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Do statins delay onset or slow progression of Alzheimer’s dementia?
Statins (coenzyme-A reductase inhibitors) should not be used with the single intent to delay the onset or slow the progression of dementia. Large randomized control trials (RCTs) found that the administration of a statin had no significant effect on preventing or slowing all-cause cognitive decline (strength of recommendation [SOR]: A, based on large RCTs with narrow confidence interval).1,2 Specifically, there is insufficient evidence that statins delay the onset or slow the progression of Alzheimer’s dementia (SOR: B, based on systematic review with heterogeneity).3
While 3 epidemiologic studies4-6 have found a decreased incidence of dementia among those taking statins, these studies have significant methodological shortcomings and do not show a causal relationship (SOR: C, based on poor-quality studies).
Evidence summary
Approximately 4 million people in the United States suffer with Alzheimer’s disease. The prevalence rises with age and is approximately 47% among those aged 85 years and older.7
Amyloid plaques are thought to be responsible for clinical changes associated with Alzheimer’s dementia. Research has indicated that amyloid precursors may be more prevalent in a cholesterol-rich environment. This led to the theory that treating hypercholesterolemia may decrease the prevalence of Alzheimer’s disease.8
The PROSPER trial, which was designed to test the effect of pravastatin (Pravachol) on coronary heart disease and stroke, randomized 5804 study participants into 1 group assigned to take pravastatin and another group assigned to take placebo. An additional study endpoint was pravastatin’s effect on cognitive function as measured by 4 different tests, including the Mini-Mental Status Exam (MMSE). Overall cognitive function declined at the same rate in treatment and placebo groups. There was no significant difference between the 2 groups over 3 years using 4 different methods of assessment. In particular, the MMSE scores differed by only 0.06 points (95% confidence interval [CI], 0.04–0.16; P=.26).
The largest RCT of a statin agent, the Heart Protection Study, enrolled more than 20,000 people and randomized them to simvastatin (Zocor) or placebo. After a median of 5 years of follow-up, there was no difference in cognitive scores or the rate of diagnosis of dementia between the 2 groups.2
A systematic review concluded that no good evidence recommended statins for reducing the risk of Alzheimer’s dementia.3 Notably, the review did find a body of inconclusive evidence that lowering serum cholesterol may retard disease pathogenesis. An observational study of 56,790 charts included in the computer databases of 3 hospitals found that the prevalence of probable Alzheimer’s dementia in the cohort taking statins was 60% to 73% (P<.001) lower than in the total patient population or in patients taking antihypertensive or cardiovascular medications.4
Also included in the review was a nested case-control study of 1364 patients that found an adjusted relative risk for dementia of 0.29 (95% CI, 0.013–0.063; P=.002) among those taking statins.5 This study did not distinguish between Alzheimer’s dementia and other forms of dementia. These studies do not demonstrate a causal relationship between statins and Alzheimer’s dementia.
The best way to determine if there is a true effect of statins on Alzheimer’s dementia is to conduct a clinical trial. Two ongoing clinical trials are designed specifically to determine if the use of statins delay the onset or slow the progression of Alzheimer’s dementia.9,10 To date, these trials have not published interim findings.
Recommendations from others
No organization has issued recommendations for the use of statins to delay the onset or slow the progression of Alzheimer’s dementia.
We are obligated to protect patients from potential risks of unnecessary medications
Seema Modi, MD
East Carolina University, Greenville, NC
Alzheimer’s disease is a difficult and emotionally charged topic. Many patients who have watched a family member suffer from Alzheimer’s disease would go to great lengths to delay or prevent developing Alzheimer’s disease themselves. As a result of direct drug marketing to consumers, plus increased lay media coverage of health issues, our patients are now better informed than ever and make more direct requests for certain medications by name.
Imagine talking with a well-read patient who has learned from a newspaper article or morning news show about 1 of the 3 epidemiological studies that show decreased incidence of dementia among statin users. The patient now stands before you, requesting a prescription for a statin. Though this patient is otherwise healthy and has a desirable cholesterol level, you will still find it difficult to explain to the patient why you will not write the prescription. As physicians, we are obligated to protect our patients from the potential risks of unnecessary medications. We are also obligated to protect our healthcare system from escalation of already high healthcare costs. Evidence from rigorous clinical trials is the tool that can help us provide this protection.
1. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-1630.
2. Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20,536 people with cerebrovascular disears or other high-risk conditions. Lancet 2004;363:757-767.
3. Scott HD, Laake K. Statins for the prevention of Alzheimer’s disease. Cochrane Database Syst Rev 2001;(3):CD003160.-
4. Wolozin B, Kellman W, Rousseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;57:1439-1443.
5. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000;356:1627-1631.
6. Zamrini E, McGwin G, Roseman JM. Association between statin use and Alzheimer’s disease. Neuroepidemiology 2004;23:94-98.
7. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA 1989;262:2551-2556.
8. Selkoe DJ. Physiological production of the beta-amyloid protein and the mechanism of Alzheimers-Disease. Trends Neurosci 1993;16:403-409.
9. Sano M, Thal LJ. Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer’s Disease Study. February 3, 2003 (Last reviewed December, 2004). Available at: www.clinicaltrials.gov/ct/show/NCT00053599?order=4. Accessed on June 8, 2005.
10. Lipitor as a Treatment of Alzheimer’s Disease. September 19, 2001 (Last reviewed November, 2004). Available at: www.clinicaltrials.gov/ct/show/NCT00024531?order=1. Accessed on June 8, 2005.
Statins (coenzyme-A reductase inhibitors) should not be used with the single intent to delay the onset or slow the progression of dementia. Large randomized control trials (RCTs) found that the administration of a statin had no significant effect on preventing or slowing all-cause cognitive decline (strength of recommendation [SOR]: A, based on large RCTs with narrow confidence interval).1,2 Specifically, there is insufficient evidence that statins delay the onset or slow the progression of Alzheimer’s dementia (SOR: B, based on systematic review with heterogeneity).3
While 3 epidemiologic studies4-6 have found a decreased incidence of dementia among those taking statins, these studies have significant methodological shortcomings and do not show a causal relationship (SOR: C, based on poor-quality studies).
Evidence summary
Approximately 4 million people in the United States suffer with Alzheimer’s disease. The prevalence rises with age and is approximately 47% among those aged 85 years and older.7
Amyloid plaques are thought to be responsible for clinical changes associated with Alzheimer’s dementia. Research has indicated that amyloid precursors may be more prevalent in a cholesterol-rich environment. This led to the theory that treating hypercholesterolemia may decrease the prevalence of Alzheimer’s disease.8
The PROSPER trial, which was designed to test the effect of pravastatin (Pravachol) on coronary heart disease and stroke, randomized 5804 study participants into 1 group assigned to take pravastatin and another group assigned to take placebo. An additional study endpoint was pravastatin’s effect on cognitive function as measured by 4 different tests, including the Mini-Mental Status Exam (MMSE). Overall cognitive function declined at the same rate in treatment and placebo groups. There was no significant difference between the 2 groups over 3 years using 4 different methods of assessment. In particular, the MMSE scores differed by only 0.06 points (95% confidence interval [CI], 0.04–0.16; P=.26).
The largest RCT of a statin agent, the Heart Protection Study, enrolled more than 20,000 people and randomized them to simvastatin (Zocor) or placebo. After a median of 5 years of follow-up, there was no difference in cognitive scores or the rate of diagnosis of dementia between the 2 groups.2
A systematic review concluded that no good evidence recommended statins for reducing the risk of Alzheimer’s dementia.3 Notably, the review did find a body of inconclusive evidence that lowering serum cholesterol may retard disease pathogenesis. An observational study of 56,790 charts included in the computer databases of 3 hospitals found that the prevalence of probable Alzheimer’s dementia in the cohort taking statins was 60% to 73% (P<.001) lower than in the total patient population or in patients taking antihypertensive or cardiovascular medications.4
Also included in the review was a nested case-control study of 1364 patients that found an adjusted relative risk for dementia of 0.29 (95% CI, 0.013–0.063; P=.002) among those taking statins.5 This study did not distinguish between Alzheimer’s dementia and other forms of dementia. These studies do not demonstrate a causal relationship between statins and Alzheimer’s dementia.
The best way to determine if there is a true effect of statins on Alzheimer’s dementia is to conduct a clinical trial. Two ongoing clinical trials are designed specifically to determine if the use of statins delay the onset or slow the progression of Alzheimer’s dementia.9,10 To date, these trials have not published interim findings.
