Journal of Alzheimer's Disease - Volume 55, issue 4

Authors: Mariani, Elena | Chattat, Rabih | Vernooij-Dassen, Myrra | Koopmans, Raymond | Engels, Yvonne

Article Type: Research Article

Abstract: Background: Care planning nowadays is a key activity in the provision of services to nursing home residents. A care plan describes the residents’ needs and the actions to address them, providing both individualized and standardized interventions and should be updated as changes in the residents’ conditions occur. Objective: The aim of this review was to identify the core elements of the implementation of changes in nursing homes’ care plans, by providing an overview of the type of stakeholders involved, describing the implementation strategies used, and exploring how care plans changed. Methods: An integrative literature review was used …to evaluate intervention studies taking place in nursing homes. Data were collected from PubMed, CINHAL-EBSCO, and PsycINFO. English language articles published between 1995 and April 2015 were included. Data analysis followed the strategy of Knafl and Whittemore. Results: Twenty-six articles were included. The stakeholders involved were professionals, family caregivers, and patients. Only a few studies directly involved residents and family caregivers in the quality improvement process. The implementation strategies used were technology implementation, audit, training, feedback, and supervision. The majority of interventions changed the residents’ care plans in terms of developing a more standardized care documentation that primarily focuses on its quality. Only some interventions developed more tailored care plans that focus on individualized needs. Conclusion: Care plans generally failed in providing both standardized and personalized interventions. Efforts should be made to directly involve residents in care planning and provide professionals with efficient tools to report care goals and actions in care plans. Show more

Keywords: Care plan, elderly residents, implementation, nursing documentation, nursing homes, quality improvement, stakeholders

DOI: 10.3233/JAD-160559

Citation: Journal of Alzheimer's Disease, vol. 55, no. 4, pp. 1621-1638, 2017

Authors: Pandya, Sneha | Kuceyeski, Amy | Raj, Ashish | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Alzheimer’s disease (AD), one of the most common causes of dementia in adults, is a progressive neurodegenerative disorder exhibiting well-defined neuropathological hallmarks. It is known that disease pathology involves misfolded amyloid-β (Aβ) and tau proteins, and exhibits a relatively stereotyped progression over decades. The relationship between AD neuropathological hallmarks (Aβ, hypometabolism, and tau proteins) and imaging biomarkers (MRI, AV-45/FDG-PET) is not fully understood. In addition, biomarker pathologies are oftentimes discordant, wherein it may show varying levels of abnormality across brain regions. Evidence based on recent elucidation of trans-neuronal “prion-like” transmission and other available data already suggests that disease spread follows …the brain’s fiber connectivity network. Thereby, the brain’s connectome information can be used to predict the process of disease spread in AD. A recently established mathematical model of AD pathology spread using a connectome-based network diffusion model was successful in encapsulating neurodegenerative progression. Motivated by these network-based findings, the current study explores whether and how network connectivity mediates the interactions between various AD biomarkers. We hypothesized that the structural connectivity matrix will mediate the cross-sectional association between regional AD-associated hypometabolism and Aβ deposition. Given recent reports of inherent or lifetime activity of brain regions as strong predictors of Aβ deposition in patients, we also tested whether healthy metabolism exerts a network-mediated effect on Aβ deposition and hypometabolism in AD patients. We found that regional Aβ deposition is best predicted by a linear combination of both regional healthy local metabolism and connectome-mediated regional healthy metabolism. Show more

Keywords: Alzheimer’s disease, amyloid-β, AV-45-PET, biomarkers, cross-sectional, FDG-PET, hypometabolism, metabolism, structural connectivity

DOI: 10.3233/JAD-160090

Citation: Journal of Alzheimer's Disease, vol. 55, no. 4, pp. 1639-1657, 2017

Authors: Sancesario, Giulia M. | Toniolo, Sofia | Chiasserini, Davide | Di Santo, Simona G. | Zegeer, Josh | Bernardi, Gaetano | for SIBioC-Study Group of Clinical Biochemistry of Biological Fluids other than Blood | Musicco, Massimo | for SINdem-ITALPLANED | Caltagirone, Carlo | Parnetti, Lucilla | Bernardini, Sergio

Article Type: Research Article

Abstract: Although the use of cerebrospinal fluid (CSF) amyloid β1-42 (Aβ42 ), tau (T-tau), and phosphorylated tau (p-tau181 ) gives added diagnostic and prognostic values, the diffusion is still limited in clinical practice and only a restricted number of patients receive an integrated clinico-biological diagnosis. By a survey, we aimed to do a “selfie” of the use and diffusion of CSF biomarkers of dementia in Italy, the standardization of pre-analytical procedures, the harmonization of ranges, and the participation to Quality Control programs. An online questionnaire was sent to the members of SIBioC and SINdem-ITALPLANED and to main neurological clinics all …over Italy. In Italy, 25 laboratories provide biomarkers analysis in addition to a network of 15 neighboring hospitals. In sum, 40 neurological centers require CSF analyses. 7/20 regions (35%) lack CSF laboratories. Standardization of pre-analytical procedures is present in 62.02% of the laboratories; only 56.00% of the laboratories participate in International Quality Control. There is no harmonization of cut-offs. In Italy, the use of CSF biomarkers is still limited in clinical practice. Standardization and harmonization of normal ranges are needed. To optimize and expand the use of CSF biomarkers, a cost–benefit analysis should be promoted by scientific societies and national health services. Show more

