Glycemic status and brain injury in older individuals: the age gene/environment susceptibility-Reykjavik study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS: This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility-Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose > or =7.0 mmol/l [11.1%]); impaired fasting glucose (IFG) (fasting blood glucose 5.6-6.9 mmol/l [36.2%]); and normoglycemic (52.7%). Outcomes were total brain volume, white and gray matter volume, white matter lesion (WML) volume, and presence of cerebral infarcts. RESULTS: After adjustment for demographic and cardiovascular risk factors, participants with type 2 diabetes had significantly lower total brain volume (72.2 vs. 71.5%; P < 0.001) and lower gray and white matter volumes (45.1 vs. 44.9%, P < 0.01 and 25.7 vs. 25.3%, P < 0.001, respectively) and were more likely to have single (odds ratio 1.45 [95% CI 1.14-1.85]) or multiple (2.27 [1.60-3.23]) cerebral infarcts compared with normoglycemic participants. Longer duration of type 2 diabetes was associated with lower total brain volume and gray and white matter volume, higher WML volume (all P(trend) < 0.05), and a greater likelihood of single and multiple cerebral infarcts (all P(trend) < 0.01). CONCLUSIONS: Type 2 diabetic participants have more pronounced brain atrophy and are more likely to have cerebral infarcts. Duration of type 2 diabetes is associated with brain changes, suggesting that type 2 diabetes has a cumulative effect on the brain

Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study

&lt;p&gt;Objective To investigate the association between visit-to-visit variability in blood pressure and cognitive function in old age (&#62;70 years).&lt;/p&gt; &lt;p&gt;Design Prospective cohort study.&lt;/p&gt; &lt;p&gt;etting PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) study, a collaboration between centres in Ireland, Scotland, and the Netherlands.&lt;/p&gt; &lt;p&gt;Participants 5461 participants, mean age 75.3 years, who were at risk of cardiovascular disease. Blood pressure was measured every three months during an average of 3.2 years. Visit-to-visit variability in blood pressure was defined as the standard deviation of blood pressure measurements between visits.&lt;/p&gt; &lt;p&gt;Main outcome measures Four domains of cognitive function, testing selective attention, processing speed, and immediate and delayed memory. In a magnetic resonance imaging substudy of 553 participants, structural brain volumes, cerebral microbleeds, infarcts, and white matter hyperintensities were measured.&lt;/p&gt; &lt;p&gt;Results Participants with higher visit-to-visit variability in systolic blood pressure had worse performance on all cognitive tests: attention (mean difference high versus low thirds) 3.08 seconds (95% confidence interval 0.85 to 5.31), processing speed −1.16 digits coded (95% confidence interval −1.69 to −0.63), immediate memory −0.27 pictures remembered (95% confidence interval −0.41 to −0.13), and delayed memory −0.30 pictures remembered (95% confidence interval −0.49 to −0.11). Furthermore, higher variability in both systolic and diastolic blood pressure was associated with lower hippocampal volume and cortical infarcts, and higher variability in diastolic blood pressure was associated with cerebral microbleeds (all P&#60;0.05). All associations were adjusted for average blood pressure and cardiovascular risk factors.&lt;/p&gt; Conclusion Higher visit-to-visit variability in blood pressure independent of average blood pressure was associated with impaired cognitive function in old age

Contributions of cerebral blood flow to associations between blood pressure levels and cognition the age, gene/environment susceptibility-Reykjavik study

