Aspects of the ecology of the greater bilby, Macrotis lagotis, in Queensland

AIMS: It has been suggested that in patients with type 2 diabetes mellitus (T2DM), brain atrophy is most pronounced in the hippocampus, but this has not been investigated systematically. The present pooled analysis of three studies examined if hippocampal atrophy is more prominent than global brain atrophy in patients with T2DM relative to controls. METHODS: Data were derived from a cohort study of patients with vascular disease (SMART-Medea (T2DM=120; no T2DM=502)), and from two case-control studies (UDES1 (T2DM=61; controls=30) and UDES2 (T2DM=54; controls=53)). In SMART-Medea and UDES1, hippocampal volume was obtained by manual tracing on 1.5 Tesla (T) MRI scans. Total brain and intracranial volume (ICV) were determined by an automated segmentation method. In UDES2, hippocampal and total brain volume were determined by FreeSurfer and ICV by manual segmentation on 3 T MRI scans. RESULTS: The pooled analyses, adjusted for age and sex, showed a significant negative relation between T2DM and total brain-to-ICV ratio (standardized mean difference=-1.24%, 95% CI: -1.63; -0.86), but not between T2DM and hippocampal-to-ICV ratio (0.00%, 95% CI: -0.01; 0.00) or between T2DM and hippocampal-to-total brain volume ratio (0.01%, 95% CI: -0.01; 0.02). In patients with T2DM no associations were found between brain volume measures and HbA1c or memory. CONCLUSION: Patients with T2DM had greater brain atrophy but not hippocampal atrophy, compared to controls. These findings do not support specific vulnerability of the hippocampus in patients with T2DM

A Role for New Brain Magnetic Resonance Imaging Modalities in Daily Clinical Practice: Protocol of the Prediction of Cognitive Recovery After Stroke (PROCRAS) Study

Neuro Imaging Researc

Vascular Cognitive Impairment: risk factors and brain MRI correlates

Vascular disease plays an important role in the development of dementia, also in patients diagnosed with Alzheimer’s disease. Risk factors such as hypertension, obesity, and type 2 diabetes, are associated with a two-fold increased risk of cognitive dysfunction and dementia. The development of cognitive impairment due to vascular disease is potentially preventable if patients are recognized and treated early. The present thesis gives more insight in the early stages of cognitive impairment in the context of vascular disease by examining 1) the development of cognitive decline, 2) the relation between vascular risk factors and late-life cognitive dysfunction, and 3) cerebral white matter correlates of cognitive dysfunction in people at risk of vascular disease. The studies in the first part of the thesis were conducted in patients with type 2 diabetes. We show that the development of cognitive decline in the majority of patients with diabetes develops slowly over time, over the course of years. However, we identified a subgroup of patients with accelerated cognitive decline, which seems to be triggered by the progression of both vascular brain lesions and a loss of brain volume on MRI. In the second part of the thesis we evaluated the time-course of vascular risk factors over 15 years in relation to late-life cognitive functioning in a large population-based cohort. We showed that late-life cognitive impairment (~70 years) was most strongly related to the presence of hypertension, adiposity, and hyperglycemia 15-20 years earlier. This indicates that long-term exposure to vascular risk factors, starting at midlife, is harmful to the brain, probably through the slow accumulation of vascular brain damage over the course of decades. Furthermore, we were also able to predict late-life cognitive impairment based on the vascular risk factor profile at midlife. This relation was independent of age and education, which supports the notion that vascular risk factor play an important role in the development of late-life cognitive dysfunction and dementia. The third part of the thesis focused on brain MRI correlates of cognitive dysfunction in patients with Alzheimer’s disease and type 2 diabetes. We demonstrated that the use of advanced brain imaging techniques: diffusion tensor imaging (DTI) and ‘deconvolution based tractography’ can increase the sensitivity to detect microstructural white matter correlates of memory dysfunction in patients with Alzheimer’s disease. This same technique also proved to be more sensitive than conventional brain imaging techniques to white matter abnormalities in patients with diabetes. These white matter abnormalities were related to reduced memory performance and slowing of information processing speed in patients. These findings suggest that microscopic white matter lesions play an important role in the pathogenesis of cognitive impairment in individuals with vascular disease, by disrupting structural and functional connectivity between brain areas. Our findings contribute to a better understanding of the pathogenesis of vascular-related cognitive impairment and contribute to identify individuals at increased risk of dementia at an early stage. This may help to delay or prevent the development of dementia in the near futur

