Neuropsychologische Korrelate zerebraler Atrophie bei der Alzheimer-Demenz

 

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Zusammenfassung

Das Ziel der vorliegenden Arbeit ist die systematische Analyse des Zusammenhanges neuropsychologischer Defizite und regionaler zerebraler atrophischer Veränderungen bei der Alzheimer-Demenz (AD). In Erweiterung bisher vorliegender Studien werden dabei neben den Substrukturen des medialen Temporallappens auch andere relevante zerebrale Regionen morphometrisch erfasst und systematisch mit standardisiert erhobenen psychometrischen Parametern in Beziehung gesetzt. Dabei wird davon ausgegangen, dass morphologische Korrelate globaler und spezifischer kognitiver Funktionsstörungen in gewissem Rahmen lokalisatorische Rückschlüsse auf die neuronale Grundlage der infrage stehenden Funktion zulassen. Hierdurch kann die funktionelle Bedeutung, die einzelnen zerebralen Strukturen bzw. Regionen bei der AD im Krankheitsgeschehen zukommt, weiter erhellt und nicht zuletzt ein Beitrag zur Aufklärung der klinisch und neuropsychologisch beobachteten Heterogenität des Krankheitsbildes geleistet werden. Bei 50 Patienten mit klinisch diagnostizierter AD (NINCDS-ADRDA-Kriterien) und 20 gesunden, älteren Kontrollpersonen wurde eine standardisierte neuropsychologische Testung sowie eine Magnetresonanztomographie (MRT) des Gehirns durchgeführt. In den MRT wurden das Ganzhirnvolumen, das Liquorraumvolumen sowie die Volumina des Amygdala-Hippokampus-Komplexes, der Frontal-, Temporal- und Parietallappen volumetrisch bestimmt. Die AD-Patienten wiesen neuropsychologische Defizite in den Bereichen Mnestik, Sprache, Praxie, kognitives Arbeitstempo sowie Aufmerksamkeit und Konzentration auf, die differenzielle Korrelationen mit den MRT-volumetrisch ermittelten regionalen atrophischen Veränderungen eingingen. Dabei fand sich eine Assoziation des Volumens des rechtshemisphärischen Amygdala-Hippokampus-Komplexes mit deklarativen Gedächtnisleistungen im non-verbalen visuellen Bereich. Ferner waren Veränderungen der linkshemisphärischen temporoparietalen Region mit Störungen des Benennens und der Praxie sowie das Volumen des linken Frontallappens mit der verbalen Flüssigkeit assoziiert. Die Validität der erhobenen Zusammenhänge wird durch die Übereinstimmung mit neuropathologischen Befunden sowie mit Ergebnissen jüngerer Untersuchungen mit funktionellen bildgebenden Verfahren gestützt. Zusammenfassend belegen die Ergebnisse der vorliegenden Studie, dass sich die neuropsychologische Heterogenität der AD mithilfe der MRT-basierten Volumetrie tatsächlich auch auf der morphologischen Ebene abbilden lässt und dass der gewählte methodische Ansatz in der Erforschung der neuronalen Grundlagen kognitiver Prozesse fruchtbar eingesetzt werden kann.

Abstract

This study aims to systematically analyze the relationship between neuropsychological deficits and regional cerebral atrophic changes in Alzheimer's dementia (AD). As an extension of previous studies we not only investigated substructures of the medial temporal lobe but also included other relevant cerebral regions such as frontal, temporal, and parietal lobes. This approach was based on the assumption that morphological correlates of global and specific cognitive dysfunction might reflect to a certain degree the neuronal basis of the respective function. Accordingly, the functional role assigned to a certain cerebral structure or region can be further elucidated which might lead to a better understanding of the clinical and neuropsychological heterogeneity of AD. Fifty patients with AD (NINCDS-ADRDA criteria) and 20 healthy elderly control subjects were included. All patients and controls were examined on a standardized neuropsychological test battery. In addition, magnetic resonance imaging (MRI) of the brain was performed. Volumes of the whole brain, CSF-spaces, amygdala-hippocampus complex, frontal lobes, temporal lobes, and parietal lobes were measured using a standardized protocol. AD-patients were characterized by neuropsychological deficits with respect to memory, language, praxia, cognitive speed as well as attention and concentration. These deficits were differentially correlated with regional atrophic changes. In particular, volumes of the right amygdala-hippocampus complex were correlated with declarative memory performance in the non-verbal visual domain. Furthermore, an association between left temporo-parietal regions and aspects of semantic memory, as well as verbal recall and left frontal regions could be established. The validity of our results is supported by recent findings from neuropathological and functional neuroimaging studies. In conclusion, our data indicate that MRI-based volumetry can be successfully used to detect morphological correlates of neuropsychological heterogeneity in AD and that this methodological approach allows to fruitfully study the neuronal basis of cognitive functions.

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Prof. Dr. med. Johannes Pantel

Klinik für Psychiatrie und Psychotherapie I

Heinrich-Hoffmann-Str. 10

60528 Frankfurt a. M.