The present study was designed to assess if treatment with acetylcholinesterase inhibitor galantamine and the cholinergic precursor choline alphoscerate (alpha-glyceryl-phosphoryl-choline) alone or in association has any protective effect on brain microanatomy in spontaneously hypertensive rats (SHR) used as an animal model of vascular dementia (VaD). Thirty-two-week-old SHR and age-matched normotensive Wistar Kyoto (WKY) rats were left untreated or treated for 4 weeks with an oral dose of 3 mg/kg/day of galantamine, of 100 mg/kg/day of choline alphoscerate or their association. The number of neurons and of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, phosphorylated neurofilament, and microtubule associated protein-2 (MAP-2) and aquaporin-4 (AQP-4) was assessed by quantitative microanatomical and immunohistochemical techniques. In SHR, the number of neurons of frontal cortex, of the CA1 subfield of hippocampus and of dentate gyrus was decreased compared to WKY rats. Astrogliosis, breakdown of phosphorylated neurofilament, unchanged MAP-2 and altered AQP-4 expression were found as well. Both galantamine and choline alphoscerate countered nerve cell loss. Choline alphoscerate but not galantamine decreased astrogliosis and restored expression of AQ-4. Galantamine countered to a greater extent than choline alphoscerate phosphorylated neurofilament breakdown. The two drugs in association displayed a more remarkable effect. This study confirms a neuroprotective effect of galantamine in SHR and indicates a neuroprotective role of choline alphoscerate in the same model. A wider neuroprotective effect of the cholinergic inhibitor/precursor association was observed. These findings suggest to assess the activity of this cholinergic association in clinical trials.