Early Alzheimer's Disease
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In the Clinical Practice article about early Alzheimer's disease, Dr. Kawas (Sept. 11 issue)1 discusses testing for reversible causes of dementia. More than 15 years ago, it was conclusively shown that true reversibility of dementia, especially in the elderly, was extremely rare.2,3 More recent work has confirmed these findings, revealing improvement in less than 1 percent of cases.4
On the basis of the evidence, one should be quite conservative, and decisions about testing should be directed primarily by the clinical clues available from the history and physical examination. Kawas cites the American Academy of Neurology's universal neuroimaging policy but does not refer to other authoritative bodies that have published more conservative recommendations, such as those from Canada.5 These guidelines have even been tested and found to do no harm.6
Geriatricians long ago learned that it is often in the patient's best interest to make haste somewhat slowly. This is especially true in the case of a frail elderly patient who presents with cognitive decline.
A. Mark Clarfield, M.D.
Ben Gurion University of the Negev
Beersheba 84101, Israel
markclar@bgumail.bgu.ac.il
References
Kawas CH. Early Alzheimer's disease. N Engl J Med 2003;349:1056-1063.
Barry P, Moskowitz MA. The diagnosis of reversible dementia in the elderly: a critical review. Arch Intern Med 1988;148:1914-1918.
Clarfield AM. The reversible dementias: do they reverse? Ann Intern Med 1988;109:476-486.
Clarfield AM. The decreasing prevalence of reversible dementias: an updated meta-analysis. Arch Intern Med 2003;163:2219-2229.
Patterson C, Gauthier S, Bergman H, et al. The recognition, assessment and management of dementing disorders: conclusions from the Canadian Consensus Conference on Dementia. Can J Neurol Sci 2001;28:Suppl 1:S3-S16.
Freter S, Bergman H, Gold S, Chertkow H, Clarfield AM. Prevalence of potentially reversible dementias and actual reversibility in a memory clinic cohort. CMAJ 1998;159:657-662.
To the Editor: Dr. Kawas enumerates causes of dementia to be ruled out before one makes a diagnosis of Alzheimer's disease. Among the tests for ruling out other causes, serologic tests for syphilis and human immunodeficiency virus (HIV) infection should be recommended as part of the differential diagnosis, especially in patients who are less than 65 years old, because both causes can improve with specific treatment.
Francisco J. Ruiz-Ruiz, M.D.
Hospital Clínico Universitario Lozano Blesa
50009 Zaragoza, Spain
fjruiz1@terra.es
To the Editor: Paroxetine is highlighted for the treatment of depression in patients with dementia, but the drawbacks of this medication should be considered. First, of the selective serotonin-reuptake inhibitors, it has the highest binding affinity for the muscarinic acetylcholine receptor1,2 (equivalent to that of nortriptyline), and such a medication should be used cautiously for the treatment of a disease marked by acetylcholine deficiency; cognitive symptoms may be exacerbated or may arise and be mistaken for progression of the illness. Second, of the selective serotonin-reuptake inhibitors, paroxetine is associated with the highest incidence of the antidepressant discontinuation syndrome,3,4 which may occur after even a single dose has been omitted. The memory loss in patients with early Alzheimer's disease places them at particular risk for this syndrome. The quality of life is affected by this syndrome, but also, some of its cardinal symptoms (disequilibrium, headache, and agitation) may be mistakenly attributed to other medical conditions (e.g., transient ischemic attack), prompting the performance of unnecessary diagnostic procedures. Antidepressants with negligible anticholinergic activity and a negligible incidence of the antidepressant discontinuation syndrome (e.g., fluoxetine, mirtazapine, and bupropion) generally may be preferable for patients with dementia who have depression.
Robert S. Hausner, M.D.
University of California, San Francisco
San Francisco, CA 94143
References
Cusack B, Nelson A, Richelson E. Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl) 1994;114:559-565.
Preskorn SH. Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 1995;56:Suppl 6:12-21.
Dominguez RA, Goodnick PJ. Adverse events after the abrupt discontinuation of paroxetine. Pharmacotherapy 1995;15:778-780.
Coupland NJ, Bell CJ, Potokar JP. Serotonin reuptake inhibitor withdrawal. J Clin Psychopharmacol 1996;16:356-362.
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To the Editor: Recommendations regarding the use of risperidone (Risperdal) for treatment of the symptoms of dementia (Table 3 of the article by Kawas) require reconsideration, for several reasons. First, risperidone has been studied in a number of controlled trials for the treatment of agitation and psychosis in patients with dementia.1,2,3 This experience suggests that a target dose of 0.5 to 2.0 mg per day (half the dose listed in Table 3) may be associated with the best ratio of benefit to tolerability. Second, it may be misleading to state that risperidone has been associated with an increased risk of stroke. Although a recent change in the U.S. prescribing information noted that, in controlled trials, more "cerebrovascular adverse events" were reported among patients with dementia who were taking risperidone than among those taking placebo, it is important to note that the majority of these events were not strokes. When "serious" events as defined in the Code of Federal Regulations — a category that includes stroke — are considered, there is no statistically significant difference between risperidone and placebo. In the United States, neither risperidone nor any other drug is approved for the treatment of dementia-related psychosis.
Ramy Mahmoud, M.D., M.P.H.
Andrew Greenspan, M.D.
Janssen Pharmaceutica
Titusville, NJ 08560
References
Katz IR, Jeste DV, Mintzer JE, Clyde C, Napolitano J, Brecher M. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. J Clin Psychiatry 1999;60:107-115.
