A Blood-Based Screening Tool for Alzheimer's Disease That Spans Serum and Plasma: Findings from TARC and ADNI

There is no rapid and cost effective tool that can be implemented as a front-line screening tool for Alzheimer's disease (AD) at the population level.To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma. status) data.Alzheimer's disease.11 proteins met our criteria and were utilized for the biomarker risk score. The random forest (RF) biomarker risk score from the TARC serum samples (training set) yielded adequate accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) = 0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI cerebral spinal fluid (CSF) analyses (t-tau/Aβ ratio AUC = 0.92). However, the full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91). The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03 (SE = 1.17; 95% CI = 4.49–14.47), the likelihood ratio of not having AD based on the algorithm (LR−) = 3.55 (SE = 1.15; 2.22–5.71), and the odds ratio of AD were calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86–69.47).It is possible to create a blood-based screening algorithm that works across both serum and plasma that provides a comparable screening accuracy to that obtained from CSF analyses

LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

<p>Abstract</p> <p>Background</p> <p>LcrG, a negative regulator of the <it>Yersinia </it>type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in <it>Y. pestis</it>. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown.</p> <p>Results</p> <p>An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity.</p> <p>Conclusion</p> <p>These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.</p

The Link between Cognitive Measures and ADLs and IADL Functioning in Mild Alzheimer's: What Has Gender Got to Do with It?

Objectives. To investigate the link between neurocognitive measures and various aspects of daily living (ADL and IADL) in women and men with mild Alzheimer's disease (AD). Methods. Participants were 202 AD patients (91 male, 111 female) with CDR global scores of ≤1. ADLs and IADLs ratings were obtained from caregivers. Cognitive domains were assessed with neuropsychological testing. Results. Memory and executive functioning were related to IADL scores. Executive functioning was linked to total ADL. Comparisons stratified on gender found attention predicted total ADL score in both men and women. Attention predicted bathing and eating ability in women only. Language predicted IADL functions in men (food preparation) and women (driving). Conclusions. Associations between ADLs/IADLs and memory, learning, executive functioning, and language suggest that even in patients with mild AD, basic ADLs require complex cognitive processes. Gender differences in the domains of learning and memory area were found

Human plasma biomarker responses to inhalational general anaesthesia without surgery

Background: Postoperative neurocognitive disorders may arise in part from adverse effects of general anaesthetics on the CNS, especially in older patients or individuals otherwise vulnerable to neurotoxicity because of systemic disease or the presence of pre-existing neuropathology. Previous studies have documented cytokine and injury biomarker responses to surgical procedures that included general anaesthesia, but it is not clear to what degree anaesthetics contribute to these responses. / Methods: We performed a prospective cohort study of 59 healthy volunteers aged 40–80 yr who did not undergo surgery. Plasma markers of neurological injury and inflammation were measured immediately before and 5 h after induction of general anaesthesia with 1 minimum alveolar concentration of sevoflurane. Biomarkers included interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), C-reactive protein (CRP), and neural injury (tau, neurofilament light [NF-L], and glial fibrillary acidic protein [GFAP]). / Results: Baseline biomarkers were in the normal range, although NF-L and GFAP were elevated as a function of age. At 5 h after induction of anaesthesia, plasma tau, NF-L, and GFAP were significantly decreased relative to baseline. Plasma IL-6 was significantly increased after anaesthesia, but by a biologically insignificant degree (<1 pg ml−1); plasma TNF-α and CRP were unchanged. / Conclusions: Sevoflurane general anaesthesia without surgery, even in older adults, did not provoke an inflammatory state or neuronal injury at a concentration that is detectable by an acute elevation of measured plasma biomarkers in the early hours after exposure. Clinical trial registration: NCT02275026

Evolving Relevance of Neuroproteomics in Alzheimer's Disease

Substantial progress in the understanding of the biology of Alzheimer's disease (AD) has been achieved over the past decades. The early detection and diagnosis of AD and other age-related neurodegenerative diseases, however, remain a challenging scientific frontier. Therefore, the comprehensive discovery (relating to all individual, converging or diverging biochemical disease mechanisms), development, validation, and qualification of standardized biological markers with diagnostic and prognostic functions with a precise performance profile regarding specificity, sensitivity, and positive and negative predictive value are warranted.Methodological innovations in the area of exploratory high-throughput technologies, such as sequencing, microarrays, and mass spectrometry-based analyses of proteins/peptides, have led to the generation of large global molecular datasets from a multiplicity of biological systems, such as biological fluids, cells, tissues, and organs. Such methodological progress has shifted the attention to the execution of hypothesis-independent comprehensive exploratory analyses (opposed to the classical hypothesis-driven candidate approach), with the aim of fully understanding the biological systems in physiology and disease as a whole. The systems biology paradigm integrates experimental biology with accurate and rigorous computational modelling to describe and foresee the dynamic features of biological systems. The use of dynamically evolving technological platforms, including mass spectrometry, in the area of proteomics has enabled to rush the process of biomarker discovery and validation for refining significantly the diagnosis of AD. Currently, proteomics-which is part of the systems biology paradigm-is designated as one of the dominant matured sciences needed for the effective exploratory discovery of prospective biomarker candidates expected to play an effective role in aiding the early detection, diagnosis, prognosis, and therapy development in AD

