Cognitive Impairment After Intracerebral Hemorrhage: A Systematic Review of Current Evidence and Knowledge Gaps

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Cognitive Impairment After Intracerebral Hemorrhage: A Systematic Review of Current Evidence and Knowledge Gaps

Thomas Potter¹, Vasileios-Arsenios Lioutas², Mauricio Tano^1,3, Alan Pan¹, Jennifer Meeks¹, Daniel Woo⁴, Sudha Seshadri⁵, Magdy Selim² and Farhaan Vahidy^1,6*

• ¹Center for Outcomes Research, Houston Methodist Research Institute, Houston Methodist, Houston, TX, United States
• ²Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States
• ³Department of Nuclear Engineering, Texas A&M University, College Station, TX, United States
• ⁴Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
• ⁵Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
• ⁶Neurological Institute, Houston Methodist, Houston, TX, United States

Background: Cognitive impairment (CI) is commonly observed after intracerebral hemorrhage (ICH). While a growing number of studies have explored this association, several evidence gaps persist. This review seeks to investigate the relationship between CI and ICH.

Methods: A two-stage systematic review of research articles, clinical trials, and case series was performed. Initial search used the keywords [“Intracerebral hemorrhage” OR “ICH”] AND [“Cognitive Impairment” OR “Dementia OR “Cognitive Decline”] within the PubMed (last accessed November 3rd, 2020) and ScienceDirect (last accessed October 27th, 2020) databases, without publication date limits. Articles that addressed CI and spontaneous ICH were accepted if CI was assessed after ICH. Articles were rejected if they did not independently address an adult human population or spontaneous ICH, didn't link CI to ICH, were an unrelated document type, or were not written in English. A secondary snowball literature search was performed using reviews identified by the initial search. The Agency for Healthcare research and Quality's assessment tool was used to evaluate bias within studies. Rates of CI and contributory factors were investigated.

Results: Search yielded 32 articles that collectively included 22,631 patients. Present evidence indicates a high rate of post-ICH CI (65–84%) in the acute phase (<4 weeks) which is relatively lower at 3 (17.3–40.2%) and 6 months (19–63.3%). Longer term follow-up (≥1 year) demonstrates a gradual increase in CI. Advanced age, female sex, and prior stroke were associated with higher rates of CI. Associations between post-ICH CI and cerebral microbleeds, superficial siderosis, and ICH volume also exist. Pre-ICH cognitive assessment was missing in 28% of included studies. The Mini Mental State Evaluation (44%) and Montreal Cognitive Assessment (16%) were the most common cognitive assessments, albeit with variable thresholds and definitions. Studies rarely (<10%) addressed racial and ethnic disparities.

Discussion: Current findings suggest a dynamic course of post-ICH cognitive impairment that may depend on genetic, sociodemographic and clinical factors. Methodological heterogeneity prevented meta-analysis, limiting results. There is a need for the methodologies and time points of post-ICH cognitive assessments to be harmonized across diverse clinical and demographic populations.

Introduction

Intracerebral hemorrhage (ICH) is the most common type of hemorrhagic stroke, accounting for 10–20% of all strokes (1), with a global incidence of 24.6 per 100,000 person-years (2). Spontaneous ICH primarily results from either hypertensive microangiopathy or cerebral amyloid angiopathy (CAA) (3), which are likely to produce varied phenotypes. Hypertensive ICH likely occurs in deep brain structures while CAA-related ICH generally occurs in lobar locations (2). Regardless of the cause, ICH is associated with poor outcomes that include early mortality (2, 4) and the loss of functional independence (2).

Cognitive Impairment (CI) commonly coexists with ICH. The majority of ICH patients exhibit acute phase CI, with impairments reported in up to 84% of patients (5). While the immediate post-ICH cognitive effects and the potential for long-term CI (6) are broadly recognized, several evidence gaps persist. The trajectory of post-ICH CI is poorly characterized and demonstrates considerable variability. Some ICH patients experience favorable recovery after an acute cognitive decline while others exhibit persistent or worsening CI (7). The significant contribution of cognitive function toward quality of life among ICH survivors has driven an increased research focus on post-ICH CI and dementia. With the growing body of literature focused on post-ICH CI, it is important to integrate the available evidence and characterize cognitive function among ICH patients. This systematic review aims to collect and summarize current evidence regarding the risk factors and trajectory of CI after spontaneous ICH, report the strength and validity of study methodologies, and highlight current knowledge gaps in the study of post-ICH CI.