Cerebrospinal fluid biomarkers of white matter lesions – cross‐sectional results from the LADIS study

  title={Cerebrospinal fluid biomarkers of white matter lesions – cross‐sectional results from the LADIS study},
  author={Michael A G Jonsson and Henrik Zetterberg and Elisabeth C. W. van Straaten and Karin Lind and Steinar Syversen and {\AA}ke Edman and Kaj Blennow and Lars E. Rosengren and Leonardo Pantoni and Domenico Inzitari and Anders Wallin},
  journal={European Journal of Neurology},
Background and purpose:  White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer’s disease (AD) and subcortical vascular dementia. 

Cerebrovascular Biomarker Profile Is Related to White Matter Disease and Ventricular Dilation in a LADIS Substudy

The link between progressive WMH and MMP-9 suggests an involvement of the enzyme in white matter degeneration, and CSF TIMP-1, NF-L, MBP and sAPPβ may function as biological markers of white matter damage.

Cerebrospinal fluid biomarkers and white matter lesions: can we know more?

The results strengthen the view of an AD-independent biochemical substrate accompanying WMLs, further explaining the actual contribution of W MLs to cognitive impairment and the importance of CSF analysis for exploring neurological conditions that are either not fully defined or not recognized yet as canonical clinical entities.

Blood and CSF biomarkers in brain subcortical ischemic vascular disease: Involved pathways and clinical applicability

  • A. Vilar‐BerguaI. Riba-Llena J. Montaner
  • Biology, Medicine
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2016
To translate these findings into clinical practice and use biomarkers to early diagnosis and monitoring vascular cognitive impairment would require the replication of candidate markers in large-scale, multicenter, and prospectively designed studies.

Cerebral white matter changes in patients with cognitive impairment - clinical and pathophysiological aspects

WMC in patients with cognitive impairment are independently related to a dysexecutive-related behavioural symptom profile, vascular disorders and a non-AD biochemical profile associated with vessel-wall pathology and demyelination and may have implications for definition and nosological knowledge of AD and vascular cognitive disorder.

Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid

Lower CSF levels of s APP-α and sAPP-β in the stroke group than in the SCI/MCI group and an inverse correlation with chronic WML indicate that ischemia lowers the levels of CSF sAPP metabolites and suggests that APP axonal transport or metabolism may be affected in SVD of the brain.

Cerebrospinal fluid biomarkers for differentiating between Alzheimer’s disease and Vascular dementia

Cerebrospinal fluid biomarkers for differentiating between Alzheimer’s disease and Vascular dementia AKADEMISK AVHANDLING Som for avlaggande av medicine doktorsexamen vid Sahlgrenska akademin vid Goteborgs Universitet kommer att offentligen forsvaras vid Molndal Torsdagen, and in combination with the clinical assessment may improve diagnostic accuracy.

White Matter Lesions Are Not Related to β-Amyloid Deposition in an Autopsy-Based Study

Both cortex and periventricular region showed no differences for β-amyloid deposition in either plaques or blood vessel walls in patients with WMLs compared to those without W MLs.

Cerebrospinal fluid neurofilament light chain is a marker of aging and white matter damage

CSF Biomarkers and Neuropsychological Profiles in Patients with Cerebral Small-Vessel Disease

The results support the idea that a dysfunction of the blood-brain-barrier might be contributing factor in the development of cognitive decline in CSVD as it seems to be of more importance than the severity of white matter lesions.



Cerebrospinal fluid markers of pathogenetic processes in vascular dementia, with special reference to the subcortical subtype.

There is a need for improvement of the diagnosis of vascular dementia (VaD). Today, the clinician has to rely on clinical examination, history, and, possibly, brain imaging to identify

Neurofilament protein in cerebrospinal fluid: A marker of white matter changes

A clear association between the presence of WMC and increased CSF NFL was found, and because NFL is located mainly in large myelinated axons, increasedCSF NFL in individuals with WMC probably reflects axonal degeneration.

CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus

Cerebrospinal fluid markers for neuronal degeneration and demyelination in idiopathic normal pressure hydrocephalus, subcortical arteriosclerotic encephalopathy, and neurologically healthy subjects are evaluated.

Potential Biological Markers for Cerebrovascular Disease

Among biochemical markers in the CSF, tau protein, phospho-tau, and beta amyloid protein are helpful to differentiate vascular dementia from Alzheimer's disease.

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study

These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.

Small Vessel Disease and General Cognitive Function in Nondisabled Elderly: The LADIS Study

The results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function, and are independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke.

Impact of Age-Related Cerebral White Matter Changes on the Transition to Disability – The LADIS Study: Rationale, Design and Methodology

The longitudinal design of the LADIS study will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life.

Research criteria for subcortical vascular dementia in clinical trials.

A modification of the NINDS-AIREN criteria is proposed as a new research criteria for subcortical VaD, which is expected to show a more predictable clinical picture, natural history, outcome, and treatment responses.

Impact of White Matter Hyperintensities Scoring Method on Correlations With Clinical Data: The LADIS Study

Background and Purpose— White matter hyperintensities (WMH) are associated with decline in cognition, gait, mood, and urinary continence. Associations may depend on the method used for measuring WMH.