Einfluss von Diabetes mellitus, Übergewicht und Bewegungsmangel auf Morbus Alzheimer – Interaktion von Insulin mit Amyloid und phosphoryliertem Tau–Protein

Mehrere prospektive epidemiologische Untersuchungen belegen, dass Diabetes mellitus das Risiko, an einer Demenz vom Alzheimer–Typ zu erkranken, um etwa den Faktor 1,6 bis 1,9 steigert. Weitere metabolische Risikofaktoren der Alzheimer–Demenz sind Übergewicht und Bewegungsmangel im mittleren Lebensalter. Die neurobiologische Basis dieses epidemiologischen Zusammenhangs ist eine komplexe Beteiligung des neuronalen Glukose– und Insulinstoffwechsels an synaptischer Plastizität und Gedächtnisprozessen. Die intrazelluläre neuronale Signaltransduktionskette von Insulin ist aber bei Alzheimer–Demenz in ähnlicher Weise gestört wie bei peripherer Insulinresistenz im Rahmen des Diabetes mellitus. Insulin interagiert an verschiedenen Stellen mit der Bildung von Amyloid und phosphoryliertem Tau–Protein. In der Zukunft besteht die Hoffnung, dass sich aus der Kenntnis dieser Zusammenhänge neue kausal wirksame Therapieprinzipien für die Alzheimer–Demenz entwickeln lassen. Bereits jetzt sollte beim einzelnen Patienten und in populationsbasierten Ansätzen die Möglichkeit genützt werden, das Alzheimer–Risiko durch vermehrte körperliche Aktivität und Vermeidung von Übergewicht um mehr als die Hälfte zu senken. Bei Diabetikern muss dem erhöhten Demenzrisiko durch eine möglichst frühzeitige Diagnostik sowie durch sorgfältige Stoffwechseleinstellung Rechnung getragen werden.

According to a growing body of evidence from prospective population–based studies, the risk of incident AlzheimerŽs disease in diabetic patients is increased by an odds ratio of approximately 1,6 to 1,9. Mid–life obesity and a sedentary life style are additional risk factors of AlzheimerŽs dementia. As a neurobiological correlate, neuronal glucose and insulin metabolism is involved in regulation of synaptic plasticity and memory processes. In AlzheimerŽs disease, intracellular signalling of insulin in neurons is impaired in a similar fashion as it is in peripheral cells from insulin resistant diabetic patients. Insulin interacts with the metabolic pathways that participate in the formation of AlzheimerŽs plaques and neurofibrillary tangles. Hopefully, this knowledge will eventually result in the design of new targets for prevention and treatment of AlzheimerŽs disease. For the time being, this evidence must be translated into individual and population–based life–style interventions that will help to reduce the risk of incident AlzheimerŽs dementia by more than 50  %. In diabetic patients, routine cognitive testing is warranted as part of the diagnostic screening for diabetes–related complications, and antihyperglycemic treatment must be optimized in order to lower the risk of cognitive decline.

Diabetes mellitus - Alzheimer's disease - obesity - prevention

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