Parkinson's disease is a highly heterogeneous disorder, where genetic factors are likely to contribute to clinical variability, including susceptibility to cognitive impairment and dementia. Monogenic forms of parkinsonism show distinct cognitive profiles, yet less is known about the impact of common genetic variants on cognition in sporadic Parkinson's disease. In a systematic review of the literature, the current results from genetic association studies of cognitive outcomes are summarized and prospects and challenges for future studies are discussed. Literature searches of the PubMed database were performed and studies using statistical methods to assess associations between genetic variation and any cognitive outcome in Parkinson's disease patients were included. For each of the candidate loci investigated in several studies, the current evidence is summarized and discussed. Sixty-one articles meeting our inclusion criteria were identified, which were highly heterogeneous with respect to study design, size and cognitive outcome measures. GBA mutations have a negative impact on cognition, whereas LRRK2-associated disease may have a milder cognitive phenotype than idiopathic Parkinson's disease. For common variants, reported results are partly conflicting, even across the larger studies, with some evidence to suggest a potential effect of APOE, MAPT, COMT and SNCA on cognitive outcomes. Future investigations should aim to collect high-quality cognitive data in a standardized way that allows for direct comparison across studies and large-scale meta-analysis. Linking genetic profiles to cognitive outcomes may have an important clinical impact, facilitating the stratification of patients for clinical trials and, ultimately, individualized treatment in Parkinson's disease.
Objective Maternal age at birth of last child has been associated with maternal longevity. The aim of this study was to determine whether elderly women with a history of late maternal age at last childbirth had a longer leukocyte telomere length compared with those with maternal age at last childbirth of 29 years or less. Methods A nested case control study was conducted utilizing data from the Long Life Family Study. Three hundred and eighty-seven women who gave birth to at least 1 child and lived to the top 5th percentile of their birth cohort, or died before the top 5th percentile of their birth cohort died, but were at least 70 years old, were studied. Logistic regression models using generalized estimating equations were used to determine the association between tertiles of telomere length and maternal age at last childbirth, adjusting for covariates. Results Age at birth of the last child was significantly associated with leukocyte telomere length. Compared with women who gave birth to their last child before the age of 29, women who were past the age of 33 when they had their last child were 2–3 times more likely to have leukocyte telomere length in the second and third tertiles than in the first tertile. Conclusion These findings show an association between longer leukocyte telomere length and a later maternal age at birth of last child, suggesting that extended maternal age at last childbirth may be a marker for longevity.
Long-live families with EC are characterized by a healthier metabolic profile which is related to the prevalence of obesity in the older family members. Our results suggest that familial exceptional longevity may be achieved through heterogeneous yet correlated pathways.
Implementation of a Vicom-VME image processing workstation for the frameless stereotactic operating microscope system has allowed an improved interpolation algorithm for more accurate reconstruction of three-dimensional data, the integration graphically of multimodality imaging information, an additional stereotactic graphics display outside of the microscope optics and optional three-dimensional displays through communication with a Convex mini-supercomputer. A precision-milled coupling for reproducible attachment of the spark gap bracket to the microscope has eliminated the need for that transformation calculation during each case. Clinical utility has been greatest in providing navigational guidance to small subcortical or deep lesions and in defining the extent of preoperatively planned resection of larger, infiltrating tumors. Mean accuracy in the past 17 cases has been 3.5–6.5 mm. The frameless methodology has also enabled extracranial stereotactic surgical procedures in 7 patients.
Neuronal accumulation of mis-folded tau is the pathological hallmark of multiple neurodegenerative disorders, including Alzheimer’s disease. Distinct from amyloid plaques, which appear simultaneously throughout the brain, tau pathology develops first in a specific brain region and then propagates to neuroanatomically connected brain regions, exacerbating the disease. Due to the implication in disease progression, prevention of tau transmission is recognized as an important therapeutic strategy that can halt disease progression in the brain. Recently, accumulating studies have demonstrated diverse cellular mechanisms associated with cell-to-cell transmission of tau. Once transmitted, mis-folded tau species act as a prion-like seed for native tau aggregation in the recipient neuron. In this review, we summarize the diverse cellular mechanisms associated with the secretion and uptake of tau, and highlight tau-trafficking receptors, which mediate tau clearance or cell-to-cell tau transmission.
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