Skip to main content
Log in

Relationships Among Structural Neuroimaging and Neurocognitive Outcomes in Adolescents and Young Adults with Congenital Heart Disease: A Systematic Review

  • Review
  • Published:
Neuropsychology Review Aims and scope Submit manuscript

Abstract

Congenital heart disease (CHD) is the most common cause of major congenital anomalies in the world. Disruptions to brain development in this population may impact cognitive outcomes. As individuals with CHD age, understanding of long-term neurocognitive and brain outcomes is essential. Synthesis of the current literature of brain-behavior relationships in adolescents and young adults with CHD is needed to understand long-term outcomes and identify literature gaps. This systematic review summarizes and integrates the current literature on the relationship between structural neuroimaging and neurocognitive outcomes in adolescents and young adults with CHD. Included papers were published through August 2, 2021. Searches were conducted on Pubmed and APA PsycInfo. Studies were eligible for inclusion if they evaluated adolescents or young adults (ages 10–35) with CHD, and without genetic comorbidity. Studies explored relationships among structural neuroimaging and neurocognitive outcomes, were in English, and were an empirical research study. A total of 22 papers were included in the current review. Data from each study was extracted and included in a table for comparison along with a systematic assessment of study quality. Results suggest worse brain outcomes (i.e., brain abnormality, reduced volume, lower fractional anisotropy, and brain topology) are related to poorer performance in neuropsychological domains of intelligence, memory, and executive functioning. Consistently, poorer memory performance was related to lower hippocampal and temporal region volumes. Statistically significant brain-behavior relationships in adolescents and young adults with CHD are generally observed across studies but there is a lack of consistency in investigated neuropsychological constructs and brain regions to be able to make specific conclusions. Further research with adult samples of CHD is needed to better understand the long-term impacts of early neurological insult.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Alloza, C., Cox, S. R., Duff, B., Semple, S. I., Bastin, M. E., Whalley, H. C., & Lawrie, S. M. (2016). Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia. Psychiatry Research: Neuroimaging, 254, 26–33.

    Article  PubMed  Google Scholar 

  • Andreasen, N. C., Flaum, M., Swayze, V., O’Leary, D. S., Alliger, R., Cohen, G., & Yuh, W. T. (1993). Intelligence and brain structure in normal individuals. American Journal of Psychiatry, 150, 130–130.

    Article  CAS  PubMed  Google Scholar 

  • Bellinger, D. C., Watson, C. G., Rivkin, M. J., Robertson, R. L., Roberts, A. E., Stopp, C., & Wypij, D. (2015). Neuropsychological status and structural brain imaging in adolescents with single ventricle who underwent the Fontan procedure. Journal of the American Heart Association, 4(12), e002302.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bellinger, D. C., Wypij, D., Rivkin, M. J., DeMaso, D. R., Robertson, R. L., Jr., Dunbar-Masterson, C., & Newburger, J. W. (2011). Adolescents with d-transposition of the great arteries corrected with the arterial switch procedure: Neuropsychological assessment and structural brain imaging. Circulation, 124(12), 1361–1369.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bernier, P.-L., Stefanescu, A., Samoukovic, G., & Tchervenkov, C. I. (2010). The challenge of congenital heart disease worldwide: epidemiologic and demographic facts. Seminars in Thoracic and Cardiovascular Surgery: Pediatric Cardiac Surgery Annual.

  • Bolduc, M. E., Lambert, H., Ganeshamoorthy, S., & Brossard-Racine, M. (2018). Structural brain abnormalities in adolescents and young adults with congenital heart defect: A systematic review. Developmental Medicine & Child Neurology, 60(12), 1209–1224.

    Article  Google Scholar 

  • Brewster, R. C., King, T. Z., Burns, T. G., Drossner, D. M., & Mahle, W. T. (2015). White matter integrity dissociates verbal memory and auditory attention span in emerging adults with congenital heart disease. Journal of the International Neuropsychological Society, 21(1), 22–33.

    Article  PubMed  Google Scholar 

  • Bucholz, E. M., Sleeper, L. A., Goldberg, C. S., Pasquali, S. K., Anderson, B. R., Gaynor, J. W., & Newburger, J. W. (2020). Socioeconomic status and long-term outcomes in single ventricle heart disease. Pediatrics, 146(4).