Recommendations from others
No organization has issued recommendations for the use of statins to delay the onset or slow the progression of Alzheimer’s dementia.
We are obligated to protect patients from potential risks of unnecessary medications
Seema Modi, MD
East Carolina University, Greenville, NC
Alzheimer’s disease is a difficult and emotionally charged topic. Many patients who have watched a family member suffer from Alzheimer’s disease would go to great lengths to delay or prevent developing Alzheimer’s disease themselves. As a result of direct drug marketing to consumers, plus increased lay media coverage of health issues, our patients are now better informed than ever and make more direct requests for certain medications by name.
Imagine talking with a well-read patient who has learned from a newspaper article or morning news show about 1 of the 3 epidemiological studies that show decreased incidence of dementia among statin users. The patient now stands before you, requesting a prescription for a statin. Though this patient is otherwise healthy and has a desirable cholesterol level, you will still find it difficult to explain to the patient why you will not write the prescription. As physicians, we are obligated to protect our patients from the potential risks of unnecessary medications. We are also obligated to protect our healthcare system from escalation of already high healthcare costs. Evidence from rigorous clinical trials is the tool that can help us provide this protection.
Statins (coenzyme-A reductase inhibitors) should not be used with the single intent to delay the onset or slow the progression of dementia. Large randomized control trials (RCTs) found that the administration of a statin had no significant effect on preventing or slowing all-cause cognitive decline (strength of recommendation [SOR]: A, based on large RCTs with narrow confidence interval).1,2 Specifically, there is insufficient evidence that statins delay the onset or slow the progression of Alzheimer’s dementia (SOR: B, based on systematic review with heterogeneity).3
While 3 epidemiologic studies4-6 have found a decreased incidence of dementia among those taking statins, these studies have significant methodological shortcomings and do not show a causal relationship (SOR: C, based on poor-quality studies).
Evidence summary
Approximately 4 million people in the United States suffer with Alzheimer’s disease. The prevalence rises with age and is approximately 47% among those aged 85 years and older.7
Amyloid plaques are thought to be responsible for clinical changes associated with Alzheimer’s dementia. Research has indicated that amyloid precursors may be more prevalent in a cholesterol-rich environment. This led to the theory that treating hypercholesterolemia may decrease the prevalence of Alzheimer’s disease.8
The PROSPER trial, which was designed to test the effect of pravastatin (Pravachol) on coronary heart disease and stroke, randomized 5804 study participants into 1 group assigned to take pravastatin and another group assigned to take placebo. An additional study endpoint was pravastatin’s effect on cognitive function as measured by 4 different tests, including the Mini-Mental Status Exam (MMSE). Overall cognitive function declined at the same rate in treatment and placebo groups. There was no significant difference between the 2 groups over 3 years using 4 different methods of assessment. In particular, the MMSE scores differed by only 0.06 points (95% confidence interval [CI], 0.04–0.16; P=.26).
The largest RCT of a statin agent, the Heart Protection Study, enrolled more than 20,000 people and randomized them to simvastatin (Zocor) or placebo. After a median of 5 years of follow-up, there was no difference in cognitive scores or the rate of diagnosis of dementia between the 2 groups.2
A systematic review concluded that no good evidence recommended statins for reducing the risk of Alzheimer’s dementia.3 Notably, the review did find a body of inconclusive evidence that lowering serum cholesterol may retard disease pathogenesis. An observational study of 56,790 charts included in the computer databases of 3 hospitals found that the prevalence of probable Alzheimer’s dementia in the cohort taking statins was 60% to 73% (P<.001) lower than in the total patient population or in patients taking antihypertensive or cardiovascular medications.4
Also included in the review was a nested case-control study of 1364 patients that found an adjusted relative risk for dementia of 0.29 (95% CI, 0.013–0.063; P=.002) among those taking statins.5 This study did not distinguish between Alzheimer’s dementia and other forms of dementia. These studies do not demonstrate a causal relationship between statins and Alzheimer’s dementia.
The best way to determine if there is a true effect of statins on Alzheimer’s dementia is to conduct a clinical trial. Two ongoing clinical trials are designed specifically to determine if the use of statins delay the onset or slow the progression of Alzheimer’s dementia.9,10 To date, these trials have not published interim findings.