Production of Inflected Novel Words in Older Adults With and Without Dementia

While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know. It is unclear whether speakers continue to use the same strategy when encountering novel words throughout the lifespan or whether adult speakers apply symbolic rules. We administered a simple speech elicitation task involving Finnish‐conforming pseudo‐words and real Finnish words to healthy older adults, individuals with mild cognitive impairment, and individuals with Alzheimer's disease (AD) to investigate inflectional choices in these groups and how linguistic variables and disease severity predict inflection patterns. Phonological resemblance of novel words to both a regular and an irregular inflectional type, as well as bigram frequency of the novel words, significantly influenced participants' inflectional choices for novel words among the healthy elderly group and people with AD. The results support theories of inflection by phonological analogy (single‐route models) and contradict theories advocating for formal symbolic rules (dual‐route models).While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know. It is unclear whether speakers continue to use the same strategy when encountering novel words throughout the lifespan or whether adult speakers apply symbolic rules. We administered a simple speech elicitation task involving Finnish-conforming pseudo-words and real Finnish words to healthy older adults, individuals with mild cognitive impairment, and individuals with Alzheimer’s disease (AD) to investigate inflectional choices in these groups and how linguistic variables and disease severity predict inflection patterns. Phonological resemblance of novel words to both a regular and an irregular inflectional type, as well as bigram frequency of the novel words, significantly influenced participants’ inflectional choices for novel words among the healthy elderly group and people with AD. The results support theories of inflection by phonological analogy (single-route models) and contradict theories advocating for formal symbolic rules (dual-route models).Peer reviewe

Educational Intervention: Improving Long Term Care Nursing Staff Comfort with Utilizing Bladder Scanner

Background: According to the CDC, UTIs result in 20-30% of illnesses reported by long-term care institutions (CDC, 2017). One must consider multiple factors regarding the elderly population and urinary retention vs. UTIs. Intermittent catheterizations cause pain, discomfort, and complications leading to hospitalizations. Among the elderly, specifically the mentally impaired, there is an increased risk for urinary retention or UTIs.Purpose: This project enhanced the staff's knowledge about bladder ultrasound technology to reduce urinary tract infections and unnecessary intermittent catheterizations. Methods: This was a quality improvement (QI) using the Plan-Do-Study-Act (PDSA) Model to identify if the education provided to the nursing staff on the use of bladder scanners would prevent unnecessary intermittent catheterizations, thus decreasing urinary tract infections (UTIs). Results: During the eight weeks of the data collection, 31 (62%) staff members (RN, LPN, CNAs) in the DNP project LTCF site participated in this staff education. The behavioral intention to use the bladder scanner improved slightly, although not statistically significant, decreasing unnecessary intermittent catheterization and UTIs. Recommendations and Conclusions: The bladder scanner is recommended for patients with urinary incontinence among the elderly within all LTCFs because of the increased risk of UTIs. Based on the results of this QI project, the use of the bladder scanner yielded a decrease in UTIs

Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study.

INTRODUCTION: Previously generated serum and plasma proteomic profiles were examined among adults with Down syndrome (DS) to determine whether these profiles could discriminate those with mild cognitive impairment (MCI-DS) and Alzheimer's disease (DS-AD) from those cognitively stable (CS). METHODS: Data were analyzed on n = 305 (n = 225 CS; n = 44 MCI-DS; n = 36 DS-AD) enrolled in the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS). RESULTS: Distinguishing MCI-DS from CS, the serum profile produced an area under the curve (AUC) = 0.95 (sensitivity [SN] = 0.91; specificity [SP] = 0.99) and an AUC = 0.98 (SN = 0.96; SP = 0.97) for plasma when using an optimized cut-off score. Distinguishing DS-AD from CS, the serum profile produced an AUC = 0.93 (SN = 0.81; SP = 0.99) and an AUC = 0.95 (SN = 0.86; SP = 1.0) for plasma when using an optimized cut-off score. AUC remained unchanged to slightly improved when age and sex were included. Eotaxin3, interleukin (IL)-10, C-reactive protein, IL-18, serum amyloid A , and FABP3 correlated fractions at r2 > = 0.90. DISCUSSION: Proteomic profiles showed excellent detection accuracy for MCI-DS and DS-AD

Home: The place the older adult can not imagine living without

<p>Abstract</p> <p>Background</p> <p>Rapidly aging populations with an increased desire to remain at home and changes in health policy that promote the transfer of health care from formal places, as hospitals and institutions, to the more informal setting of one's home support the need for further research that is designed specifically to understand the experience of home among older adults. Yet, little is known among health care providers about the older adult's experience of home. The aim of this study was to understand the experience of home as experienced by older adults living in a rural community in Sweden.</p> <p>Methods</p> <p>Hermeneutical interpretation, as developed by von Post and Eriksson and based on Gadamer's philosophical hermeneutics, was used to interpret interviews with six older adults. The interpretation included a self examination of the researcher's experiences and prejudices and proceeded through several readings which integrated the text with the reader, allowed new questions to emerge, fused the horizons, summarized main and sub-themes and allowed a new understanding to emerge.</p> <p>Results</p> <p>Two main and six sub-themes emerged. Home was experienced as the place the older adult could not imagine living without but also as the place one might be forced to leave. The older adult's thoughts vacillated between the well known present and all its comforts and the unknown future with all its questions and fears, including the underlying threat of loosing one's home.</p> <p>Conclusions</p> <p>Home has become so integral to life itself and such an intimate part of the older adult's being that when older adults lose their home, they also loose the place closest to their heart, the place where they are at home and can maintain their identity, integrity and way of living. Additional effort needs to be made to understand the older adult's experience of home within home health care in order to minimize intrusion and maximize care. There is a need to more fully explore the older adult's experience with health care providers in the home and its impact on the older adult's sense of "being at home" and their health and overall well-being.</p