High glucose levels may be a risk factor for dementia, even among persons without diabetes, according to a study published August 8 in the New England Journal of Medicine. Researchers examined 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2,067 participants (1,228 women) without dementia. Participants’ mean age at baseline was 76. Of the total population, 232 participants had diabetes. During a median follow-up of 6.8 years, 524 participants developed dementia (74 with diabetes). Among participants without diabetes, higher average glucose levels within the preceding five years were related to an increased risk of dementia. A glucose level of 115 mg/dL, compared with 100 mg/dL, was associated with an adjusted hazard ratio for dementia of 1.18.
A majority of Alzheimer’s disease investigators favor disclosing amyloid imaging results to participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), according to a survey published online ahead of print August 21 in Neurology. Shortly before the FDA approved the amyloid-binding radiotracer florbetapir, all ADNI investigators and personnel were asked to complete an anonymous online survey that contained fixed-choice and free-text questions. Although ADNI participants often requested amyloid imaging results, the majority of ADNI investigators (approximately 90%) did not return amyloid imaging results to the participants. Most investigators reported that if the FDA approved florbetapir, they would support the return of amyloid imaging results to participants with mild cognitive impairment and normal cognition, however. ADNI investigators emphasized the need for guidance on how to provide these results to participants.
A sudden decrease of testosterone may induce nigrostriatal pathologies in mice through a decrease in glial-derived neurotrophic factor (GDNF) mediated by inducible nitric-oxide synthase (iNOS), investigators reported in the July 19 Journal of Biological Chemistry. Levels of iNOS, glial markers, and α-synuclein were higher in the nigra of castrated male mice than in normal male mice. After castration, the level of GDNF markedly decreased in the nigra of male mice, however. Subcutaneous implantation of 5 α-dihydrotestosterone pellets reversed nigrostriatal pathologies in castrated male mice, suggesting that the male sex hormone plays a role in castration-induced nigrostriatal pathology. Castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study Parkinson’s disease-related nigrostriatal pathologies, thus facilitating the screening of drugs against Parkinson’s disease, said the researchers.
IV thrombolysis within 90 minutes may be associated with excellent outcomes in patients with moderate and mild stroke, according to research published online ahead of print August 22 in Stroke. Investigators prospectively collected data for consecutive ischemic stroke patients who received IV thrombolysis at 10 European stroke centers. Logistic regression analysis suggested that shorter onset-to-treatment time was significantly associated with excellent outcome. Patients with onset-to-treatment time of 90 minutes or less had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, the researchers found that onset-to-treatment time of 90 minutes or less was associated with excellent outcome in patients with NIH Stroke Scale (NIHSS) score from 7 to 12, but not in patients with baseline NIHSS score greater than 12 and baseline NIHSS 0 to 6.
A neo-substrate approach involving the adenosine triphosphate (ATP) analog kinetin triphosphate (KTP) can increase the activity of Parkinson’s disease–related mutant PINK1G309D and PINK1WT, according to research published on August 15 in Cell. Investigators found that the normal and mutated versions of PINK1 bind to KTP. The application of KTP precursor kinetin to cells resulted in biologically significant increases in PINK1 activity, which were manifest as higher levels of Parkin recruitment to depolarized mitochondria, reduced mitochondrial motility in axons, and lower levels of apoptosis. Kinetin could treat patients with a known PINK1 mutation and also slow disease progression in patients without a family history of the disease, said the researchers. The search for neo-substrates for kinases could provide a novel way of regulating kinase activity, they concluded.
The effect of copper on brain amyloid-β homeostasis depends on whether it is accumulated in the capillaries or in the parenchyma, researchers reported online ahead of print August 19 in Proceedings of the National Academy of Sciences. In aging mice, the accumulation of copper in brain capillaries was associated with its reduction in low-density lipoprotein receptor–related protein 1 (LRP1) and higher brain amyloid-β levels. In human brain endothelial cells, normal labile levels of copper caused the downregulation of LRP1 by inducing nitrotyrosination and subsequent proteosomal-dependent degradation, partly because of interactions between copper, cellular prion protein, and LRP1. In APPsw/0 mice, copper downregulated LRP1 in brain capillaries and increased amyloid-b production and neuroinflammation. The effect resulted from the accumulation of copper in brain capillaries and in the parenchyma.