Histopathological and immunocytochemical studies in age-associated dementias : the importance of rigorous histopathological criteria for classification of progressive dementia disorders

Abstract: Dementia is an age-associated organic brain disorder, recogniz­able by the essential features of psychological or behavioral abnormality associated with permanent dysfunction of the brain interfering with social and occupational functioning.There are two clinical and three histopathological forms of dementia 1) primary degenerative dementia, (PDD), or Alzhei­mer's dementia/Senile dementia of Alzheimers type (AD/SDAT) which is associated with clinical features of uniform progres­sion and insidious onset of symptoms and histopathologically i- dentified by the occurrence of neurofibrillary tangles (NFT) and senile/neuritic plaques (SP/NP) in various cortical and subcor- tical regions; 2) vascular dementia, or multi-infarct dementia (MID), which is associated with clinical features of stepwise progress and patchy distribution of deficits, and histopatholo­gically identified by the occurrence of multiple large and/or small haemorrhagic and/or ischaemic infarcts in various cortical and subcortical regions and 3) intermediate form of dementia or "mixed” ("combined") dementia (AD-MID), which is histopatho- logically associated with the coexistance of symptoms and le­sions observed in AD/SDAT and MID, and clinically referred to the MID group. The DSM-III criteria separate the demented into two groups, AD/SDAT and MID, while there are no unique clinical criteria for the AD-MID patients. The clinical diagnosis of dementia according to the DSM-III criteria was shown to be in­sufficient . Histopathological diagnostic criteria were postu­lated by us for 1) pathological changes developing in mentallyunimpaired ageing, 2) AD/ SPAT, 3) MID and 4) AD-MID.These histopathological classes could be separated, by means of multivariate data analysis. The pathology in AD-MID was shown not to be merely a linear combination of the AD/SDATand MID pathology.Intrathecal synthesis of Ig, oligoclonal bands or other abnormal proteins in the CSF could not be demonstrated in aged non-demen- ted and demented patients.The blood-cerebrospinal barrier (B-CSF-B) or blood-brain barrier (BBB) function alters with age and this alteration was shown to be more pronounced in MID and AD-MID patients. In MID and AD-MID patients the BBB alteration involves primarily the grey matter while in AD/SDAT patients the alteration would appear to involve only the white matter. The BBB dysfunction and a possible complement activation, either through antibody-anti- gen activation or other complement activators, was visualized in MID and AD-MID patients as perivascular serum protein depo­sits in the grey matter, always with a capillary in the center. The occurrence of some serum proteins in plaques, and the previously descibed localization of plaques in close relation­ship to the capillaries, suggest that altered BBB function and serum factors may be involved in the etiology and maturation of plaques while the etiology and maturation of tangles may not be directly dependent on these factors, as they were never labelled with any of the antisera studied.