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Background Subcortical brain structures play a key role in pathological processes of age-related neurodegenerative disorders. Mounting evidence also suggests that early-life factors may have an impact on the development of common late-life neurological diseases, including genetic factors that can influence both brain maturation and neurodegeneration. Methods Using large population-based brain imaging datasets across the lifespan (N 40,628) we aimed to: (i) estimate the heritability of subcortical volumes in young ( 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ), middle (35-65), and older age (65+), and their genetic correlation across age groups; (ii) identify whether genetic loci associated with subcortical volumes in older persons also show associations in early adulthood, and explore underlying genes using transcriptome-wide association studies; (iii) explore their association with neurological phenotypes. Results Heritability of subcortical volumes consistently decreased with increasing age. Genetic risk scores for smaller caudate nucleus, putamen and hippocampus volume in older adults were associated with smaller volumes in young adults. Individually, ten loci associated with subcortical volumes in older adults also showed associations in young adults. Within these loci, transcriptome-wide association studies showed that expression of several genes in brain tissues (especially MYLK2 and TUFM) was associated with subcortical volumes in both age-groups. One risk variant for smaller caudate nucleus volume (TUFM locus) was associated with lower cognitive performance. Genetically-predicted Alzheimer’s disease was associated with smaller subcortical volumes in middle and older age. Conclusions Our findings provide novel insights into the genetic determinants of subcortical volumes across the lifespan. More studies are needed to decipher the underlying biology and clinical impact.

Chronic kidney disease is emerging as a novel risk factor for cerebrovascular disease, but this association remains largely unexplored in older adults. Cystatin C is a more accurate measure than creatinine of kidney function in the elderly. We evaluated cystatin C, cognitive function, and brain imaging in 193 participants from The 90+ Study neuroimaging component. The mean age was 93.9 years; 61% were women. Mean cystatin C was 1.62 mg/L with estimated glomerular filtration rate 39.2 mL/min/1.73 m2. Performance on measures of global cognition, executive function, and visual-spatial ability declined at higher tertiles of cystatin C (lower kidney function). Higher cystatin C was significantly associated with infratentorial microbleeds and lower gray matter volume. Adjusted risk of incident dementia was increased in the middle and high cystatin C tertile groups compared with the low group (hazard ratio in highest tertile 3.81 [95% confidence interval 1.14–12.7]), which appeared to be explained in part by the presence of cerebral microbleeds. Overall, cystatin C was associated with cognitive performance, brain imaging pathology, and decline to dementia in this oldest-old cohort.

Level of education is often regarded as a proxy for cognitive reserve in older adults. This implies that brain degeneration has a smaller effect on cognitive decline in those with more education, but this has not been directly tested in previous research. We examined how education, quantitative magnetic resonance imaging–based measurement of brain degeneration, and their interaction affect cognitive decline in diverse older adults spanning the spectrum from normal cognition to dementia. Gray matter atrophy was strongly related to cognitive decline. While education was not related to cognitive decline, brain atrophy had a stronger effect on cognitive decline in those with more education. Importantly, high education was associated with slower decline in individuals with lesser atrophy but with faster decline in those with greater atrophy. This moderation effect was observed in Hispanics (who had high heterogeneity of education) but not in African-Americans or Caucasians. These results suggest that education is an indicator of cognitive reserve in individuals with low levels of brain degeneration, but the protective effect of higher education is rapidly depleted as brain degeneration progresses.

Highlights • Amyloid burden only slightly improved predictions of memory and executive function. • With regular cognitive assessments, amyloid-PET may not improve cognitive prognosis. • These findings support the value of routine cognitive assessments in clinical care., Background Amyloid β (Aβ) is thought to initiate a cascade of pathology culminating in Alzheimer’s disease-related cognitive decline. Aβ accumulation in brain tissues may begin one to two decades prior to clinical diagnosis of Alzheimer’s disease. Prior studies have demonstrated that Aβ detected in vivo with positron emission tomography with amyloid ligands (amyloid-PET) predicts contemporaneously measured cognition and future cognitive trajectories. Prior studies have not evaluated the added value of Aβ measures in predicting future cognition when repeated past cognitive measures are available. We evaluated the extent to which amyloid-PET improves prediction of future cognitive changes over and above predictions based only on sociodemographics and past cognitive measures. Methods We used data from participants in the University of California Davis Alzheimer’s Disease Research cohort who were cognitively normal at baseline, participated in amyloid-PET imaging, and completed at least three cognitive assessments prior to amyloid-PET imaging (N = 132 for memory andN = 135 for executive function). We used sociodemographic and cognitive measures taken prior to amyloid-PET imaging to predict cognitive trajectory after amyloid-PET imaging and assessed whether measures of amyloid burden improved predictions of subsequent cognitive change. Improvements in prediction were characterized as percent reduction in the mean squared error (MSE) in predicted cognition post amyloid-PET and increase in percent variance explained. Results The base model using only sociodemographics and past cognitive performance explained the majority of variance in both predicted memory measures (55.6%) and executive function measures (74.5%) following amyloid-PET. Adding amyloid positivity to the model reduced the MSE for memory by 0.2%, 95% CI: (0%, 2.6%), p = 0.48 and for executive function by 3.4%, 95% CI: (0.6%, 10.2%), p = 0.002. This corresponded to an increase in the percent variance explained of 0.1%, 95% CI: (0%, 1.2%) for memory and 0.9%, 95% CI: (0.1%, 2.8%) for executive function. Similar results were obtained using a continuous measure of amyloid burden. Conclusion In this cohort, the addition of amyloid burden slightly improved predictions of executive function compared to models based only on past cognitive assessments and sociodemographics. When repeated cognitive assessments are available, the additional utility of amyloid-PET in predicting future cognitive impairment may be limited.