Recommendations from others
No organization has issued recommendations for the use of statins to delay the onset or slow the progression of Alzheimer’s dementia.
We are obligated to protect patients from potential risks of unnecessary medications
Seema Modi, MD
East Carolina University, Greenville, NC
Alzheimer’s disease is a difficult and emotionally charged topic. Many patients who have watched a family member suffer from Alzheimer’s disease would go to great lengths to delay or prevent developing Alzheimer’s disease themselves. As a result of direct drug marketing to consumers, plus increased lay media coverage of health issues, our patients are now better informed than ever and make more direct requests for certain medications by name.
Imagine talking with a well-read patient who has learned from a newspaper article or morning news show about 1 of the 3 epidemiological studies that show decreased incidence of dementia among statin users. The patient now stands before you, requesting a prescription for a statin. Though this patient is otherwise healthy and has a desirable cholesterol level, you will still find it difficult to explain to the patient why you will not write the prescription. As physicians, we are obligated to protect our patients from the potential risks of unnecessary medications. We are also obligated to protect our healthcare system from escalation of already high healthcare costs. Evidence from rigorous clinical trials is the tool that can help us provide this protection.
1. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-1630.
2. Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20,536 people with cerebrovascular disears or other high-risk conditions. Lancet 2004;363:757-767.
3. Scott HD, Laake K. Statins for the prevention of Alzheimer’s disease. Cochrane Database Syst Rev 2001;(3):CD003160.-
4. Wolozin B, Kellman W, Rousseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;57:1439-1443.
5. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000;356:1627-1631.
6. Zamrini E, McGwin G, Roseman JM. Association between statin use and Alzheimer’s disease. Neuroepidemiology 2004;23:94-98.
7. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA 1989;262:2551-2556.
8. Selkoe DJ. Physiological production of the beta-amyloid protein and the mechanism of Alzheimers-Disease. Trends Neurosci 1993;16:403-409.
9. Sano M, Thal LJ. Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer’s Disease Study. February 3, 2003 (Last reviewed December, 2004). Available at: www.clinicaltrials.gov/ct/show/NCT00053599?order=4. Accessed on June 8, 2005.
10. Lipitor as a Treatment of Alzheimer’s Disease. September 19, 2001 (Last reviewed November, 2004). Available at: www.clinicaltrials.gov/ct/show/NCT00024531?order=1. Accessed on June 8, 2005.
1. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-1630.
2. Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20,536 people with cerebrovascular disears or other high-risk conditions. Lancet 2004;363:757-767.
3. Scott HD, Laake K. Statins for the prevention of Alzheimer’s disease. Cochrane Database Syst Rev 2001;(3):CD003160.-
4. Wolozin B, Kellman W, Rousseau P, Celesia GG, Siegel G. Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. Arch Neurol 2000;57:1439-1443.
5. Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet 2000;356:1627-1631.
6. Zamrini E, McGwin G, Roseman JM. Association between statin use and Alzheimer’s disease. Neuroepidemiology 2004;23:94-98.
7. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA 1989;262:2551-2556.
8. Selkoe DJ. Physiological production of the beta-amyloid protein and the mechanism of Alzheimers-Disease. Trends Neurosci 1993;16:403-409.
9. Sano M, Thal LJ. Cholesterol Lowering Agent to Slow Progression (CLASP) of Alzheimer’s Disease Study. February 3, 2003 (Last reviewed December, 2004). Available at: www.clinicaltrials.gov/ct/show/NCT00053599?order=4. Accessed on June 8, 2005.
10. Lipitor as a Treatment of Alzheimer’s Disease. September 19, 2001 (Last reviewed November, 2004). Available at: www.clinicaltrials.gov/ct/show/NCT00024531?order=1. Accessed on June 8, 2005.
Evidence-based answers from the Family Physicians Inquiries Network
Is neurosurgery referral warranted for small brain aneurysms?
The risk of rupture of a small cerebral aneurysm (<10 mm) is very low in asymptomatic patients who have never had a subarachnoid hemorrhage. Because the risk of morbidity and mortality from surgical intervention significantly exceeds that of nonsurgical monitoring for this group, primary care physicians do not need to refer patients with this condition to a neurosurgeon for clipping (strength of recommendation [SOR]: B, based on cohort and case-control studies). For patients managed conservatively, annual office follow-up and imaging evaluation should be considered, and is necessary if a specific symptom should arise (SOR: C, based on expert opinion).
