Aging of cerebral white matter: a review of MRI findings

Gunning-Dixon, Faith M.; Brickman, Adam M.; Cheng, Janice; Alexopoulos, George S.

doi:10.1002/gps.2087

Cited by 479 publications

(407 citation statements)

References 83 publications

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“…There existed a significant association between white matter lesion load and severity of DTI and MTR measures in the normalappearing white matter with the microstructural changes in normal brain tissue being more closely related to the patients' clinical presentation than the volume of visible white matter abnormalities [9,32,52,61,69,70,74,92,93]. These observations clearly indicate that age-related small vessel disease of the brain is a diffuse process affecting the entire brain and that white matter lesions are probably only the tip of the iceberg.…”

Section: Age-related White Matter Changes and Normal-appearing Brain mentioning

confidence: 83%

Heterogeneity in age-related white matter changes

et al. 2011

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White matter changes occur endemically in routine magnetic resonance imaging (MRI) scans of elderly persons. MRI appearance and histopathological correlates of white matter changes are heterogeneous. Smooth periventricular hyperintensities, including caps around the ventricular horns, periventricular lining and halos are likely to be of non-vascular origin. They relate to a disruption of the ependymal lining with subependymal widening of the extracellular space and have to be differentiated from subcortical and deep white matter abnormalities. For the latter a distinction needs to be made between punctate, early confluent and confluent types. Although punctate white matter lesions often represent widened perivascular spaces without substantial ischemic tissue damage, early confluent and confluent lesions correspond to incomplete ischemic destruction. Punctate abnormalities on MRI show a low tendency for progression, while early confluent and confluent changes progress rapidly. The causative and modifying pathways involved in the occurrence of sporadic age-related white matter changes are still incompletely understood, but recent microarray and genome-wide association approaches increased the notion of pathways that might be considered as targets for therapeutic intervention. The majority of differentially regulated transcripts in white matter lesions encode genes associated with immune function, cell cycle, proteolysis, and ion transport. Genome-wide association studies identified six SNPs mapping to a locus on chromosome 17q25 to be related to white matter lesion load in the general population. We also report first and preliminary data that demonstrate apolipoprotein E (ApoE) immunoreactivity in white matter lesions and support epidemiological findings indicating that ApoE is another factor possibly related to white matter lesion occurrence. Further insights come from modern MRI techniques, such as diffusion tensor and magnetization transfer imaging, as they provide tools for the characterization of

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Section: Age-related White Matter Changes and Normal-appearing Brain mentioning

confidence: 83%

Heterogeneity in age-related white matter changes

et al. 2011

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“…Consistently, higher SHBG levels were associated with lower BMI and insulin levels in our sample (Table S4). WM alterations, such as compromised microstructural integrity, volume loss, and WM lesions have been linked to aging (Gunning‐Dixon, Brickman, Cheng, & Alexopoulos, 2009) and poorer cardio‐metabolic health (Launer et al., 2015; Segura et al., 2009). In parallel, the association of higher SHBG levels with smaller GM volume may be related to SHBG's role in regulating sex‐hormone‐related mechanisms, wherein higher SHBG typically indicate lower bioavailable T and estrogen levels.…”

Section: Discussionmentioning

confidence: 99%

Sex hormones and brain volumes in a longitudinal study of middle‐aged men in the CARDIA study

et al. 2017

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IntroductionSeveral findings suggest that testosterone (T) is neuroprotective and that declining T levels during aging are associated with cognitive and brain pathologies; however, little is known on T and brain health in middle‐age. We examined the relationships of total T, bioavailable T, and sex hormone binding globulin (SHBG) levels with total and regional gray matter (GM) and white matter (WM) volumes in middle‐aged men. We also evaluated the association of sex hormone levels with cognitive function.MethodsAnalysis included 267 community‐dwelling men participating in the Coronary Artery Risk Development in Young Adults (CARDIA) brain magnetic resonance imaging (MRI) substudy. Total T, bioavailable T, and SHBG levels were measured at three times from the 2nd to 4th decade of life; brain volumes were measured at the ages of 42–56. Associations were estimated using linear regression models, adjusted for several potential confounders.ResultsHigher SHBG levels were associated with greater total WM volume (+3.15 cm3 [95% confidence interval [CI] = 0.01, 6.28] per one standard deviation higher SHBG). Higher SHBG levels were associated with lower total and regional GM volumes overall and significantly with smaller parietal GM volume (−0.96 cm3 [95%CI = −1.71, −0.21]). T levels were not related to brain volumes. Neither T nor SHBG levels were associated with cognitive function.ConclusionResults suggest a role for SHBG in structural brain outcomes in men and emphasize the value of investigating SHBG levels as modulators of sex hormone and metabolic pathways regulating brain and behavioral characteristics in men.

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“…The way in which the impact of low-grade systemic inflammation on cognition is mediated is at present unclear. The known association between cognitive ageing and white matter pathology (Gunning-Dixon et al 2009) raises the possibility that a proinflammatory state could result in acceleration of white matter damage or progressive loss of white matter integrity on the basis of microvascular damage. This idea is supported by the Rotterdam Study of 1,033 dementiafree elders (aged 60-90 years) which reported a significant association between elevated CRP and the presence and 3-year progression of white matter lesions on magnetic resonance imaging (van Dijk et al 2005).…”

Section: Discussionmentioning

confidence: 99%

The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study

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Smith

Agars

et al. 2011

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Inflammation may contribute to cognitive decline and dementia. This study examined the cross-sectional relationships between markers of systemic inflammation (C-reactive protein, interleukins-1β, -6, -8, -10, -12, plasminogen activator inhibitor, serum amyloid A, tumour necrosis factor-α and vascular adhesion molecule-1) and cognitive function in 873 non-demented community-dwelling elderly participants aged 70-90 years. Regression analyses were performed to determine the relationships between cognitive domains and inflammatory markers, controlling for age, sex, education, cardiovascular risk factors, obesity and other metabolic factors, smoking, alcohol consumption, depression and presence of the apolipoprotein ε4 genotype. Regression analyses were repeated using four factors derived from a factor analysis of the cognitive tests. After Bonferroni correction for multiple testing, associations remained between raised levels of interleukin-12 and reduced performance in processing speed. Marked sex differences were noted in the abovementioned findings, with only females being significantly affected. Using the AGE

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Aging of cerebral white matter: a review of MRI findings

Abstract: Background-Cerebral aging is a complex and heterogeneous process that is associated with a high degree of inter-individual variability. Structural magnetic resonance imaging (MRI) can be used to identify and quantify non-disease-related aging of the cerebral white matter.

Cited by 479 publications

References 83 publications

Heterogeneity in age-related white matter changes

Heterogeneity in age-related white matter changes

Sex hormones and brain volumes in a longitudinal study of middle‐aged men in the CARDIA study

The association between systemic inflammation and cognitive performance in the elderly: the Sydney Memory and Ageing Study

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