Differential aging of the brain: Patterns, cognitive correlates and modifiers

Raz, Naftali; Rodrigue, Karen M.

doi:10.1016/j.neubiorev.2006.07.001

Cited by 1,014 publications

(919 citation statements)

References 227 publications

Supporting

Mentioning

838

Contrasting

Unclassified

Order By: Relevance

“…In contrast to supratentorial fiber systems, the two infratentorial systems examined (pontocerebellar and cerebellar hemisphere bundles) showed no signs of aging whatsoever, a finding consistent with a fiber tracking study of children and young adults (Liston et al, 2006) and a region-of-interest study of adult aging (Yoon et al, 2007). As has been speculated, demonstrated, and replicated with region-of-interest and voxel-based analyses (for reviews, Minati et al, 2007;Moseley, 2003;Pfefferbaum and Sullivan, 2005a;Pfefferbaum, 2003, 2007;Wozniak and Lim, 2006), these patterns of normal aging provide support for subtle disruption of frontal systems in explaining age-related decline in selective cognitive and motor functions (Craik and Salthouse, 2008;Fazekas et al, 2005;Raz and Rodrigue, 2006). Degradation of anterior commissural fibers may curtail deployment of bilateral compensatory mechanisms to enhance performance when age-related decline reduces performance efficiency by the preferred gray matter system (c.f., Dennis and Cabeza, 2008).…”

Section: Discussionsupporting

confidence: 70%

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Sullivan

Rohlfing

Pfefferbaum

2010

Neurobiology of Aging

302

307

View full text Add to dashboard Cite

The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5 T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (λL), an index of axonal length or number, and transverse diffusivity (λT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of age's effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.

show abstract

Section: Discussionsupporting

confidence: 70%

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Sullivan

Rohlfing

Pfefferbaum

2010

Neurobiology of Aging

302

307

View full text Add to dashboard Cite

show abstract

“…In our study, the MTR decreases in the frontal white matter and basal forebrain were likely to be related to vascular pathology because they were negatively correlated with diffusion (ADC, Table 4), a measure that is known to be sensitive to capillary expansion, swelling of perivascular spaces, and vascular insults (Moseley, 2002;Pfefferbaum et al, 2003;Raz and Rodrigue, 2006;Wozniak and Lim, 2006). 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;.…”

Section: Discussionmentioning

confidence: 55%

Basal forebrain integrity and cognitive memory profile in healthy aging

Düzel¹,

Münte²,

Lindenberger³

et al. 2010

Brain Research

View full text Add to dashboard Cite

Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are assumed to contribute to age-associated impairment of explicit memory. Both neurotransmitters also modulate attention, working memory, and processing speed. To date, in vivo evidence linking structural age-related changes in these neuromodulatory systems to dysfunction within or across these cognitive domains remains scarce. Using a factor analytical approach in a cross-sectional study including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30 years) adults, we assessed the relationship between structural integrity-as measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain (major origin of cortical cholinergic projections), frontal white matter (FWM), and hippocampus to neuropsychological and psychosocial scores. Basal forebrain MTR and FWM changes correlated with a factor combining verbal learning and memory and working memory and, as indicated by measures of diffusion, were most likely due to vascular pathology. These findings suggest that frontal white matter integrity and cholinergic neuromodulation provide clues as to why age-related cognitive decline is often correlated across cognitive domains. IntroductionAge-related decline in learning and memory, often termed age-associated memory impairment (AAMI) (Crook et al., 1986), is a well-documented finding in healthy older adults (Balota et al., 2000;Cabeza et al., 2000;Craik, 1994;Salthouse, 2003), but the neurobiological correlates of this decline are still under debate. A consistent pattern of AAMI is a decrement in declarative memory (Tulving, 1985) most clearly apparent in impaired free recall and recollection (Buckner, 2004;Craik, 2006;Hedden and Gabrieli, 2004;Nilsson, 2003). Evidence from lesion studies in humans and animals indicates that

show abstract

“…AlsoFin this specific sampleFthe whole brain was larger in the depressed subjects than in the comparison subjects. Thus, we chose to use the volume of the primary visual cortex (the calcarine area) to control for individual variations in brain size, as this is one of the regions with minimal inter-subject variation as well as with minimal agerelated variation (Raz and Rodrigue, 2006).…”

Section: Methodsmentioning

confidence: 99%

Gray Matter Changes in Late Life Depression—a Structural MRI Analysis

Andreescu

Butters

Begley

et al. 2007

Neuropsychopharmacol

127

120

View full text Add to dashboard Cite

Multiple brain morphometric changes have been reported in late-life depression (LLD), mostly in studies comparing volumes of circumscribed brain areas. The aim of our study is to characterize the volumetric changes of multiple gray matter regions in relation to age of onset/duration of illness. We predicted that the association of gray matter volumes with total duration of illness and age of onset would differ depending on whether the region was susceptible to the toxic effects of chronic exposure to cortisol or to the vascular/ neurodegenerative changes accompanying prodromal dementia. Seventy-one elderly depressed subjects were studied along with thirtytwo comparison subjects. High-resolution T1-weighted brain MRIs were processed using an automated labeling pathway technique. To protect against type-I error, we combined the right and left hemisphere volume data. We sampled 24 regions of interest (ROIs). We used the primary visual cortex volume to normalize for individual variations in brain size. LLD Subjects had smaller volumes than nondepressed subjects in 17 of the 24 examined ROIs. Shorter duration of illness and later age of onset was correlated with smaller volumes of parahippocampal area and parietal inferior area. A later age of onset was also correlated with smaller volumes of several frontal and temporal areas, cingulum, and putamen. Our findings support a dementia prodrome model more strongly than a toxic stress model in this group of subjects. However, it remains likely that both processes as well as other factors contribute to the heterogeneity of volumetric brain changes in LLD.

show abstract

Differential aging of the brain: Patterns, cognitive correlates and modifiers

Cited by 1,014 publications

References 227 publications

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance

Basal forebrain integrity and cognitive memory profile in healthy aging

Gray Matter Changes in Late Life Depression—a Structural MRI Analysis

Contact Info

Product

Resources

About