  • Cabrera-Mino, C., Roy, B., Woo, M. A., Singh, S., Moye, S., Halnon, N. J., & Pike, N. A. (2020). Reduced brain mammillary body volumes and memory deficits in adolescents who have undergone the Fontan procedure. Pediatric Research, 87(1), 169–175.

    Article  PubMed  Google Scholar 

  • Clark, S. V., Semmel, E. S., Aleksonis, H. A., Steinberg, S. N., & King, T. Z. (2021). Cerebellar-Subcortical-Cortical Systems as Modulators of Cognitive Functions. Neuropsychology Review. https://doi.org/10.1007/s11065-020-09465-1

    Article  PubMed  PubMed Central  Google Scholar 

  • Cooper, J. M., Gadian, D. G., Jentschke, S., Goldman, A., Munoz, M., Pitts, G., & Deanfield, J. (2015). Neonatal hypoxia, hippocampal atrophy, and memory impairment: Evidence of a causal sequence. Cerebral Cortex, 25(6), 1469–1476.

    Article  PubMed  Google Scholar 

  • Ehrler, M., Latal, B., Kretschmar, O., von Rhein, M., & Tuura, R. O. G. (2020). Altered frontal white matter microstructure is associated with working memory impairments in adolescents with congenital heart disease: a diffusion tensor imaging study. NeuroImage: Clinical, 25, 102123.

  • Ehrler, M., Schlosser, L., Brugger, P., Greutmann, M., Oxenius, A., Kottke, R., & Latal, B. (2021). Altered white matter microstructure is related to cognition in adults with congenital heart disease. Brain Communications, 3(1), fcaa224.

  • Fontes, K., Rohlicek, C. V., Saint-Martin, C., Gilbert, G., Easson, K., Majnemer, A., & Brossard-Racine, M. (2019). Hippocampal alterations and functional correlates in adolescents and young adults with congenital heart disease. Human Brain Mapping, 40(12), 3548–3560.

    PubMed  PubMed Central  Google Scholar 

  • Hackman, D. A., & Farah, M. J. (2009). Socioeconomic status and the developing brain. Trends in Cognitive Sciences, 13(2), 65–73.

    Article  PubMed  PubMed Central  Google Scholar 

  • Heinrichs, A. K. M., Holschen, A., Krings, T., Messmer, B. J., Schnitker, R., Minkenberg, R., & Hövels-Gürich, H. H. (2014). Neurologic and psycho-intellectual outcome related to structural brain imaging in adolescents and young adults after neonatal arterial switch operation for transposition of the great arteries. The Journal of Thoracic and Cardiovascular Surgery, 148(5), 2190–2199.

    Article  PubMed  Google Scholar 

  • Hoffman, J. I., & Kaplan, S. (2002). The incidence of congenital heart disease. Journal of the American College of Cardiology, 39(12), 1890–1900.

    Article  PubMed  Google Scholar 

  • Huisenga, D., La Bastide-Van Gemert, S., Van Bergen, A., Sweeney, J., & Hadders-Algra, M. (2021). Developmental outcomes after early surgery for complex congenital heart disease: A systematic review and meta-analysis. Developmental Medicine & Child Neurology, 63(1), 29–46.

    Article  Google Scholar 

  • Ilardi, D., Ono, K. E., McCartney, R., Book, W., & Stringer, A. Y. (2017). Neurocognitive functioning in adults with congenital heart disease. Congenital Heart Disease, 12(2), 166–173.

    Article  PubMed  Google Scholar 

  • Jayakar, R., King, T. Z., Morris, R., & Na, S. (2015). Hippocampal volume and auditory attention on a verbal memory task with adult survivors of pediatric brain tumor. Neuropsychology, 29(2), 303.

    Article  PubMed  Google Scholar 

  • Kessler, N., Feldmann, M., Schlosser, L., Rometsch, S., Brugger, P., Kottke, R., & Latal, B. (2020). Structural brain abnormalities in adults with congenital heart disease: Prevalence and association with estimated intelligence quotient. International Journal of Cardiology, 306, 61–66.

    Article  PubMed  Google Scholar 

  • Khan, A., & Gurvitz, M. (2018). Epidemiology of ACHD: What has changed and what is changing? Progress in Cardiovascular Diseases, 61(3–4), 275–281.

    Article  PubMed  Google Scholar 

  • Kirby, R. S. (2017). The prevalence of selected major birth defects in the United States. Seminars in perinatology.

