Background and Purpose-Citicoline (cytidine-5Ј-diphosphocholine; CDP-choline) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation. A previous dose-comparison trial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects. Methods-The current trial was a 33-center, randomized, double-blind, efficacy trial in 394 patients comparing placebo (nϭ127) with citicoline (nϭ267) (500 mg po daily) for 6 weeks, with a 6-week posttreatment follow-up period. Patients with acute (24 hours) ischemic strokes clinically assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale (NIHSS) Ն5 were enrolled. Results-Mean time to treatment was 12 hours, and mean age was 71 for placebo and 70 for citicoline. Although mean baseline NIHSS were similar for both groups, there was a higher percentage of placebo patients with NIHSS Ͻ8 (34% vs 22%; PϽ0.01). The incidence and type of side effects were similar between the groups. The planned primary analysis (logistic regression: 5 categories Barthel) failed the proportional odds assumption and was rendered unreliable. There were no between-group differences seen on the planned secondary assessment analyses at 90 days, including the Barthel Index Ն95 at 12 weeks (last observation carried forward: placebo 40%; citicoline 40%) or mortality rate (placebo 18%; citicoline 17%). However, post hoc analyses in a subgroup of patients with baseline NIHSS Ն8 found that citicoline-treated patients were more likely to have a full recovery (Barthel Ն95): placebo 21%; citicoline 33%; Pϭ0.05; whereas no difference was seen in patients with baseline NIHSSϽ8 (placebo 77%; citicoline 69%; PϾ0.1. Conclusions-The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial. Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit. (Stroke. 1999;30:2592-2597.)

Objective To provide characterization of Mexican Americans who meet criteria for Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI). Methods 1069 participants ages 40 and above who self-identified as either non-Hispanic white (n=633) or Mexican American (n=436); were recruited using a community-based participatory research (CBPR) approach. Global cognition was assessed via the Mini Mental State Exam (MMSE), dementia severity by the Clinical Dementia Rating Scale (CDR) and depression via the Geriatric Depression Scale 30-item version. Age, gender, education, ApoEε4 allele frequency and diabetic diagnoses were also analyzed. Results Mexican Americans (normal controls, MCI and AD) were younger, less highly educated, performed more poorly on the MMSE, endorsed more symptoms of depression, were more likely to be diagnosed with diabetes, and possessed the ApoEε4 allele less frequently. Age was the only significant risk factor for cognitive dysfunction (AD/MCI) among Mexican Americans (OR=1.06, 95% CI = 1.03–1.09). Age (B=0.07, std=0.02, p<0.001) and ApoEε4 presence (B=0.9, std=0.4, p=0.02) were significantly related to increased disease severity. Conclusions Given the rapidly growing and aging Mexican American population, there is a substantial need for research into cognitive aging, MCI and AD among this ethnic group. The current findings hold important implications for both clinic and research settings and point to additional research needs.

ObjectivesTo analyze the association between chronic kidney disease (CKD) and mild cognitive impairment (MCI) in Mexican Americans and to determine whether there is a blood‐based proteomic profile linking CKD to MCI.DesignRetrospective analysis of cohort study.SettingHealth and Aging Brain among Latino Elders study.ParticipantsMexican Americans (N = 437, 105 men, 332 women).MeasurementsData were analyzed to examine the link between estimated glomerular filtration rate (eGFR) and detailed neuropsychological functioning. Serum proteomic markers were also examined.ResultsLower eGFR levels were associated with significantly poorer neuropsychological functioning across multiple domains. After adjusting for age, sex, education, and diabetes mellitus, participants with an eGFR less than 45 mL/min per 1.73 m2 performed significantly worse than those with an eGFR from 45 to 59 mL/min per 1.73 m2 or 60 mL/min per 1.73 m2 and higher in processing speed (F = 14.1, P < .001), executive functioning (F = 4.5, P = .01), visuospatial skills (F = 4.8, P = .009), and global cognitive functioning (F = 6.2, P = .002). Participants with an eGFR less than 45 mL/min per 1.73 m2 also performed significantly worse than those with an eGFR of 60 mL/min per 1.73 m2 or greater on delayed memory (F = 3.8, P = .02). There was a trend toward lower eGFR levels being associated with greater risk of MCI (odds ratio (OR) = 2.4, 95% confidence interval (CI) = 0.91–6.1, P = .07), which was stronger for men (OR = 9.6, 95% CI = 1.3–74.3, P = .03). A serum proteomic profile consisting of Factor VII, interleukin‐10, C‐reactive protein, and fatty acid binding protein was 93% accurate in detecting CKD‐related MCI.ConclusionLower eGFR was associated with significantly poorer neuropsychological functioning in Mexican Americans. A blood‐based profile was generated that was highly accurate in detecting CKD‐related MCI. A blood profile capable of predicting CKD‐related cognitive impairment would be of benefit for the design of clinical interventions.

