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Updated: Aug 23, 2026
Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
Published on: April 23, 2021
White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease
R Schmidt1, Ph Scheltens, T Erkinjuntti
1Department of Neurology, Medical University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. reinhold.schmidt@meduni-graz.at
Abstract:
There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.
Insights
Measuring white matter lesion progression via MRI may serve as a surrogate marker for cerebral small-vessel disease in clinical trials. This approach could streamline research on treatments for ischemic brain damage and dementia.
Area of Science:
- Neurology
- Radiology
- Geriatrics
Background:
- Confluent white matter lesions on MRI in elderly individuals are linked to ischemic brain damage from microangiopathy.
- Current clinical trials for cerebral small-vessel disease primarily use cognitive impairment and dementia as outcomes.
Purpose of the Study:
- To investigate the potential of measuring white matter lesion progression on MRI as a surrogate outcome marker in clinical trials.
- To evaluate the feasibility of using MRI-based lesion changes to assess disease progression in cerebral small-vessel disease.
Main Methods:
- Analysis of follow-up MRI data from community-dwelling subjects to assess white matter lesion progression.
- Calculation of sample size needed to detect a 20% reduction in disease progression over 3 years.
Main Results:
- A mean increase in white matter lesion volume of 5.2 cm³ was observed over 3 years.
- A clinical trial would require approximately 195 subjects per arm to detect a 20% reduction in progression rate.
Conclusions:
- Changes in white matter lesion volume on MRI show rapid progression, supporting its potential as a surrogate marker.
- The utility of MRI metrics as primary outcomes must be validated by demonstrating patient-relevant functional improvements.