Objective α-Cyclodextrin (α-CD), a soluble dietary fiber derived from corn, marketed under the trade name FBCx®, has the potential to help individuals manage their weight and improve their lipid profiles. Initial studies in healthy overweight and/or obese diabetic individuals found that, in those consuming a normal to high fat diet over a 4 or 12 week period, α-CD use was associated with weight loss or maintenance and a reduction in triglyceride (TG) and cholesterol levels in hyperlipidemic individuals. Furthermore, α-CD use was associated with the positive effects of increasing insulin and leptin sensitivities. To date, the immediate post-prandial glucose and lipid responses to a fat-containing meal have not been reported. Materials/Method This double blinded placebo controlled cross-over trial examined the effect of 2 g of α-CD taken immediately following consumption of a commercially prepared high-fat breakfast meal on the acute postprandial responses in healthy adults. Results The coincidental consumption of α-CD with a fat-containing meal was associated with a significant reduction in postprandial TG responses over time when compared to placebo. When incremental area under the curve was calculated, the area under the curve associated with α-CD consumption was significantly smaller than the Placebo area (0.30 ± 1.07 mmol/L/3 h vs. 0.98 ± 0.88 mmol/L/3 h, p Conclusion α-Cyclodextrin was shown to significantly lower acute postprandial blood triglyceride levels.

Topographic maps are commonly constructed from electrical scalp recordings (such as EEGs and ERPs) using several different interpolation methods. It is important to determine the accuracy of such maps. Previous assessments of interpolation methods have been based on global error measures and the visual appearance of the topographic maps. However, the relationship of interpolation error to local contributing factors requires a more detailed analysis. In this paper, we use simulations to explore and quantify the relationship of error to global and local factors for different interpolation methods. We find that among the best interpolation methods, adequate electrode density is more important than the method used. For shallow sources, we show that local interpolation error is most correlated with potential gradient, and has a lesser correlation with distance to nearest electrode. The greatest correlation, however, is with the product of gradient and distance. Thus, interpolation error can be controlled locally by making the interelectrode distance inversely proportional to the expected potential gradient. With shallow sources, areas far from any electrode and having high apparent gradient are likely to have high interpolation error. Moreover, all areas far from any electrode may contain high interpolation errors, and should be interpreted with caution.

Summary Angular velocity expressed in radians/sec of the rotation movement of the QRS loop at intervals of 2.5 msecs was calculated from a computer program written in Fortran IV. Frontal, horizontal and left sagittal planes were recorded in 125 normal subjects for analysis. The range of angular velocity for 375 QRS loops was from a few radians/sec to a maximum of 95 radians/sec. Average values of maximum angular velocities were: frontal plane, 46.2 radians/sec, horizontal plane, 41 radians/sec, and left sagittal plane, 34.1 radians/sec. Angular velocity expressed as a periodic function of the vector loop is characterized by polyphasic curves. In the frontal plane, curves tend to be more symmetrical with maximum values in the middle. Angular velocity curves are an alternate expression of analysis of planar vector loops employed in clinical practice. Their normal ranges are given in this paper.

Summary Inhalation of a few puffs on a cigarette increases the velocity of conduction and shortens the effective refractory period of the A-V node. These effects are attributed to adrenergic stimulation produced by minute amounts of nicotine absorbed. Wenckebach block is abolished whether induced by atrial pacing or occurring spontaneously. Conduction velocity in the His-Purkinje system and in the anomalous pathways in the WPW syndrome were not affected. Smoking increases the ventricular rate in atrial fibrillation, and antagonizes the cholinergic effects of digitalis.