Alzheimer’s disease: only a few therapies provide proof of benefit to patients

There is still no therapy that has a decisive impact on Alzheimer's disease and which could thus control insidious memory loss in the long term. The only proof from studies is that some drugs can slightly alleviate certain symptoms in the short term or delay their occurrence. There is a lack of corresponding scientific proof for the effectiveness of the many different non-drug interventions. However, in recent years, supporting research into Alzheimer's disease has increased markedly. If it bears fruit, it could lead to an improvement in therapy options in the long term. However, a totally fresh approach is probably required for a really successful treatment for dementia.

This is the conclusion that the Institute for Quality and Efficiency in Health Care (IQWiG) came to on completion of its comprehensive commission package on the topic of Alzheimer's disease. At the behest of the Federal Joint Committee (G-BA), the Institute investigated what benefit - and what harm - various therapy options might have for patients. For this purpose, not only the drugs cholinesterase inhibitors, memantine and Ginkgo biloba were put under the microscope, but also a large number of non-drug therapies, such as training for family caregivers and cognitive methods.

Benefit only proven for individual aspects

In collaboration with external experts, IQWiG scientists established that drugs in the cholinesterase inhibitor group have ositive effects on cognition. Patients at a mild or moderate stage of the disease who took a cholinesterase inhibitor for at least 4 months in studies could, for example, remember things better than those who were given a placebo.

On the other hand, preparations containing Ginkgo biloba appeared to have a favourable effect on the ability to cope with everyday life, if taken in high enough doses (240 mg daily). IQWiG also found proof of this in studies with patients suffering from mild or moderate dementia. However, the effect size remains unclear because the results varied greatly in the individual studies.

The potential benefit to patients, however, is only proven for these limited outcomes. For other treatment aspects, such as concomitant symptoms (e.g. agitation, depression), quality of life or care dependency, the studies either do not provide relevant proof or the data cannot be interpreted with sufficient certainty - in some cases they were not even collected.

No evidence of benefit for memantine

In the third group of Alzheimer drugs, in the case of the substance memantine, there is no evidence that patients benefit more from this drug than from a placebo for any aspect of the disease - not even for memory performance or activities of daily living.

Memantine is approved for the treatment of moderate and severe Alzheimer's disease. Ginkgo may also be prescribed in these cases. However, on the basis of available study data, it is not possible to state whether and to what extent ginkgo has an effect on patients suffering from severe dementia. This is because there is a lack of studies targeting this patient group.

Long-term effects of drugs remain unclear

Although the 3 above-mentioned drugs were tested in comparator trials, there are conspicuous research gaps: Most of the trials had a maximum duration of 6 months, so that it remains unclear what effects the preparations would have in longer term use. This also applies particularly to adverse side effects, which can be considerable in cholinesterase inhibitors in particular (nausea, vomiting, diarrhoea).

Moreover, there is a lack of valid trials that compare the drugs with each other or with non-drug therapies.

There is a great need for good quality studies on non-drug procedures

The gaps in the research into non-drug therapies are even more serious. The result of insufficient investment in research and of study methods that are not fully developed is that no reliable conclusions can be drawn even for procedures with potential, and consequently no proof of benefit is provided.

There is a wide range of approaches and some appear to be promising: from groupwork on memory training or activities in daily living to training for family caregivers. The scientists found a whole range of studies, but weaknesses in planning or carrying out meant that the results could not be reliably interpreted. Thus, IQWiG could not establish a proof of benefit for any of the procedures.

Widespread use without proof of benefit cannot be justified

As far as study methods are concerned, the non-drug procedures generally lag behind the drugs. One important reason for the delay is that there are no approval procedures and thus no body that calls for studies with a minimum methodological standard. Moreover, in contrast to the pharmaceutical industry, there are in general few financially strong companies which finance studies.

Nevertheless, IQWiG does not believe an exception on those grounds can be justified for the widespread use of certain therapies without proof of benefit since inadequately evaluated therapies can harm patients both mentally and physically, and place an unnecessary financial burden on the community of SHI insured citizens.

Supporting research could spur development of new therapies

"What we lack in Germany is public funding, independent of industry, for research into topics that are important for the treatment of patients. This is painfully obvious in specific therapy approaches to Alzheimer's disease”, remarked IQWiG Director, Prof. Dr. med. Peter Sawicki. "We have to make public sources of money available for controlled clinical trials.”

In the case of Alzheimer's disease, at least, there have been changes in recent years: the German Federal Ministry of Health (BMG) launched its own research promotion programme at the end of 2007. The Dementia Lighthouse Project allocates funding for the "systematic analysis of the latest scientific findings” within the topic of "Ensuring evidence-based care”. At the end of June 2009 the German Centre for Neurodegenerative Diseases (DZNE), also financed by the state, was set up in Bonn. Its budget of 60 million euros per year will be used primarily for research into dementia.

The German Federal Ministry of Education and Research (BMBF) has also been funding the Competence Network for Degenerative Dementias (KNDD). At present, 3 research networks are addressing in particular the onset and course of Alzheimer's disease. A total of 50 million euros has been made available to them for 12 years.

Peter Sawicki, the Institute's director, sees this as a step in the right direction: "We will probably have closed several research gaps in a few years' time.” At the same time, however, he warned against premature hopes: "We might be able to cure patients of dementia at some time in the future, but until that time it is important to improve the social and medical care of patients and relieve the burden on the family. We need reliable facts concerning which of the available options can best help them. That is why it is important to improve the investigation of relevant therapy and care approaches in studies.”

Contact: Tel. 0221 35685-0, info@iqwig.de