Differential Vulnerability of Anterior White Matter in Nondemented Aging with Minimal Acceleration in Dementia of the Alzheimer Type: Evidence from Diffusion Tensor Imaging

Abstract

White matter microstructural integrity was assessed using diffusion tensor imaging (DTI) in 25 young adults, 25 nondemented older adults, and 25 age-matched older adults with dementia of the Alzheimer type (DAT). For each individual, measures of anisotropy and diffusivity were obtained from atlas-transformed images in the anterior and posterior callosum and in the frontal, parietal, temporal and occipital white matter. These data revealed age differences in anisotropy and diffusivity in all assessed regions. Age effects were greater in the anterior as opposed to the posterior corpus callosum and greater in the frontal white matter than in the temporal, parietal and occipital white matter, suggesting age-associated differences in white matter that exhibit a roughly anterior-to-posterior gradient. In contrast, individuals with early-stage dementia exhibited minimal, if any, additional change in anterior regions but did show greater deterioration of white matter in posterior lobar regions. Taken collectively, these results indicate that nondemented aging is characterized by significant changes in white matter most prominently in anterior brain regions. The dissociation between the regional effects of age and dementia status suggests that the mechanisms underlying age-associated cognitive decline are likely distinct from those underlying DAT.

Basal forebrain integrity and cognitive memory profile in healthy aging

“…Previous studies of WM tract integrity have reported reduced FA in healthy elderly subjects most prominently in FWM and the corpus callosum (Head et al, 2004;Pfefferbaum et al, 2005;Salat et al, 2005;. In our study, MTR was not correlated with FA.…”

Development of large-scale functional networks over the lifespan

“…Several factors may account for this agedependent adaptation of connectivity. The well-documented agedependent decline of white matter tracts (Head et al, 2004;Pfefferbaum et al, 2000Pfefferbaum et al, , 2005Sullivan et al, 2001) can be a good explanation for the changes in functional connectivity reported here. Stereological investigations showing a progression of white matter demyelination in normal aging (Tang et al, 1997) lend further credibility to this interpretation.…”

“…This view is strongly supported by studies reporting a linear decline of gray matter volume with advancing age (Bartzokis et al, 2001;Hutton et al, 2009) and the work by Sowell and colleagues (Sowell et al, 2003) showing a nonlinear decrease of gray matter density with increasing age. Studies investigating white matter alterations in the human brain also show a general decrease in older age (Head et al, 2004;Pfefferbaum et al, 2000Pfefferbaum et al, , 2005Sullivan et al, 2001). However, white matter volume seems to increase until the middle age of about 45 years and to decrease thereafter (Bartzokis et al, 2001;Sowell et al, 2003).…”

Socioeconomic status is positively correlated with frontal white matter integrity in aging

“…The unique correlations in the senior group raise the possibility that high SES may neuroprotect some agerelated frontal WM integrity declines. The anatomical specificity of the observed SES-frontal relationship may in part reflect that frontal WM tracts, because they are especially vulnerable to age-related declines (Head et al 2004;O'Sullivan et al 2001;Salat et al 2005a, b), also carry greater chance of incurring protective benefits from high SES than other regions.…”