Texte remanié de: Proefschrift--Letteren--Tilburg--Katholieke Universiteit Brabant, 1994. / Résumé en anglais. Bibliogr. p. 131-139.

Proefschrift--Katholieke universiteit Brabant, 1997. / Bibliogr. p. 356-369. Index.

In neurologic disorders, there are progressive losses in regional brain structural integrity, circuitry, and neuronal process that threaten individuals' ability to express functional capacity at several levels of severity. The classification of (a) patients on the basis of diagnosis, risk prognosis, and intervention outcome forms the basis of clinical staging and (b) laboratory animals on the basis of animal model of brain disorder, extent of insult and dysfunctional expression, provides the components for the clinical staging and preclinical staging, respectively, of the disease state with certain associated epidemiological, biological, and genetic characteristics. The investigation of epigenetics and biomarkers is intrinsic to any analysis of the progressive nature of the neurogenerative disorders, in the present account disorders relating to Alzheimer's disease, Parkinson's disease, depression, and diabetes.

The notion of staging in the neurodegenerative disorders is modulated by the constant and progressive loss of several aspects of brain structural integrity, circuitry, and neuronal processes. These destructive processes eventually remove individuals' abilities to perform at sufficient and necessary functional capacity at several levels of disease severity. The classification of (a) patients on the basis of diagnosis, risk prognosis, and intervention outcome, forms the basis of clinical staging, and (b) laboratory animals on the basis of animal model of brain disorder, extent of insult, and dysfunctional expression, provides the components for the clinical staging and preclinical staging, respectively, expressing associated epidemiological, biological, and genetic characteristics. The major focus of clinical staging in the present account stems from the fundamental notions of Braak staging as they describe the course and eventual prognosis for Alzheimer's disease, Lewy Body dementia, and Parkinson's disease. Mild cognitive impairment, which expresses the decline in episodic and semantic memory performance below the age-adjusted normal range without marked loss of global cognition or activities of daily living, and the applications of longitudinal magnetic resonance imaging, major instruments for the monitoring of either disease progression in dementia, present important challenges for staging concepts. Although Braak notions present the essential basis for further developments, current staging conceptualizations seem inadequate to comply with the massive influx of information dealing with neurodegenerative processes in brain, advanced both under clinical realities, and discoveries in the laboratory setting. The contributions of various biomarkers of disease progression, e.g., amyloid precursor protein, and neurotransmitter system imbalances, e.g., dopamine receptor supersensitivity and interactive propensities, await their incorporation into the existing staging models thereby underlining the ongoing, dynamic feature of the staging of brain disorders.