Epidemiology of Cognitive impairment after stroke- natural history, risk factors, outcomes, treatments and interaction with depression

Abstract

Background Recovery from stroke poses physical and psychological challenges with significant consequences, not only on patients, but also on families, informal caregivers and stroke services. Early risk profiling, patient needs identification, and intervention of cognitive disorders could potentially offer increased psychological follow-up and support to those at risk. Aims This PhD project aims to investigate the long-term natural history of post-stroke cognitive impairment, identify risk factors, treatments, outcomes, and interaction with depression. Methods Study (i) is a systematic review of systematic reviews (umbrella review) of the risk factors and interventions to prevent cognitive decline in stroke patients. Studies (ii, iii and iv) analyse data from the South London Stroke Register, examining the natural history of post-stroke cognitive impairment, the association of primary and secondary preventive treatments as well as stroke management strategies on the risk of post-stroke cognitive impairment, and long-term outcomes in stroke patients with cognitive impairment, respectively. Study (v) uses stroke and cognition data (STROKOG), to generalise results of the fourth study on data from an international consortium. Study (vi) examine the interactions between post-stroke cognitive impairment and depression using stroke register. Results: Study (i), an umbrella review, included 22 systematic reviews. The major risk factorts of cognitive impairment included atrial fibrillation, leukoaraiosis, and multiple and recurrent strokes. The main interventions that could improve cognitive function were physical activity or cognitive rehabilitation. Study (ii) found that the prevalence of cognitive impairment was around one-third and remained stable at this level within 15 years of follow up, with incidence ranging from 6% to 20%; almost two-thirds of the patients with cognitive impairment at stroke onset had recovered within the first year after stroke. Study (iii) found that admission to acute stroke unit and preventive treatment strategies especially with combined treatments of antihypertensive, lipid lowering and anti-thrombotic, were associated with significant risk reduction of cognitive impairment. Study (iv) observed that during the first three-months post-stoke, approximately one-third of these stroke survivors with cognitive impairment either cognitively improved (37%), deteriorated (30%), or remained unchanged (33%). Early presentation of cognitive impairment, and further deterioration in cognitive function within the first three months after stroke were associated significantly with negative health outcomes, including mortality, depression, physical dependency, being institutionalised and further cognitive decline. Study (v) generalise results of the study (iv) on international data from seven different countries. The pooled prevalence across international data was 28% (95% confidence interval=19%-37%). Compared to patients with normal cognitive function measured by MMSE or AMT at three months, there was a 47% increased risk of depression in patients with cognitive impairment (risk ratio (RR)=1.47, 95% CI=0.96-2.24), a 69% increased risk of further cognitive decline (RR=1.69, CI=1.56-1.83), a two-fold increased risk of physical dependence (RR=2.14, CI=1.20-3.81) and a close to three-fold increased risk of mortality (RR=2.71, CI=2.00-3.66) at one year. Study (vi) found that cognitive impairment interacts significantly with depression symptoms where the co-existence of both conditions was associated with a potential increased risk of negative outcomes. Conclusion: This thesis provides an insight into the burden of post-stroke cognitive impairment, its risk factors, and the current state of evidence around prevention. Cognitive impairment after stroke is common and fluctuating, and is strongly associated with po