title: Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline.
abstract: White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a "pre-visible" stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65-84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment.
authors.affiliation: Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Jokinen
authors.affiliation: Department of Information and Computer Science, Aalto University School of Science Espoo, Finland.
authors.forename: Nicolau
authors.initials: N
authors.lastname: Gonçalves
authors.affiliation: Department of Information and Computer Science, Aalto University School of Science Espoo, Finland ; Department of Physics, University Nova of Lisbon Lisbon, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Vigário
authors.affiliation: Institute of Behavioural Sciences, University of Helsinki Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Lipsanen
authors.affiliation: Department of Neurology and MRI Institute, Medical University of Graz Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: Department of Neurology and MRI Institute, Medical University of Graz Graz, Austria.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Department of Radiology and Neurology, VU University Medical Center Amsterdam, Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria Lisbon, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Madureira
authors.affiliation: Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria Lisbon, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Verdelho
authors.affiliation: Department of Neurological and Psychiatric Sciences, University of Florence Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
authors.affiliation: Department of Neurological and Psychiatric Sciences, University of Florence Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pantoni
authors.affiliation: Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Erkinjuntti
keywords: MRI; cognition; executive functions; image analysis; neuropsychology; small vessel disease; white matter lesions