Summary Background Previous studies have identified effects of age and vascular risk factors on brain injury in elderly individuals. We aimed to establish whether the effects of high blood pressure ...in the brain are evident as early as the fifth decade of life. Methods In an investigation of the third generation of the Framingham Heart Study, we approached all participants in 2009 to ask whether they would be willing to undergo MRI. Consenting patients underwent clinical assessment and cerebral MRI that included T1-weighted and diffusion tensor imaging to obtain estimates of fractional anisotropy, mean diffusivity, and grey-matter volumes. All images were coregistered to a common minimum deformation template for voxel-based linear regressions relating fractional anisotropy, mean diffusivity, and grey-matter volumes to age and systolic blood pressure, with adjustment for potential confounders. Findings 579 (14·1%) of 4095 participants in the third-generation cohort (mean age 39·2 years, SD 8·4) underwent brain MRI between June, 2009 and June, 2010. Age was associated with decreased fractional anisotropy and increased mean diffusivity in almost all cerebral white-matter voxels. Age was also independently associated with reduced grey-matter volumes. Increased systolic blood pressure was linearly associated with decreased regional fractional anisotropy and increased mean diffusivity, especially in the anterior corpus callosum, the inferior fronto-occipital fasciculi, and the fibres that project from the thalamus to the superior frontal gyrus. It was also strongly associated with reduced grey-matter volumes, particularly in Brodmann's area 48 on the medial surface of the temporal lobe and Brodmann's area 21 of the middle temporal gyrus. Interpretation Our results suggest that subtle vascular brain injury develops insidiously during life, with discernible effects even in young adults. These findings emphasise the need for early and optimum control of blood pressure. Funding National Institutes of Health and National Heart, Lung, and Blood Institute; National Institute on Aging; and National Institute of Neurological Disorders and Stroke.
White matter hyperintensities (WMHs) are associated with progressive age-related cognitive decline and cardiovascular risk factors, but their biological relevance as indicators of generalized white ...matter injury is unclear. Diffusion tensor imaging provides more sensitive indications of subtle white matter disruption and can therefore clarify whether WMHs represent foci of generalized white matter damage that extends over a broader neighborhood.
Two hundred eight participants from the University of California, Davis Alzheimer's Disease Center received a comprehensive clinical evaluation and brain MRI including fluid-attenuated inversion recovery and diffusion tensor imaging sequences. Voxelwise maps of WMHs were produced from fluid-attenuated inversion recovery using a standardized WMH detection protocol. Fractional anisotropy maps were calculated from diffusion tensor imaging. All WMH and fractional anisotropy maps were coregistered to a standardized space. For each normal-appearing white matter voxel in each subject fluid-attenuated inversion recovery scan, a neighborhood white matter injury score was calculated that increased with increasing number and proximity of WMH in the vicinity of the normal-appearing white matter voxel. Fractional anisotropy was related to neighborhood white matter injury using a nonlinear mixed effect model controlling for relevant confounding factors.
Fractional anisotropy was found to decrease as neighborhood white matter injury increased (β = -0.0017/%, P < 0.0001) with an accelerated rate (P < 0.0001) for neighborhood white matter injury >0.4. An increase of 1% in neighborhood white matter injury score was associated with a decrease in mean fractional anisotropy of 0.012 (P < 0.001).
WMH may represent foci of more widespread and subtle white matter changes rather than distinct, sharply delineated anatomic abnormalities. We use the term white matter hyperintensities penumbra to explain this phenomenon.
To investigate the effects of baseline white matter hyperintensity (WMH) and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function).
A total of ...150 individuals including cognitively normal elderly individuals and those with Alzheimer disease and mild cognitive impairment completed serial episodic memory and executive function evaluations and serial MRI scans sufficient for longitudinal measurement of WMH (mean delay 4.0 years). Incident WMH voxels were categorized as extended (baseline WMH that grew larger) or emergent (newly formed WMH). We used a stepwise regression approach to investigate the effects of baseline WMH and rates of WMH extension and emergence on rate of change in cognition (episodic memory and executive function).
WMH burden significantly increased over time, and approximately 80% of incident WMH voxels represented extensions of existing lesions. Each 1 mL/y increase in WMH extension was associated with an additional 0.70 SD/y of subsequent episodic memory decrease (p = 0.0053) and an additional 0.55 SD/y of subsequent executive function decrease (p = 0.022). Emergent WMHs were not found to be associated with a change in cognitive measures.
Aging-associated WMHs evolve significantly over a 4-year period. Most of this evolution represents worsening injury to the already compromised surround of existing lesions. Increasing WMH was also significantly associated with declining episodic memory and executive function. This finding supports the view that white matter disease is an insidious and continuously evolving process whose progression has clinically relevant cognitive consequences.
Previous work from the Framingham Heart Study suggests that brain changes because of arterial aging may begin in young adulthood and that such changes precede cognitive deficits. The objective of ...this study was to determine the association of arterial stiffness with measures of white matter and gray matter (GM) integrity in young adults.
