Neural substrates of spatial and temporal disorientation in Alzheimer's disease

To examine the neuroanatomical correlates of spatial and temporal disorient ation in Alzheimer's disease (AD), we performed an anterograde clinicopatho logical study of 29 patients with clinically and neuropathologically confir med AD. Spatial and temporal disorientation was assessed using the location al orientation subtests of the Mini Mental State Examination and the Benton 's test for temporal orientation. Quantitative analysis of neurofibrillary tangles and senile plaques were performed in the CA1 field of the hippocamp us, layers II and V of the entorhinal cortex, and layers II-Ill and V-VI of areas 9, 7, 39, 19, 37, 20 and 23 in the right hemisphere. Forward stepwis e logistic regression was used to assess the relationship between lesion de nsities and the presence of either spatial or temporal disorientation; seve rity scores and brain weight were included as covariants. A statistically s ignificant relationship was found between neurofibrillary tangle densities in Brodmann's areas 7, 23 and the CA1 field of hippocampus and both spatial and temporal disorientation. Senile plaque counts did not correlate with a ny of the neuropsychological parameters. Both temporal and spatial disorien tation in AD are related to the degeneration of the same pathways linking t he hippocampus with the superior parietal and posterior cingulate cortex in the right hemisphere. These observations are discussed with respect to the notion of global corticocortical disconnection in AD.