Abstract
Background
Cholinesterase inhibitors (ChE-Is) are among the drugs more largely used for the treatment
of mild-to-moderate symptoms of Alzheimer's disease (AD), but beneficial long-term
effects of these compounds on the cognitive, functional, and behavioural symptoms
of the disease are small and not always apparent in practice. Preclinical investigations
have suggested that association between ChE-Is and the cholinergic precursor choline
alphoscerate enhances cholinergic neurotransmission more effectively than single compounds
alone. The ongoing clinical trial on the “Effect of association between a ChE-I and
choline alphoscerate on cognitive deficits in Alzheimer's disease associated with
cerebrovascular injury” (ASCOMALVA) was designed to assess if association of the ChE-I
donepezil with choline alphoscerate has a more favourable clinical profile than monotherapy
with donepezil alone.
Methods
ASCOMALVA is a double-blind multicentre trial that has completed the first 12 months of observation of 91 patients of the 210 planned. Patients were aged between
56 and 91 years (mean 75±10 years) and were included in the protocol with a MMSE score between 15 and 24. Patients
with AD diagnosed according to the DSM IV criteria suffer from ischemic brain damage
documented by neuroimaging (MRI and CT scan), with a score≥2 in at least one subfield of the New Rating Scale for Age-Related White Matter Changes
(ARWMC). Patients were randomly allotted to an active treatment group (donepezil+choline alphoscerate) or to a reference treatment group (donepezil+placebo) and were examined after 3, 6, 9 and 12 months of treatment.
Results
Cognitive functions, patient's daily activities and behavioural symptoms were assessed
by the Mini‐Mental State Evaluation (MMSE), Alzheimer's Disease Assessment Scale Cognitive
subscale (ADAS-cog), Basic Activities of Daily Living (BADL), Instrumental Activities
of Daily Living (IADL) and Neuropsychiatric Inventory (NPI), of severity and of caregiver
distress measures (NPI-F and NPI-D). Patients of the reference group (donepezil+placebo) showed along the course of the 12 months of observation, a slight time-dependent worsening of MMSE, ADAS-cog, IADL and
NPI-D scores and no changes in the BADL and NPI-F scores. Donepezil plus choline alphoscerate
improved compared to donepezil alone the different items analysed except the BADL.
Conclusions
The first results of the ASCOMALVA trial suggest that association of choline alphoscerate
to the standard treatment with a ChE-I may represent an option to prolong beneficial
effects of cholinergic therapies in AD with concomitant ischemic cerebrovascular injury.
Keywords
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Article info
Publication history
Published online: September 10, 2012
Accepted:
July 2,
2012
Received in revised form:
June 6,
2012
Received:
February 28,
2012
Identification
Copyright
© 2012 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