  • Klouda, L., Franklin, W. J., Saraf, A., Parekh, D. R., & Schwartz, D. D. (2017). Neurocognitive and executive functioning in adult survivors of congenital heart disease. Congenital Heart Disease, 12(1), 91–98.

    Article  PubMed  Google Scholar 

  • Kovacs, A. H., & Bellinger, D. C. (2021). Neurocognitive and psychosocial outcomes in adult congenital heart disease: A lifespan approach. Heart, 107(2), 159–167.

    Article  PubMed  Google Scholar 

  • Latal, B., Helfricht, S., Fischer, J. E., Bauersfeld, U., & Landolt, M. A. (2009). Psychological adjustment and quality of life in children and adolescents following open-heart surgery for congenital heart disease: A systematic review. BMC Pediatrics, 9(1), 1–10.

    Article  Google Scholar 

  • Latal, B., Patel, P., Liamlahi, R., Knirsch, W., Tuura, R. O. G., & von Rhein, M. (2016). Hippocampal volume reduction is associated with intellectual functions in adolescents with congenital heart disease. Pediatric Research, 80(4), 531–537.

    Article  PubMed  PubMed Central  Google Scholar 

  • Liamlahi, R., & Latal, B. (2019). Neurodevelopmental outcome of children with congenital heart disease. Handbook of Clinical Neurology, 162, 329–345.

    Article  PubMed  Google Scholar 

  • Marelli, A., Miller, S. P., Marino, B. S., Jefferson, A. L., & Newburger, J. W. (2016). Brain in congenital heart disease across the lifespan: The cumulative burden of injury. Circulation, 133(20), 1951–1962.

    Article  PubMed  PubMed Central  Google Scholar 

  • Marino, B. S., Lipkin, P. H., Newburger, J. W., Peacock, G., Gerdes, M., Gaynor, J. W., & Johnson, W. H., Jr. (2012). Neurodevelopmental outcomes in children with congenital heart disease: Evaluation and management: A scientific statement from the American Heart Association. Circulation, 126(9), 1143–1172.

    Article  PubMed  Google Scholar 

  • Mills, R., McCusker, C. G., Tennyson, C., & Hanna, D. (2018). Neuropsychological outcomes in CHD beyond childhood: A meta-analysis. Cardiology in the Young, 28(3), 421–431.

    Article  PubMed  Google Scholar 

  • Muñoz-López, M., Hoskote, A., Chadwick, M. J., Dzieciol, A. M., Gadian, D. G., Chong, K., & Mishkin, M. (2017). Hippocampal damage and memory impairment in congenital cyanotic heart disease. Hippocampus, 27(4), 417–424.

    Article  PubMed  PubMed Central  Google Scholar 

  • Naef, N., Schlosser, L., Brugger, P., Greutmann, M., Oxenius, A., Wehrle, F., & O’Gorman, R. T. (2021). Brain volumes in adults with congenital heart disease correlate with executive function abilities. Brain Imaging and Behavior, 1–9.

  • Noorani, S., Roy, B., Sahib, A. K., Cabrera-Mino, C., Halnon, N. J., Woo, M. A., & Kumar, R. (2020). Caudate nuclei volume alterations and cognition and mood dysfunctions in adolescents with single ventricle heart disease. Journal of Neuroscience Research, 98(10), 1877–1888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., & Brennan, S. E. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Bmj, 372.

  • Panigrahy, A., Schmithorst, V. J., Wisnowski, J. L., Watson, C. G., Bellinger, D. C., Newburger, J. W., & Rivkin, M. J. (2015). Relationship of white matter network topology and cognitive outcome in adolescents with d-transposition of the great arteries. NeuroImage: Clinical, 7, 438–448.

  • Penke, L., Maniega, S. M., Bastin, M. E., Hernandez, V., Murray, C., Royle, N. A., & Deary, I. J. (2012). Brain white matter tract integrity as a neural foundation for general intelligence. Molecular Psychiatry, 17(10), 1026–1030.

    Article  CAS  PubMed  Google Scholar 

  • Peyvandi, S., Latal, B., Miller, S. P., & McQuillen, P. S. (2019). The neonatal brain in critical congenital heart disease: Insights and future directions. NeuroImage, 185, 776–782.

