Disconnected aging: Cerebral white matter integrity and age-related differences in cognition

Abstract

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging.

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

“…Similarly, in alcohol users with comorbid HIV infection, lower FA and higher diffusivity in the corpus callosum was found to correlate with slowed motor speed (Pfefferbaum, Rosenbloom, Adalsteinsson, & Sullivan, 2007). Further investigation of these associations is highly important given the mediating role of white matter in cognitive aging (Bennett & Madden, 2014).…”

“…On the other hand, when age and motor function were controlled for in cognitively normal adults, associations were identified between executive functioning, memory, and information processing, and white matter tract integrity in the corresponding functional regions (Sasson, Doniger, Pasternak, Tarrasch, & Assaf, 2012). There is further evidence from healthy adults to suggest that variability in neurocognitive performance may also be attributed to global reductions in white matter degradation with coinciding tract-specific reductions (Bennett & Madden, 2014).…”

“…During development, myelination for higher-order cortical brain regions, specifically the prefrontal cortex, is the last to take place (Toga, Thompson, & Sowell, 2006), and these same regions are the first to degrade in the context of normal aging, following an anterior-posterior gradient (Bennett & Madden, 2014). Admittedly, these typical trajectories may not generalize to a highly multimorbid population.…”

Cortical correlates of response time slowing in older adults: ERP and ERD/ERS analyses during passive ankle movement

“…However, the latency changes due to these non-encephalic structures of the nervous system are relatively small and cannot account for the cortical response latency changes found experimentally. At higher levels of the central nervous system, the loss of dopamine and dopaminergic receptors (Kaasinen et al, 2000;Volkow et al, 2000) and decreased white matter volume (Guttmann et al, 1998;Davis et al, 2009;Bennett and Madden, 2014) are documented to occur with aging and are likely contributing to increases in the central processing time.…”

Neurobiological underpinnings of bipolar disorder focusing on findings of diffusion tensor imaging: a systematic review

“…73 These cognitive impairment domains seem to have a close correlation with WM and brain connectivity deterioration. [74][75][76] Recently, a neuroinflammatory component has been implicated in the pathophysiology of certain psychiatric disorders, 77 and offers a plausible explanation as to why WM lesions are present in patients with BD. 78 Of note, WM is particularly vulnerable to the inflammatory neurotoxic Diffusion tensor imaging in BD effects of BD.…”