One thousand nine hundred three participants from the Framingham Heart Study Third Generation (mean age, 46±8.7 years) had complete tonometry measurements and brain magnetic resonance imaging (T1-weighted and diffusion tensor imaging). Tonometry measures included carotid-femoral pulse wave velocity, augmentation index, carotid-brachial pressure amplification, and central pulse pressure. Fractional anisotropy and GM density images were computed from diffusion tensor imaging and T1 images. Registration to a common anatomic template enabled voxel-based linear regressions relating measures of fractional anisotropy and GM to tonometry measures, adjusting for relevant covariables.
Higher carotid-femoral pulse wave velocity was associated with lower regional fractional anisotropy, including the corpus callosum and the corona radiata (8.7 and 8.6 cc, respectively, P<0.001), as well as lower GM density in the thalamus region (0.9 cc, P<0.001). Analyses did not reveal significant associations between other tonometry measures and fractional anisotropy or GM.
Among young healthy adults, higher aortic stiffness was associated with measures of reduced white matter and GM integrity in areas implicated in cognitive decline and Alzheimer's disease. Greater aortic stiffness may result in subclinical vascular brain injury at ages much younger than previously described.
Chronic systemic sterile inflammation is implicated in the pathogenesis of cerebrovascular disease and white matter injury. Non-invasive blood markers for risk stratification and dissection of ...inflammatory molecular substrates in vivo are lacking. We sought to identify whether an interconnected network of inflammatory biomarkers centered on IL-18 and all previously associated with white matter lesions could detect overt and antecedent white matter changes in two populations at risk for cerebral small vessel disease. In a cohort of 167 older adults (mean age: 76, SD 7.1, 83 females) that completed a cognitive battery, physical examination, and blood draw in parallel with MR imaging including DTI, we measured cerebral white matter hyperintensities (WMH) and free water (FW). Concurrently, serum levels of a biologic network of inflammation molecules including MPO, GDF-15, RAGE, ST2, IL-18, and MCP-1 were measured. The ability of a log-transformed population mean-adjusted inflammatory composite score (ICS) to associate with MR variables was demonstrated in an age and total intracranial volume adjusted model. In this cohort, ICS was significantly associated with WMH (β = 0.222, p = 0.013), FW (β = 0.3, p = 0.01), and with the number of vascular risk factor diagnoses (r = 0.36, p<0.001). In a second cohort of 131 subjects presenting for the evaluation of acute neurologic deficits concerning for stroke, we used serum levels of 11 inflammatory biomarkers in an unbiased principal component analysis which identified a single factor significantly associated with WMH. This single factor was strongly correlated with the six component ICS identified in the first cohort and was associated with WMH in a generalized linear regression model adjusted for age and gender (p = 0.027) but not acute stroke. A network of inflammatory molecules driven by IL-18 is associated with overt and antecedent white matter injury resulting from cerebrovascular disease and may be a promising peripheral biomarker for vascular white matter injury.
Complaints about memory are common in older people but their relationship with underlying brain changes is controversial.
To investigate the relationship between subjective memory impairment and ...previous or subsequent changes in white matter lesions and brain volumes.
In a community cohort study of 1336 people without dementia, 4-year changes in brain magnetic resonance imaging measures were investigated as correlates of subjective memory impairment at baseline and follow-up.
Subjective memory impairment at baseline was associated with subsequent change in hippocampal volume and at follow-up impairment was associated with previous change in hippocampal, cerebrospinal fluid and grey matter volume and with subcortical white matter lesion increases. All associations with volume changes were U-shaped with significant quadratic terms - associations between least decline and subjective memory impairment were potentially explained by lower baseline hippocampal volumes in the groups with least volume change. Associations between hippocampal volume change and subjective memory impairment at follow-up were independent of cognitive decline and depressive symptoms, they were stronger in participants with the apolipoprotein E (APOE) ε4 allele and in those without baseline subjective memory impairment.
Complaints of poor memory by older people, particularly when new, may be a realistic subjective appraisal of recent brain changes independent of observed cognitive decline.
Le corpus étudié dans cet ouvrage forme un ensemble de quatre cents figurines en terre cuite trouvées à la fin du xixe s. sur les rives du lac salé de Larnaca, au sud-est de Chypre. À partir du ...dépouillement des archives de l’époque, l’auteure reconstitue un catalogue complet et détaillé des objets dont elle précise l’origine. Ces représentations, largement dominées par la figure d’une femme trônant coiffée d’un haut calathos végétal, mettent en lumière tous les aspects de l’artisanat de l’argile dans le milieu chypro-phénicien, des savoir-faire et de leur transmission, de l’organisation du travail à l’intérieur des ateliers. Elles révèlent aussi les procédés techniques ingénieux dont usaient les Kitiens. L’étude s’intéresse en détail aux modalités d’utilisation et d’intégration des types iconographiques en contextes rituels. Elle met encore plus en évidence la question de la présence d’Aphrodite et d’Artémis dans les cultes périurbains, mais aussi de dieux d’origine phénicienne ou égyptienne comme Astarté, Umm, Eshmoun-Melqart et Bès. L’analyse des liens entre l’environnement marin et le caractère des divinités permet à l’auteure de mettre en lumière la dimension culturelle et rituelle liée au sel et à la mer dans le paysage religieux chypriote, phénicien et levantin. L’ensemble de l’étude révèle, en somme, l’importance historique du développement des cultes dans le royaume de Kition au ive s. av. J.-C.
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