The cumulative effect of small vessel disease lesions is reflected in structural brain networks of memory clinic patients

Background and purpose: Mechanisms underlying cognitive impairment in patients with small vessel disease (SVD) are still unknown. We hypothesized that cognition is affected by the cumulative effect of multiple SVD-related lesions on brain connectivity. We therefore assessed the relationship between the total SVD burden on MRI, global brain network efficiency, and cognition in memory clinic patients with vascular brain injury. Methods: 173 patients from the memory clinic of the University Medical Center Utrecht underwent a 3 T brain MRI scan (including diffusion MRI sequences) and neuropsychological testing. MRI markers for SVD were rated and compiled in a previously developed total SVD score. Structural brain networks were reconstructed using fiber tractography followed by graph theoretical analysis. The relationship between total SVD burden score, global network efficiency and cognition was assessed using multiple linear regression analyses. Results: Each point increase on the SVD burden score was associated with 0.260 [−0.404 - -0.117] SD units decrease of global brain network efficiency (p < .001). Global network efficiency was associated with information processing speed (standardized B = −0.210, p = .004) and attention and executive functioning (B = 0.164, p = .042), and mediated the relationship between SVD burden and information processing speed (p = .027) but not with executive functioning (p = .12). Conclusion: Global network efficiency is sensitive to the cumulative effect of multiple manifestations of SVD on brain connectivity. Global network efficiency may therefore serve as a useful marker for functionally relevant SVD-related brain injury in clinical trials. Keywords: Cerebral small vessel disease, Vascular cognitive impairment, Diffusion-weighted imaging, Cognition, Magnetic resonance imagin

Hippocampal disconnection in early Alzheimer's disease: a 7 tesla MRI study

Item does not contain fulltextBACKGROUND: In patients with Alzheimer's disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts. OBJECTIVE: We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and parahippocampal cingulum (PHC) microstructure in patients with early AD. METHODS: Twenty-five patients with amnestic mild cognitive impairment (aMCI) (n = 15) or early AD (n = 10) and 17 controls underwent 3 tesla diffusion MRI to obtain fractional anisotropy (FA) of the fornix and PHC and 7 tesla MRI to obtain ERC and hippocampal subfield volumes. Linear regression analyses were performed, adjusted for age, gender, and intracranial volume. RESULTS: Fornix FA was significantly lower and subiculum, cornu ammonis (CA) 1, and dentate gyrus &CA4 volume were significantly smaller in patients with MCI or AD as compared to controls. In patients with MCI or AD, fornix FA was positively associated with subiculum volume (beta = 0.53, 95% CI 0.10; 0.96), but not with ERC/other subfield volumes. PHC FA was not associated with ERC/subfield volumes. CONCLUSION: These findings indicate that in early AD subiculum atrophy is associated with lower FA of the fornix, which primarily consists of axons originating in the subiculum. This suggests that degeneration of subicular cell bodies and their axons are related processes in early AD

Vascular retinopathy in relation to cognitive functioning in an older population--the Hoorn Study

To the Editor: Cognitive impairment and dementia are important health problems that may be caused by vascular damage in the brain.[1] The cerebral vasculature is anatomically, embryologically, and physiologically related to that of the retina, and both are sensitive to exposure to vascular risk factors.[2, 3] Vascular damage to the retina is easy to measure noninvasively. Hence, visualization of retinal vessels may offer insight into the status of the vessels in the brain and thus provide insight into vascular causes of late-life cognitive impairment. A recent systematic review found variable associations between retinal vascular changes and performance on various cognitive domains in persons without dementia.[4, 5] The goal of the current study was to extend these findings by assessing these associations in a population-based cohort using a detailed neuropsychological examination

Parietal Involvement in Constructional Apraxia as Measured Using the Pentagon Copying Task

