The association of ventral tegmental area histopathology with adult dementia.

Six cases of adult dementia with mesolimbic pathology are reported. The core clinical syndrome consists of parkinsonism, progressive dementia, and behavioral disturbances (generally depression). The histopathologic findings uniformly include a loss of pigmented neurons in the ventral tegmental area plus neurofibrillary tangles and/or cell loss in the entorhinal cortex and pyramidal cell layer of the hippocampus (perforant pathway). Neuronal depletion in the ventral tegmental area frequently is associated with similar cell loss in the adjacent substantia nigra and in the locus ceruleus. The development of neurofibrillary tangles in the perforant pathway occurs in the absence of senile plaques and is possibly related to diminished dopaminergic input.