Volume Analysis of Brain Cognitive Areas in Alzheimer's Disease: Interim 3-Year Results from the ASCOMALVA Trial

J Alzheimers Dis. 2020;76(1):317-329. doi: 10.3233/JAD-190623.

Abstract

Background: Cerebral atrophy is a common feature of several neurodegenerative disorders, including Alzheimer's disease (AD). In AD, brain atrophy is associated with loss of gyri and sulci in the temporal and parietal lobes, and in parts of the frontal cortex and cingulate gyrus.

Objective: The ASCOMALVA trial has assessed, in addition to neuropsychological analysis, whether the addition of the cholinergic precursor choline alphoscerate to treatment with donepezil has an effect on brain volume loss in patients affected by AD associated with cerebrovascular injury.

Methods: 56 participants to the randomized, placebo-controlled, double-blind ASCOMALVA trial were assigned to donepezil + placebo (D + P) or donepezil + choline alphoscerate (D + CA) treatments and underwent brain magnetic resonance imaging and neuropsychological tests every year for 4 years. An interim analysis of 3-year MRI data was performed by voxel morphometry techniques.

Results: The D + P group (n = 27) developed atrophy of the gray and white matter with concomitant increase in ventricular space volume. In the D + CA group (n = 29) the gray matter atrophy was less pronounced compared to the D + P group in frontal and temporal lobes, hippocampus, and amygdala. These morphological data are consistent with the results of the neuropsychological tests.

Conclusion: Our findings indicate that the addition of choline alphoscerate to standard treatment with the cholinesterase inhibitor donepezil counters to some extent the loss in volume occurring in some brain areas of AD patients. The observation of parallel less pronounced decrease in cognitive and functional tests in patients with the same treatment suggests that the morphological changes observed may have functional relevance.

Keywords: Alzheimer’s disease; association; brain atrophy; cerebrovascular injury; choline alphoscerate; donepezil.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / psychology*
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Cognition / physiology*
  • Donepezil / pharmacology
  • Donepezil / therapeutic use
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging / trends*
  • Male
  • Nootropic Agents / pharmacology
  • Nootropic Agents / therapeutic use
  • Organ Size / physiology

Substances

  • Nootropic Agents
  • Donepezil