Introduction:Little is known about how antecedent vascular risk factor (VRF) profiles impact late-life brain health. Methods: We examined baseline VRFs, and cognitive testing and neuroimaging measures (β-amyloid [Aβ] PET, MRI) in a diverse longitudinal cohort (N = 159; 50% African-American, 50% White) from Wake Forest's Multi-Ethnic Study of Atherosclerosis Core. Results: African-Americans exhibited greater baseline Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham stroke risk profile (FSRP), and atherosclerotic cardiovascular disease risk estimate (ASCVD) scores than Whites. We observed no significant racial differences in Aβ positivity, cortical thickness, or white matter hyperintensity (WMH) volume. Higher baseline VRF scores were associated with lower cortical thickness and greater WMH volume, and FSRP and CAIDE were associated with Aβ. Aβ was cross-sectionally associated with cognition, and all imaging biomarkers were associated with greater 6-year cognitive decline. Discussion: Results suggest the convergence of multiple vascular and Alzheimer's processes underlying neurodegeneration and cognitive decline.

The biomarker profile of aMCI was shown to be different from our previously generated AD profile among Mexican Americans, which was largely metabolic in nature. The findings implicate a possible interplay between inflammatory and metabolic processes and additional work is needed to further examine this.

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The descending and the intrinsic components of the serotoninergic (5HT) innervation of the Atlantic stingray spinal cord were described by comparing the distributions of neuronal elements exhibiting 5HT-like immunoreactivity (peroxidase-antiperoxidase method) in sections caudal and rostral to spinal transections. The cells of origin of the descending 5HT system were located with a double labeling method for both retrogradely transported horseradish peroxidase (HRP) and 5HT staining. The descending system provides virtually the entire 5HT innervation of the dorsal horn, the intermediate zone, and the dorsal and lateral portions of the ventral horn. Fibers of the descending 5HT system course in the lateral funiculus, the dorsal portion of the ventral funiculus, and in the submeningeal zones of the dorsal and lateral aspects of the spinal cord. This projection primarily originates from the 5HT cell groups of the caudal rhombencephalon (groups II and III; Ritchie et al., '83), with a minor contribution from group IV in the rostral rhombencephalon. The organization of the descending 5HT system in stingrays is remarkably similar to that of mammals. The intrinsic spinal 5HT system consists of cells distributed in the ventromedial spinal cord that have processes extending longitudinally in a ventral submeningeal fiber network. Fibers were traced from the submeningeal system to the ventral horn, where varicose processes were restricted largely to the neuropil ventral to the somata of the fin motoneurons. The existence of a well-defined intrinsic 5HT system in stingrays supports the hypothesis that such a system exists in the spinal cords of a variety of vertebrates.

In spinally transected stingrays, electrical stimulation of a site just ventral to the dorsal root entry zone or a site in the intermediate portions of the lateral funiculus produced rhythmic swimming like movements of the contralateral pectoral fin. Electromyographic (EMG) records collected during cord-stimulated rhythms had the same pattern of activity and sometimes the same intersegmental coordination as those collected during spontaneous swimming of the same animal. In paralyzed, high-spinal stingrays, the only stimulation sites that produced rhythmic activity (fictive swimming) in the pectoral fin motor nerves were in the intermediate portion of the lateral funiculus. The evoked rhythm occurred in the motor nerves that were contralateral to the stimulated side of the spinal cord. The effects of subtotal lesions of the rostral spinal cord on spontaneous swimming behavior were assessed by analysis of EMG records taken before and after the lesions were made. Severe deficits in swimming occurred after bilateral ablation of intermediate portions of the lateral funiculi. In agreement with previous results, the stimulation experiments indicate that the stingray spinal cord contains an inherent capacity to generate properly coordinated rhythmic swimming. The current experiments also suggest that the descending pathways(s) that normally functions to initiate swimming projects through the intermediate aspects of the lateral funiculi.