Associations between pattern separation and hippocampal subfield structure and function vary along the lifespan:A 7 T imaging study

Pattern separation (PS) describes the process by which the brain discriminates similar stimuli from previously encoded stimuli. This fundamental process requires the intact processing by specific subfields in the hippocampus and can be examined using mnemonic discrimination tasks. Previous studies reported different patterns for younger and older individuals between mnemonic discrimination performance and hippocampal subfield activation. Here, we investigated the relationship between the lure discrimination index (LDI) and hippocampal subfield volume and activity across the adult lifespan (20-70 years old). Using ultra-high field functional and structural magnetic resonance imaging at 7 T, we found that lower DG volume and higher CA3 activation was associated with worse LDI performance in individuals (>60 years), suggesting that this higher activation may be an indication of aberrant neurodegenerative-related processes. In fact, higher activation in the CA1 and DG was associated with lower volumes in these subfields. For individuals around 40-50 years old, we observed that greater left and right DG volume, and greater activity in the CA3 was associated with lower LDI performance. Taken together, these results suggest that the relationship between memory and hippocampal subfield structure or function varies nonlinearly and possibly reciprocally with age, with midlife being a critically vulnerable period in life

Shades of white:diffusion properties of T1- and FLAIR-defined white matter signal abnormalities differ in stages from cognitively normal to dementia

The underlying pathology of white matter signal abnormalities (WMSAs) is heterogeneous and may vary dependent on the magnetic resonance imaging contrast used to define them. We investigated differences in white matter diffusivity as an indicator for white matter integrity underlying WMSA based on T1-weighted and fluid-attenuated inversion recovery (FLAIR) imaging contrast. In addition, we investigated which white matter region of interest (ROI) could predict clinical diagnosis best using diffusion metrics. One hundred three older individuals with varying cognitive impairment levels were included and underwent neuroimaging. Diffusion metrics were extracted from WMSA areas based on T1 and FLAIR contrast and from their overlapping areas, the border surrounding the WMSA and the normal-appearing white matter (NAWM). Regional diffusivity differences were calculated with linear mixed effects models. Multinomial logistic regression determined which ROI diffusion values classified individuals best into clinically defined diagnostic groups. T1-based WMSA showed lower white matter integrity compared to FLAIR WMSA-defined regions. Diffusion values of NAWM predicted diagnostic group best compared to other ROI's. To conclude, T1- or FLAIR-defined WMSA provides distinct information on the underlying white matter integrity associated with cognitive decline. Importantly, not the "diseased" but the NAWM is a potentially sensitive indicator for cognitive brain health status.</p

Capillary Rarefaction Associates with Albuminuria: The Maastricht Study

Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria

White matter hyperintensities mediate the association between blood-brain barrier leakage and information processing speed

Blood-brain barrier (BBB) leakage is considered an important underlying process in both cerebral small vessel disease (cSVD) and Alzheimer's disease (AD). The objective of this study was to examine associations between BBB leakage, cSVD, neurodegeneration, and cognitive performance across the spectrum from normal cognition to dementia. Leakage was measured with dynamic contrast-enhanced magnetic resonance imaging in 80 older participants (normal cognition, n = 32; mild cognitive impairment, n 34; clinical AD-type dementia, n = 14). Associations between leakage and white matter hyperintensity (WMH) volume, hippocampal volume, and cognition (information processing speed and memory performance) were examined with multivariable linear regression and mediation analyses. Leakage within the gray and white matter was positively associated with WMH volume (gray matter, p = 0.03; white matter, p = 0.01). A negative association was found between white matter BBB leakage and information processing speed performance, which was mediated by WMH volume. Leakage was not associated with hippocampal volume. WMH pathology is suggested to form a link between leakage and decline of information processing speed in older individuals with and without cognitive impairment. (C) 2019 Elsevier Inc. All rights reserved.</p