Jornal da doença de Alzheimer e parkinsonismo

Abstrato

Neuropathology of Dementia Disorders

Kurt A Jellinger

Dementia, being not a specific disease but a syndrome characterized by deficits in several cognitive domains, is a major public health and socio-economic problem of our century. It is caused by dysfunction/loss of synapses and neurons inducing default neuronal networks. Despite updated concensus criteria for the clinical diagnosis of the major neurodegenerative disorders and new biomarkers, the diagnostic accuracy ranges from 65 to 96% (for Alzheimer’s disease /AD), with a sensitivity versus other dementias of around 85.4% and a specificity of up to 77.7%. Pathologic assessment, using genetic and molecular biological methods, based on homogenous definitions, harmonized interlaboratory and assessment standards, can achieve a classification in up to 95%, without, however, clarifying the etiology of most of these disorders. The new National Institute on Aging-Alzheimer Association guidelines (“ABC” score) for the neuropathologic diagnosis of AD combine β-amyloid plaque phases and Braak neurofibrillary scores, also considering other concomitant pathologies, but do not consider distinct clinico-pathologic subtypes of AD. Revised research criteria are available for dementia with Lewy bodies, Parkinson disease-dementia, frontotemporal lobe degeneration, vascular cognitive impairment, prion diseases, and other degenerative dementias. However, due to overlap between proteinopathies, frequent confounding lesions and co-occurence of multiple pathologies in aged brains, human postmortem studies entail biases that affect both their general applicability and validity. Although most degenerative dementias are incurable at present, prospective studies using validated protocols and data fusion may overcome the limitations of the current diagnostic framework as a basis for future personalized therapy options.