Dementia risk after transient ischaemic attack and stroke
Authors: Martin Dichgans
Journal: The Lancet Neurology (2019)

About 20% of patients who are admitted to hospital for stroke develop dementia within the first year after the event; incidence is higher in those with recurrent stroke and lower in those with first-ever stroke.1Pendlebury ST Rothwell PM Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis.Lancet Neurol. 2009; 8: 1006-1018Summary Full Text Full Text PDF PubMed Scopus (1127) Google Scholar Furthermore, roughly one in ten patients with first-ever stroke already has dementia at event onset.1Pendlebury ST Rothwell PM Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis.Lancet Neurol. 2009; 8: 1006-1018Summary Full Text Full Text PDF PubMed Scopus (1127) Google Scholar As survival rates after stroke increase, dementia has become a growing concern for patients, families, and health-care providers. Previous studies have identified predictors of post-stroke dementia, including age, low educational attainment, previous stroke, stroke severity, dysphasia, diabetes, atrial fibrillation, and leucoaraiosis on brain imaging.1Pendlebury ST Rothwell PM Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis.Lancet Neurol. 2009; 8: 1006-1018Summary Full Text Full Text PDF PubMed Scopus (1127) Google Scholar, 2Mok VCT Lam BYK Wang Z et al.Delayed-onset dementia after stroke or transient ischemic attack.Alzheimers Dement. 2016; 12: 1167-1176Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 3Georgakis M, Duering M, Wardlaw J, Dichgans M. WMH and long-term outcomes in ischemic stroke: a systematic review and meta-analysis. Neurology (in press).Google Scholar However, this information mostly originates from hospital-based studies, which are prone to selection bias and other biases, including attrition. There are few data for dementia risk after transient ischemic attack or minor stroke, which together account for about 70% of cerebrovascular events. Also, information is scarce about the extent to which the incidence of dementia after transient ischaemic attack or stroke is higher than age-specific dementia incidence in the general population. In The Lancet Neurology, Sarah T Pendlebury and Peter M Rothwell report the incidence of and risk factors for dementia before and after transient ischaemic attack and stroke, in a population-based study of 92 728 people from Oxfordshire, UK.4Pendlebury ST Rothwell PM Incidence and prevalence of dementia associated with transient ischaemic attack and stroke: analysis of the population-based Oxford Vascular Study.Lancet Neurol. 2019; 18: 248-258Summary Full Text Full Text PDF PubMed Scopus (193) Google Scholar They prospectively recruited 2305 patients with acute cerebrovascular events that occurred between 2002 and 2012, and followed up these patients for 5 years with regular interviews. The authors used several methods of case ascertainment and comprehensive measures to minimise attrition, and found a stepwise association between severity of the index event and both pre-event and post-event dementia, irrespective of age. The prevalence of pre-event dementia ranged from 4·9% (95% CI 3·4–6·9) in patients with a transient ischaemic attack to 20·6% (15·8–26·5) in those with severe stroke (ie, a score >10 on the US National Institutes of Health Stroke Scale [NIHSS]). The incidence of post-event dementia at one year was 5·2% (95% CI 3·4–7·0) after transient ischaemic attack and 34·4% (29·7–41·5) after severe stroke. These estimates should be kept in mind when counselling patients and families, organising care, planning trials, and interpreting trial findings. However, the results must also be viewed in the context of largely variable mortality rates in this study. In patients who did not have pre-event dementia, 176 (75%) of 235 with severe stroke died before the 5-year follow-up, compared with 141 (22%) of 655 with transient ischaemic attack. Indeed, competing-risk results suggest that the long-term risk of dementia might be greatest in patients with NIHSS scores of 3–10. Compared with published UK population estimates of dementia, in Pendlebury and Rothwell's study the risk of dementia 1–5 years after severe stroke was 6·5 times higher, and after transient ischaemic attack was 1·5 times higher. These figures are important for counselling and long-term follow-up of patients. As expected, a substantial proportion of post-event dementia was diagnosed in the first year after the event, particularly in patients with severe stroke. This finding reflects the immediate effects of the index lesion on brain function, but could also relate to variations in stroke recurrence or secondary processes within the brain (eg, inflammation or secondary neurodegeneration). Detailed neuroimaging studies should help to disentangle these factors. The baseline predictors of post-event dementia identified by Pendlebury and Rothwell were mostly in line with those reported previously for post-stroke dementia,1Pendlebury ST Rothwell PM Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis.Lancet Neurol. 2009; 8: 1006-1018Summary Full Text Full Text PDF PubMed Scopus (1127) Google Scholar, 2Mok VCT Lam BYK Wang Z et al.Delayed-onset dementia after stroke or transient ischemic attack.Alzheimers Dement. 2016; 12: 1167-1176Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 3Georgakis M, Duering M, Wardlaw J, Dichgans M. WMH and long-term outcomes in ischemic stroke: a systematic review and meta-analysis. Neurology (in press).Google Scholar except that atrial fibrillation was not associated with dementia risk, which is somewhat surprising in view of previous results.1Pendlebury ST Rothwell PM Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis.Lancet Neurol. 2009; 8: 1006-1018Summary Full Text Full Text PDF PubMed Scopus (1127) Google Scholar, 5de Bruijn RF Heeringa J Wolters FJ et al.Association between atrial fibrillation and dementia in the general population.JAMA Neurol. 