Researchers identify crucial risk factors for cognitive decline after stroke

In a recent study published in The Lancet Healthy Longevity, researchers performed a meta-analysis to investigate factors that increase post-stroke cognitive impairment (PSCI) and dementia (PSD) risks.

The increasing number of stroke survivors worldwide has highlighted the long-term consequences of stroke, particularly cognitive impairments and dementia. This burden on patients, caregivers, and healthcare systems is significant.

Understanding the factors predisposing individuals to stroke-related complications is crucial for patient counseling and prevention trials. However, systematic reviews and meta-analyses are scarce, and there is a lack of pooled estimates for PSCI independent of well-recognized risk factors such as stroke severity and patient age.

About the study

In the present meta-analysis, researchers explored PSCI and PSD risk factors other than stroke severity and age.

The team searched the Cochrane and MEDLINE databases for articles on risk factors for post-stroke cognitive deficits published in English through September 15, 2023. A researcher screened the data, and another researcher resolved discrepancies.

Studies included observational studies, retrospective and prospective cohort-type research, post-hoc analysis from randomized clinical trials, and case-control-type studies of acute stroke patients (hemorrhagic, ischemic, and transient ischemic attack [TIA]), exploring factors contributing to PSD or PSCI risks after 3 months follow-up.

Included records reported summary estimates for binary outcomes (PSD or PSCI) based on predetermined diagnostic criteria, or thresholds in neuropsychological tests, or both; include ≥30 adult patients; and assess risk factors within the first three months after stroke. The researchers also searched the reference lists of the included articles to identify additional records.

They used the Newcastle-Ottawa scale (NOS) to assess the quality of the included studies. They determined the pooled values for relative risks (RRs) by random-effects-type meta-analytical research, including meta-regressions, sensitivity, and subgroup analyses.

Exclusion criteria included animal studies, cross-sectional studies, randomized clinical trials, stroke patients with specific brain regions, subjective studies, cohorts with pre-stroke dementia, cognitive impairment or diseases that may alter cognitive function, and studies without stroke severity and age adjustments. 

The team also excluded studies focusing on cognitive impairment, genetic predispositions, stroke-free controls, continuous cognitive outcomes, trajectories of cognitive performance, domain-specific performance or impairment, and meta-analysis studies without stroke severity and age adjustments.

Results

Out of 13,127 initially identified records, 162 were eligible for the systematic review and 113 (89 studies, including 160,783 stroke patients) for the meta-analysis. The median NOS score for the included studies was 5. 

Most studies were hospital-based (73 studies, 29,341 patients), while fewer were population- or registry-based. PSCI effect estimates were correlated significantly with those for PSD, with a beta regression coefficient of 0.7 indicating larger effect sizes for PSD than PSCI.

Cognitive impairment at baseline contributed the most to PSCI (relative risk [RR], 2.0) and PSD risks (RR, 3.1). The researchers identified diabetes (RR, 1.3), atrial fibrillation history or presence (RR, 1.3), moderate to severe hyperintensities in white matter (RR, 1.5), and white matter hyperintensity severity (RR, 1.3) as modifiable-type PSCI risk factors, irrespective of stroke severity and age.  

The researchers identified diabetes (RR, 1.4), moderate to severe white matter hyperintensities (RR, 1.6), and white matter hyperintensity severity (RR, 1.6, 1) as modifiable risk factors for PSD. Other risk factors were a lower level of education, prior stroke history, brain atrophy, stroke in the left hemisphere of the brain, the presence of at least three lacunes, and low functional status at baseline. The researchers found considerable heterogeneity and reporting bias in the included studies.

In the subgroup analysis, studies on diabetes and atrial fibrillation showed larger effect sizes for post-dementia stress disorder (PDS) when published before 2009 in a hospital-based setting using a neuropsychological test battery rather than cognitive screening tools.

Meta-regressions showed that a later recruitment date attenuated the association of the National Institute of Health Stroke Scale/Score (NIHSS), educational attainment, and white matter hyperintensity severity with PSD, and a later publication date attenuated the association of NIHSS, educational attainment, and atrial fibrillation with PSD.

Conclusions

Overall, the study findings showed that cognitive impairments in the acute period following stroke are the strongest predictor of post-stroke stroke complications (PSCI) and stroke-related stroke complications (PSD). Diabetes was identified as the main cardiovascular risk factor for cognitive impairments and dementia after stroke, while the role of atrial fibrillation in PSD development is less clear.

Other factors for post-stroke cognitive decline include lower education, prior stroke history, cerebral small vessel disease (cSVD)-associated neuroimaging markers, left hemisphere stroke, urinary incontinence, medial temporal lobe atrophy (MTA), and lower functional status and cognitive performance. Screening for cognitive dysfunction during the acute period after stroke may aid in identifying individuals at increased risks of long-term post-stroke cognitive impairments and dementia.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.