Why not Racetams Front Line Dementia Treatments
Evidence in dementia
Small arsenal against Alzheimer's
Acetylcholinesterase inhibitors. The guideline gives the following recommendations for the three active ingredients currently approved for mild to moderate Alzheimer's dementia, donepezil, galantamine and rivastigmine, some of which require off-label use (see Fig.). They state that acetylcholinesterase inhibitors are effective in terms of the ability to carry out everyday activities, the improvement of cognitive functions and the overall medical impression in the case of mild to moderate illness. Treatment is recommended (grade of recommendation B, see box "Grades of recommendation"), whereby the highest tolerated dose should be aimed for (grade of recommendation A). Since there is insufficient evidence for clinically relevant differences in the effectiveness of the available substances, the selection should primarily be based on the side and interaction profile (recommendation grade B). Acetylcholinesterase inhibitors can be given continuously if they are well tolerated in the mild to medium stage (recommendation grade B). With long-term treatment and clinical progression to moderate to severe disease, discontinuation of acetylcholinesterase inhibitors is associated with a risk of clinical deterioration in Alzheimer's dementia. A withdrawal attempt is therefore only recommended if there is any doubt about a favorable ratio of benefit to side effects (recommendation grade 0). If necessary, switching to another acetylcholinesterase inhibitor can then be considered (recommendation grade B). There is evidence that donepezil is effective in Alzheimer's dementia in the severe stage of the disease on cognition, everyday functions and overall clinical impression, and of galantamine on cognition. The (off-label) further treatment of pretreated patients who enter the severe stage or the initial treatment of patients in the severe stage can be recommended (recommendation grade B).
Memantine. The non-competitive NMDA antagonist memantine is approved in Germany for the treatment of moderate to severe Alzheimer's dementia, but not for mild forms of the disease. Its use is recommended by the guideline (recommendation grade B), since memantine is effective on cognition, everyday function and the overall clinical impression in patients with moderate to severe Alzheimer's disease. Because of its unproven benefit, memantine should not be used for the treatment of patients with mild Alzheimer's disease (recommendation grade A). There is less evidence regarding combination therapy with memantine and acetylcholinesterase inhibitors. It can be considered, for example, if the disease worsens under an acetylcholinesterase inhibitor, i. H. there is a transition from the moderate to the severe form. The data on add-on treatment with memantine in patients with severe Alzheimer's dementia receiving donepezil is contradicting itself. An add-on treatment can be considered (recommendation grade 0), it would currently be off label. For an add-on treatment with memantine in patients with Alzheimer's dementia in the mild, moderate (MMST *: 10-14 points) to upper moderate range (MMST: 15-22 points) who are already receiving an acetylcholinesterase inhibitor, no superiority over acetylcholinesterase inhibitor monotherapy was demonstrated. It is therefore not recommended (recommendation grade B).
Ginkgo biloba. Ginkgo biloba was not recommended in the previous version of the dementia guideline. According to the updated edition, treatment with the extract EGb 761 can be considered (recommendation grade 0), as there are efficacy indications on cognition in patients with mild to moderate Alzheimer's dementia or vascular dementia and non-psychotic behavioral symptoms. A detailed assessment of the evidence of ginkgo biloba in dementia can be found on page 32 of this issue.
Other therapeutics. A therapy for Alzheimer's dementia with Vitamin E. is not recommended due to the lack of evidence for efficacy and the risk of side effects (recommendation grade A), since risks such as increased general mortality and more frequent cardiovascular events have been observed in healthy individuals.
For an effectiveness of nonsteroidal anti-inflammatory drugs (Rofecoxib, naproxen, diclofenac, indomethacin) there is no convincing evidence on the symptoms of Alzheimer's dementia, treatment is therefore not recommended (recommendation grade A).
For postmenopausal women, one should Hormone replacement therapy are not used to reduce cognitive impairments (recommendation grade B). This recommendation is based inter alia. based on a meta-analysis of five RCTs that had shown no evidence of the effectiveness of hormone replacement therapy on cognition in women with dementia. There are also indications of an increased risk, including: for stroke, thrombosis or breast cancer, for hormone replacement therapy.
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