EDITORIAL
rtPA in acute stroke patients with history of cognitive impairment Do not hesitate to treat
Gustavo C. Román, MD, FAAN, FANA Antoine M. Hakim, MD, PhD, FAAN
Correspondence to Dr. Hakim: [email protected] Neurology® 2014;82:2044–2045
A solid body of evidence has accumulated over the past 20 years confirming the critical role of cerebrovascular disease in Alzheimer disease (AD) and other dementias of the aged.1–6 Most recently, data from the National Alzheimer’s Coordinating Center7 demonstrated the presence of vascular pathology in 79.9% of 4,629 brains from patients with neuropathologically confirmed AD. Lesions included atherosclerosis in the circle of Willis, arteriosclerotic leukoencephalopathy, arteriolosclerosis, large infarcts, lacunes, multiple microinfarcts, and hemorrhages. Notably, cerebral amyloid angiopathy was present in less than half of the brains (40.8%). Given the absence of an effective treatment to halt the progression of AD, the current emphasis is on dementia prevention by appropriate treatment of vascular risk factors for stroke.8,9 Once stroke occurs, optimal treatment of the acute ictus with prompt restoration of flow in the occluded vessels improves the cognitive outcome. In contrast, stroke complications such as aspiration pneumonia, hypoxemia, seizures, hypotension, or cardiac arrhythmias increase the risk of poststroke cognitive impairment 4-fold.10 However, clinicians may consider it futile to use IV recombinant tissue plasminogen activator (rtPA) treatment in acute stroke in patients with prestroke cognitive impairment. In this issue of Neurology®, an international team directed by Didier Leys and Kei Murao, from Lille, France, and Fukuoka, Japan, respectively, presents the results of the OPHELIECOG study, which aimed to evaluate the influence of prestroke cognitive impairment on the clinical outcome of acute ischemic stroke patients with cognitive impairment treated with rtPA in France and Japan.11 Although this was not a placebo-controlled trial, as it would be unethical to withhold rtPA from stroke patients, the trial nonetheless provides valuable information: no previous studies have prospectively and systematically evaluated the safety of IV rtPA in this multiethnic patient population. The combined French and Japanese multicenter trial recruited 205 consecutive patients (51.7% men, median age 70 years, median NIH Stroke Scale (NIHSS) score 8, 17.6% Japanese). About one-third of the participants (n 5 62, 30.2%) met criteria for
prestroke cognitive impairment using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). The Lille group has extensive experience with the use of the IQCODE, an instrument that provides accurate determination of functional capacity and cognitive function in the absence of more traditional neuropsychological evaluations.12 As expected, cognitively impaired patients were 11 years older (p , 0.001) than patients without cognitive impairment. None of the trial’s 4 endpoints differed in this group after adjusting for age, baseline NIHSS score, or onset to needle time, but they had more hemorrhagic complications and were less independent after 3 months. The authors concluded that ischemic stroke patients with mild cognitive impairment should receive rtPA, if eligible. Since severe cases were excluded from the study, this conclusion cannot be extended to patients with severe cognitive impairment or to patients with severe strokes defined by a prestroke modified Rankin Scale score of 2 or more. These data suggest that a history of preexisting mild cognitive impairment should not deter neurologists from using IV rtPA in otherwise eligible patients with acute stroke. STUDY FUNDING No targeted funding reported.
DISCLOSURE The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
REFERENCES 1. Chui HC, Zarow C, Mack WJ, et al. Cognitive impact of subcortical vascular and Alzheimer’s disease pathology. Ann Neurol 2006;60:677–687. 2. Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:2672–2713. 3. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011;12:723–738. 4. Yarchoan M, Xie SX, Kling MA, et al. Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias. Brain 2012;135:3749–3756.
See page 2048 From the Department of Neurology (G.C.R.), Methodist Neurological Institute, Houston Methodist Hospital, TX; and The Brain and Mind Institute (A.M.H), University of Ottawa, Canada. 2044
© 2014 American Academy of Neurology
5.
6.
7.
8.
Toledo JB, Toledo E, Weiner MW, et al. Cardiovascular risk factors, cortisol, and amyloid-beta deposition in the Alzheimer’s Disease Neuroimaging Initiative. Alzheimer Dement 2012;8: 483–489. Bennett DA, Wilson RS, Arvanitakis Z, Boyle PA, de Toledo-Morrell L, Schneider JA. Selected findings from the religious orders study and Rush memory and aging project. J Alzheimer Dis 2013;33:S397–S403. Toledo JB, Arnold SE, Raible K, et al. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 2013;136:2697–2706. Román GC, Nash DT, Fillit H. Translating current knowledge into dementia prevention. Alzheimer Dis Assoc Disord 2012;26:295–299.
9.
10.
11.
12.
Willis KJ, Hakim AM. Stroke prevention and cognitive reserve: emerging approaches to modifying risk and delaying onset of dementia. Front Neurol 2013;4:13. Desmond DW, Moroney JT, Paik MC, et al. Frequency and clinical determinants of dementia after stroke. Neurology 2000;54:1124–1131. Murao K, Leys D, Jacquin A, et al; on behalf of the OPHELIE-COG investigators. Thrombolytic therapy for stroke in patients with preexisting cognitive impairment. Neurology 2014;82:2048–2054. Sikkes SA, van den Berg MT, Knol DL, et al. How useful is the IQCODE for discriminating between Alzheimer’s disease, mild cognitive impairment and subjective memory complaints? Dement Geriatr Cogn Disord 2010;30: 411–416.
Neurology 82
June 10, 2014
2045
rtPA in acute stroke patients with history of cognitive impairment: Do not hesitate to treat Gustavo C. Román and Antoine M. Hakim Neurology 2014;82;2044-2045 Published Online before print May 14, 2014 DOI 10.1212/WNL.0000000000000502 This information is current as of May 14, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/82/23/2044.full.html
References
This article cites 12 articles, 5 of which you can access for free at: http://www.neurology.org/content/82/23/2044.full.html##ref-list-1
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
rtPA in acute stroke patients with history of cognitive impairment Do not hesitate to treat
Gustavo C. Román, MD, FAAN, FANA Antoine M. Hakim, MD, PhD, FAAN
Correspondence to Dr. Hakim: [email protected] Neurology® 2014;82:2044–2045
A solid body of evidence has accumulated over the past 20 years confirming the critical role of cerebrovascular disease in Alzheimer disease (AD) and other dementias of the aged.1–6 Most recently, data from the National Alzheimer’s Coordinating Center7 demonstrated the presence of vascular pathology in 79.9% of 4,629 brains from patients with neuropathologically confirmed AD. Lesions included atherosclerosis in the circle of Willis, arteriosclerotic leukoencephalopathy, arteriolosclerosis, large infarcts, lacunes, multiple microinfarcts, and hemorrhages. Notably, cerebral amyloid angiopathy was present in less than half of the brains (40.8%). Given the absence of an effective treatment to halt the progression of AD, the current emphasis is on dementia prevention by appropriate treatment of vascular risk factors for stroke.8,9 Once stroke occurs, optimal treatment of the acute ictus with prompt restoration of flow in the occluded vessels improves the cognitive outcome. In contrast, stroke complications such as aspiration pneumonia, hypoxemia, seizures, hypotension, or cardiac arrhythmias increase the risk of poststroke cognitive impairment 4-fold.10 However, clinicians may consider it futile to use IV recombinant tissue plasminogen activator (rtPA) treatment in acute stroke in patients with prestroke cognitive impairment. In this issue of Neurology®, an international team directed by Didier Leys and Kei Murao, from Lille, France, and Fukuoka, Japan, respectively, presents the results of the OPHELIECOG study, which aimed to evaluate the influence of prestroke cognitive impairment on the clinical outcome of acute ischemic stroke patients with cognitive impairment treated with rtPA in France and Japan.11 Although this was not a placebo-controlled trial, as it would be unethical to withhold rtPA from stroke patients, the trial nonetheless provides valuable information: no previous studies have prospectively and systematically evaluated the safety of IV rtPA in this multiethnic patient population. The combined French and Japanese multicenter trial recruited 205 consecutive patients (51.7% men, median age 70 years, median NIH Stroke Scale (NIHSS) score 8, 17.6% Japanese). About one-third of the participants (n 5 62, 30.2%) met criteria for
