Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology

Abstract

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review the evidence on the drug treatment for dementia. The level of evidence (types) was rated using a standard system: Types 1a and 1b (evidence from meta-analysis of randomised controlled trials or at least one controlled trial respectively); types 2a and 2b (one well-designed study or one other type of quasi experimental study respectively); type 3 (non-experimental descriptive studies); and type 4 (expert opinion). There is type 1a evidence for cholinesterase inhibitors (donepezil, rivastigmine and galantamine) for mild to moderate Alzheimer's disease; memantine for moderate to severe Alzheimer's disease; and for the use of bright light therapy and aromatherapy. There is type 1a evidence of no effect of anti inflammatory drugs or statins. There is conflicting evidence regarding oestrogens, with type 2a evidence of a protective effect of oestrogens but 1b evidence of a harmful effect. Type 1a evidence for any effect of B12 and folate will be forthcoming when current trials report. There is type 1b evidence for gingko biloba in producing a modest benefit of cognitive function; cholinesterase inhibitors for the treatment of people with Lewy body disease (particularly neuropsychiatric symptoms); cholinesterase inhibitors and memantine in treatment cognitive impairment associated with vascular dementia; and the effect of metal collating agents (although these should not be prescribed until more data on safety and efficacy are available). There is type 1b evidence to show that neither cholinesterase inhibitors nor vitamin E reduce the risk of developing Alzheimer's disease in people with mild cognitive impairment; and there is no evidence that there is any intervention that can prevent the onset of dementia. There is type 1b evidence for the beneficial effects of adding memantine to cholinesterase inhibitors, and type 2b evidence of positive switching outcomes from one cholinesterase inhibitor to another. There is type 2a evidence for a positive effect of reminiscence therapy, and type 2a evidence that cognitive training does not work. There is type 3 evidence to support the use of psychological interventions in dementia. There is type 2 evidence that a clinical diagnosis of dementia can be made accurately and that brain imaging increases that accuracy. Although the consensus statement dealt largely with medication, the role of dementia care in secondary services (geriatric medicine and old age psychiatry) and primary care, along with health economics, was discussed. There is ample evidence that there are effective treatments for people with dementia, and Alzheimer's disease in particular. Patients, their carers, and clinicians deserve to be optimistic in a field which often attracts therapeutic nihilism.

Pharmacotherapy of Alzheimer Disease

“…Alternative models of analysis, including mixed-effects models, regression techniques, or assigning an average or worst-case outcome scenario to dropouts are being considered. 59 Other issues that need to be considered include the use of multiple comparisons and the correction of level of significance. 59 Responder analysis is becoming a very important component of planned analysis in clinical trials for AD.…”

“…59 Other issues that need to be considered include the use of multiple comparisons and the correction of level of significance. 59 Responder analysis is becoming a very important component of planned analysis in clinical trials for AD. The ability to determine which drug class or drug within a class will help individual patients, according to their genotype and (or) disease phenotype, their age of onset, or the severity of their symptoms at time of treatment initiation, will become part of the long-term management of AD.…”

Influence of Galantamine on Vasomotor Reactivity in Alzheimer’s Disease and Vascular Dementia Due to Cerebral Microangiopathy

“…13 Furthermore, we aimed to compare VMR of patients with AD to VMR changes caused by microangiopathy in patients with vascular dementia (VaD) as previously shown for cerebral microangiopathy by our group. 14 We further hypothesized that the plant alkaloid galantamine, which is routinely used for the treatment of AD, 15 improves VMR due to the increased cholinergic neurotransmission caused by its acetylcholine esterase inhibitor (AChE inhibitor) activity and its potentiating effect on nicotinergic acetylcholine receptors. 16 This hypothesis is supported by a recent report that another AChE inhibitor, donepezil, can restore disturbed dynamic cerebrovascular regulation in AD.…”

The UPS and autophagy in chronic neurodegenerative disease: Six of one and half a dozen of the other—Or not?

“…1 Dementia with Lewy bodies is a clinical syndrome but Lewy bodies are also a consistent feature of so-called "comorbid" chronic neurodegenerative disease where brains contain mixed pathology indicative of Alzheimer disease, Parkinson disease and dementia with Lewy bodies. 43 The recent demonstration of the fundamental importance of the 26S proteasome for neuronal survival 1 indicates that in humans any 26S proteasome malfunction in brain neurons (and glia) may be the primary cause of neurodegeneration. 44 Finally, those working in the field of chronic neurodegeneration have been disappointed that over a decade of transgenic overexpression of amyloidogenic proteins has not led to neurodegeneration or progress in understanding and combating disease.…”