Treatment of dementia

ementia describes a chronic and progressive clinical syndrome characterised by cognitive impairment (particularly memory loss), inability to perform activities of daily living, and neuropsychiatric features (psychiatric symptoms and behavioural disturbances, also known as behavioural and psychological symptoms of dementia or BPSD).It affects an estimated 800 000 people in the UK and four million in the USA.Alzheimer's disease (AD) is the most common cause of dementia (60%), followed by vascular dementia (VaD) (20%) (although 20% of people have both AD and VaD) and dementia with Lewy bodies (DLB) (15%).There have been significant advances in treatments available for dementia in the last few years. CHOLINESTERASE INHIBITORS cCholinesterase inhibitors (ChEIs) are the mainstay of treatment of Alzheimer's disease.Randomised controlled trials (RCTs) have reported statistically significant, and clinically modest, effects of ChEIs.Trials have been short, conducted over six months, although effects have been reported, in open label extensions, to last up to five years.The primary aim of the trials has been to assess the treatment response for cognitive decline.This is most often measured using the Alzheimer's disease assessment scale (ADAS-Cog), 1 which assesses multiple cognitive outcomes and is an accepted standard for measuring cognitive abilities in clinical trials.The total score of the ADAS-Cog ranges from 0-70, the higher score indicating greater impairment.Over a six month period untreated patients with mild to moderate AD typically deteriorate as signified by an increase of 3-4 points on the ADAS-Cog.Patients with moderate to severe AD have an increase of 4-6 points over the same period of time. 2 The Cochrane Review of donepezil for AD found an improvement at 24 weeks of 2.9 on the ADAS-Cog compared with placebo. 3Similar findings were reported in the Cochrane reviews of galantamine 4 and rivastigmine. 5Another primary aim of trials has been to assess changes in subjects' functional abilities.This is measured using a global assessment such as the clinician's interview-based impression of change plus caregiver input (CIBIC-plus). 6A subjective interview by a clinician with a patient and caregiver, assessing the patient's function, in four areas determines whether overall the patient has improved, stayed the same or deteriorated, using a 7 point scale.If an effect is detected during the clinician's interview it is assumed that it is clinically relevant.The Cochrane Reviews 3-5 dichotomised rating scale data into those who had no change or improvement versus those who worsened and found a statistically significant effect in favour of treatment, with an odds ratio of approximately 2. The Cochrane Reviews also report significant improvements on rating scales for activities of daily living and neuropsychiatric symptoms.The Cochrane Review of donepezil for AD 3 reports a low dropout rate of under 20%, with similar numbers for treatment and control groups within a study, except for the treatment group taking 10 mg/day of donepezil which had slightly higher dropout rates.Apart from Cochrane Reviews there have been several other meta-analyses that conclude there is a significant benefit from treatment with ChEIs.There are, however, concerns regarding the quality of evidence and the size of the benefits, which are felt, by some, to be minimal. 7It has been suggested that many systematic reviews have not stringently assessed the quality of studies 7 and that most, if not all, ChEIs trials have flawed methodology, which questions their validity.There is also a shortage of evidence of improvement of quality of life using validated, dementia specific measures, while pharmacoeconomic evaluations of ChEIs have so far been conducted in retrospect.