Präklinische Phase der Alzheimer-Krankheit und der spinozerebellären Ataxien

Zusammenfassung

Traditionell werden Diagnosen neurodegenerativer Krankheiten aufgrund klinischer Kriterien gestellt. Zum Zeitpunkt der Diagnose sind aber in der Regel bereits ausgedehnte neuropathologische Veränderungen vorhanden, die nach heutige Kenntnis mehr als 10 Jahre vor Auftreten von Symptomen beginnen können. Dies hat zu neuen Krankheitskonzepten geführt, die derzeit Eingang in den klinischen Alltag finden. Grundlage dafür sind die Entwicklung neuer, krankheitsspezifischer Biomarker und die Ergebnisse von Untersuchungen an Trägern von Mutationen in Genen für autosomal dominante vererbte neurodegenerative Krankheiten. Basierend auf einem Vorschlag der Arbeitsgruppe des National Institute on Aging-Alzheimer’s Association (NIA-AA) wird die Alzheimer-Krankheit (AD) in 3 präklinische Stadien, das Stadium der leichten kognitive Störung (minimal cognitive impairment, MCI) und das finale Demenzstadium eingeteilt. Eine vergleichbare Klassifikation wurde von der International Working Group (IWG) vorgenommen. Bei scheinbar gesunden Mutationsträgern für spinozerebelläre Ataxien (SCA) wurden leichte Koordinationsstörungen, eine erhöhte Prävalenz unspezifischer neurologischer Symptome und beginnende Atrophie von Kleinhirn und Hirnstamm nachgewiesen. Das große Interesse, das die klinische Forschung derzeit an präklinischen Krankheitsstadien hat, erklärt sich daraus, dass nach allgemeiner Überzeugung in frühen Krankheitsstadien begonnene Therapien oder präventive Interventionen größere Erfolgsaussichten haben als Therapien, die erst dann angewandt werden, wenn die diagnostischen Kriterien der Krankheit erfüllt sind.

Abstract

Traditionally, diagnoses of neurodegenerative diseases are made on the basis of clinical criteria. At the time of diagnosis, however, neuropathological changes are already present and these may have started more than 10 years before the onset of clinical symptoms. This has led to new concepts of neurodegenerative disease, which have been now introduced into clinical practice. The basis for this development is new disease-specific biomarkers und findings in studies of mutation carriers for autosomal dominantly inherited neurodegenerative diseases. Based on a proposal of a working group of the National Institute on Aging Alzheimer’s Association (NIA-AA), Alzheimer disease (AD) is divided into 3 preclinical stages, a stage of minimal cognitive impairment (MCI) and the final dementia stage. The International Working Group (IWG) proposed a similar classification. In apparently healthy mutation carriers of spinocerebellar ataxias (SCA), mild coordination deficits, an increased prevalence of unspecific neurological symptoms and onset of cerebellar atrophy and brainstem were found. The current great interest of clinical research in preclinical disease stages is due to the belief that therapies or preventive interventions that are initiated in early disease stages may have a greater success rate than therapies that are applied only when the diagnostic criteria are met.

Schlüsselwörter

Alzheimer-Krankheit - Mutationsträger - minimale kognitive Beeinträchtigung - präklinisches Krankheitsstadium - spinozerebelläre Ataxien

Keywords

Alzheimer disease - mutation carrier - minimal cognitive impairment - preclinical disease stage - spinocerebellar ataxias

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