Related Experiment Video

Updated: Jul 7, 2026

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans
08:29

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

Published on: December 18, 2016

Critical and non-critical connections not differently associated with either Alzheimer's disease or vascular

Naomi Vlegels1, Bruno M de Brito Robalo1, Alberto de Luca1,2

  • 1Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.

Medrxiv : the Preprint Server for Health Sciences
|February 12, 2026
PubMed

Insights

Critical white matter connections are not more vulnerable to SVD or Alzheimer's disease (AD) pathologies than non-critical connections. White matter hyperintensity volume equally affected both connection types, with AD markers also showing similar effects.

Area of Science:

  • Neuroscience
  • Neuropathology
  • Medical Imaging

Background:

  • Pilot studies suggested critical white matter (WM) connections are not uniquely vulnerable to SVD or AD.
  • Systematic evaluation is needed to understand the relationship between SVD, AD, and WM connection vulnerability.

Purpose of the Study:

  • To systematically evaluate the association between SVD and AD pathologies and critical versus non-critical WM connections.
  • To determine if critical WM connections exhibit greater vulnerability to SVD and AD than non-critical connections.

Main Methods:

  • Diffusion tensor imaging (DTI) was used to reconstruct WM networks in patients with CADASIL, mixed pathology, and autosomal dominant AD (ADAD).
  • Critical and non-critical connections were defined within these networks.
  • Linear regression analyses assessed associations between SVD markers (WMH volume) and AD markers (CSF Aβ42, p-tau, EYO) with connection strengths.

Main Results:

  • White matter hyperintensity (WMH) volume demonstrated equally strong associations with both critical and non-critical WM connections.
  • Alzheimer's disease markers (Aβ-positivity, Aβ42 levels, p-tau levels, EYO) showed similar effect sizes for both critical and non-critical connections.
  • Sensitivity analyses confirmed these findings across different connectivity definitions, indicating SVD burden impacts WM integrity more than AD, but without differential vulnerability for critical connections.

Conclusions:

  • Neither SVD nor AD pathologies show a greater vulnerability in critical white matter connections compared to non-critical ones.
  • SVD burden appears to have a more pronounced effect on overall WM integrity than AD.
  • The findings challenge the hypothesis of critical WM connections being uniquely susceptible to neurodegenerative disease processes like SVD and AD.

Keywords:
CADASILcerebral small vessel diseasediffusion magnetic resonance imagingfamilial Alzheimer’s diseasestructural brain networkwhite matter

More Related Videos

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment08:43

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment

Published on: August 7, 2017

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions07:30

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions

Published on: April 23, 2021

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...
Dementia01:30

Dementia

Dementia is a collective term for cognitive disorders primarily affecting memory, thinking, and reasoning. It is not a specific disease but a syndrome, with Alzheimer's disease being the most common cause, accounting for approximately 60-80% of cases. Other types include vascular dementia, Lewy body dementia, and frontotemporal dementia. Dementia affects millions worldwide, particularly older adults, though it is not a normal part of aging.
The progression of dementia is generally gradual.
Ischemic Stroke ll: Pathophysiology01:15

Ischemic Stroke ll: Pathophysiology

An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...
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...
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...
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...