Alzheimer Demenz versus vaskuläre Demenz - Dichotomie oder Interaktion?

Zusammenfassung

Die strikte Trennung der demenziellen Alterserkrankungen in die beiden häufigsten Ätiologien Alzheimer Demenz (AD) und vaskuläre Demenz (VD) folgt oder erfolgt nach pathophysiologischen Erkenntnissen und klinisch operationalen Kriterien. Sie ist aber auf der Grundlage neuerer Forschungsergebnisse in dieser kategorischen Form zu relativieren. Das Risiko, eine neurodegenerative Demenz im Alter zu entwickeln, ist polygenetisch determiniert und alterskorreliert, wobei die Ablagerung von β-Amyloid-Peptiden als wesentlicher Endpunkt in der Pathophysiologie der AD verstanden wird. Für die VD wurden insbesondere mikroangiopathische inkomplette Infarkte auf der Grundlage einer Fibrohyalinose als pathophysiologisch bedeutsam erkannt. Kontrovers diskutiert wird die Koinzidenz von genetisch determinierten Risikofaktoren für die AD oder die VD. Gut belegt sind Interaktionen von perivaskulären Mediatoren und den die Zirkulation beeinträchtigenden Faktoren für die beiden Formen der Altersdemenz. Aus diesen und weiteren neuropathologischen und therapeutischen Erkenntnissen wird die Hypothese abgeleitet, dass die jeweiligen spezifischen Ätiopathogenesen von AD und VD miteinander interagieren und die Phänomenologie der demenziellen Entwicklung von individuellen vaskulären Risikofaktoren modifiziert wird. Sowohl eine kategoriale Trennung von AD und VD als auch die Vorstellung der AD als eine Form der VD sind dagegen wenig überzeugend.

Abstract

Alzheimer's dementia (AD) and vascular dementia (VD) are the two major forms of dementia in the elderly. They have been separated categorically on the basis of pathophysiological findings and clinical operationalized criteria. However, this strict separation has to be reevaluated in the light of recent data. The risk to develop a neurodegenerative dementia in old age is determined by various susceptibility genes and correlated with aging. In AD, the current understanding of pathophysiology focuses on the amyloid cascade hypothesis as the major endpoint of the complex cellular pathology. In VD, incomplete microangiopathic infarcts due to fibrohyalinosis are regarded as the major pathophysiological event. A controversial discussion exists about the coincidence or interaction of genetically determined risk factors of AD and/or VD. Further interactions between AD and VD exist with regard to perivascular mediators and those factors which impair cerebral blood flow. Based on these and other recent neuropathological and therapeutic findings the hypothesis is proposed that the two specific etiopathologies of AD and VD interact to precipitate clinical dementia in the individual and that the individual phenomenology of these dementias is modified by vascular risk factors. Neither, a categorical separation of AD and VD nor the recent idea to regard AD as a distinct form of vascular dementia, do appear convincing.

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