2015; 72: 1288-1294Crossref PubMed Scopus (164) Google Scholar As a notable finding, a score of less than 24 on the mini-mental state examination at baseline was among the strongest predictors of dementia risk, a finding that further emphasises the prognostic usefulness of early cognitive testing after cerebrovascular events.6Zietemann V Georgakis MK Dondaine T et al.Early MoCA predicts long-term cognitive and functional outcome and mortality after stroke.Neurology. 2018; 91: e1838-e1850Crossref PubMed Scopus (66) Google Scholar Pendlebury and Rothwell's findings provide an important reference for physicians, policy makers, and researchers. Yet several questions remain, including the potential utility of a simple risk score for post-event dementia; the rates and characteristics of, and predictors for, cognitive impairment not meeting the criteria for dementia; and the effect of mild cognitive impairment on quality of life after stroke. Clarification of the extent to which characteristics of the index lesion (eg, volume, number, location) and markers of pre-existing brain injury (eg, leucoaraiosis, brain atrophy) add to the prediction of cognitive decline beyond factors accessible by clinical examination is important. The generalisability of Pendlebury and Rothwell's findings to other ethnicities and health-care systems is also unclear. In the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort,7Levine DA Wadley VG Langa KM et al.Risk factors for poststroke cognitive decline: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke).Stroke. 2018; 49: 987-994Crossref PubMed Scopus (53) Google Scholar acute declines in cognitive function after stroke were greater in survivors who were black and had cardioembolic or large artery stroke. Declines in global cognitive function during the years after stroke were greater in survivors residing outside the Stroke Belt (a region in southeastern USA which has been recognised to have an unusually high incidence of stroke).7Levine DA Wadley VG Langa KM et al.Risk factors for poststroke cognitive decline: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke).Stroke. 2018; 49: 987-994Crossref PubMed Scopus (53) Google Scholar How the prevalence of and risk factors for dementia in patients with primary intracerebral haemorrhage compare with those in patients with ischaemic events needs further investigation. In Pendlebury and Rothwell's study, there was some indication of a higher risk of post-event dementia after intracerebral haemorrhage compared with ischaemic stroke (although this difference was not significant).4Pendlebury ST Rothwell PM Incidence and prevalence of dementia associated with transient ischaemic attack and stroke: analysis of the population-based Oxford Vascular Study.Lancet Neurol. 2019; 18: 248-258Summary Full Text Full Text PDF PubMed Scopus (193) Google Scholar The Prognosis of Intracerebral Haemorrhage (PITCH) study8Moulin S Labreuche J Bombois S et al.Dementia risk after spontaneous intracerebral haemorrhage: a prospective cohort study.Lancet Neurol. 2016; 15: 820-829Summary Full Text Full Text PDF PubMed Scopus (139) Google Scholar identified various imaging features that predict risk of dementia, underscoring the value of integration of neuroimaging findings into risk-prediction models. Additional work is needed to better understand the trajectories of cognitive function after transient ischaemic attack and stroke, including how the determinants of delayed-onset dementia (ie, dementia that manifests months or years from stroke) differ from those of immediate-onset dementia;2Mok VCT Lam BYK Wang Z et al.Delayed-onset dementia after stroke or transient ischemic attack.Alzheimers Dement. 2016; 12: 1167-1176Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar the mechanisms underlying the association between diabetes and dementia risk, and whether this risk can be modified by more intensive glycaemic control;9Biessels GJ Despa F Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications.Nat Rev Endocrinol. 2018; 14: 591-604Crossref PubMed Scopus (466) Google Scholar and whether the risk of dementia in patients with atrial fibrillation can be lowered by oral anticoagulation (which would be expected as a result of the effects on stroke prevention). Finally, whether the risk of post-event dementia can be reduced by acute stroke therapy needs to be investigated. Secondary analyses from the REVASCAT trial suggest that endovascular treatment in patients with anterior circulation proximal arterial occlusion improves cognitive outcomes, particularly in patients with good functional outcomes.10Lopez-Cancio E Jovin TG Cobo E et al.Endovascular treatment improves cognition after stroke: a secondary analysis of REVASCAT trial.Neurology. 2017; 88: 245-251Crossref PubMed Scopus (20) Google Scholar I have received grants from the EU's Horizon 2020 research and innovation programme ([email protected]; grant no 666881), the Fondation Leducq (Transatlantic Networks of Excellence on the Pathogenesis of Small Vessel Disease of the Brain), the German Research Foundation (DI 722/13-1), and the Vascular Dementia Research Foundation, and speaker's honoraria from Boehringer Ingelheim, Bayer Vital, and Pfizer. Incidence and prevalence of dementia associated with transient ischaemic attack and stroke: analysis of the population-based Oxford Vascular StudyThe incidence of dementia in patients who have had a transient ischaemic attack or stroke varies substantially depending on clinical characteristics including lesion burden and susceptibility factors. Incidence of dementia is nearly 50 times higher in the year after a major stroke compared with that in the general population, but excess risk is substantially lower after transient ischaemic attack and minor stroke. Full-Text PDF Open Access