Parental Age and the Risk for Alzheimer's Disease in Offspring: Systematic Review and Meta-Analysis.

Background: Alzheimer's disease (AD) is the most common cause of dementia worldwide, accounting for 50-75% of all cases. While older maternal and paternal age at childbirth are established risk factors for Down syndrome which is associated with later AD, it is still not entirely clear whether parental age is a risk factor for AD. Previous studies have suggested contradictory findings.

Objectives: We conducted a systematic review and meta-analysis to examine whether parental (maternal and paternal) age at birth was associated with AD and whether individuals born to younger or older parents were at an increased risk for AD.

Methods: Two reviewers searched the electronic database of PubMed for relevant studies. Eligibility for the meta-analysis was based on the following criteria: (1) studies involving patients with AD and an adequate control group, (2) case control or cohort studies, (3) studies investigating parental age. All statistical analyses were completed in STATA/IC version 16.

Results: Eleven studies involving 4,371 participants were included in the systematic review and meta-analysis. Meta-analysis demonstrated no significant association between maternal (weighted mean difference [WMD] 0.49, 95% CI -0.52 to 1.49, p = 0.34) and paternal age and AD (WMD 1.00, 95% CI -0.55 to 2.56, p = 0.21). Similarly, individuals born to younger (<25 years) or older parents (>35 years) did not demonstrate a differential risk for AD.

Conclusions: Overall, this meta-analysis did not demonstrate an association between parental age and the risk of AD in offspring. These findings should be interpreted with caution given the limited power of the overall meta-analysis and the methodological limitations of the underlying studies as in many cases no adjustment for potential confounders was included.