prestroke cognitive impairment using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). The Lille group has extensive experience with the use of the IQCODE, an instrument that provides accurate determination of functional capacity and cognitive function in the absence of more traditional neuropsychological evaluations.12 As expected, cognitively impaired patients were 11 years older (p , 0.001) than patients without cognitive impairment. None of the trial’s 4 endpoints differed in this group after adjusting for age, baseline NIHSS score, or onset to needle time, but they had more hemorrhagic complications and were less independent after 3 months. The authors concluded that ischemic stroke patients with mild cognitive impairment should receive rtPA, if eligible. Since severe cases were excluded from the study, this conclusion cannot be extended to patients with severe cognitive impairment or to patients with severe strokes defined by a prestroke modified Rankin Scale score of 2 or more. These data suggest that a history of preexisting mild cognitive impairment should not deter neurologists from using IV rtPA in otherwise eligible patients with acute stroke. STUDY FUNDING No targeted funding reported.
DISCLOSURE The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
REFERENCES 1. Chui HC, Zarow C, Mack WJ, et al. Cognitive impact of subcortical vascular and Alzheimer’s disease pathology. Ann Neurol 2006;60:677–687. 2. Gorelick PB, Scuteri A, Black SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:2672–2713. 3. Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 2011;12:723–738. 4. Yarchoan M, Xie SX, Kling MA, et al. Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias. Brain 2012;135:3749–3756.
See page 2048 From the Department of Neurology (G.C.R.), Methodist Neurological Institute, Houston Methodist Hospital, TX; and The Brain and Mind Institute (A.M.H), University of Ottawa, Canada. 2044
© 2014 American Academy of Neurology
5.
6.
7.
8.
Toledo JB, Toledo E, Weiner MW, et al. Cardiovascular risk factors, cortisol, and amyloid-beta deposition in the Alzheimer’s Disease Neuroimaging Initiative. Alzheimer Dement 2012;8: 483–489. Bennett DA, Wilson RS, Arvanitakis Z, Boyle PA, de Toledo-Morrell L, Schneider JA. Selected findings from the religious orders study and Rush memory and aging project. J Alzheimer Dis 2013;33:S397–S403. Toledo JB, Arnold SE, Raible K, et al. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 2013;136:2697–2706. Román GC, Nash DT, Fillit H. Translating current knowledge into dementia prevention. Alzheimer Dis Assoc Disord 2012;26:295–299.
9.
10.
11.
12.
Willis KJ, Hakim AM. Stroke prevention and cognitive reserve: emerging approaches to modifying risk and delaying onset of dementia. Front Neurol 2013;4:13. Desmond DW, Moroney JT, Paik MC, et al. Frequency and clinical determinants of dementia after stroke. Neurology 2000;54:1124–1131. Murao K, Leys D, Jacquin A, et al; on behalf of the OPHELIE-COG investigators. Thrombolytic therapy for stroke in patients with preexisting cognitive impairment. Neurology 2014;82:2048–2054. Sikkes SA, van den Berg MT, Knol DL, et al. How useful is the IQCODE for discriminating between Alzheimer’s disease, mild cognitive impairment and subjective memory complaints? Dement Geriatr Cogn Disord 2010;30: 411–416.
Neurology 82
June 10, 2014
2045
rtPA in acute stroke patients with history of cognitive impairment: Do not hesitate to treat Gustavo C. Román and Antoine M. Hakim Neurology 2014;82;2044-2045 Published Online before print May 14, 2014 DOI 10.1212/WNL.0000000000000502 This information is current as of May 14, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/82/23/2044.full.html
References
This article cites 12 articles, 5 of which you can access for free at: http://www.neurology.org/content/82/23/2044.full.html##ref-list-1
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