Cerebral hypoperfusion leads to adverse sequalae including dementia. Midlife higher blood pressure (BP) can lead to low cerebral blood flow (CBF), but older persons may need higher BP to maintain cerebral perfusion. We investigated the associations among late-life BP, CBF, and cognition. Data are from 2498 participants with a mean age of 79.8 (SD, 4.7) years of the second exam of the AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study. BP was measured, and phase-contrast (PC) magnetic resonance imaging was acquired to estimate total brain CBFPC. Cognitive outcomes included verbal and working memory, processing speed, mild cognitive impairment, and all-cause dementia. Relationships among late-life BP, CBFPC, and cognition were assessed with regression models, controlling for socio-demographics, BP level at midlife (at a mean age of 49.6 [SD, 5.9] years), cardiovascular factors, and total brain volume. In fully adjusted models, each mm Hg increase in late-life diastolic BP was associated with a -0.082 mL/min per 100 mL (95% CI -0.123 to -0.041) lower CBFPC. In contrast, each mm Hg increase in late-life systolic BP or pulse pressure was associated with a 0.027 mL/min per 100 mL (95% CI, 0.0065-0.048) and 0.061 mL/min per 100 mL (95% CI, 0.038-0.084) higher late-life CBFPC, respectively. Higher CBFPC was significantly related to higher cognitive scores for psychomotor speed, verbal, and working memory and to a lower odd of mild cognitive impairment or dementia, irrespective of late-life BP level. Higher late-life diastolic BP and systolic BP were differentially associated with CBFPC. Our findings suggest CBF is an important correlate of late-life cognition, independent of BP level.Neuro Imaging Researc

Birth size and brain function 75 years later.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageThere are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size to late-age measures of brain structure and function in a large cohort of older men and women and explored the modifying effect of education on these associations.Within the AGES (Age Gene/Environment Susceptibility)-Reykjavik population-based cohort (born between 1907 and 1935), archived birth records were abstracted for 1254 men and women who ∼75 years later underwent an examination that included brain MRI and extensive cognitive assessment.Adjustment for intracranial volume, demographic and medical history characteristics, and lower Ponderal index at birth (per kg/m(3)), an indicator of third-trimester fetal wasting, was significantly associated with smaller volumes of total brain and white matter; βs (95% confidence intervals) were -1.0 (-1.9 to -0.0) and -0.5 (-1.0 to -0.0) mL. Furthermore, lower Ponderal index was associated with slower processing speed and reduced executive functioning but only in those with low education (β [95% confidence interval]: -0.136 [-0.235 to -0.036] and -0.077 [-0.153 to -0.001]).This first study of its kind provides clinical measures suggesting that smaller birth size, as an indicator of a suboptimal intrauterine environment, is associated with late-life alterations in brain tissue volume and function. In addition, it shows that the effects of a suboptimal intrauterine environment on late-life cognitive function were present only in those with lower educational levels

Retinal and cerebral microvascular signs and diabetes: the age, gene/environment susceptibility-Reykjavik study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain are associated and whether this association differs among people with and without diabetes. RESEARCH DESIGN AND METHODS: The analysis included 4,218 participants of the Icelandic population-based Age, Gene/Environment Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing, arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on digital retinal images of both eyes. Cerebral microbleeds (CMBs) were evaluated from magnetic resonance images. Data were analyzed with logistic and multinomial logistic regression models controlling for demographics, major cardiovascular risk factors, cerebral infarcts, and white matter lesions. RESULTS: Evidence of brain microbleeds was found in 485 (11.5%) people, including 192 with multiple (>or=2) microbleeds. Subjects with signs of retinal microvascular lesions were at a significantly increased likelihood for having multiple CMBs. People with diabetes in combination with the presence of either retinal AV nicking (odds ratio [OR] 2.47 [95% CI 1.42-4.31]) or retinal microaneurysms/hemorrhages (2.28 [1.24-4.18]) were significantly more likely to have multiple CMBs. CONCLUSIONS: Retinal microvascular abnormalities and brain microbleeds may occur together in older adults. People with both diabetes and signs of retinal microvascular lesions (AV nicking and microaneurysms/hemorrhages) are more likely to have multiple microbleeds in the brain. Microvascular disease in diabetes extends to the brain

Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: cross-sectional findings from the AGES-Reykjavik Study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Arterial stiffness may contribute to depression via cerebral microvascular damage, but evidence for this is scarce. We therefore investigated whether arterial stiffness is associated with depressive symptoms and whether cerebral small vessel disease contributes to this association.This cross-sectional study included a subset of participants from the AGES-Reykjavik study second examination round, which was conducted from 2007 to 2011. Arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]), depressive symptoms (15-item geriatric depression scale [GDS-15]) and cerebral small vessel disease (MRI) were determined. Manifestations of cerebral small vessel disease included higher white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces and lower total brain parenchyma volume.We included 2058 participants (mean age 79.6 yr; 59.0% women) in our analyses. Higher CFPWV was associated with a higher GDS-15 score, after adjustment for potential confounders (β 0.096, 95% confidence interval [CI] 0.005-0.187). Additional adjustment for white matter hyperintensity volume or subcortical infarcts attenuated the association between CFPWV and the GDS-15 score, which became nonsignificant (p > 0.05). Formal mediation tests showed that the attenuating effects of white matter hyperintensity volume and subcortical infarcts were statistically significant. Virchow-Robin spaces, cerebral microbleeds and cerebral atrophy did not explain the association between CFPWV and depressive symptoms.Our study was limited by its cross-sectional design, which precludes any conclusions about causal mediation. Depressive symptoms were assessed by a self-report questionnaire.Greater arterial stiffness is associated with more depressive symptoms; this association is partly accounted for by white matter hyperintensity volume and subcortical infarcts. This study supports the hypothesis that arterial stiffness leads to depression in part via cerebral small vessel disease.National Institutes of Health (NIH) N01-AG-12100 Intramural Research Program of the National Institute on Aging, USA Icelandic Heart Association Icelandic Parliament, Iceland National Institutes of Health, National Heart, Lung and Blood Institute HL094898 National Institute of Diabetes and Digestive and Kidney Diseases DK08244

The AGES-Reykjavik study atlases: Non-linear multi-spectral template and atlases for studies of the ageing brain

Neuro Imaging Researc

The clinical course of acute otitis media in high-risk Australian Aboriginal children: a longitudinal study

BACKGROUND: It is unclear why some children with acute otitis media (AOM) have poor outcomes. Our aim was to describe the clinical course of AOM and the associated bacterial nasopharyngeal colonisation in a high-risk population of Australian Aboriginal children. METHODS: We examined Aboriginal children younger than eight years who had a clinical diagnosis of AOM. Pneumatic otoscopy and video-otoscopy of the tympanic membrane (TM) and tympanometry was done every weekday if possible. We followed children for either two weeks (AOM without perforation), or three weeks (AOM with perforation), or for longer periods if the infection persisted. Nasopharyngeal swabs were taken at study entry and then weekly. RESULTS: We enrolled 31 children and conducted a total of 219 assessments. Most children had bulging of the TM or recent middle ear discharge at diagnosis. Persistent signs of suppurative OM (without ear pain) were present in most children 7 days (23/30, 77%), and 14 days (20/26, 77%) later. Episodes of AOM did not usually have a sudden onset or short duration. Six of the 14 children with fresh discharge in their ear canal had an intact or functionally intact TM. Perforation size generally remained very small (<2% of the TM). Healing followed by re-perforation was common. Ninety-three nasophyngeal swabs were taken. Most swabs cultured Streptococcus pneumoniae (82%), Haemophilus influenzae (71%), and Moraxella catarrhalis (95%); 63% of swabs cultured all three pathogens. CONCLUSION: In this high-risk population, AOM was generally painless and persistent. These infections were associated with persistent bacterial colonisation of the nasopharynx and any benefits of antibiotics were modest at best. Systematic follow up with careful examination and review of treatment are required and clinical resolution cannot be assumed

A Non-Detection of Iron in the First High-Resolution Emission Study of the Lava Planet 55 Cnc e

Close-in lava planets represent an extreme example of terrestrial worlds, but their high temperatures may allow us to probe a diversity of crustal compositions. The brightest and most well-studied of these objects is 55 Cancri e, a nearby super-Earth with a remarkably short 17-hour orbit. However, despite numerous studies, debate remains about the existence and composition of its atmosphere. We present upper limits on the atmospheric pressure of 55 Cnc e derived from high-resolution time-series spectra taken with Gemini-N/MAROON-X. Our results are consistent with current crustal evaporation models for this planet which predict a thin $\sim$ 100 mbar atmosphere. We conclude that, if a mineral atmosphere is present on 55 Cnc e, the atmospheric pressure is below 100 mbar.Comment: Accepted to the AJ. 7 pages, 5 figure