It would take more than half a century until we recognized that “senile dementia” and “Alzheimer’s disease” were one and the same. Most people who develop this dread condition, marked by cognitive changes (memory loss being the earliest and most striking example), behavioral changes (agitation and often paranoia), and ultimately, total dependence on others for the most basic functions of daily life, are in their seventies or eighties. Less commonly, they develop the same symptoms at a much younger age. Often these individuals have a hereditary form of the disease—but it is fundamentally exactly the same disorder.
How much progress have we made in understanding and treating Alzheimer’s disease in the past 100 years? An article in the British periodical, The Lancet, (Konrad Maurer, Ian McKeith, Jeffrey Cummings et al, “Has the Management of Alzheimer’s Disease Changed Over the Past 100 Years?” Lancet 2006; 368: 1619-1621) argues that many of the basic approaches to care remain unchanged, though the number of available medications has increased enormously. The authors indicate that already a century ago, Alzheimer understood that a key element of care was the environment. Patients with dementia need calm and compassionate caregivers and an atmosphere that is distracting but not excessively stimulating.
But what about all those medications we use today—Donezpezil (Aricept) and Memantine (Namenda) and drugs such as Risperidone (Risperdal) and Olanzapine (Zyprexa)? Just how much better are they than the small doses of alcohol and sedatives such as chloral hydrate and paraldehyde that were used in Alois Alzheimer’s day? Today’s pharmacologic agents may have fewer side effects than their predecessors, certainly an important consideration, but they are far from benign—the antipsychotics, for example, have been associated with an increased risk of stroke.
What concerns me is that the effectiveness of the medications we routinely and liberally use in Alzheimer’s disease is regrettably only modest. The cholinesterase inhibitors (such as Aricept) result in a statistically significant improvement in measures of global function—but it’s far from clear that they make a real difference in the daily lives of most patients and their caregivers. A review of all studies on these drugs by the British National Institute for Health and Clinical Excellence concluded the evidence for real benefit was so questionable that they should not be considered the standard of care (see my blog posting, “Americans, Alzheimer’s, and Aricept..”) The antipsychotic drug that are commonly used for agitation, restlessness, paranoia and other major behavioral features of Alzheimer’s have just been examined at in the most sophisticated and careful study to date. Unfortunately, the conclusion of this study is that these medicines are usually no more effective than placebo (See Lois Schneider, Pierre Tariot, Karen Dagerman et al, “Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer’s Disease,” New England Journal of Medicine 2006; 355:1525-1538). And the glutamatergic antagonists (ie Memantine) have been shown to slow the progression of disease in patients whose dementia is already advanced—an effect which some might regard as tantamount to leaving patients suspended in a condition worse than death. (See Barry Reisenberg, Rachelle Doody, Albrecht Stoffler et al, “Memantine in Moderate-to-Severe Alzheimer’s Disease,” New England Journal of Medicine 2003; 343:1333-41).
Scientists have made remarkable strides in understanding the genetic and biochemical underpinnings of Alzheimer’s disease. Several promising avenues of research into treatment are being vigorously pursued—a vaccine, tested in mice, has led to dramatic regression of plaques in the brain. But bran diseases are extraordinarily complicated and those affecting thinking are particularly recalcitrant to treatment. Perhaps we should spend as much effort on designing more humane environments in which to care for people with dementia as we do searching for a pharmacologic fix.