Effect of white matter lesions on manual dexterity in healthy middle-aged persons

Abstract

Objectives: We hypothesized that integrated motor-visual functions measured by manipulative manual dexterity are affected by white matter lesion (WML) burden as measured on cranial MRI across relevant brain regions in subjects at risk of preclinical occult vascular disease.Methods: A real-time cross-sectional study of healthy subjects aged 29 to 74 years with a family history of early-onset coronary artery disease (n 5 714; mean age, 51 6 11 years; mean education, 14 6 3 years; 42% male; 38% black) were identified from probands with coronary artery disease diagnosed before age 60 years. WMLs on 3-tesla brain MRI and Grooved Pegboard scores were measured.Results: WMLs were observed at all ages. Mean pegboard scores were 108 6 18, similar to normal populations. In unadjusted analysis, WMLs and pegboard scores were significantly correlated by region (total WMLs, r 5 0. . In multivariate analysis predicting (log) pegboard score adjusted for age, sex, race, education, regional or total volumes, and familial nonindependence, total WML volume (p 5 5.79E 2 05) and regional WML volumes (p , 0.01) retained statistical significance in all but the youngest age quartile (29-43 years).Conclusions: Greater WML volumes in different brain regions are associated with higher pegboard scores (worse performance) independent of age, sex, race, education, and total or regional volumes. This suggests that small vessel cerebrovascular disease may be present in healthy individuals in a preclinical state with measurable impact on complex integrative functions in individuals with excess risk of clinical vascular disease. Neurology ® 2015;84:1920-1926 GLOSSARY CAD 5 coronary artery disease; FLAIR 5 fluid-attenuated inversion recovery; MMSE 5 Mini-Mental State Examination; MPRAGE 5 magnetization-prepared rapid-gradient echo; TOADS 5 topology-preserving anatomy-driven segmentation; WML 5 white matter lesion.White matter lesions (WMLs) appearing as hyperintense regions on fluid-attenuated inversion recovery (FLAIR) and T2 MRIs are thought to be caused by small vessel cerebrovascular disease.1 WML volume and number are associated with age and are most notable in older age groups.1,2 Overall, WML burden is an independent predictor of clinical dementia and of decrements in motor function, including gait, psychomotor speed, and motor apraxia. [3][4][5][6] We have published data that show a high prevalence of occult coronary artery disease (CAD) and cerebral small vessel lesions in younger and middle-aged people from families with a history of early-onset CAD.7-9 High-risk individuals may also be at increased risk of functional consequences of occult small vessel cerebrovascular disease. 9 To date, most studies of WMLs have addressed older populations and persons with cognitive functional decline or clinical dementia. 2The Northern Manhattan Study, which was conducted in a healthy community population, found that patients with a WML volumetric threshold at the 75th percentile performed

Disrupted white matter integrity and network connectivity are related to poor motor performance

“…A few previous studies have investigated the association of white matter structure and upper extremity functions. A population-based study 23 and a study conducted in families with a history of early-onset coronary artery disease 22 found greater WMH volume was associated with decreased manual dexterity (Grooved Pegboard Test). However, the two studies did not assess white matter microstructural integrity.…”

“…Compared with the lower extremity, manual dexterity was more important for fine motor skills in daily activities, such as feeding, dressing, and grooming, especially in the elderly 21 . Although sparse, exiting findings have also linked poor manual dexterity and worse finger task performance to greater white matter hyperintensities (WMH) 22 , 23 volume and disrupted white matter tract integrity 24 , 25 . Few studies have investigated how upper extremity and lower extremity functions relate to brain structural lesions in the same sample 26 .…”

A Robust Energy Minimization Algorithm for MS-Lesion Segmentation

“…Their shapes are deformable, their location and area across patients may differ significantly [2–5]. There are many automatic and semiautomatic approaches for brain segmentation [6, 7], Similar to those methods, the MS lesions segmentation approaches include a variety of methods such as region partitioning, markov random field model, adaptive outlier detection and feature extraction [8–11].…”

White Matter Lesion Progression and Cognitive Function Over 5 Years in a Young Susceptible Population

“…In a prior cross-sectional study of 563 cognitively normal middle-aged relatives, we found a high prevalence of early white matter hyperintensity lesions (WMHL) [1–3], and further, observed lower cognitive function scores among those with higher WMHL volumes [4]. Most prior WMHL studies have occurred in the elderly or in populations with dementia [5].…”

“…All volumes were measured with an automated standard pipeline as described previously [3]. Cognitive function was measured using standard tests, [4] and traditional vascular risk factors were assessed. Changes over 5 years are presented on the Table.…”