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Olfactory impairment is present in up to 90% of patients with Alzheimer’s disease (AD) and is present in certain cases of mild cognitive impairment (MCI), a transient phase between normal aging and dementia. Subjects affected by MCI have a higher risk of developing dementia compared to the general population, and studies have found that olfactory deficits could be an indicator of whether such a conversion might happen. Following these assumptions, aim of this study was to investigate olfactory perception in MCI patients. We recruited 12 MCI subjects (mean age 70 ± 6.7 years) through the Alzheimer Assessment Unit (UVA Unite) of ASL Lecce (Italy), and 12 healthy geriatric volunteers (HS) as the control group (mean age 64 ± 6.0 years), all of whom were first evaluated via a panel of neuropsychological tests. Subjects were asked to perform an olfactory recognition task involving two scents: rose and eucalyptus, administrated in the context of an oddball task during EEG recordings. Olfactory event-related potential (OERP) components N1 and Late Positive Potential (LPC) were then analyzed as measures of the sensorial and perceptive aspects of the olfactory response, respectively. It was determined that, in the MCI group, both the N1 and LPC components were significantly different compared to those of the HS group during the execution of the oddball task. In particular, the N1 amplitude, was reduced, while the LPC amplitude was increased, indicating that a degree of perceptive compensation can occur when sensorial function is impaired. Further, a correlation analysis, involving OERP components and neuropsychological battery scores, indicated that impairment of olfactory perception may share common pathways with impairments of the spatial system and long-term memory processing.

Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS)-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction and NF-kB activation downregulation. Coextensively, in the in vivo model, both glial fibrillary acidic protein and ionized calcium-binding adapter molecule-1 expression, two markers of inflammation, were reduced by mofezolac to a rank depending on the encephalon area analyzed. The increase of COX-1 expression observed in all the brain sections of LPS-treated mice was selectively downregulated by the in vivo treatment with mofezolac as well as PGE2 release and Ikβα phosphorylation amount assayed in the brain areas tested. These results indicate the capability of P6 and mofezolac to modulate the NF-kB signaling pathway, emphasizing the neuroprotective effect and therapeutic potential of COX-1 inhibitors in the control of neuroinflammatory diseases.