De Deyn PP, Rabheru K, Rasmussen A, et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999;53:946-955.
Brodaty H, Ames D, Snowdon J, et al. A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry 2003;64:134-143.
On the basis of the evidence, one should be quite conservative, and decisions about testing should be directed primarily by the clinical clues available from the history and physical examination. Kawas cites the American Academy of Neurology's universal neuroimaging policy but does not refer to other authoritative bodies that have published more conservative recommendations, such as those from Canada.5 These guidelines have even been tested and found to do no harm.6
Geriatricians long ago learned that it is often in the patient's best interest to make haste somewhat slowly. This is especially true in the case of a frail elderly patient who presents with cognitive decline.
A. Mark Clarfield, M.D.
Ben Gurion University of the Negev
Beersheba 84101, Israel
markclar@bgumail.bgu.ac.il
References
Kawas CH. Early Alzheimer's disease. N Engl J Med 2003;349:1056-1063.
Barry P, Moskowitz MA. The diagnosis of reversible dementia in the elderly: a critical review. Arch Intern Med 1988;148:1914-1918.
Clarfield AM. The reversible dementias: do they reverse? Ann Intern Med 1988;109:476-486.
Clarfield AM. The decreasing prevalence of reversible dementias: an updated meta-analysis. Arch Intern Med 2003;163:2219-2229.
Patterson C, Gauthier S, Bergman H, et al. The recognition, assessment and management of dementing disorders: conclusions from the Canadian Consensus Conference on Dementia. Can J Neurol Sci 2001;28:Suppl 1:S3-S16.
Freter S, Bergman H, Gold S, Chertkow H, Clarfield AM. Prevalence of potentially reversible dementias and actual reversibility in a memory clinic cohort. CMAJ 1998;159:657-662.
To the Editor: Dr. Kawas enumerates causes of dementia to be ruled out before one makes a diagnosis of Alzheimer's disease. Among the tests for ruling out other causes, serologic tests for syphilis and human immunodeficiency virus (HIV) infection should be recommended as part of the differential diagnosis, especially in patients who are less than 65 years old, because both causes can improve with specific treatment.
Francisco J. Ruiz-Ruiz, M.D.
Hospital Clínico Universitario Lozano Blesa
50009 Zaragoza, Spain
fjruiz1@terra.es
To the Editor: Paroxetine is highlighted for the treatment of depression in patients with dementia, but the drawbacks of this medication should be considered. First, of the selective serotonin-reuptake inhibitors, it has the highest binding affinity for the muscarinic acetylcholine receptor1,2 (equivalent to that of nortriptyline), and such a medication should be used cautiously for the treatment of a disease marked by acetylcholine deficiency; cognitive symptoms may be exacerbated or may arise and be mistaken for progression of the illness. Second, of the selective serotonin-reuptake inhibitors, paroxetine is associated with the highest incidence of the antidepressant discontinuation syndrome,3,4 which may occur after even a single dose has been omitted. The memory loss in patients with early Alzheimer's disease places them at particular risk for this syndrome. The quality of life is affected by this syndrome, but also, some of its cardinal symptoms (disequilibrium, headache, and agitation) may be mistakenly attributed to other medical conditions (e.g., transient ischemic attack), prompting the performance of unnecessary diagnostic procedures. Antidepressants with negligible anticholinergic activity and a negligible incidence of the antidepressant discontinuation syndrome (e.g., fluoxetine, mirtazapine, and bupropion) generally may be preferable for patients with dementia who have depression.
Robert S. Hausner, M.D.
University of California, San Francisco
San Francisco, CA 94143
References
Cusack B, Nelson A, Richelson E. Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl) 1994;114:559-565.
Preskorn SH. Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 1995;56:Suppl 6:12-21.
Dominguez RA, Goodnick PJ. Adverse events after the abrupt discontinuation of paroxetine. Pharmacotherapy 1995;15:778-780.
Coupland NJ, Bell CJ, Potokar JP. Serotonin reuptake inhibitor withdrawal. J Clin Psychopharmacol 1996;16:356-362.
--------------------------------------------------------------------------------
To the Editor: Recommendations regarding the use of risperidone (Risperdal) for treatment of the symptoms of dementia (Table 3 of the article by Kawas) require reconsideration, for several reasons. First, risperidone has been studied in a number of controlled trials for the treatment of agitation and psychosis in patients with dementia.1,2,3 This experience suggests that a target dose of 0.5 to 2.0 mg per day (half the dose listed in Table 3) may be associated with the best ratio of benefit to tolerability. Second, it may be misleading to state that risperidone has been associated with an increased risk of stroke. Although a recent change in the U.S. prescribing information noted that, in controlled trials, more "cerebrovascular adverse events" were reported among patients with dementia who were taking risperidone than among those taking placebo, it is important to note that the majority of these events were not strokes. When "serious" events as defined in the Code of Federal Regulations — a category that includes stroke — are considered, there is no statistically significant difference between risperidone and placebo. In the United States, neither risperidone nor any other drug is approved for the treatment of dementia-related psychosis.
Ramy Mahmoud, M.D., M.P.H.
Andrew Greenspan, M.D.
Janssen Pharmaceutica
Titusville, NJ 08560
References
Katz IR, Jeste DV, Mintzer JE, Clyde C, Napolitano J, Brecher M. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. J Clin Psychiatry 1999;60:107-115.
De Deyn PP, Rabheru K, Rasmussen A, et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999;53:946-955.
Brodaty H, Ames D, Snowdon J, et al. A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia. J Clin Psychiatry 2003;64:134-143.