Result card

  • CUR12: How are the Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) currently managed according to published guidelines and in practice?

How are the Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) currently managed according to published guidelines and in practice?

Authors: Antonio Migliore, Tapani Keranen, Sinikka Sihvo

Internal reviewers: Kristian Lampe

There are no effective interventions available for MCI {16}. Two meta-analyses of the three studies reporting  conversion MCI to dementia gave no clear evidence of a beneficial effect of cholinesterase inhibitors (ChEI) on the progression to dementia at one, two or three years {70} {79}. The risk ratio (RR) for conversion at two years was significantly different from unity (0.67; 95% CI 0.55–0.83), but this is based on only two studies reported in the same article. There were essentially no clinically meaningful symptomatic effects of ChEI on cognitive test scores {70}. Other pharmacological interventions, such as huperzine A {88}, a chemical derived from a type of club moss (Huperzia serrate), vitamin E {24}, piribedil, nicotine, gingko biloba, B vitamins, nonsteroidal anti-inflammatory drugs, and omega-3 polysaturated fatty acids {16} have failed to reduce the risk of conversion to AD.

Non-pharmacological interventions physical activity and cognitive exercise may improve memory and executive functions in older people with MCI {67} {77}. Cognitive training interventions may improve some cognitive aspects in patients with MCI such as memory performance, executive functioning and attention but effects of these improvements on ADL functions is unclear {67}. Physical exercise may also have some positive effects {63} {77}. Treatment of modifiable risk factors in MCI, such as hypertension, diabetes mellitus, and hyperlipidemia, is recommended although there are no data of positive effects of interventions against these disorders {23}.

Currently available drug treatments for AD are considered symptomatic. It is recommended that patients with AD and mild to moderate dementia are initially treated with one of the cholinesterase inhibitors (ChEIs), i.e. donepezil, galantamine, or rivastigmine {30} {38} {89}. These drugs have been shown as having efficacy on cognitive function, global outcome, and ADL functions {38}. The effects of ChEis have been demonstrated mainly in studies lasting up to six months and the magnitude of the effects seems to be at the best modest {21} {38}. ChEIs have generally shown no meaningful improvement in the quality of life in patients with AD. The most common adverse effects of ChEIs are nausea, vomiting, diarrhea, abdominal pain, malaise, fatique, dizziness and headache. There is no conclusive evidence of any differenced in the efficacy or safety of the three ChEis {30} {38}. There are some discrepancies in the conclusions of different guidelines in respect to the use of ChEIs in severe AD: The NICE guidance {89} limits the use of ChEIs for mild to moderate AD whereas the European Federations of Neurological Sciences (EFNS) guideline and a Canadian guideline recommend the use of ChEIs also in the severe AD {30} {38}.

Memantine is a non-competetive N-methyl-D-aspartate receptor agonist which has been approved for use in moderate to severe AD. Evidence for the efficacy of memantine monotherapy in mild AD is lacking {71}. Recently, its efficacy as monotherapy in moderate to severe AD has been challenged {45}. The benefits of adding memantine to ChEI treatment are not clear {38} {61}. Systematic reviews suggest that the combination treatment with memantine and ChEIs may have beneficial effects on cognition, functional outcome and neuropsychiatric symptoms in patients with moderate to severe AD but the clinical relevance of the effects is unclear {25} {60}. The NICE guidance recommends the use of memantine in patients moderate AD who are intolerant or have a contraindication for ChEIs or for patients who have severe stage of AD {89}. The Canadian guideline concludes that there is insufficient evidence to recommend for or against the combined use of ChEIs and memantine {30}. Behavioral and psychic symptoms are prevalent in patients with AD the symptomatology tends to worsen with the progression of the disease. ChEIs have been shown to reduce behavioral and psychological symptoms in patients with mild to severe AD but the clinical relevance of the effects us unclear {11} {38}. ChEIs may have beneficial effects on psychosis and apathy {38}. Memantine may have efficacy on delusions, agitation, aggression and irritability in patients with severe AD {38}. Antidepressants may reduce agitation in patients with AD {74}. Risperidone and olanzapine are useful in reducing aggression in AD, and risperidone reduces psychotic symptoms in AD patient, but these drugs are associated with serous adverse cardiovascular events and extrapyramidal as well as with a small increase in the risk of death symptoms {6} {72}. Guidelines suggest that atypical antipsychotics can be used for severe agitation, aggression and psychosis at low doses and with careful monitoring {30} {38}. Mood stabilizers are ineffective or even harmful in AD {87}.

It has been shown that occupational therapies and exercise interventions may slow functional decline in AD but the clinical significance of the findings is uncertain {52}.

Migliore A et al. Result Card CUR12 In: Migliore A et al. Health Problem and Current Use of the Technology In: Jefferson T, Cerbo M, Vicari N [eds.]. Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 2 December 2022]. Available from: