Structural changes in ageing and dementia of Alzheimer's type with special reference to recent etiologic and therapeutic theories.

On the basis of a large material of organic dementia, accumulated during a 20 year long prospective study, certain basic structural changes in dementia, mainly of Alzheimer's type (DAT) viz. the topography of lesions, the amyloid angiopathy and white matter changes are discussed with respect to their relevance for modern etiologic and pathogenetic theories and implications for the clinical picture and treatment in DAT. The topographic pattern and its evolution appears to be a relevant basis for the symptomatology and the picture shown by PET and regional cerebral blood flow studies. It lends some support to theories implicating the spread of a causative agent via olfactory pathways. The amyloid depositions, particularly those in the vessels present, both with regard to amount and topography, features which to some extent validate the modern etiological gene theories but which in other respects lend little or no support to the etiologic or pathogenetic importance ascribed to amyloid. The white matter changes, common in DAT and of an incomplete infarction type, may blur the DAT clinic and also serve to block axonal transport through the white matter and cause dysfunction or death of neurons dependent upon routes involved. It might thus influence therapeutic measures such as administration of transmitter substitutes or their precursors and the outgrowth or efficacy of transplanted cholinergic replacement neurons.