Evidence summary
Intracranial aneurysms are not rare. Based on autopsy data, prevalence has been estimated to be 0.2% to 9.9% of the population.1 Ten to 15 million Americans may have unruptured intracranial aneurysms, most of which remain undiagnosed.2
Conditions leading to the diagnosis of unruptured intracranial aneurysms include:
- headache (in 36% of patients)
- ischemic cerebrovascular disease (17.6%)
- cranial nerve deficits (15.4 %)
- aneurysmal mass effect (5.7%)
- ill-defined “spells” (4.8%)
- convulsive disorder (4.2%)
- subdural or intracerebral hemorrhage (2.7%)
- brain tumor (1.7%)
- nervous system degenerative disease (0.5%).2
No randomized controlled trials have examined whether unruptured intracranial aneurysms should be treated surgically. In the absence of a clinical trial, the evidence to answer this question is based on observational, cohort, and case-control studies, where the risks of the natural history of the condition are weighed against the risks of surgical intervention.3
One study of the natural history of unruptured cerebral aneurysm included 130 patients with 161 unruptured intracranial aneurysms who were followed for a mean of 8.3 years.4,5 This prospective investigation found that 15 patients suffered an intracranial hemorrhage. There were no ruptures of the 102 aneurysms that were ≤10 mm in diameter at the time of discovery.4,5
In the largest cohort study to date, patients without a history of subarachnoid hemorrhage had an overall risk of rupture of 0.05% per year over 7.5 years. This study also found that surgery-related morbidity and mortality at 1 year among patients aged <45 years was 6.5%, compared with 14.4% for those aged 45 to 64 years, and 32% for those aged >64 years.2
Recommendations from others
The Stroke Council of the American Heart Association recommends that observation is generally appropriate for incidental, small (<10-mm) aneurysms in patients without previous subarachnoid hemorrhage. However, special consideration for treatment should be given to young patients in this group, small aneurysms approaching the 10-mm size, and aneurysms with daughter sac formation ( Figure). In addition, patients with a family history of aneurysm or aneurysmal subarachnoid hemorrhage deserve special consideration for treatment.
For patients managed conservatively, periodic follow-up imaging should be considered; imaging is necessary if a specific symptom should arise. If changes in aneurysmal size or configuration are observed, special consideration for treatment should be made.6
Aneurysm with daughter sac
Wail Malaty, MD
Mountain Area Health Education Center Hendersonville, NC
Department of Family Medicine, University of North Carolina Chapel Hill
Asymptomatic cerebral aneurysms are potentially disastrous, since rupture can result in permanent neurologic disability or death. The diagnosis causes anxiety and fear in many patients. I try to explain to them, in clear and simple language, the minimal risk of rupture if the aneurysm is observed vs the higher risk of surgical intervention. I allow patients to express their fear and anxiety. I also elicit their input into the decision to refer. If their fear and anxiety cannot be allayed, I will refer them to a neurosurgeon. I invite them to return after the referral to discuss any further course of action.
1. Raaymakers TW, Rinkel GJ, Limburg M, Algra A. Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 1998;29:1531-1538.
2. International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 1998;339:1725-1733.
3. Brennan JW, Schwartz ML. Unruptured intracranial aneurysms: appraisal of the literature and suggested recommendations for surgery, using evidence-based medicine criteria. Neurosurgery 2000;47:1359-1372.
4. Wiebers DO, Whisnant JP, O’Fallon WM. The natural history of unruptured intracranial aneurysms. N Engl J Med 1981;304:696-698.
5. Wiebers DO, Whisnant JP, Sundt TM, Jr, O’Fallon WM. The significance of unruptured intracranial saccular aneurysms. J Neurosurg 1987;66:23-29.
6. Bederson JB, Awad IA, Wiebers DO, et al. Recommendations for the management of patients with unruptured intracranial aneurysms: A statement for healthcare professionals from the Stroke Council of the American Heart Association. Circulation 2000;102:2300-2308.
