Chapter 10

Challenges in the Morphological Diagnosis of Dementias

Kurt A. Jellinger


Dementia is a major public health problem that threatens to become the scourge of the 21st century. It is caused by dysfunction/loss of synapses and neurons inducing default neuronal networks. Consensus criteria for the diagnosis of the major dementia disorders have recently been updated. Clinical diagnostic accuracy using revised criteria and new biomarkers ranges from 65 to 96% (for Alzheimer disease), with a sensitivity vs. other dementias of 71 to 87% and specificity of 44 to 71%. Morphological assessment, using modern molecular biological and genetic methods, and based on homogeneous definitions, harmonized inter-laboratory techniques and assessment standards, can achieve a diagnosis/classification in almost 99%, without, however, clarifying the etiology of most of these disorders. The new National Institute on Aging-Alzheimer Association (ABC) guidelines for the pathological diagnosis of Alzheimer disease combine β-amyloid plaque phases, Braak neurofibrillary and neuritic plaque scores, also considering other pathologies. Major difficulties arise from recent separation of distinct clinico-pathological subtypes (tangle- and plaque intensive, tangle predominant, limbic-predominant and -sparing) from classical Alzheimer disease. Revised research criteria are available for dementia with Lewy bodies, Parkinson disease-dementia, frontotemporal lobe degeneration, vascular cognitive impairment, prion diseases, and other neurodegenerative dementias. However, due to considerable overlap between various neurodegenerative proteinopathies and cases with mixed pathologies, human postmortem studies entail numerous biases that affect both their general applicability and the validity of correlations. Although most neurodegenerative dementias are incurable at present, concerted prospective clinico-pathological studies using validated protocols and data fusion are warranted to overcome the limitations of the current diagnostic framework as a basis for efficient new therapy options.

Total Pages: 367-410 (44)

Purchase Chapter  Book Details


.Frontiers in Clinical Drug Research - CNS and Neurological Disorders.
.Frontiers in Clinical Drug Research-Dementia.
.Advances in Alzheimer Research.
.Recent Advances in the Treatment of Neurodegenerative Disorders.
.Advances in Alzheimer Research.
.Cellular and Molecular Biology of Autism Spectrum Disorders.