiatric characteristics, while women with 2–4 children appeared less likely to meet criteria for any MCI subtype (χ²(18)=29.80, p=.039). No associations were found in regard to dementia in women (χ²(12)=20.83, p=.053). 

Conclusions:
Parental status is differentially associated with dementia and MCI subtypes in men and women. Yet, it appears that moderate reproductive history (having 2-4 children) is associated with neuroprotection in both sexes. Further studies are needed to map sex-specific associations between reproductive history and cognitive aging.

Dardiotis, E., Kosmidis, M. H., Yannakoulia, M., Hadjigeorgiou, G. M., & Scarmeas, N. (2014). The Hellenic Longitudinal Investigation of Aging and Diet (HELIAD): rationale, study design, and cohort description. Neuroepidemiology, 43(1), 9-14.