Classification of dementias based on functional morphology

Abstract

Dementia syndromes in adults can be caused by many different conditions that find their pathological correlates in seven major groups of CNS disorders: 1. presenile and senile dementia of the Alzheimer type (AD/DAT), the diagnosis of which is based on quantitative assessment of neuritic changes — neuritic plaques, neurofibrillary tangles — probably representing end-stage markers or epiphenomena of primary neuronal degeneration of hitherto unknown origin; 2. other degenerative diseases, e.g. Parkinson’s disease associated with AD, Diffuse Lewy body disease, Pick’s lobar atrophy, Huntington’s disease, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophies; 3. vascular dementia (VD) with several subtypes — multiinfarct encephalopathy, strategic and small vessel infarct dementia (multilacunar state, subcortical type Binswanger, granular cortical atrophy); 4. mixed type dementia (MIX) due to coexistence of AD/DAT and vascular pathologies; 5. Prion diseases or transmissible spongiform encephalopathies (e.g. Creutzfeldt-Jakob disease); 6. normal pressure hydrocephalus; 7. various organic brain diseases, such as tumors, chronic infections, alcoholic and metabolic encephalopathies. In large autopsy series, AD/DAT account for 70 to 80%, VD and MIX for 8 to 10%, each while the remaining disorders are of minor importance. While most cohorts show VD as the second most frequent type of dementia, in some series it is Lewy body dementia. In a personal consecutive postmortem series of 1200 aged subjects (mean age 79.5% years), 78% fulfilled the pathologic criteria for AD, but only 43% were “pure” forms, 15.5% had additional minor vascular lesions, 10% Lewy body pathology, 5.5% were MIX type dementia, 13% VD with no or only little AD pathology; 8.7% revealed other CNS disorders, and 0.6% displayed no abnormality beyond age-related changes. While the pathogenesis of rare dementia forms, e.g. infections, is well elucidated, for the majority of degenerative dementia disorders including AD/DAT, the etiology and pathogenesis are poorly understood. The morphologic diagnosis and clinico-pathological correlations of degenerative dementias need more standardized criteria; elucidation of their etiology as a basis of treatment strategies is subject of intense current research efforts of basic and clinical neurosciences.