Leritz EC, Salat DH, Williams VJ, et al. Thickness of the human cerebral cortex is associated with metrics of cerebrovascular health in a normative sample of community dwelling older adults

Geriatric Research, Education and Clinical Center (GRECC), VA Boston Healthcare System, Boston, MA 02130, USA.
NeuroImage (Impact Factor: 6.36). 10/2010; 54(4):2659-71. DOI: 10.1016/j.neuroimage.2010.10.050
Source: PubMed


We examined how wide ranges in levels of risk factors for cerebrovascular disease are associated with thickness of the human cerebral cortex in 115 individuals ages 43-83 with no cerebrovascular or neurologic history. Cerebrovascular risk factors included blood pressure, cholesterol, body mass index, creatinine, and diabetes-related factors. Variables were submitted into a principal components analysis that confirmed four orthogonal factors (blood pressure, cholesterol, cholesterol/metabolic and glucose). T1-weighted MRI was used to create models of the cortex for calculation of regional cortical thickness. Increasing blood pressure factor scores were associated with numerous regions of reduced thickness. Increasing glucose scores were modestly associated with areas of regionally decreased thickness. Increasing cholesterol scores, in contrast, were associated with thicker cortex across the whole brain. All findings were primarily independent of age. These results provide evidence that normal and moderately abnormal levels of parameters used to assess cerebrovascular health may impact brain structure, even in the absence of cerebrovascular disease. Our data have important implications for the clinical management of vascular health, as well as for what is currently conceptualized as "normal aging" as they suggest that subclinical levels of risk may impact cortical gray matter before a disease process is evident.

