Apathy Treatment in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial

Background: Apathy is a common symptom in Alzheimer's disease (AD), but no treatment has proven to be effective, although administration of cholinesterase inhibitors has been associated with moderate improvements in the short term.

Objective: This study has compared apathy scores of patients included in "ASCOMALVA" trial treated for two years with donepezil plus a cholinergic precursor (choline alphoscerate), to those of patients receiving donepezil alone with the purpose of assessing if the availability of a higher amount of acetylcholine by combining precursor loading and inhibition of neurotransmitter breakdown would counter apathy in AD.

Methods: Apathy was measured at baseline and 3, 6, 9, 12, 18, and 24 months using the apathy subtest of the Neuropsychiatric Inventory in 113 mild-moderate AD patients. Two matched groups were compared: group 1 (56 subjects) treated with donepezil plus choline alphoscerate and group 2 (57 subjects) treated with donepezil alone. Frontal functions were explored by the Frontal Assessment Battery (FAB) at baseline.

Results: Group 1 subjects showed, as a whole, a lower apathy score after 12 to 24 months. The caregiver distress was descreased after 6 to 24 months. Results were unrelated with cognitive scores measured by the MMSE and ADAS-cog test. Subjects with FAB in the normal range had significantly lower scores.

Conclusions: The combination of donepezil with choline alphoscerate is more effective than donepezil alone in countering symptoms of apathy in AD. This suggests that the availability in brain of a higher amount of acetylcholine could affect apathy in AD subjects with spared executive functions.