    Article  PubMed  Google Scholar 

  • Pike, N. A., Poulsen, M. K., & Woo, M. A. (2017). Validity of the Montreal cognitive assessment screener in adolescents and young adults with and without congenital heart disease. Nursing Research, 66(3), 222.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pike, N. A., Roy, B., Moye, S., Cabrera-Mino, C., Woo, M. A., Halnon, N. J., & Kumar, R. (2021). Reduced hippocampal volumes and memory deficits in adolescents with single ventricle heart disease. Brain and Behavior, 11(2), e01977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ris, M. D., & Noll, R. B. (1994). Long-term neurobehavioral outcome in pediatric brain-tumor patients: Review and methodological critique. Journal of Clinical and Experimental Neuropsychology, 16(1), 21–42.

    Article  CAS  PubMed  Google Scholar 

  • Rollins, C. K., Watson, C. G., Asaro, L. A., Wypij, D., Vajapeyam, S., Bellinger, D. C., & Rivkin, M. J. (2014). White matter microstructure and cognition in adolescents with congenital heart disease. The Journal of Pediatrics, 165(5), 936–944. e932.

  • Rolls, E. T. (2000). Memory systems in the brain. Annual Review of Psychology, 51(1), 599–630.

    Article  CAS  PubMed  Google Scholar 

  • Schmithorst, V. J., Panigrahy, A., Gaynor, J. W., Watson, C. G., Lee, V., Bellinger, D. C., & Newburger, J. W. (2016). Organizational topology of brain and its relationship to ADHD in adolescents with d-transposition of the great arteries. Brain and Behavior, 6(8), e00504.

    Article  PubMed  PubMed Central  Google Scholar 

  • Semmel, E. S., Dotson, V. M., Burns, T. G., Mahle, W. T., & King, T. Z. (2018). Posterior cerebellar volume and executive function in young adults with congenital heart disease. Journal of the International Neuropsychological Society, 24(9), 939–948.

    Article  PubMed  Google Scholar 

  • Singh, S., Kumar, R., Roy, B., Woo, M. A., Lewis, A., Halnon, N., & Pike, N. (2018). Regional brain gray matter changes in adolescents with single ventricle heart disease. Neuroscience Letters, 665, 156–162.

    Article  CAS  PubMed  Google Scholar 

  • Van Der Linde, D., Konings, E. E., Slager, M. A., Witsenburg, M., Helbing, W. A., Takkenberg, J. J., & Roos-Hesselink, J. W. (2011). Birth prevalence of congenital heart disease worldwide: A systematic review and meta-analysis. Journal of the American College of Cardiology, 58(21), 2241–2247.

    Article  PubMed  Google Scholar 

  • Van Petten, C., Plante, E., Davidson, P. S., Kuo, T. Y., Bajuscak, L., & Glisky, E. L. (2004). Memory and executive function in older adults: Relationships with temporal and prefrontal gray matter volumes and white matter hyperintensities. Neuropsychologia, 42(10), 1313–1335.

    Article  PubMed  Google Scholar 

  • von Rhein, M., Buchmann, A., Hagmann, C., Huber, R., Klaver, P., Knirsch, W., & Latal, B. (2014). Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease. Brain, 137(1), 268–276.

    Article  Google Scholar 

  • von Rhein, M., Scheer, I., Loenneker, T., Huber, R., Knirsch, W., & Latal, B. (2011). Structural brain lesions in adolescents with congenital heart disease. The Journal of Pediatrics, 158(6), 984–989.

    Article  Google Scholar 

  • Watson, C. G., Stopp, C., Wypij, D., Bellinger, D. C., Newburger, J. W., & Rivkin, M. J. (2018). Altered white matter microstructure correlates with IQ and processing speed in children and adolescents post-fontan. The Journal of Pediatrics, 200(140–149), e144.

    Google Scholar 

Download references

Funding

The first author (HA) was funded by the Georgia State University’s Brains and Behavior Fellowship. No other funds, grants, or other support was received.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tricia Z. King.

Ethics declarations

Conflict of Interest

The authors have no conflicts of interest to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aleksonis, H.A., King, T.Z. Relationships Among Structural Neuroimaging and Neurocognitive Outcomes in Adolescents and Young Adults with Congenital Heart Disease: A Systematic Review. Neuropsychol Rev 33, 432–458 (2023). https://doi.org/10.1007/s11065-022-09547-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11065-022-09547-2

Keywords

Navigation