The cholinesterase inhibitors like Aricept (i.e., donepezil, rivastigmine, and galantamine) have been available for treatment of dementias such as Alzheimer’s disease since the mid 1990s. These medications slow the progression of Alzheimer’s disease (in those who tolerate them) and discontinuing them after extended use may induce a rapid decline even in those so impaired that they are in skilled nursing facilities. Despite these facts, the cholinesterase inhibitors are often maligned, not used, or discontinued too soon because they do not produce dramatic effects and do not arrest or reverse decline.
Although Alzheimer’s and similar dementias are classified as memory disorders, they actually have an impact on many brains skills or domains. In addition to memory, Alzheimer’s disease may produce impairments in attention, language such as word finding, visuospatial skills like drawing/handiwork, personality, mood, and/or executive functions. All of these skills are affected by changes in acetylcholine, the neurotransmitter that is increased by use of cholinesterase inhibitors. If we were to understand the benefits of these medications as consumers, it would be helpful to know what specific domains of possible benefits to expect.
This was the question addressed by “Treatment effects in multiple cognitive domains in Alzheimer’s disease: a two-year cohort study (Alzheimer’s Research and Therapy, 2014, 6, 48-60, PMID 25484926). As pointed out by the authors, there have been 4 large clinical trials demonstrating the benefits of cholinesterase inhibitors on global cognitive functioning (such as changes in the total score on the MMSE) for at least two years when compared to untreated matched control cases. However, there has been very little study of the specific domains or brain skills that respond to this treatment. It is especially important to understand the effects on executive functions as they are strongly correlated with activities such as cooking, driving, shopping, and managing the checkbook.
The focus of the study was to determine the effects of cholinesterase inhibitors on treated and untreated persons with Alzheimer’s disease for up to two years. Both measures of global functioning (MMSE and Dementia Rating Scale (DRS) total scores) and domain specific (e.g., memory, executive function) scores were obtained. The two groups were well matched in terms of age, education, and beginning MMSE and DRS scores. Treatment produced benefits on total score on both the MMSE and the DRS. For example; the average MMSE score began at 24.2 and declined to 20.2 in the treated group but declined from 22.9 to 16.4 in the untreated group.
More importantly, the major effects of treatment were in the domains of attention, visuoconstructive skills, and executive function. Despite being thought of as memory enhancers, these medications had little benefit on memory. In short, cholinesterase inhibitors do not improve short-term memory. Rather they slow the rate of decline in critical skills such as word finding, engaging in the world, and thinking abstractly. They reduce the burden of care by keeping together routines and self care skills longer than in the absence of treatment. These are important benefits despite the progressive nature of these dementias; treatment with cholinesterase inhibitors buys time.