Rolle vaskulärer Risikofaktoren für die Entstehung und Progression der Alzheimer-Demenz

Zusammenfassung

Vaskuläre Risikofaktoren spielen eine zentrale Rolle bei der Entstehung und Progression von Demenzerkrankungen. Nicht nur bei der vaskulären Demenz, wo der Zusammenhang naheliegend zu sein scheint, sondern insbesondere auch bei der Demenz vom Alzheimer Typ können vaskuläre Risikofaktoren dazu beitragen, dass eine Demenz früher und stärker auftritt als bei Personen ohne Risikofaktoren. Grundlage für diese Erkenntnis sind vor allem große Kohortenstudien, welche die Bedeutung von vaskulären Risikofaktoren nicht nur für die Entwicklung von Herz-Kreislauf-Erkrankungen oder Tumorerkrankungen sondern eben auch für die Entstehung von Demenzen in den letzten Jahren gezeigt haben. Aus Autopsiestudien ist zwar schon lange bekannt, dass es eine enge Verknüpfung von Alzheimerpathologie und vaskulärer Pathologie in Gehirnen von Demenzpatienten gibt, kausale Aussagen sind aber wegen der hohen Prävalenz auch bei asymptomatischen Personen schwierig. Verschiedene Risikofaktoren sind neben genetischen Faktoren und möglichen Umweltfaktoren als synergistische Faktoren in der Demenzentstehung anzusehen. Sie entscheiden in der Summe darüber, ob, wann und mit welch rascher Progredienz eine Demenz auftritt. Als wichtigste nicht modifizierbare Risikofaktoren sind das Alter und eine genetische Prädisposition wie der Apolipoprotein-E-Genotyp zu nennen. Demgegenüber stehen modifizierbare vaskuläre Risikofaktoren wie Bluthochdruck, Hypercholesterinämie, Rauchen, Diabetes mellitus und ein Lebensstil ohne ausreichende körperliche Aktivität. Aktuelle Daten aus großen Interventionsstudien zeigen, dass das Konzept eines multimodalen Ansatzes mit konsequenter Behandlung möglichst aller modifizierbaren Risikofaktoren durchaus Erfolge zeigen kann. Dabei zielen die aktuellen Studien sogar auf relativ späte Interventionszeitpunkte, welche schneller messbare Ergebnisse versprechen. Es bleibt zum gegenwärtigen Zeitpunkt Spekulation, ob die Effekte nicht noch viel größer wären, wenn die Intervention bereits viel früher im Leben ansetzen würde. Immerhin ist bekannt, dass bspw. Bluthochdruck und fehlende körperliche Aktivität bereits im mittleren Lebensalter einen Risikofaktor für die spätere Entwicklung einer Demenz darstellen. In diese Richtung könnten Daten aus aktuellen großen epidemiologischen europäischen Studien interpretiert werden, die eine leichte Reduktion der Demenzprävalenz in modernen Kohorten zeigen. Sie sind möglicherweise ein Hinweis darauf, dass einige der bereits in breiten Patientengruppen umgesetzten Maßnahmen wie eine bessere Blutdruckeinstellung und eine Reduktion des Raucheranteils in der Bevölkerung erste Effekte in der Demenzprävention zeigen. Den modifizierbaren Risikofaktoren kommt in der heutigen Zeit eine besonders große Bedeutung in der Prävention und möglicherweise auch Behandlung von Demenzerkrankungen zu, da effektive kausale Therapien bei praktisch allen Demenzerkrankungen noch fehlen. Wenn es gelingen würde, die Prävalenz der modifizierbaren Risikofaktoren auf Bevölkerungsebene zu reduzieren, würde dies eine erhebliche Reduktion der Demenzprävalenz bedeuten. Die so mit relativ einfachen Maßnahmen realistisch erreichbare Reduktion von Demenzerkrankungen hätte nicht nur medizinisch, sondern auch gesellschaftlich und ökonomisch eine große Bedeutung. So lange keine effektive Therapie von Demenzerkrankungen vorliegt, sollten wir zumindest alles daran setzen, die bereits bekannten Möglichkeiten zur Reduktion der Demenzfälle besser auszuschöpfen.

Abstract

Vascular risk factors play a key role in the onset and progression of dementia. This is true not only for vascular dementias but also for neurodegenerative dementias such as Alzheimer’s disease. Co-existing vascular risk factors can lead to earlier onset of dementias and a more progressive course of the disease. Our understanding of these correlations comes mainly from large cohort studies showing a major impact of vascular risk factors not only on cardiovascular diseases and cancer but also on dementias. Autopsy studies already revealed connections between vascular disease and neurodegenerative dementias, but they are difficult to interpret because of the high prevalence of asymptomatic carriers of pathologically proven vascular and Alzheimer pathology. There are several vascular risk factors besides genetic and environmental ones that contribute in a synergistic manner to the evolution of dementia. All of these factors sum up to an individual dementia risk, and they can also influence the point of time when dementia starts and the severity and speed of progression. The most important non-modifiable risk factors include age and genetic risk like apolipoprotein-E carrier status. However, many risk factors are modifiable, including high blood pressure, dyslipidaemia, smoking, diabetes and a sedentary life style. Current data from large intervention studies show promising results of a multimodal treatment concept with systematic treatment of the modifiable risk factors that can reduce the prevalence of dementia. These results are even more inspiring because the interventions in current studies started quite late to get answers in a reasonable time. To date, it remains speculative if the effects would not be even better if interventions are started earlier in life. At least, it is well established that, some risk factors, if present during mid-life, like elevated blood pressure and lack of physical activity, raise the risk of dementia. Some large epidemiological studies seem to support this hypothesis: they showed a significant decrease in dementia prevalence in modern cohorts compared to very similar cohorts examined many years before. These studies suggest that some preventive measures that are already partly implemented like reduced numbers of smokers or better control of blood pressure exert early effects. Nowadays, modifiable risk factors carry a huge potential for prevention and maybe also treatment of dementias as effective causal treatments are still missing for most types of dementia. If modifiable risk factors could be controlled in a more effective way, this would lead to a significantly reduced number of dementia cases. The potential reduction of dementia cases that could be achieved with better control of vascular risk factors would have major significance not only from a medical point of view but also have an effect on a social and economic level. As long as effective therapies for most dementia cases are still lacking, we should increase our efforts to optimize the implementation of all preventive measures that are already known and available.

Schlüsselwörter

Demenz - Alzheimer - vaskulär - Risikofaktor - Prävention

Keywords

Dementia - Alzheimer - vascular - risk factor - prevention

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