Proceedings of the 34th National Congress of the Italian Society of Histochemistry

Cholinergic hypofunction is a trait of Alzheimer’s disease(AD)and of other forms of dementias such as vascular dementia(VaD) and Lewy bodies dementia (LBD). The acetylcholinesterase(AChE)/cholinesterase (ChE) inhibitors (Is) areone of the two classes of drug approved for AD treatment.ChE-Is are licensed for the symptomatic relief of mild to moderateAD. These drugs are used out of label as a therapeuticapproach for treating cognitive disorders other than AD suchas VaD and LBD. A main problem deriving from their use isthat the benefits of AD symptomatic treatment are modest andnot long lasting. It is also thought that the magnitude of benefitof this class of drugs can elicit is apparently marginal anddifficult to detect and to measure clinically. Moreover, widespreaduse of AChE/ChE inhibitors may be accompanied byserious adverse events. Cholinergic precursors represent an oldapproach to treat cholinergic dysfunction, but the first drugsproposed did not show clinical benefit on symptoms of AD.Actually, evidence for an enhancement of ACh biosynthesis bycholine or lecithin is faint. The same is not true for cytidine 5'-diphosphocholine and choline alphoscerate for which a modestimprovement of cognitive dysfunction in dementia disorders isdocumented. The association of ChE-Is with phospholipidsinvolved in choline biosynthetic pathways was proposed to furtherenhance cholinergic neurotransmission compared to singlecompounds. It could represent a strategy to provide a strongercholinergic challenge in dementia. This study reviews thecholinergic hypothesis of geriatric memory dysfunction and discussesbased on original finding the neurochemical bases of theassociation between ChE-Is and cholinergic precursors.Evidence of a possible neuroprotective effect of the associationin animal models is also presented