Long-Term Effects of Secondary Prevention on Cognitive Function in Stroke Patients

Douiri A, McKevitt C, Emmett ES, et al.
Circulation August 9, 2013, doi: 10.1161/​CIRCULATIONAHA.113.002236

Background

Cognitive impairment is a common long-term effect of stroke [1-5]. Control of vascular risk factors for stroke is important in secondary prevention initiatives, not only to reduce the risk of recurrent stroke, but possibly also to reduce the risk of other vascular consequences such as cognitive impairment. Recommended pharmacotherapy for secondary stroke prevention includes antithrombotic treatment and control of blood pressure and lipid levels.
One multicenter randomised clinical trial showed that patients who recently had a stroke or TIA and were given combined antihypertensive treatments of ACE-inhibitors and diuretics to control blood pressure, had a 19% reduced risk of cognitive decline (>3 points decline on MMSE score) [6]. Preliminary data of another large study could not replicate these findings with an angiotensin receptor blocker, nor with antiplatelet regimens, extended-release dipyridamole plus aspirin or clopidogrel monotherapy [7].
Thus, the effect of secondary prevention of vascular risk on long-term cognitive impairment remain unknown. This study investigated the relationship between use of secondary prevention drug therapies to control vascular risk in stroke patients and long-term cognitive impairment in patients after first ever stroke and up to 10 years follow-up, in the community-based, prospective South London Stroke Register (SLSR)[8].

Main results

• 1682 stroke survivors were able to undergo a cognitive assessment at 3 months after stroke. Crude prevalence of cognitive impairment at this time point was 31% (95%CI: 29.2-33.7).
• A multivariate analysis controlling for socio-demographic factors, pre-stroke vascular risk factors, case-mix, stroke recurrence and stroke subtypes, revealed that stroke survivors had a 55% higher risk (95%CI: 1.32-1.83) of cognitive impairment at 3 months post-stroke if they had diabetes, and a 30% (95%CI: 1.09-1.54) higher risk if they had atrium fibrillation. Patients with a history of hypercholesterolemia had a lower risk of cognitive impairment (RR: 0.76, 95%CI: 0.64-0.90).
• In a longitudinal analysis adjusting for 3 month cognitive status and the other confounding factors, lipid-lowering medication was associated with a decreased risk of cognitive impairment at any time after stroke (up to ten years). Optimal therapy that included anticoagulant, antiplatelet and antihypertensive drugs was associated with reduced cognitive impairment after 2, 3,5 and 7 years of treatment after stroke.
• Hypertension increased the risk of long-term cognitive impairment in stroke survivors up to 10 years after stroke (RR: 1.2, 95%CI: 1.06-1.35).
• Interaction-terms analyses of vascular risk factors and specific treatment regimens showed differential risk or protective effects for certain conditions.

Conclusion

This population-based study shows that appropriate management of vascular risk factors is associated with improved long-term cognitive outcome after stroke. Lipid-lowering was associated with a lower risk of cognitive impairment, already at 3 months post-stroke, indicating that lipid control may have prevented the incidence of cognitive impairment, rather than reduced its progression. Different therapeutic strategies had different effects, suggesting that an optimal, personalised combination of antithrombotic, antihypertensive and lipid-lowering agents may protect patients from cognitive impairment after ischemic stroke.

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