Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?

Inhibition of endogenous acetylcholine degradation through cholinesterase inhibitors represents a milestone in symptomatic treatment of cognitive symptoms in mild to moderate stages of Alzheimer's disease. Cholinesterase inhibitors are also under investigation for treating cognitive dysfunction of cerebrovascular origin, but to date they do not have specific indication for vascular dementia or vascular cognitive impairment. This paper reviews the main clinical studies assessing the activity of cholinergic precursors in the treatment of adult-onset dementia disorders of vascular origin. The first cholinergic precursor used phosphatidylcholine (lecithin) did not show any clear clinical benefit on symptoms of dementia disorders. The same is not true for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) and choline alphoscerate for which a modest improvement of cognitive dysfunction in dementia of neurodegenerative and vascular origin is documented. Positive results obtained with selected cholinergic precursors cannot be generalized due to the small numbers of patients studied in appropriate clinical trials. However, they probably would justify reconsideration of the most promising molecules in larger carefully controlled studies.