Near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) both allow non-invasive monitoring of cerebral cortical oxygenation responses to various stimuli. To compare these methods in elderly subjects and to determine the effect of age on cortical oxygenation responses, we determined motor-task-related changes in deoxyhemoglobin concentration ([HHb]) over the left motor cortex in six healthy young subjects (age 35 +/- 9 years, mean +/- SD) and five healthy elderly subjects (age 73 +/- 3 years) by NIRS and blood-oxygen-level-dependent (BOLD) fMRI simultaneously. The motor-task consisted of seven cycles of 20-sec periods of contralateral finger-tapping at a rate as fast as possible alternated with 40-sec periods of rest. Time-locked averages over the seven cycles were used for further analysis. Task-related decreases in [HHb] over the motor cortex were measured by NIRS, with maximum changes of -0.83 +/- 0.38 mumol/L (P < 0.01) for the young and -0.32 +/- 0.17 mumol/L (P < 0.05) for the elderly subjects. The BOLD-fMRI signal increased over the cortex volume under investigation with NIRS, with maximum changes of 2.11 +/- 0.72% (P < 0.01) for the young and 1.75 +/- 0.71% (P < 0.01) for the elderly subjects. NIRS and BOLD-fMRI measurements showed good correlation in the young (r = -0.70, r(2) = 0.48, P < 0.001) and elderly subjects (r = -0.82, r(2) = 0.67, P < 0.001). Additionally, NIRS measurements demonstrated age-dependent decreases in task-related cerebral oxygenation responses (P < 0.05), whereas fMRI measurements demonstrated smaller areas of cortical activation in the elderly subjects (P < 0.05). These findings demonstrate that NIRS and fMRI similarly assess cortical oxygenation changes in young subjects and also in elderly subjects. In addition, cortical oxygenation responses to brain activation alter with aging.

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BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

The human cerebellum develops over a long time, extending from the early embryonic period until the first postnatal years. This protracted development makes the cerebellum vulnerable to a broad spectrum of developmental disorders. The development of the cerebellum occurs in four basic steps: 1) characterization of the cerebellar territory at the midbrain-hindbrain boundary; 2) formation of two compartments for cell proliferation: first, the Purkinje cells and the deep cerebellar nuclei arise from the ventricular zone of the metencephalic alar plate; second, granule cell precursors are formed from a second compartment of proliferation, i. e. the upper rhombic lip; 3) inward migration of the granule cells: granule precursor cells form the external granular layer, from which (and continuing into the first postnatal year), granule cells migrate inwards to their definite position in the internal granular layer, and 4) formation of cerebellar circuitry and further differentiation. The precerebellar nuclei, i. e. the pontine nuclei and the inferior olive, arise from the lower rhombic lip. Developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei. In this review the development of the cerebellum and some of its more frequent developmental disorders, such as the Dandy-Walker and related midline malformations, and the pontocerebellar hypoplasias, are discussed.

Near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) both allow non-invasive monitoring of cerebral cortical oxygenation responses to various stimuli. To compare these methods in elderly subjects and to determine the effect of age on cortical oxygenation responses, we determined motor-task-related changes in deoxyhemoglobin concentration ([HHb]) over the left motor cortex in six healthy young subjects (age 35 +/- 9 years, mean +/- SD) and five healthy elderly subjects (age 73 +/- 3 years) by NIRS and blood-oxygen-level-dependent (BOLD) fMRI simultaneously. The motor-task consisted of seven cycles of 20-sec periods of contralateral finger-tapping at a rate as fast as possible alternated with 40-sec periods of rest. Time-locked averages over the seven cycles were used for further analysis. Task-related decreases in [HHb] over the motor cortex were measured by NIRS, with maximum changes of -0.83 +/- 0.38 mumol/L (P < 0.01) for the young and -0.32 +/- 0.17 mumol/L (P < 0.05) for the elderly subjects. The BOLD-fMRI signal increased over the cortex volume under investigation with NIRS, with maximum changes of 2.11 +/- 0.72% (P < 0.01) for the young and 1.75 +/- 0.71% (P < 0.01) for the elderly subjects. NIRS and BOLD-fMRI measurements showed good correlation in the young (r = -0.70, r(2) = 0.48, P < 0.001) and elderly subjects (r = -0.82, r(2) = 0.67, P < 0.001). Additionally, NIRS measurements demonstrated age-dependent decreases in task-related cerebral oxygenation responses (P < 0.05), whereas fMRI measurements demonstrated smaller areas of cortical activation in the elderly subjects (P < 0.05). These findings demonstrate that NIRS and fMRI similarly assess cortical oxygenation changes in young subjects and also in elderly subjects. In addition, cortical oxygenation responses to brain activation alter with aging.