"My doctor says it's hardening of the arteries." That was a statement I heard innumerable times well into the 1980s when I had a busy general neurology practice that included many patients with dementia. Then, I patiently explained to concerned and burdened spouses and children that, "Yes, your loved one may have atherosclerosis, but that is unlikely to be the cause of the problem. He has Alzheimer disease." Now, however, in the past couple of decades, steady progress has been made in parsing the dementias so that we have a much clearer picture of the extensive variety of neuropathologic, neurochemical, and immunologic changes that occur with these syndromes. In this issue of Continuum, Dr Michael Geschwind and his assembled faculty of experts will inform you of the major, as well as the sometimes nuanced, differences among dementing illnesses. Alas, progress in the therapeutics of dementia has not kept pace with advances in differential diagnosis and basic science. Nonetheless, by better understanding the varieties of dementia and the behavioral consequences, you will be equipped to provide the best care for these patients whose illness strikes at the very core of what distinguishes us as human beings.
To be sure, Alzheimer disease (AD) remains the "big gorilla" among the dementias. Thus, it is fitting that a chapter on an update on AD by Dr Brandy Matthews kicks off this issue. Dr Geschwind, himself, has a particular interest in rapidly progressive dementias, and his chapter focuses on prion diseases as well as other disorders with this temporal profile. For more than 40 years, the biologic quirks of prion diseases have fascinated scientists, resulting in the awarding of two Nobel prizes. The first went to Dr Carleton Gajdusek, who demonstrated the transmissibility of these disorders, and the second was awarded to Dr Stanley Prusiner, one of very few neurologists to receive this coveted prize, who coined the term prionand has contributed mightily to our understanding of the biologic peculiarity of these conformationally transformed proteins.
In recent years we have increasingly recognized that Parkinson disease and other parkinsonian syndromes don't simply feature disturbances of motor function and control. Rather they are complex disorders with a variety of nonmotor manifestations, commonly including cognitive dysfunction. Drs Katherine Possin and Daniel Kaufer clarify the differences among the parkinsonian dementias, including the pathologic division into synucleinopathies and tauopathies. Their chapter includes discussion of the cognitive problems in Parkinson disease itself, dementia with Lewy bodies, and the cognitive abnormalities in the sometimes-called Parkinson-plus syndromes, including multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. In a later chapter, Drs Gorsev Yener, Howard Rosen, and John Papatriantafyllou elucidate and dissect the behaviorally fascinating varieties of frontotemporal degeneration. While these entities have clinical manifestations that may overlap AD, their phenotypes are often unique. Better understanding of these differences should allow you to avoid some therapeutic pitfalls and to provide optimal care for patients suffering from these disorders. Indeed, the behavioral consequences, particularly of those patients with frontal lobe symptomatology, are often a source of great embarrassment and frustration for caregivers, who need tremendous support and education from their physicians and other health care providers.
Important, albeit relatively uncommon, the immunotherapy-responsive dementias and encephalopathies are thoroughly reviewed by Drs Andrew McKeon, Vanda Lennon, and Sean Pittock. These conditions, often but not always associated with cancer, are exciting, not only because of their intriguing neurobiology, but because they sometimes respond substantially to treatment. Also among the less commonly encountered dementias, the leukoencephalopathies and leukodystrophies, a variety of genetic metabolic disorders, must not be overlooked by neurologists as a potential cause of dementia in an occasional patient. Dr Gregory Pastores brings you up to speed on this group of diseases.
Dementia is not the only important neuropsychiatric disorder that neurologists will encounter. In fact, you can look forward later this year to another issue of Continuum that will be devoted to behavioral neurology. Over the years, we, as neurologists, have been taught the importance of distinguishing delirium from dementia. The former remains a very serious condition, most frequently encountered in the hospital setting. Recognizing delirium, determining its etiology, and providing effective management-clearly discussed in a chapter by Drs Vanja Douglas and S. Andrew Josephson-are critical because this condition is associated with significant morbidity and mortality. We are accustomed to thinking of schizophrenia and bipolar disorder as purely psychiatric illnesses, but we are relatively recently discovering that these conditions are frequently associated with cognitive impairments and decline that warrant our attention as neurologists. Drs Barton Palmer, Ms Casey Loughran, and Dr Thomas Meeks will update you on progress in this area.
In the modern era, neurologic diagnosis is often greatly aided by proper utilization of a variety of neuroimaging techniques. This is true for dementia, and Drs Maria Tartaglia, Paolo Vitali, Raffaella Migliaccio, Federica Agosta, and Howard Rosen review the utility of both neuroanatomic and neurophysiologic imaging techniques. In addition, in order to tease apart the various dementias, as well as to help patients and caregivers cope better with theconditions, proper neurocognitive assessment is critical. In their chapter on this subject, Drs Casey Krueger and Joel Kramer provide expert guidance.
Each issue of Continuum also features short sections on ethical perspectives and practice issues related to the subject. Herein we feature a discussion by Drs Peter Rabins and Betty Black of the ethics involved in a decision about the off-label use of medication and an analysis by Dr David Knopman about issues related to the placement of demented patients in long-term care facilities.
As usual, Continuum readers may enhance their educational experience by working through the Patient Management Problem, crafted for this issue by Dr Gil Rabinovici, and by tackling the multiple-choice questions developed by Drs Ronnie Bergen and Douglas Gelb. Also, in this issue, for the first time we add a new feature to Continuum, a table of codes relevant to the issue's subject matter. We hope you will find this addition helpful.
I believe that both the breadth and depth of this issue of Continuum will impress you with how far the field has come in better understanding the wide variety of circumstances associated with dementia. We are all indebted to Dr Geschwind and his large, talented faculty for enhancing our knowledge of this subject. We can only hope that the years to come will bring us not only increasing ability to better diagnose and understand our patients with dementia, but also the possibility to provide effective therapy to halt or even reverse their devastating cognitive decline.
-Aaron E. Miller, MD