The risk of rupture of a small cerebral aneurysm (<10 mm) is very low in asymptomatic patients who have never had a subarachnoid hemorrhage. Because the risk of morbidity and mortality from surgical intervention significantly exceeds that of nonsurgical monitoring for this group, primary care physicians do not need to refer patients with this condition to a neurosurgeon for clipping (strength of recommendation [SOR]: B, based on cohort and case-control studies). For patients managed conservatively, annual office follow-up and imaging evaluation should be considered, and is necessary if a specific symptom should arise (SOR: C, based on expert opinion).
Evidence summary
Intracranial aneurysms are not rare. Based on autopsy data, prevalence has been estimated to be 0.2% to 9.9% of the population.1 Ten to 15 million Americans may have unruptured intracranial aneurysms, most of which remain undiagnosed.2
Conditions leading to the diagnosis of unruptured intracranial aneurysms include:
- headache (in 36% of patients)
- ischemic cerebrovascular disease (17.6%)
- cranial nerve deficits (15.4 %)
- aneurysmal mass effect (5.7%)
- ill-defined “spells” (4.8%)
- convulsive disorder (4.2%)
- subdural or intracerebral hemorrhage (2.7%)
- brain tumor (1.7%)
- nervous system degenerative disease (0.5%).2
No randomized controlled trials have examined whether unruptured intracranial aneurysms should be treated surgically. In the absence of a clinical trial, the evidence to answer this question is based on observational, cohort, and case-control studies, where the risks of the natural history of the condition are weighed against the risks of surgical intervention.3
One study of the natural history of unruptured cerebral aneurysm included 130 patients with 161 unruptured intracranial aneurysms who were followed for a mean of 8.3 years.4,5 This prospective investigation found that 15 patients suffered an intracranial hemorrhage. There were no ruptures of the 102 aneurysms that were ≤10 mm in diameter at the time of discovery.4,5
In the largest cohort study to date, patients without a history of subarachnoid hemorrhage had an overall risk of rupture of 0.05% per year over 7.5 years. This study also found that surgery-related morbidity and mortality at 1 year among patients aged <45 years was 6.5%, compared with 14.4% for those aged 45 to 64 years, and 32% for those aged >64 years.2
Recommendations from others
The Stroke Council of the American Heart Association recommends that observation is generally appropriate for incidental, small (<10-mm) aneurysms in patients without previous subarachnoid hemorrhage. However, special consideration for treatment should be given to young patients in this group, small aneurysms approaching the 10-mm size, and aneurysms with daughter sac formation ( Figure). In addition, patients with a family history of aneurysm or aneurysmal subarachnoid hemorrhage deserve special consideration for treatment.
For patients managed conservatively, periodic follow-up imaging should be considered; imaging is necessary if a specific symptom should arise. If changes in aneurysmal size or configuration are observed, special consideration for treatment should be made.6
Aneurysm with daughter sac
Wail Malaty, MD
Mountain Area Health Education Center Hendersonville, NC
Department of Family Medicine, University of North Carolina Chapel Hill
Asymptomatic cerebral aneurysms are potentially disastrous, since rupture can result in permanent neurologic disability or death. The diagnosis causes anxiety and fear in many patients. I try to explain to them, in clear and simple language, the minimal risk of rupture if the aneurysm is observed vs the higher risk of surgical intervention. I allow patients to express their fear and anxiety. I also elicit their input into the decision to refer. If their fear and anxiety cannot be allayed, I will refer them to a neurosurgeon. I invite them to return after the referral to discuss any further course of action.
The risk of rupture of a small cerebral aneurysm (<10 mm) is very low in asymptomatic patients who have never had a subarachnoid hemorrhage. Because the risk of morbidity and mortality from surgical intervention significantly exceeds that of nonsurgical monitoring for this group, primary care physicians do not need to refer patients with this condition to a neurosurgeon for clipping (strength of recommendation [SOR]: B, based on cohort and case-control studies). For patients managed conservatively, annual office follow-up and imaging evaluation should be considered, and is necessary if a specific symptom should arise (SOR: C, based on expert opinion).