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    • "The region of reduced CThk was smaller in spatial extent but overlapping with the CVR results, which is a novel finding relative to the literature that has primarily focused on CThk in T2DM (Ajilore et al., 2010; Brundel et al., 2010; Chen et al., 2013; Leritz et al., 2011; Seo et al., 2012) and HTN separately (Seo et al., 2012; Vuorinen et al., 2013). A previous study involving older adults demonstrated that blood glucose levels and blood pressure were both associated with CThk thinning in occipital regions, among others (Leritz et al., 2011). These metrics of metabolic and hypertensive control identify regions that may be preferentially impacted by T2DM and HTN. "
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    ABSTRACT: Objective Type 2 diabetes mellitus is characterized by metabolic dysregulation in the form of hyperglycemia and insulin resistance and can have a profound impact on brain structure and vasculature. The primary aim of this study was to identify brain regions where the combined effects of type 2 diabetes and hypertension on brain health exceed those of hypertension alone. A secondary objective was to test whether vascular impairment and structural brain measures in this population are associated with cognitive function. Research design and methods We enrolled 18 diabetic participants with hypertension (HTN + T2DM, 7 women, 71.8 ± 5.6 years) and 22 participants with hypertension only (HTN, 12 women, 73.4 ± 6.2 years). Cerebrovascular reactivity (CVR) was assessed using blood oxygenation level dependent (BOLD) MRI during successive breath holds. Grey matter structure was evaluated using cortical thickness (CThk) measures estimated from T1-weighted images. Analyses of cognitive and blood data were also performed. Results Compared to HTN, HTN + T2DM had decreased CVR and CThk in a spatially overlapping region of the right occipital lobe (P < 0.025); CVR group differences were more expansive and included bilateral occipito-parietal areas (P < 0.025). Whereas CVR showed no significant associations with measures of cognitive function (P > 0.05), CThk in the right lingual gyrus ROI and regions resulting from a vertex-wise analysis (including posterior cingulate, precuneus, superior and middle frontal, middle and inferior temporal regions (P < 0.025) were associated with executive function. Conclusions Individuals with T2DM and HTN showed decreased CVR and CThk compared to age-matched HTN controls. This study identifies brain regions that are impacted by the combined effects of comorbid T2DM and HTN conditions, with new evidence that the corresponding cortical thinning may contribute to cognitive decline.
    Clinical neuroimaging 12/2014; 5. DOI:10.1016/j.nicl.2014.05.020 · 2.53 Impact Factor
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    • "However, the plasma Ab 1–42 /Ab 1–40 ratio predicts cognitive decline and AD progression (Koyama et al. 2012) as well as volume changes in the medial temporal lobe of healthy older (HO) subjects (Sun et al. 2011). Animal evidence also supports a link between alterations in lipid metabolism and AD pathogenesis (Pappolla et al. 2003; Shobab et al. 2005; Panza et al. 2006; Ghribi 2008; Martins et al. 2009; Di Paolo and Kim 2011), suggesting that elevated levels of cholesterol might contribute to accelerate AD progression (Simons et al. 1998; Grimm et al. 2008; Xiong et al. 2008) and to increase the risk for brain lesions and dementia (Leritz et al. 2011; Williams et al. 2013). However, no studies to date have investigated whether blood levels of Ab and/or lipids are related to changes in the resting-state functional anatomy of the brain in aMCI subjects. "
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    ABSTRACT: Growing evidence suggests that decreased functional connectivity in cortical networks precedes clinical stages of Alzheimer's disease (AD), although our knowledge about cerebral and biological correlates of this phenomenon is limited. To shed light on this issue, we have investigated whether resting-state oscillatory connectivity patterns in healthy older (HO) and amnestic mild cognitive impairment (aMCI) subjects are related to anatomical grey matter (GM) and functional (2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET) changes of neuroelectric sources of alpha rhythms, and/or to changes in plasma amyloid-beta (Aβ) and serum lipid levels, blood markers tied to AD pathogenesis and aging-related cognitive decline. We found that aMCI subjects showed decreased levels of cortical connectivity, reduced FDG-PET intake of the precuneus, and GM atrophy of the thalamus, together with higher levels of Aβ and apolipoprotein B (ApoB) compared to HO. Interestingly, levels of high-density lipoprotein (HDL) cholesterol were positively correlated with the strength of neural-phase coupling in aMCI subjects, and increased triglycerides accompanied bilateral GM loss in the precuneus of aMCI subjects. Together, these findings provide peripheral blood correlates of reduced resting-state cortical connectivity in aMCI, supported by anatomo-functional changes in cerebral sources of alpha rhythms. This framework constitutes an integrated approach to assess functional changes in cortical networks through neuroimaging and peripheral blood markers during early stages of neurodegeneration.
    Brain Structure and Function 11/2014; DOI:10.1007/s00429-014-0930-6 · 5.62 Impact Factor
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    • "Midlife cholesterol levels influence the development of Alzheimer's disease later in life, also possibly involving mechanisms other than the vascular pathway [12]. Cardiovascular risk contributes to regional brain structure changes in aging in the absence of cerebrovascular disease [13], which can be detected in vivo using magnetic resonance imaging (MRI). These data also suggest a higher vulnerability of specific brain regions when compared with others. "
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    ABSTRACT: Cardiovascular risk factors influence onset and progression of Alzheimer's disease. Among cognitively healthy people, changes in brain structure and function associated with high blood pressure, diabetes, or other vascular risks suggest differential regional susceptibility to neuronal damage. In patients with Alzheimer's disease, hippocampal and medial temporal lobe atrophy indicate early neuronal loss preferentially in key areas for learning and memory. We wanted to investigate whether this regional cortical thinning would be modulated by cardiovascular risk factors. We utilized high-resolution magnetic resonance imaging and a cortical unfolding technique to determine the cortical thickness of medial temporal subregions in 30 patients with Alzheimer's disease. Cardiovascular risk was assessed using a sex-specific multivariable risk score. Greater cardiovascular risk was associated with cortical thinning in the hippocampus CA2/3/dentate gyrus area but not other hippocampal and medial temporal subregions. APOE genotype, a family history of Alzheimer's disease, and age did not influence cortical thickness. Alzheimer's disease-related atrophy could mask the influence of genetic risk factors or age on regional cortical thickness in medial temporal lobe regions, whereas the impact of vascular risk factors remains detectable. This highlights the importance of cardiovascular disease prevention and treatment in patients with Alzheimer's disease.
    International Journal of Alzheimer's Disease 10/2013; 2013(7300):108021. DOI:10.1155/2013/108021
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