Regional white matter volume differences in nondemented aging and Alzheimer's disease

Abstract

Accumulating evidence suggests that altered cerebral white matter (WM) influences normal aging, and further that WM degeneration may modulate the clinical expression of Alzheimer's disease (AD). Here we conducted a study of differences in WM volume across the adult age span and in AD employing a newly developed, automated method for regional parcellation of the subcortical WM that uses curvature landmarks and gray matter (GM)/WM surface boundary information. This procedure measures the volume of gyral WM, utilizing a distance constraint to limit the measurements from extending into the centrum semiovale. Regional estimates were first established to be reliable across two scan sessions in 20 young healthy individuals. Next, the method was applied to a large clinically-characterized sample of 299 individuals including 73 normal older adults and 91 age-matched participants with very mild to mild AD. The majority of measured regions showed a decline in volume with increasing age, with strong effects found in bilateral fusiform, lateral orbitofrontal, superior frontal, medial orbital frontal, inferior temporal, and middle temporal WM. The association between WM volume and age was quadratic in many regions suggesting that WM volume loss accelerates in advanced aging. A number of WM regions were further reduced in AD with parahippocampal, entorhinal, inferior parietal and rostral middle frontal WM showing the strongest AD-associated reductions. There were minimal sex effects after correction for intracranial volume, and there were associations between ventricular volume and regional WM volumes in the older adults and AD that were not apparent in the younger adults. Certain results, such as the loss of WM in the fusiform region with aging, were unexpected and provide novel insight into patterns of age associated neural and cognitive decline. Overall, these results demonstrate the utility of automated regional WM measures in revealing the distinct patterns of age and AD associated volume loss that may contribute to cognitive decline.

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

“…Given that AD and vascular brain injury are commonly co-morbid (Sonnen et al 2009), it is possible that earlier findings of lower FA in AD patients reflected vascular disturbances as opposed to a specific effect of AD pathology. Salat et al (2009) described an AD-specific decline in WM volume in the parahippocampal and entorhinal cortices, regions that traditionally suffer from atrophy with AD. Longitudinal scans that contrasted subjects with stable MCI and those that converted to AD showed increased WM atrophy in the temporal lobe (Davatzikos et al 2011).…”

The effect of interference on temporal order memory for random and fixed sequences in nondemented older adults

“…Specifically, volumetric reductions have been reported in the medial temporal and prefrontal regions of the human brain (Kramer et al 2007;Fjell and Walhovd 2010;Raz et al 2010;Cardenas et al 2011). Age-related white matter changes also have been reported in frontal and temporal regions of the human brain (Davis et al 2009;Salat et al 2009;Murray et al 2010;Ziegler et al 2010). These structural changes in gray and white matter have been associated with age-related cognitive decline (Kramer et al 2007;Fjell and Walhovd 2010;Murray et al 2010;Ziegler et al 2010;Cardenas et al 2011).…”

The effect of lifelong bilingualism on regional grey and white matter volume

“…In grey matter, the trajectory of these age-related changes is variable across the brain such that more rapid decline is observed in regions of the frontal and parietal lobes than in the temporal and occipital lobes (Fjell et al, 2013;Kennedy & Raz, 2009;Raz et al, 2004Raz et al, , 2005Resnick et al, 2000;Resnick et al, 2003;Walhovd et al, 2005Walhovd et al, , 2011. In white matter, some studies have reported a more diffuse pattern of volumetric reductions across the brain with age (Fjell et al, 2013;Resnick et al, 2000Resnick et al, , 2003Salat et al, 2009;Walhovd et al, 2005Walhovd et al, , 2011, whereas others have reported greater reduction in frontal lobe white matter compared to other regions (Brickman et al, 2006;Ferreira et al, 2014;Head et al, 2004).…”