Cognitive performance in patients with Alzheimer's disease receiving cholinesterase inhibitors for up to 5 years

Abstract

The cholinesterase inhibitors (ChE-Is)--rivastigmine, donepezil and galantamine--demonstrated efficacy in large, 6-month, double-blind, placebo-controlled trials, and are widely used for the symptomatic treatment of patients with mild-to-moderate Alzheimer's disease (AD). Over the past few years, data have emerged, suggesting that these agents may have long-term benefits. These data have been summarized in this study, followed by an interpretation of clinical relevance. Data were identified by searches of Medline((R)) and references from relevant English-language articles. The search words 'Alzheimer', 'donepezil', 'rivastigmine', 'galantamine' and 'long term' were used. In addition, recent data presented at international congresses and/or provided by colleagues in this field of research were included in order to ensure maximum topicality. Data are available showing cognitive performance in patients remaining on rivastigmine for up to 5 years (n = 83), donepezil for up to 4.9 years (n = 18) and galantamine for up to 4 years (n = 185). Most of these data come from open-label studies and need to be interpreted with caution. The data appear to suggest that patients, caregivers and physicians will still see some decline on ChE-Is after a period of stabilization, but this may be slower and later than expected if the patients were left untreated. This applies across all domains of AD - not simply cognition - and function can be relatively preserved, even if cognitive scores are falling. Despite the limitations of current data, the information reviewed in this study may help practising doctors assess the long-term value of ChE-Is in this consistently progressive disease.

Rivastigmine effects on EEG spectra and three-dimensional LORETA functional imaging in Alzheimer’s disease

“…In fact, the typical annual decline in untreated patients has been reported to be two to four points on the MMSE (Bullock and Dengiz 2005). Specifically, 8 of our 16 AD patients cognitively benefited from the treatment, in line with previous observations that a positive response to the medication occurs on average in 30-70% of treated patients (e.g., Farlow et al 2000;Feldman and Lane 2007).…”

“…Clinical studies have confirmed the efficacy of ChE-I treatment in AD on cognitive and neuropsychiatric symptoms (see Bullock and Dengiz 2005, for a review) and a series of recent positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies reported an increase of cortical activity due to ChE-I therapy at temporo-parietal and frontal regions (e.g., Bohnen et al 2005;Ceravolo et al 2004;Mega et al 2001), in the hippocampus (Mega et al 2001), and in the posterior cingulum (Bohnen et al 2005;Ceravolo et al 2004), i.e., in regions that have been shown to be the most affected cortical areas in AD (e.g., Jagust et al 1997).…”

Pharmacotherapy of Alzheimer Disease

“…[32][33][34] Analyses of data collected over 5 years suggest benefits over a range of domains, including cognition, providing rationale for long-term treatment with a ChEI. 35 However, it is important to bear in mind that studies with open-label extensions have several biases, including selective dropout and survivor effects, and the results may not be generalizable to patients at large.…”

Long-Term Response to Cholinesterase Inhibitor Treatment Is Related to Functional MRI Response in Alzheimer's Disease

“…According to previous studies, it seems that at least one third of the treated patients derive no clinically meaningful benefit from ChEI treatment [6,7,8,9,10], and in the clinical setting it is difficult to predict who will respond to treatment. However, even patients with severe [11,12] AD may benefit from the treatment; some may even have 5 years of beneficial effects [13]. Although no specific tests are available to identify patients likely to respond to these drugs, a number of clinical features have been proposed as possible response predictors, including younger age, a faster rate of progression, a moderate rather than mild level of cognitive dysfunction, the presence of symptoms suggesting Lewy body pathology, concomitant vascular pathology and brain perfusion changes after a testing dose as well as the neuropsychological profile and an initial clinical response to treatment [14,15,16,17].…”