Related Experiment Video

Updated: May 29, 2026

An Alternative Approach to Study Primary Events in Neurodegeneration Using Ex Vivo Rat Brain Slices
07:57

An Alternative Approach to Study Primary Events in Neurodegeneration Using Ex Vivo Rat Brain Slices

Published on: April 11, 2018

Chronic divalproex sodium use and brain atrophy in Alzheimer disease

A S Fleisher1, D Truran, J T Mai

  • 1Banner Alzheimer's Institute, 901 E Willetta Street, Phoenix, AZ 85006, USA. Adam.fleisher@bannerhealth.com

Neurology
|September 16, 2011
PubMed
Abstract

Insights

Divalproex sodium, used for Alzheimer's disease (AD), accelerated brain volume loss and cognitive decline in patients over one year. Further research is needed to understand the long-term clinical impact.

Area of Science:

  • Neurology
  • Neuroimaging
  • Pharmacology

Background:

  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
  • Valproic acid, formulated as divalproex sodium, is used in neurological conditions.
  • The impact of divalproex sodium on brain structure in AD is not fully understood.

Purpose of the Study:

  • To evaluate the effect of divalproex sodium on brain volumes in patients with mild to moderate Alzheimer's disease (AD).
  • To assess changes in cognitive and behavioral effects associated with divalproex sodium treatment in AD patients.

Main Methods:

  • A 24-month, parallel-group trial involving 313 participants with mild to moderate AD.
  • MRI scans were performed at baseline and 12 months on 89 participants.
  • Primary outcomes included annual percent changes in whole brain, ventricular, and hippocampal volumes.

Main Results:

  • Divalproex treatment group showed significantly greater rates of decline in hippocampal and brain volumes compared to placebo.
  • Ventricular expansion was significantly greater in the divalproex group (24.5% vs 9.9%).
  • Mini-Mental State Examination scores declined more rapidly in the divalproex group through 12 months (p = 0.037).

Conclusions:

  • Divalproex sodium treatment was associated with accelerated brain volume loss over one year in AD patients.
  • The treatment may be linked to greater cognitive impairment, particularly in the short term.
  • The long-term clinical significance of these observed changes remains unknown.

More Related Videos

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly12:50

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Published on: April 14, 2014

Related Concept Videos

Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
Alzheimer's Disease: Treatment01:22

Alzheimer's Disease: Treatment

Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
Dementia l: Introduction01:22

Dementia l: Introduction

Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...
Hepatic Encephalopathy01:29

Hepatic Encephalopathy

DefinitionHepatic encephalopathy is a reversible neurologic syndrome that results from advanced liver dysfunction or portosystemic shunting. It leads to disturbances in cognition, behavior, and motor function due to the brain’s exposure to gut-derived toxins that the liver fails to detoxify.EtiologyThis condition develops either in the setting of acute fulminant hepatitis or progressively during chronic liver disease, such as cirrhosis and portal hypertension. Portosystemic shunting—including...