Keywords: Alzheimer’s disease diagnosis, cerebrospinal fluid, neurodegenerative biomarkers, survey

DOI: 10.3233/JAD-160975

Citation: Journal of Alzheimer's Disease, vol. 55, no. 4, pp. 1659-1666, 2017

Authors: Hilt, Silvia | Tang, Tang | Walton, Jeffrey H. | Budamagunta, Madhu | Maezawa, Izumi | Kálai, Tamás | Hideg, Kálmán | Singh, Vikrant | Wulff, Heike | Gong, Qizhi | Jin, Lee-Way | Louie, Angelique | Voss, John C.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is characterized by depositions of the amyloid-β (Aβ) peptide in the brain. The disease process develops over decades, with substantial neurological loss occurring before a clinical diagnosis of dementia can be rendered. It is therefore imperative to develop methods that permit early detection and monitoring of disease progression. In addition, the multifactorial pathogenesis of AD has identified several potential avenues for AD intervention. Thus, evaluation of therapeutic candidates over lengthy trial periods also demands a practical, noninvasive method for measuring Aβ in the brain. Magnetic resonance imaging (MRI) is the obvious choice for such measurements, but contrast enhancement for …Aβ has only been achieved using Gd(III)-based agents. There is great interest in gadolinium-free methods to image the brain. In this study, we provide the first demonstration that a nitroxide-based small-molecule produces MRI contrast in brain specimens with elevated levels of Aβ. The molecule is comprised of a  fluorene (a molecule with high affinity for Aβ) and a nitroxide spin label (a paramagnetic MRI contrast species). Labeling of brain specimens with the spin-labeled fluorene produces negative contrast in samples from AD model mice whereas no negative contrast is seen in specimens harvested from wild-type mice. Injection of spin-labeled fluorene into live mice resulted in good brain penetration, with the compound able to generate contrast 24-h post injection. These results provide a proof of concept method that can be used for early, noninvasive, gadolinium-free detection of amyloid plaques by MRI. Show more

Keywords: Alzheimer’s disease, amyloid-β, amyloid MRI contrast, magnetic resonance imaging, nitroxide spin label, spin-labeled fluorene

DOI: 10.3233/JAD-160279

Citation: Journal of Alzheimer's Disease, vol. 55, no. 4, pp. 1667-1681, 2017

Authors: Wang, Ying | Zhou, Zhu | Tan, Hua | Zhu, Shenghua | Wang, Yiran | Sun, Yingxia | Li, Xin-Min | Wang, Jun-Feng

Article Type: Research Article

Abstract: Nitric oxide can attack thiol groups of cysteine residues in proteins and induce protein cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer’s disease. Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles, which is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and that S-nitrosylation of these transporters inhibits vesicular uptake of acetylcholine and glutamate. To understand the role of VAChT and VGLUT1 nitrosylation in the pathophysiological development of Alzheimer’s disease, we analyzed nitrosylation of VAChT and VGLUT1 in brain of …amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice, an animal model for Alzheimer’s disease. Using a Morris water maze test, we found that 9- and 12-month-old APP/PS1 mice showed memory deficit, compared to wild type mice. We further found that total protein nitrosylation was increased in frontal cortex and hippocampus of 9- and 12-month-old APP/PS1 mice. Although nitrosylation of VAChT and VGLUT1 was not changed in hippocampus of 9- and 12-month-old APP/PS1 mice, nitrosylation of VAChT and VGLUT1 was significantly increased in frontal cortex of APP/PS1 mice at these ages. We also found that nitrosylation of VAChT and VGLUT1 was increased in hippocampus (but not frontal cortex) of 3-month-old APP/PS1 mice. These findings suggest that nitrosylation of VAChT and VGLUT1 may be associated with dysfunctional acetylcholinergic and glutamatergic neurotransmission in Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, oxidative stress, protein nitrosylation, vesicular acetylcholine transporter, vesicular glutamate transporter

DOI: 10.3233/JAD-160700

Citation: Journal of Alzheimer's Disease, vol. 55, no. 4, pp. 1683-1692, 2017

Article Type: Other

Citation: Journal of Alzheimer's Disease, vol. 55, no. 4, pp. 1693-1711, 2017