Ansgar Felbecker, MD, from the Clinic for Neurology, Cantonal Hospital St. Gallen, discussed issues related to Alzheimer’s dementia with HAUSARZT PRAXIS. Current epidemiological figures, pathogenetic findings, and diagnostic and therapeutic approaches were the focus of the discussion. Much has been achieved in recent years, although the decisive therapeutic breakthrough is still a long time coming.
Dr. Felbecker, how many people are currently affected by Alzheimer’s dementia in Switzerland?
Dr. Felbecker: Precise prevalence figures for dementia are not so easy to collect. They also depend on where you draw the line between “healthy” and “sick” and how accurately you test. According to the current diagnostic criteria, we currently assume that there are about 110,000 dementia patients in Switzerland, of which approximately 65,000 people are likely to suffer from Alzheimer’s dementia.
Are our social and medical structures prepared for a future increase in prevalence, or what efforts are being made here at the national level?
Societal and medical structures are already more than stretched to capacity, so they are certainly not prepared for an increase in prevalence at this time. However, there is no doubt that great efforts are currently being made to address these problems. One example is the national dementia strategy of the Federal Office of Public Health. However, the question remains open today whether the prevalence will really increase in the future. Although our life expectancy is increasing, there are also studies that indicate that preventive measures are indeed effective and that the increase in prevalence may develop less strongly than feared.
According to current knowledge, how does the familial form of AD differ from the sporadic form in terms of pathogenesis?
In the familial form of Alzheimer’s dementia, mutations in certain genes can be detected in some cases. However, in the pathological processes taking place in the brain, the differences are not so great.
According to the latest findings, what causes overproduction or reduced degradation of amyloid-β in the brain in the first place?
Researchers around the world are still gnashing their teeth over this question. Whoever succeeds in definitively clarifying this question can have high hopes of winning a Nobel Prize. At the moment, we are relying on hypotheses: The critical process is not overproduction but degradation. Even in healthy individuals, a great deal of amyloid-β is produced every day, which must be reliably broken down. What is certain is that there are certain genetic conditions that also influence amyloid-β degradation. Mutations have even been identified in certain genes, the presence of which provides relatively reliable protection against Alzheimer’s dementia. The big question at the moment, however, is whether the “amyloid hypothesis” is correct at all or whether a completely different, hitherto misunderstood process is not at the beginning of the pathological changes.
What is the percentage of agreement between the clinical diagnosis (neuropsychological tests, self-report and external history) and the definitive diagnosis of AD (postmortem by autopsy)?
The agreement between clinical and pathological diagnosis is relatively poor. Even the best expert centers “only” manage a rate of 80-90%. This rate drops significantly if diagnoses are not made by experts in the field and without additional diagnostics such as neuropsychological testing, cerebral imaging, and CSF diagnostics, for example. In principle, the rates for Alzheimer’s dementia are somewhat better than for other forms of dementia, such as Lewy body disease, if only because of its prevalence at older ages. This is significantly underdiagnosed during lifetime.
What biomarkers (e.g., amyloid-β, neurofibrils, glucose metabolism) can be detected with positron emission tomography (PET) today and in the future?
The standard today is FDG-PET, which images glucose metabolism in brain cells. This has recently been covered by health insurance in Switzerland under certain conditions. However, I strongly recommend that this diagnosis should only be initiated by specialists in the field of dementia, because the results must always be interpreted in conjunction with the clinic. In other countries, such as the USA, various amyloid tracers are already approved that can specifically detect so-called amyloid deposits. I think it is very likely that these will also find wider application. However, these tests, which enable early diagnosis, will only become relevant when we have more effective therapies available. Other tracers, such as those that visualize tau deposits, have only scientific value to date.
What do you think of the early diagnoses by means of eye and smell tests (e.g. UPSIT) that are currently causing a lot of discussion?
It is indeed the case that olfaction in particular often declines very early in the course of Alzheimer’s dementia. It is not uncommon for loss of smell to even precede dementia. This can be explained pathophysiologically, since early pathological abnormalities in Alzheimer’s dementia are often detectable in the entorhinal cortex. However, since this clinical observation is equally true for other neurodegenerative diseases such as Parkinson’s disease, such testing procedures are completely nonspecific and of little use in clinical practice.
The search for other, less invasive and reliable testing methods for early diagnosis of Alzheimer’s dementia continues. In addition to blood tests, this also includes the detection of amyloid, e.g. in the retina of the eye. However, whether these test methods are also sufficiently sensitive and specific in a broad application must first be proven in large studies.
Under what circumstances might current therapies also negatively affect the patient and worsen the clinical picture instead of improving it?
Current therapies include, on the one hand, medicinal measures. These therapies have some side effects, but should not directly worsen the disease. However, a “rebound” phenomenon is sometimes observed, in which there is a worsening after discontinuation of the medication. However, from my point of view, this only reflects the previously delayed course of the disease, which then approaches the original course again.
With regard to the much more important other therapeutic measures, such as physiotherapy and occupational therapy, we expect hardly any negative effects if they are carried out professionally.
What are the developments in acetylcholinesterase inhibitors (e.g., transdermal patches) and what is your position on the controversial Ginkgo biloba debate?
Most suppliers of acetylcholinesterase inhibitors have launched new dosage forms such as patches or sublingual tablets in recent years. In individual cases, these actually facilitate drug application, but none of them have brought about a decisive breakthrough in the therapy of the disease.
In my view, ginkgo preparations definitely have a certain value in the treatment of dementia. Although large meta-analyses have not been able to provide definitive evidence of efficacy, there are studies that have shown effects at sufficiently high doses, especially in mild dementia. As with other substances, the effect must be regularly evaluated and weighed against any side effects.
What are the goals of non-prescription approaches to medical nutrition such as Souvenaid®?
In principle, it has been known for some time from large cohort studies that certain diets such as the “Mediterranean diet” appear to have a dementia-preventive effect – as, incidentally, does regular exercise. However, I am not at all convinced that the “magic formula” of a Mediterranean diet can be easily packaged into a supplement bottle. Moreover, it is an open question when one would have to start such a diet to see protective effects. Most of the positive studies on this topic were more or less supported by the manufacturing companies. Since they are not drugs, the rules regarding e.g. advertising and study design are quite different from those in the strictly controlled pharmaceutical market. In other words, companies are allowed to advertise things that are not necessarily considered proven according to strict scientific criteria.
Until we get confirmation of the results here from large independent studies, I would rather spend the five or so francs a day on other things.
Interview: Andreas Grossmann
HAUSARZT PRAXIS 2014; 9(10): 29-31