Evidence summary
Intracranial aneurysms are not rare. Based on autopsy data, prevalence has been estimated to be 0.2% to 9.9% of the population.1 Ten to 15 million Americans may have unruptured intracranial aneurysms, most of which remain undiagnosed.2
Conditions leading to the diagnosis of unruptured intracranial aneurysms include:
- headache (in 36% of patients)
- ischemic cerebrovascular disease (17.6%)
- cranial nerve deficits (15.4 %)
- aneurysmal mass effect (5.7%)
- ill-defined “spells” (4.8%)
- convulsive disorder (4.2%)
- subdural or intracerebral hemorrhage (2.7%)
- brain tumor (1.7%)
- nervous system degenerative disease (0.5%).2
No randomized controlled trials have examined whether unruptured intracranial aneurysms should be treated surgically. In the absence of a clinical trial, the evidence to answer this question is based on observational, cohort, and case-control studies, where the risks of the natural history of the condition are weighed against the risks of surgical intervention.3
One study of the natural history of unruptured cerebral aneurysm included 130 patients with 161 unruptured intracranial aneurysms who were followed for a mean of 8.3 years.4,5 This prospective investigation found that 15 patients suffered an intracranial hemorrhage. There were no ruptures of the 102 aneurysms that were ≤10 mm in diameter at the time of discovery.4,5
In the largest cohort study to date, patients without a history of subarachnoid hemorrhage had an overall risk of rupture of 0.05% per year over 7.5 years. This study also found that surgery-related morbidity and mortality at 1 year among patients aged <45 years was 6.5%, compared with 14.4% for those aged 45 to 64 years, and 32% for those aged >64 years.2
Recommendations from others
The Stroke Council of the American Heart Association recommends that observation is generally appropriate for incidental, small (<10-mm) aneurysms in patients without previous subarachnoid hemorrhage. However, special consideration for treatment should be given to young patients in this group, small aneurysms approaching the 10-mm size, and aneurysms with daughter sac formation ( Figure). In addition, patients with a family history of aneurysm or aneurysmal subarachnoid hemorrhage deserve special consideration for treatment.
For patients managed conservatively, periodic follow-up imaging should be considered; imaging is necessary if a specific symptom should arise. If changes in aneurysmal size or configuration are observed, special consideration for treatment should be made.6
Aneurysm with daughter sac
Wail Malaty, MD
Mountain Area Health Education Center Hendersonville, NC
Department of Family Medicine, University of North Carolina Chapel Hill
Asymptomatic cerebral aneurysms are potentially disastrous, since rupture can result in permanent neurologic disability or death. The diagnosis causes anxiety and fear in many patients. I try to explain to them, in clear and simple language, the minimal risk of rupture if the aneurysm is observed vs the higher risk of surgical intervention. I allow patients to express their fear and anxiety. I also elicit their input into the decision to refer. If their fear and anxiety cannot be allayed, I will refer them to a neurosurgeon. I invite them to return after the referral to discuss any further course of action.
1. Raaymakers TW, Rinkel GJ, Limburg M, Algra A. Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 1998;29:1531-1538.
2. International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 1998;339:1725-1733.
3. Brennan JW, Schwartz ML. Unruptured intracranial aneurysms: appraisal of the literature and suggested recommendations for surgery, using evidence-based medicine criteria. Neurosurgery 2000;47:1359-1372.
4. Wiebers DO, Whisnant JP, O’Fallon WM. The natural history of unruptured intracranial aneurysms. N Engl J Med 1981;304:696-698.
5. Wiebers DO, Whisnant JP, Sundt TM, Jr, O’Fallon WM. The significance of unruptured intracranial saccular aneurysms. J Neurosurg 1987;66:23-29.
6. Bederson JB, Awad IA, Wiebers DO, et al. Recommendations for the management of patients with unruptured intracranial aneurysms: A statement for healthcare professionals from the Stroke Council of the American Heart Association. Circulation 2000;102:2300-2308.
1. Raaymakers TW, Rinkel GJ, Limburg M, Algra A. Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 1998;29:1531-1538.
2. International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms—risk of rupture and risks of surgical intervention. N Engl J Med 1998;339:1725-1733.
3. Brennan JW, Schwartz ML. Unruptured intracranial aneurysms: appraisal of the literature and suggested recommendations for surgery, using evidence-based medicine criteria. Neurosurgery 2000;47:1359-1372.
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Evidence-based answers from the Family Physicians Inquiries Network