MRI-leukoaraiosis thresholds and the phenotypic expression of dementia

Abstract

Objective: To examine the concept of leukoaraiosis thresholds on working memory, visuoconstruction, memory, and language in dementia.Methods: A consecutive series of 83 individuals with insidious onset/progressive dementia clinically diagnosed with Alzheimer disease (AD) or small vessel vascular dementia (VaD) completed neuropsychological measures assessing working memory, visuoconstruction, episodic memory, and language. A clinical MRI scan was used to quantify leukoaraiosis, total white matter, hippocampus, lacune, and intracranial volume. We performed analyses to detect the lowest level of leukoaraiosis associated with impairment on the neuropsychological measures.Results: Leukoaraiosis ranged from 0.63% to 23.74% of participants' white matter. Leukoaraiosis explained a significant amount of variance in working memory performance when it involved 3% or more of the white matter with curve estimations showing the relationship to be nonlinear in nature. Greater leukoaraiosis (13%) was implicated for impairment in visuoconstruction. Relationships between leukoaraiosis, episodic memory, and language measures were linear or flat.Conclusions: Leukoaraiosis involves specific threshold points for working memory and visuoconstructional tests in AD/VaD spectrum dementia. These data underscore the need to better understand the threshold at which leukoaraiosis affects and alters the phenotypic expression in insidious onset dementia syndromes. Neurology Optimal clinical management of dementia requires an appreciation of MRI-detected leukoaraiosis (LA). LA can alter cognitive dysfunction, 1 everyday living abilities, 2 and anti-cholinesterase effectiveness.3 It remains uncertain, however, how much LA is needed to alter the dementia phenotypic expression. Some have suggested that 25% of white matter needs to contain LA for dysexecutive impairment to supersede amnestic impairment. 4 This has been shown in 2 separate studies 4,5 using the Junque Scale of LA, 6 a 40-point visual rating scale. When divided into thirds, a Junque score greater than/equal to 18 (suggesting Ͼ25% LA) was associated with greater executive vs episodic memory impairment in dementia. A score less than 10 reflected striking anterograde memory impairment. A score between 10 and 17 resulted in similar executive and episodic memory dysfunction.The present study was designed to further investigate the threshold effect of LA with newer, more objective imaging techniques examining LA as a proportion of white matter while also controlling for intracranial volume which can modify brain structure-function associations. 7,8 It was hypothesized that among dementia patients this method would be positively correlated with the Junque LA Scale, but demonstrate a unique burden threshold only on measures

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“…Via functional neuroimaging, this test associates with dorsal and medial frontal lobe (54)(55)(56), and parietal lobe (57), thereby implicating the involvement of large frontal-parietal and frontal-subcortical white matter networks. Leukoaraiosis and lacunae disrupt these connections (21). Thus, the Stroop Color-Word Test warrants consideration as a key neuropsychological measure in future POCD investigations.…”

“…Leukoaraiosis associates with demyelination and hyalinosis narrowing of small brain arterioles. This signifies microvascular burden to frontal-subcortical white matter pathways important for executive functions (20)(21)(22). Lacunae suggest ischemic strokes (often considered "silent").…”

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“…LA was assessed in native space from FLAIR protocols with semi-automated volumetrics shown to have criterion validity relative to a LA visual rating scale 23 . A reliable rater (inter-rater range: 0.84 – 0.93; intra-rater range > 0.99) measured all brain scans using in-house macros for ImageJ (http://rsbweb.nih.gov/ij/docs/index.html) 24, 25 .…”

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“…Structures in the right medial temporal lobe, including the anterior hippocampus, are hypothesized to play a role in the spatial working memory that may be required for performing the RCFT copy trial (Feigenbaum, Polkey, & Morris, 1996). WMH has been implicated to play a role in visuoconstructional impairment (Price et al, 2012). The memory domain score had significant associations with bilateral hippocampal volumes, reflecting the encoding and consolidation of both verbal and nonverbal stimuli in the domain composition (Squire & Zola-Morgan, 1991).…”