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

Abstract

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. 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. 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. 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. 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.