Kidney function and cognitive performance and decline in older men

OBJECTIVES: To examine the association between kidney function and cognitive impairment and decline in elderly men. DESIGN: Observational prospective cohort. SETTING: Community based. PARTICIPANTS: Five thousand five hundred twenty‐nine community dwelling men aged 65 and older (mean age 73.6 ± 5.9). MEASUREMENTS: Estimated glomerular filtration rate (eGFR) calculated using the standardized Modification of Diet in Renal Disease (MDRD) equation; cognitive function assessed using the Modified Mini‐Mental State Examination (3MS) and Trail Making Test B (Trails B). RESULTS: At baseline, 148 (2.7%) and 494 (9.1%) men were classified as cognitively impaired and, in the 5‐year prospective analysis, 931 (23%) and 432 (11.6%) met the criteria for cognitive decline at follow‐up defined according to 3MS and Trails B performance, respectively. In unadjusted analysis, the odds of prevalent cognitive impairment and risk of cognitive decline were significantly higher in men with an eGFR less than 45 and 45 to 59 mL/min per 1.73 m² than in men with an eGFR 60 mL/min per 1.73 m² or greater. Differences in age, race, and education between eGFR categories largely explained these associations, with the exception of the association between poorer renal function and higher odds of impairment based on Trails B test score, which persisted despite adjustment for multiple potential confounders. CONCLUSION: This study found evidence of an independent association between mild to moderate reductions in kidney function and poor executive function at baseline but not with global cognitive impairment or risk of cognitive decline in older men.     

Electrical stimulation promotes the survival of oligodendrocytes in mixed cortical cultures

Oligodendrocyte (OLG) death plays a major role in white matter dysfunction and demyelination following injury to the CNS. Axonal contact, communication, and neuronal activity appear to promote OLG survival and function in cell culture and during development. The application of electrical stimulation to mixed neural cultures has been shown to promote OLG differentiation and the formation of myelin in vitro. Here we show that OLG viability can be significantly enhanced in mixed cortical cultures by applying biphasic pulses of electrical stimulation (ESTIM). Enhanced survival via ESTIM requires the presence of neurons and is suppressed by inhibition of voltage-gated sodium channels. Additionally, contact between the axon and OLG is necessary for ESTIM to promote OLG survival. This report suggests that patterned neuronal activity could repress delayed progression of white matter injury and promote CNS repair in neurological conditions that involve white matter damage.     

Primary amoebic meningoencephalitis with subsequent organ procurement: a case study

Primary amoebic meningoencephalitis (PAM) is a rare and rapidly fatal disease caused by the Naegleria fowleri amoeba. It is a diagnosis rarely seen by medical personnel, yet this amoeba is frequently encountered by people who frequent freshwater bodies of water in certain states. The disease primarily affects children and young adults who swim or take part in water sports in the waters in which the amoeba thrive. The disease presents with symptomatology similar to bacterial meningitis: headache, stiff neck, altered mental status, seizures, and coma with a quick progression to death. Rapid diagnosis is imperative to facilitate prompt treatment, although PAM has 95% mortality. There have been only 10 survivors reported in medical literature. This disease is a public-health risk to those living in affected areas of the country. Healthcare providers need to be cognizant of the disease as well, and, although recovery is rare, focus on prevention and risk reduction strategies is imperative. It is not completely understood why, of the millions of people are exposed to freshwater with the amoeba, only a few become infected with it. The Centers for Disease Control and Prevention have suggested that all freshwater areas should always assume a level of risk in waters, even when signage is not posted. This case study will review a fatal case of Naegleria fowleri infection in a young patient and will include the pathophysiology, diagnosis, treatment, nursing and public health implications, and organ procurement that occurred with the patient.     

Small rare recurrent deletions and reciprocal duplications in 2q21.1, including brain-specific ARHGEF4 and GPR148

We have identified a rare small (~450 kb unique sequence) recurrent deletion in a previously linked attention-deficit hyperactivity disorder (ADHD) locus at 2q21.1 in five unrelated families with developmental delay (DD)/intellectual disability (ID), ADHD, epilepsy and other neurobehavioral abnormalities from 17 035 samples referred for clinical chromosomal microarray analysis. Additionally, a DECIPHER (http://decipher.sanger.ac.uk) patient 2311 was found to have the same deletion and presented with aggressive behavior. The deletion was not found in either six control groups consisting of 13 999 healthy individuals or in the DGV database. We have also identified reciprocal duplications in five unrelated families with autism, developmental delay (DD), seizures and ADHD. This genomic region is flanked by large, complex low-copy repeats (LCRs) with directly oriented subunits of ~109 kb in size that have 97.7% DNA sequence identity. We sequenced the deletion breakpoints within the directly oriented paralogous subunits of the flanking LCR clusters, demonstrating non-allelic homologous recombination as a mechanism of formation. The rearranged segment harbors five genes: GPR148, FAM123C, ARHGEF4, FAM168B and PLEKHB2. Expression of ARHGEF4 (Rho guanine nucleotide exchange factor 4) is restricted to the brain and may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function. GPR148 encodes a G-protein-coupled receptor protein expressed in the brain and testes. We suggest that small rare recurrent deletion of 2q21.1 is pathogenic for DD/ID, ADHD, epilepsy and other neurobehavioral abnormalities and, because of its small size, low frequency and more severe phenotype might have been missed in other previous genome-wide screening studies using single-nucleotide polymorphism analyses.     

Association Between Serum 25(OH) Vitamin D and the Risk of Cognitive Decline in Older Women

Background: Results of prospective studies examining the association between 25 hydroxyvitamin D (25[OH]D) levels and cognitive decline have been inconsistent. We tested the hypothesis that lower 25(OH)D levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. Methods: The study is a cross-sectional and longitudinal analysis of a prospective cohort of 6,257 community-dwelling elderly women followed for 4 years. Global cognitive function was measured by the Modified Mini-Mental State Examination and executive function was measured by Trail Making Test Part B (Trails B). Cognitive impairment at baseline was defined as a score >1.5 SD below the sample mean; cognitive decline was defined as decline from baseline to follow-up >1 SD from mean change in score. Results: Women with very low vitamin D levels had an increased odds of global cognitive impairment at baseline: odds ratio (95% confidence interval), 1.60 (1.05-2.42) for women with 25(OH)D <10 ng/mL (25 nmol/L) compared with those with 25(OH)D levels ≥30 ng/mL (75 nmol/L). Compared with women with baseline 25(OH)D level ≥30 ng/mL (75 nmol/L), women with lower levels had an increased risk of global cognitive decline: odds ratio (95% confidence interval), 1.58(1.12-2.22) for women with levels <10 ng/mL (25 nmol/L), and 1.31 (1.04-1.64) for those with levels 10-19.9 ng/mL (25-49 nmol/L). Levels of 25(OH)D were not associated with executive cognitive function. Conclusions: Low 25(OH)D levels among older women were associated with a higher odds of global cognitive impairment and a higher risk of global cognitive decline.