Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment

Layer II of the entorhinal cortex contains the cells of origin for the perf orant path, plays a critical role in memory processing, and consistently de generates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of entorhinal cortex is related to mild cognitive impairment w ithout dementia has not been extensively investigated. We analyzed 29 parti cipants who came to autopsy from our ongoing longitudinal study of aging an d dementia composed of religious clergy (Religious Orders Study). All indiv iduals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimer's disease (n = 11). Sec tions through the entorhinal cortex were immunoreacted with an antibody dir ected against a neuron-specific nuclear protein (NeuN). Stereological count s of NeuN-immunoreactive stellate cells, their volume, and the volume of la yer II entorhinal cortex were estimated, Cases exhibiting no cognitive impa irment averaged 639,625 +/- 184,600 layer II stellate neurons in the right entorhinal cortex. Individuals with mild cognitive impairment (63.5%; p < 0 .0003) and mild or moderate Alzheimer's disease (46.06%; p < 0.0017) displa yed significant losses of layer II entorhinal cortex neurons relative to th ose with no cognitive impairment but not relative to each other (p > 0.33). There was also significant atrophy of layer II entorhinal cortex neurons i n individuals with mild cognitive impairment (24.1%) and Alzheimer's diseas e (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzhe imer's disease (46.4%). The loss and atrophy of layer II entorhinal cortex neurons significantly correlated with performance on clinical tests of decl arative memory. Atrophy of layer II entorhinal cortex and the neurons withi n this layer significantly correlated with performance on the Mini Mental S tatus Examination. These data indicate that atrophy and loss of layer II en torhinal cortex neurons occur in elderly subjects with mild cognitive impai rment prior to the onset of dementia and suggests that these changes are no t exacerbated in early Alzheimer's disease.