Deficits in copying ("constructional apraxia") is generally defined as a multifaceted deficit. The exact neural correlates of the different types of copying errors are unknown. To assess whether the different categories of errors on the pentagon drawing relate to different neural correlates, we examined the pentagon drawings of the MMSE in persons with subjective cognitive complaints, mild cognitive impairment, or early dementia due to Alzheimer's disease. We adopted a qualitative scoring method for the pentagon copy test (QSPT) which categorizes different possible errors in copying rather than the dichotomous categories "correct" or "incorrect." We correlated (regional) gray matter volumes with performance on the different categories of the QSPT. Results showed that the total score of the QSPT was specifically associated with parietal gray matter volume and not with frontal, temporal, and occipital gray matter volume. A more fine-grained analysis of the errors reveals that the intersection score and the number of angles share their underlying neural correlates and are associated with specific subregions of the parietal cortex. These results are in line with the idea that constructional apraxia can be attributed to the failure to integrate visual information correctly from one fixation to the next, a process called spatial remapping

DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice.

Contains fulltext : 79884.pdf (publisher's version ) (Closed access)Cholesterol and docosahexenoic acid (DHA) may affect degenerative processes in Alzheimer's Disease (AD) by influencing Abeta metabolism indirectly via the vasculature. We investigated whether DHA-enriched diets or cholesterol-containing Typical Western Diets (TWD) alter behavior and cognition, cerebral hemodynamics (relative cerebral blood volume (rCBV)) and Abeta deposition in 8- and 15-month-old APP(swe)/PS1(dE9) mice. In addition we investigated whether changes in rCBV precede changes in Abeta deposition or vice versa. Mice were fed regular rodent chow, a TWD-, or a DHA-containing diet. Behavior, learning and memory were investigated, and rCBV was measured using contrast-enhanced MRI. The Abeta load was visualized immunohistochemically. We demonstrate that DHA altered rCBV in 8-month-old APP/PS1 and wild type mice[AU1]. In 15-month-old APP/PS1 mice DHA supplementation improved spatial memory, decreased Abeta deposition and slightly increased rCBV, indicating that a DHA-enriched diet can diminish AD-like pathology. In contrast, TWD diets decreased rCBV in 15-month-old mice. The present data indicate that long-term dietary interventions change AD-like pathology in APP/PS1 mice. Additionally, effects of the tested diets on vascular parameters were observed before effects on Abeta load were noted. These data underline the importance of vascular factors in the APP/PS1 mouse model of AD pathology

Mild depressive symptoms do not influence cognitive functioning in patients with type 2 diabetes.

Type 2 diabetes (T2DM) is associated both with cognitive decrements and depressive symptoms. Since depression in itself has been associated with cognitive decrements we aimed to investigate the influence of depressive symptoms on the relation between T2DM and cognitive functioning. Data were derived from three independent studies on cognitive functioning in patients with T2DM (n=366) and controls without diabetes (n=204), two with longitudinal and one with only cross-sectional assessments. Depressive symptoms were measured with self-report inventories (CES-D or BDI-II). The composite z-score of the domains memory, information-processing speed, and attention and executive function was the primary cognitive outcome measure. Mixed linear regression analyses were used in a stepped approach to compare cognitive functioning between (1) patients with T2DM and controls (cross-sectionally and longitudinally), (2) participants with and without depressive symptoms, separately for patients and controls, and (3) patients and controls after adjustment for depressive symptoms. In addition the mediating effect of depressive symptoms was assessed with a bootstrapping technique. Depressive symptoms were present in 11% of the patients with T2DM and in 7% of controls (p=0.15). Cognitive performance in patients with T2DM was worse than in controls (overall difference composite z-score -0.13). However, T2DM was not associated with accelerated cognitive decline over three years of follow-up relative to controls. Controls with depressive symptoms performed worse than those without depressive symptoms, although not statistically significant. Performance in patients with T2DM with and without depressive symptoms was similar. Adjustment for depressive symptoms and estimation of the mediating effect showed that the difference between patients and controls was not mediated by depressive symptoms. In conclusion, the modest cognitive decrements that are associated with T2DM are not due to the presence of mild depressive symptoms