الفهرس 
Acknowledgement
Treatment of cognitive disorders and Alzheimer’s diseaseOnly 14 pages are availabe for public view
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Abstract
PDEIs improved behavioral, histological, biochemical and receptor gene expression (AD-like alterations) in animals as follows:
1- They enhanced the cognitive function (learning & memory).
2- They reduced the brain injury as they decreased the degenerative cell in brain of T2D rats
3- They reduced the accumulation of extracellular Aβ and intracellular p-tau.
4- They reduced the biomarkers of neurodegeneration (caspase 3 and AChE activities).
5- They normalized the lipid profile (TC, TGs, LDL), glucose level and AUC (measuring insulin resistance)
6- They enhanced the suppressed GluRs gene expression (AMPA GluR1 and NMDA NR1, NR2A & NR2B).
These effects may be attributed to:
A- Improvement of insulin resistance, glucose level and decrease in GSK-3β activity.
B- Reduction of hypercholesterolemia
C- Reduction of oxidative stress and enhancement of antioxidant natural defense (MDA, GSH & TAC).
D- Reduction of the expression of proinflammatory cytokines (TNF-α, IL-6 & IL-1α).
We suggest that apremilast, apremilast plus caffeine and combination of CSZ plus caffeine, could stop the progression of AD through their possible disease–modifying effect.