By Vijay Kumar MalesuReviewed by Danielle Ellis, B.Sc.Dec 5 2023

In a recent study published in Hypertension Research, a group of researchers examined the link between hypertensive disorders of pregnancy (HDP) and the increased risk of dementia, utilizing a systematic review and meta-analysis approach on cohort studies.

Background 

As populations age, particularly in Western and East-Asian countries, the prevalence and incidence of dementia are rising significantly. Dementia, as a syndrome containing many different manifestations of cognitive failure, has significant social costs and financial implications for society.

Dementia presents as a significant risk factor associated with hypertension, where blood pressure control has been proven effective in preserving cognitive abilities and reducing the chances of dementia occurrence. Preeclampsia and eclampsia, which is a very common pregnancy complication, may be associated with an elevated risk of cognitive dementia in HDP also.

There is a need for further research into the management of HDP and its role in preventing dementia, as well as exploring the underlying biology behind the association between HDP and dementia risk.

About the study 

The study's methodology was framed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. However, it was not registered with the International Prospective Register of Systematic Reviews (PROSPERO).

Individually, researchers undertook an exhaustive literature search of the PubMed and Scopus databases for studies in the English language. The objective was to make fresh updates on an earlier meta-analysis by adding the latest studies that focused on the interaction between HDP and varied forms of dementia, such as all-cause dementia, vascular dementia, and Alzheimer's disease (AD).

In their process, they precisely filtered the identified studies to ensure relevance and quality. This involved removing duplicates, unrelated data, review articles, and studying without using cohort design or HDP specifically related to dementia as an outcome. They also excluded irrelevant studies, including one involving only AD mortality and one that had few numbers of dementia cases in the preeclampsia group.

For the statistical analysis, the researchers employed the R-3.2.0 statistical package, using the Metafor meta-analysis package. In addition, they employed tests for publication bias using funnel plot asymmetries, guaranteeing the accuracy of their evidence in a meta-analysis.

Study results 

The researchers performed a systematic review of all available scientific literature to find the best studies for the meta-analysis. Initially, they removed duplicates, irrelevant records, review articles, and studies that did not meet specific criteria, such as employing a cohort design or focusing on dementia as an outcome and HDP as an exposure. For example, an AD mortality study was excluded; likewise, there was only one case of dementia among the patients who had preeclampsia. Thus, through intensive review, six cohort studies were adopted for analysis.

However, the research had some challenges as the two assessed similar populations, but the scope of research was different. Earlier investigations considered any HDP, which was followed by one looking only at preeclampsia & gestational hypertension. The team decided to include the previous study in a main meta-analysis and used the results of the subsequent research for sensitivity analyses due to preserving analytical rigor.

The results of the meta-analysis revealed a significant association between HDP and dementia. When analyzing the impact of preeclampsia or gestational hypertension from the later Andolf study instead of the broader HDP results from the earlier study, the pooled hazard ratios (HRs) did not change substantially, affirming the findings. Specifically, the association of HDP with vascular dementia was notable, showing a pooled HR of 1.66 (95% CI: 1.13-2.43), which was stronger than the association with Alzheimer's disease (pooled HR: 1.29, 95% CI: 0.97-1.72).

The study's findings were placed in the context of previous meta-analyses on the topic. Prior analyses had revealed mixed results, with one meta-analysis reporting unadjusted relative risks (RRs) that suggested a significant association between HDP and dementia, yet the pooled RR was not statistically significant. Another analysis of two cohort studies found no association between HDP and dementia risk.

These inconsistencies, coupled with the limited number of studies included in previous analyses, highlighted the importance of this more comprehensive review, which included five cohort studies and provided a clearer picture of the relationship between HDP and dementia risk.

Conclusions 

To summarize, this meta-analysis synthesized data from six cohort studies, revealing a significant correlation between HDP and an increased risk of dementia, particularly vascular dementia. In contrast to previous meta-analyses that reported mixed results due to smaller sample sizes and the inclusion of studies with methodological limitations, this analysis demonstrates a more definitive association.

Notably, the relationship between HDP and dementia appears to differ depending on the subtype of dementia and the specific nature of HDP. For instance, some forms of HDP were linked to a higher risk of both all-cause and vascular dementia. These findings underscore the need for future research to differentiate between dementia and HDP subtypes to understand these complex interactions fully.