ous sociomedical problems of aging societies in industrialized countries. Despite enor-
mous worldwide research efforts, there is as yet no satisfactory pharmacotherapy
available for these brain disorders. There are a number of well-established animal
models of ischemic brain damage for VaD and stroke, although they do not mimic the
chronic development of the underlying vascular pathology (arteriosclerosis). There
are, however, no good pathophysiological animal models for degenerative dementia of
the Alzheimer’s type since the etiopathology of AD is still largely unknown. There is
increasing evidence, however, for common pathophysiological features of degenera-
tive and vascular dementia.
Possible common elements of AD and VaD include microglial activation, inflam-
mation (2), glutamate toxicity (6), disturbances of intracellular calcium homeosta-
sis (69), and neuronal death. Inflammatory processes induced by pathological stimuli
and linked to the proliferation of microglial cells are involved in both AD and VaD,
and the resultant generation of cytokines (e.g., interleukin lp [IL-lp] and tumor ne-
crosis factor alpha [TNF-a]) and neurotoxic oxygen free radicals may also be com-
mon elements of these diseases (39). Free-radical-induced aggregation of P-amyloid
peptide, for example, may be an essential part of the pathogenesis of amyloid plaques
(31). The loss of cholinergic neurons in the basal forebrain has been implicated in the
cognitive decline in AD, and possibly in VaD (4). In addition, neurodegenerative
processes and/or ischemia cause formation of reactive astrocyte subtypes with a re-