- Email: [email protected]
Commentary on “Diagnosis of Alzheimer’s disease: Two decades of progress.” Perspectives on “Perspectives”
Alzheimer’s & Dementia 1 (2005) 124 –125
Commentary on “Diagnosis of Alzheimer’s disease: Two decades of progress.” Perspectives on “Perspectives” John P. Blass* Burke Research Institute, Weill-Cornell Medical College, 785 Manaroneck Avenue, White Plains, NY 10605 USA
The article by Dr. Zaven Khachaturian is a superb, concise summary of the development of our understanding of dementias in general and of Alzheimer’s disease (AD) in particular. It documents that good leadership from the Federal Government can be part of the solution. It also provides sound counsel on what needs to be done now. As indicated in that article, improvement in the diagnosis of AD or other dementia in the clinical setting is not now a pressing problem. Dementia can be recognized with confidence on the basis of medical history (anamenusis) and neuropsychological testing. Treatable conditions that contribute to cognitive disability can be detected by the nowstandardized dementia workup, given reasonable clinical acumen on the part of the examiner. Serial brain imaging studies can indicate whether there is evidence of accelerated atrophy even before symptoms become debilitating, in time for people to make appropriate practical arrangements. The diagnosis of AD can be made with more than 90% confidence on the basis of a careful evaluation, as documented by a number of studies in which patients were followed up until autopsy. The course of AD is hard to predict in any individual patient, except for the generalization that worse illness tends to progress more rapidly, ie, that the best available predictor of the future is the past. However, there is no current clinical reason to make the diagnosis in the earliest stages of the disease. People in the age range at risk for AD are also at risk for other debilitating illnesses, such as strokes. They should make sound financial and personal plans including a living will and a health care proxy regardless of whether they might be in the early stages of AD. More pressing problems are scientific: ● What is the definition of AD in its early, “presymptomatic” stages?
*Tel.: 914-597-2351; fax: 914-597-2757. E-mail address: [email protected]; [email protected]
● Should it then be treated? ● If so, how? The conventional definition of AD has broadened since 1985, when the consensus of neurologists was that clinical disability had to be present to make the diagnosis in addition to the classical neuropathology. At that time, the assumption was widely held that the neuropathology was almost always accompanied by symptoms. However, prospective studies sponsored by the NIA and elsewhere have shown robustly that people can have the full neuropathologic picture of AD without clinically significant cognitive disabilities. Nor is this so rare an event as to be statistically unimportant. These people may have relatively minor, nondisabling abnormalities on detailed neuropsychological testing. However, the significance of such abnormalities is a fraught subject. The author of this commentary has had clear evidence of brain damage on detailed neuropsychological testing and even on skilled neurologic examination since his childhood, which did not prevent him from getting through graduate and medical school. Many workers now refer to the neuropathologic changes of AD and specifically to amyloid accumulation without significant clinical symptoms as “preclinical AD.” In other words, AD is increasingly being defined as cerebral amyloidosis independent of symptoms. Noninterventive imaging techniques to identify amyloid deposits in brain in vivo are improving rapidly, and it may soon be possible to diagnose cerebral amyloidosis by relatively objective radiologic techniques. Defining AD as cerebral amyloidosis will not do any harm as long as it is just a change in conventional nomenclature among scientists and health care professionals. It will do harm if it leads to inappropriate interventions in patients. The question will inevitably come up of whether to treat asymptomatic cerebral amyloidosis. Currently, the most widely accepted theories of AD give a central role to the toxicity of amyloid itself. They imply that prevent-
1552-5260/05/$ – see front matter © 2005 The Alzheimer’s Association. All rights reserved. doi:10.1016/j.jalz.2005.10.003
J.P. Blass / Alzheimer’s & Dementia 1 (2005) 124 –125
ing the accumulation of amyloid would benefit asymptomatic patients and might even prevent the development of clinical disability. This view is widespread, even though immunologic treatments directed against amyloid in people with established AD have given disappointing results, at least so far. Preventing AD before it causes disability is a wonderful goal. On the other hand, the history of medicine is full of well-meaning attempts to prevent illness that have turned out to do more harm than good, even though those attempts were based on sound and robust research results. Postmenopausal estrogen for
125
women is a recent example. Any intervention, no matter how “reasonable” or how much in tune with “the cuttingedge of mainstream science,” must be tested directly in appropriate clinical trials in people before it is widely applied to other human beings. Fortunately, the AD community and specifically the National Institute on Aging (NIA) have established expertise in obtaining the relevant information. That expertise needs to be used, even if doing so involves money and delays “in getting the treatment to the people.” The watchword must remain “First, do no harm.”
