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  • Review Article
  • Published:

Early-onset and delayed-onset poststroke dementia — revisiting the mechanisms

Key Points

  • Early-onset poststroke dementia (PSD) depends on a complex interplay between features of the stroke lesion, such as large size or strategic site, and brain resilience, such as cognitive reserve and brain reserve

  • Delayed-onset PSD is driven mostly by severe small vessel disease (SVD), rather than by recurrent stroke or concurrent Alzheimer disease pathology

  • Measures to control cardiovascular risk factors and enhance brain resilience can probably reduce the risk of developing PSD

  • Future clinical trials should target severe SVD and explore strategies to prevent delayed-onset PSD, to be used in addition to conventional secondary stroke preventive treatments

Abstract

Incident stroke has long been recognized to cause dementia shortly after the event. Patients who survive stroke without early-onset poststroke dementia (PSD) are at a high risk of developing dementia months to years after the initial stroke incident, which has generated enthusiasm for exploring treatments to prevent delayed-onset PSD in survivors of stroke. However, results from clinical trials completed in the past 10–15 years have been disappointing. In light of these results, the present Review revisits the mechanisms of both early-onset and delayed-onset PSD and proposes preventive strategies and directions for future clinical trials. Early-onset PSD results from a complex interplay between stroke lesion features and brain resilience, whereas delayed-onset PSD is associated mainly with the presence of severe sporadic small vessel disease (SVD), and to a lesser extent with Alzheimer disease pathology or recurrent stroke. As well as preventing stroke and delivering acute stroke treatments to reduce initial brain damage, measures to increase brain resilience could also reduce the risk of developing dementia if an incident stroke occurs. Future efforts to prevent delayed-onset PSD should focus on the study of sporadic SVD and on evaluating whether other strategies, in addition to conventional secondary stroke prevention, are effective in dementia prevention in this high-risk group.

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Figure 1: Model of mechanisms in early-onset PSD.
Figure 2: A case of early-onset PSD.

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Acknowledgements

V.C.T.M. is supported by the Therese Pei Fong Chow Research Centre for Prevention of Dementia (in memory of Donald H. K. Chow), the Lui Che Woo Institute of Innovative Medicine and the Brain and Mind Institute of the Chinese University of Hong Kong. B.Y.K.L. is supported by the Therese Pei Fong Chow Research Centre for Prevention of Dementia (in memory of Donald H. K. Chow). A.W. is supported by the Health and Health Services Research Fund (03140936) of the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, the Chinese University Direct Grant for Research (2014.2.020) and the Therese Pei Fong Chow Research Centre for Prevention of Dementia (in memory of Donald H. K. Chow). H.K. is supported by the Gerald Choa Neuroscience Centre, Faculty of Medicine and the Chinese University of Hong Kong. H.S.M. is supported by a National Institute for Health Research (NIHR) Senior Investigator award and by the NIHR Cambridge Biomedical Research Centre. L.K.S.W. is supported by the Lui Che Woo Institute of Innovative Medicine.

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All authors contributed to discussion of content and the review and/or editing of the manuscript before submission. V.C.T.M., B.Y.K.L., A.W. and H.S.M. wrote the article, and V.C.T.M. and B.Y.K.L. researched data for the article.

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Correspondence to Lawrence K. S. Wong.

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Mok, V., Lam, B., Wong, A. et al. Early-onset and delayed-onset poststroke dementia — revisiting the mechanisms. Nat Rev Neurol 13, 148–159 (2017). https://doi.org/10.1038/nrneurol.2017.16

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