Decreased White Matter Integrity in Neuropsychologically Defined Mild Cognitive Impairment Is Independent of Cortical Thinning

Abstract

Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as Mild Cognitive Impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically-based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and DTI scans were completed. Tract-Based Spatial Statistics was applied and a priori selected ROIs were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for cortical thickness, the MCI group showed decreased average FA and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes.

Structural brain markers are differentially associated with neurocognitive profiles in socially marginalized people with multimorbid illness.

“…Moreover, evidence suggests that indices of gray and white matter integrity independently contribute to the differentiation of normal versus pathological neurocognitive aging (Stricker et al, 2013;Wang et al, 2012). Such findings highlight structural brain indices as viable biomarkers that could be used to inform the degree and type of intervention required to maximize treatment gains and outcomes.…”

“…In Study 2, we adopted a similar approach to examine the association between white matter integrity and neurocognition, thereby providing a more comprehensive understanding of structure-function relationships in a socially marginalized sample. Examining both gray and white matter structural properties of the brain is important considering that these have demonstrated independent contributions to neurocognitive dysfunction (Stricker et al, 2013).…”

Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum

“…Eighty-two participants were part of the Understanding Cerebrovascular and Alzheimer’s Risk in the Elderly (UCARE) program, recruited through the Boston University Alzheimer’s Disease Center (BUADC) based on the criteria of being neurologically healthy and having a first-degree family relative with AD. Data were analyzed on a subset of individuals presented previously (Stricker et al, 2013). Participants were excluded for the following: history of head trauma of “mild” severity or greater (Holm et al, 2005; within our sample loss of consciousness did not exceed 15 minutes), more than one head injury, any neurological disorder including dementia (i.e., Parkinson’s disease, AD, vascular dementia), severe psychiatric illness, or brain surgery.…”

“…White matter changes are well-documented in Alzheimer’s dementia (AD) (Brun and Englund, 1986; Salat et al, 2010; Stricker et al, 2009) and its prodromal stages, including Mild Cognitive Impairment (MCI) (Delano-Wood et al, 2010; Fellgiebel et al, 2005; Parente et al, 2008; Stricker et al, 2013; Wang et al, 2009). However, the pattern and underlying mechanism of these changes remain unclear.…”

Mild Cognitive Impairment: A Concept and Diagnostic Entity in Need of Input from Neuropsychology

“…When these requirements are met, we illustrate with a second series of articles that neuropsychological measures associate strongly with neuroimaging and cerebrospinal (CSF) biomarkers in expected patterns and that often reflect pathology beyond or instead of typical AD distributions (Hantke et al, 2013; Nordlund et al, 2008; Stricker et al, 2013). Finally, when prerequisite conditions exist, people with MCI may demonstrate mild but identifiable functional difficulties, and a challenge for neuropsychology is how to incorporate this information to better define MCI and delineate it from early dementia (Aretouli, Okonkwo, Samek, & Brandt, 2011; Bangen et al, 2010; Okonkwo et al, 2008; Sherod et al, 2009).…”