Neuropathological Changes in Adult and Old Rats Following Early Post-Natal Iron Administration

Abstract

acetylcholine esterase (AChE) activity. Evidence for cholinergic dysfunction in early stages of Alzheimer’s disease (AD) or mild cognitive impairment (MCI) is inconclusive, and human studies of the relationship of cholinergic function with neuropsychological performance in vivo are rare. Methods: We included 21 healthy controls, 20 MCI and 15 mild AD patients. A comprehensive neuropsychological battery was administered to indicate the general cognitive function and to define performance of verbal and non-verbal memory, language, executive function and visuoconstructive abilities. [11C]-MP4A PET was applied in all subjects, parametric images of tracer hydrolysis rate constant k3 were generated and analysed using standard atlas regions. After principal component analysis (PCA) of k3 values correlational analysis with neuropsychological test results was performed. Results: The mean global k3 values of MCI (0.076 6 0.011 min-1) and AD patients (0.066 6 0.009 min-1) were significantly lower than that of controls (0.084 6 0.006 min-1) (p < 0.05 and p < 0.001, respectively) with the temporal regions showing the strongest decline in both patient groups. PCA revealed three main components representing frontal and parietal regions (PC1), temporal regions (PC2) and hippocampus and amygdala (PC3). PC 2 could separate all three diagnostic groups. Significant correlations in the whole group between PC2 and neuropsychological performances were found, most strongly with impaired verbal and visual memory function as well as impaired working memory, but also with deficient visuo-spatial and executive functions. The association of verbal and non-verbal memory with the ‘‘temporal’’ PC 2 was confirmed in MCI patients. This is in line with neuropathological studies showing the greatest and most consistent loss of cholinergic neurons in AD in the posterior part of the nucleus basalis Meynert (nbM-Ch4p), which primarily sends cholinergic projections to the temporal cortex (Geula and Mesulam, 1999). Conclusions: Cholinergic dysfunction in the temporal lobe is an early hallmark in MCI and mild AD and it is associated with impaired neuropsychological function.