Although treatments for Alzheimer’s disease (AD) currently focus on symptomatic therapies, we are entering into an era of disease-modifying therapies. Central to disease modification is early diagnosis; the disease should be slowed as early as possible, maximizing the preservation of cognitive integrity. Ideally, AD should be diagnosed before the onset of dementia, perhaps with the use of biomarkers.
Some therapies suggest that cholinesterase inhibitors and memantine have disease-modifying properties, though not all studies agree. Doody and colleagues have produced data suggesting that these agents may modify the course of AD, but it is not clear that they affect the underlying mechanisms that lead to cell death. Rather than being disease-modifying agents, cholinesterase inhibitors and memantine have potential as disease-course-modifying agents. Language precision will be extremely important in describing these therapies. One European consensus conference concluded that affecting disease course is not adequate for disease modification, but this has not been largely endorsed.
Symptomatic therapies are those affecting the course of the disease. Their benefits are multidimensional, improving cognition, global assessment, activities of daily living, behavior, and caregiver burden. Symptomatic therapies should defer decline. Clinical trials show that symptomatic therapies produce an initial improvement above baseline. However, some patients experience observable changes and some experience none. These therapies are believed to produce ~1 point improvement on the Mini-Mental State Examination (MMSE) average, and a decline that is otherwise parallel to a placebo group after a period of delayed progression (Slide 1).