Commentary on “Diagnosis of Alzheimer’s disease: Two decades of progress.” Perspectives on “Perspectives” John P. Blass* Burke Research Institute, Weill-Cornell Medical College, 785 Manaroneck Avenue, White Plains, NY 10605 USA
The article by Dr. Zaven Khachaturian is a superb, concise summary of the development of our understanding of dementias in general and of Alzheimer’s disease (AD) in particular. It documents that good leadership from the Federal Government can be part of the solution. It also provides sound counsel on what needs to be done now. As indicated in that article, improvement in the diagnosis of AD or other dementia in the clinical setting is not now a pressing problem. Dementia can be recognized with confidence on the basis of medical history (anamenusis) and neuropsychological testing. Treatable conditions that contribute to cognitive disability can be detected by the nowstandardized dementia workup, given reasonable clinical acumen on the part of the examiner. Serial brain imaging studies can indicate whether there is evidence of accelerated atrophy even before symptoms become debilitating, in time for people to make appropriate practical arrangements. The diagnosis of AD can be made with more than 90% confidence on the basis of a careful evaluation, as documented by a number of studies in which patients were followed up until autopsy. The course of AD is hard to predict in any individual patient, except for the generalization that worse illness tends to progress more rapidly, ie, that the best available predictor of the future is the past. However, there is no current clinical reason to make the diagnosis in the earliest stages of the disease. People in the age range at risk for AD are also at risk for other debilitating illnesses, such as strokes. They should make sound financial and personal plans including a living will and a health care proxy regardless of whether they might be in the early stages of AD. More pressing problems are scientific: ● What is the definition of AD in its early, “presymptomatic” stages?
*Tel.: 914-597-2351; fax: 914-597-2757. E-mail address: [email protected]; [email protected]
● Should it then be treated? ● If so, how? The conventional definition of AD has broadened since 1985, when the consensus of neurologists was that clinical disability had to be present to make the diagnosis in addition to the classical neuropathology. At that time, the assumption was widely held that the neuropathology was almost always accompanied by symptoms. However, prospective studies sponsored by the NIA and elsewhere have shown robustly that people can have the full neuropathologic picture of AD without clinically significant cognitive disabilities. Nor is this so rare an event as to be statistically unimportant. These people may have relatively minor, nondisabling abnormalities on detailed neuropsychological testing. However, the significance of such abnormalities is a fraught subject. The author of this commentary has had clear evidence of brain damage on detailed neuropsychological testing and even on skilled neurologic examination since his childhood, which did not prevent him from getting through graduate and medical school. Many workers now refer to the neuropathologic changes of AD and specifically to amyloid accumulation without significant clinical symptoms as “preclinical AD.” In other words, AD is increasingly being defined as cerebral amyloidosis independent of symptoms. Noninterventive imaging techniques to identify amyloid deposits in brain in vivo are improving rapidly, and it may soon be possible to diagnose cerebral amyloidosis by relatively objective radiologic techniques. Defining AD as cerebral amyloidosis will not do any harm as long as it is just a change in conventional nomenclature among scientists and health care professionals. It will do harm if it leads to inappropriate interventions in patients. The question will inevitably come up of whether to treat asymptomatic cerebral amyloidosis. Currently, the most widely accepted theories of AD give a central role to the toxicity of amyloid itself. They imply that prevent-
1552-5260/05/$ – see front matter © 2005 The Alzheimer’s Association. All rights reserved. doi:10.1016/j.jalz.2005.10.003
J.P. Blass / Alzheimer’s & Dementia 1 (2005) 124 –125
ing the accumulation of amyloid would benefit asymptomatic patients and might even prevent the development of clinical disability. This view is widespread, even though immunologic treatments directed against amyloid in people with established AD have given disappointing results, at least so far. Preventing AD before it causes disability is a wonderful goal. On the other hand, the history of medicine is full of well-meaning attempts to prevent illness that have turned out to do more harm than good, even though those attempts were based on sound and robust research results. Postmenopausal estrogen for
125
women is a recent example. Any intervention, no matter how “reasonable” or how much in tune with “the cuttingedge of mainstream science,” must be tested directly in appropriate clinical trials in people before it is widely applied to other human beings. Fortunately, the AD community and specifically the National Institute on Aging (NIA) have established expertise in obtaining the relevant information. That expertise needs to be used, even if doing so involves money and delays “in getting the treatment to the people.” The watchword must remain “First, do no harm.”