Age-related decline in white matter tract integrity and cognitive performance: A DTI tractography and structural equation modeling study

Abstract

Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) setshifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial Disclosure statementDr. Bruce Pollock receives research support from the National Institute of Health. Within the past year he has been a member of the advisory board of Lundbeck, Canada, and has served 1 time as a consultant for Wyeth Pharmaceuticals (October 2008). He is currently a faculty member of the Lundbeck International Neuroscience Foundation (LINF). Dr. Benoit Mulsant has in the past received research support or honoraria from AstraZeneca, Corcept, EISAI, Eli Lilly, Lundbeck, Forest, GlaxoSmithKline, Janssen, and Pfizer. Dr. Mulsant owns stock of less than $10,000 in value in Akzo-Nobel, Alkermes, AstraZeneca, Biogen Idec, Ceslsion, Elan, Eli Lilly, Forest, General Electric, and Orchestra Therapeutics. The remaining authors have no financial disclosures to report. The study was approved by the Review and Ethics Board of the Centre for Addiction and Mental Health (Toronto, Canada) and all participants provided informed, written consent. construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging. NIH Public Access

White Matter Development is Potentially Influenced in Adolescents with Vertically Transmitted HIV Infections: A Tract-Based Spatial Statistics Study

“…24 The corpus callosum is also involved with memory and executive function. 25 Moreover, deceased FA is also found in the anterior and superior corona radiata in HIV-infected participants. 10,11 The anterior corona radiata is associated with functions of the executive network.…”

The Speed-Accuracy Tradeoff in the Elderly Brain: A Structural Model-Based Approach

“…Voineskos et al, 2010). According to the striatal hypothesis of the SAT, these two sets of seemingly unrelated results are in fact causally related, as the control over threshold settings is assumed to be instantiated via the corticostriatal network.…”

Study of human structural brain connectivity in healthy aging based on tracts

“…Therefore, from the fitted linear relationship, even when our study is not longitudinal, we can suggest that white matter alterations as detected by MRI are more sensitive than cortical thickness variations. This evidence confirms previous studies indicating FA decrease and MD increase in WM as sensitive markers of aging (GIORGIO et al, 2010;HUGENSCHMIDT et al, 2008;MICHIELSE et al, 2010;TEIPEL et al, 2014;VOINESKOS et al, 2012). …”

“…The absence of neuronal loss for whole-brain cell counting with increasing age, can be due to changes in the cortical structure, associated with WM structural changes, like changes in neuronal size, dendritic and axonal simplifications or glia cells alterations, rather than neuronal loss, implicating in age-related cognitive changes (FREEMAN et al, 2008;PAKKENBERG;GUNDERSEN, 1997 (GIORGIO et al, 2010;HUGENSCHMIDT et al, 2008;MICHIELSE et al, 2010;TEIPEL et al, 2014;VOINESKOS et al, 2012). An anteroposterior gradient of age-related decline in FA is presented (SULLIVAN; ADALSTEINSSON;PFEFFERBAUM, 2006), and hypothesized as underlying cognitive decline of frontally-based functions (KOCHUNOV et al, 2007;SALAT et al, 2005 RAZ, 2016;VOINESKOS et al, 2012;WANG et al, 2016) and inferior occipitofrontal fasciculus (BENDER; VOLKLE; RAZ, 2016;WANG et al, 2016).…”