Alzheimer's Disease Therapeutics
Alzheimer's Disease Therapeutics
It has been 100 years since Alois Alzheimer discovered the unique histological findings that pathologically define the disease named after him. However, over the subsequent decades, Alzheimer’s disease (AD) received relatively little attention in the medical community. In fact, it is only within the past 15 years that pharmacological agents have been available as treatment for AD.
This delay in recognition of AD as a major neurological disease of aging does not reflect its impact.There are the personal tragedies that accompany the disease—the tragedy of having one’s memories, accumulated over a lifetime, gradually stripped away; the tragedy of watching someone you have loved and admired slowly losing their powers of thought, language, and often their personality; and the tragedy that comes with caregivers having to sacrifice to provide needed care, often at the expense of family disruption, financial loss, and depression. In addition, the economic cost to society is substantial; it has been estimated that close to US$100 billion is spent in the US per year in care and treatment of AD patients.
Due to the increased longevity of the US population, the absolute number of people afflicted by AD is expected to grow substantially.1 The US will see a 44% increase in the number of individuals with AD by 2025, affecting close to eight million Americans.Yet, given the demographics of the disease, if a treatment was developed that would push back the onset of the disease by only five years, the number of people with AD would be reduced by approximately half.
Of the current therapies for AD, most are based on the idea of neurotransmitter replacement. The most successful class of medications has been the cholinesterase inhibitors (tacrine, donepezil, rivistigmine, and galantamine). By enhancing cholinergic transmission, these drugs attempt to address the marked cholinergic deficits (up to 90%) seen in AD. The benefit of these medications is modest, but replicable across agents. On average, patients taking cholinesterase inhibitors (CEIs) may experience a transient improvement in cognitive performance measures, trending back to their baseline by six to 12 months.2 Similarly, differences between treated and untreated patients can also be seen on functional and behavioral scales. Due to the absence of multi-year placebo-controlled trials, the long-term effect of CEIs in AD is unclear. However, using data obtained from treated patients that have been followed in open label studies, there may be a sustained benefit lasting at least five years compared to historical controls.
Side effects of these medications are generally tolerable and include nausea, anorexia, and diarrhea. Often these bothersome cholinergic effects can be avoided by slow titration of the drug, or managed by concurrent use of peripheral anticholinergics such as glycopyralate or dicyclomine.
Some have questioned the cost-effectiveness of using CEIs. Many, but not all, pharmacoeconomic studies have found that this class of drugs is either cost neutral or actually results in cost savings, mostly by deferring placement in residential care or reducing caregiver time spent assisting patients.3
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- Knopman D, “Current treatment of mild cognitive impairment and Alzheimer’s Disease”, Curr Neurol Neurosci Rep (2006);6: pp. 365–371.
- Reisberg B, Doody R, Stoffler A et al., “Memantine Study Group. Memantine in moderate to severe Alzheimer’s Disease”, N Engl J Med (2003);348: pp. 1333–1341.
- Morgan D,“Immunotherapy for Alzheimer’s Disease”, J Alzheimer’s Dis (2006);9: pp. 425–432.
- Schneider L,Tariot P, Dagerman K et al.,“Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s Disease”,N Engl J Med (2006);355: pp. 1525–1538.
