TREATMENT OF COGNITION

Abstract

Treatment with cholinesterase inhibitors modestly improves cognition, activities of daily living and global clinician rating of patients with mild, moderate and severe Alzheimer's disease (AD). Improvements are close to minimal clinically important values such that clinicians should not expect to be able to make decisions about response in an individual treated patient. Treatment decisions will often be influenced by experience of side-effects, in particular nausea, vomiting, diarrhoea, vivid dreams and cramps. These drugs do not improve non-cognitive AD symptoms and there is no convincing evidence for additional cognitive or functional benefit with higher than standard (>10mg donepezil) dosing. Although most trials have been of short duration, treatment benefits appear to be sustained, even in severely affected individuals, and this should be considered in discontinuation decisions. Meta-analyses report cognitive benefits in patients with dementia with Lewy bodies and Parkinson's disease dementia. Although not recommended for patients with frontotemporal or vascular dementia, patients with mixed vascular and AD pathology may benefit from treatment. Memantine improves cognition, activities of daily living and global rating, but benefits are smaller than those seen with cholinesterase inhibitors, often not reaching clinically important levels and is often used for patients who cannot tolerate a cholinesterase inhibitor. Combination treatment with a cholinesterase inhibitor is associated with very small additional benefit compared to cholinesterase inhibitor alone. Cognitive stimulation therapy has better evidence to support claims for improving cognition in AD than cognitive training and cognitive rehabilitation. It is important to bear in mind that most cognitive intervention studies have not included active control interventions or strategies to blind outcome assessors that would allow meaningful comparison with the results of pharmaceutical trials. Finally, physical exercise may improve activities of daily living in AD, but reported effects on cognition have not been consistent. Together with the difficulties in interpretation of efficacy associated again with failure to include adequate control interventions or to blind outcome assessors, it is still unclear whether the intensity of prescribed exercise needs to exceed a threshold above which cognitive benefits can be demonstrated.