Dissociation of Alzheimer's morphological pathology from cognitive impairment

We observed the Alzheimer's morphological pathology, amyloid production induces Alzheimer's cognitive impairment, was dissociated from the cognitive impairment. The earlier Alzheimer's pathological changes can be induced in normal C57BL mice, by B6 deficient feeding 4 months with no amyloid, and this cognitive and memory impairments were completely inhibited by anti-homocysteic acid antibody. According to Koch's postulate, if a pathogen of Alzheimer's disease is administrated to the normal animal, we would observe the Alzheimer's cognitive impairment in the normal animal. We actually have observed this cognitive impairment in normal C57BL male mice with no amyloid. From our observations, it is suggested the dissociation of Alzheimer's morphological pathology may be possible from the cognitive impairment

The conceptual relevance of assessment measures in patients with mild/mild-moderate Alzheimer\u27s disease

Introduction: This study aims to evaluate the conceptual relevance of four measures of disease activity in patients with mild/mild-moderate Alzheimer\u27s disease (AD): (1) the Alzheimer\u27s Disease Assessment Scale–Cognitive Subscale; (2) the Alzheimer\u27s Disease Cooperative Study–Activities of Daily Living Inventory; (3) the Neuropsychiatry Inventory; and (4) the Dependence Scale. Methods: A conceptual model depicting patient experience of mild AD was developed via literature review; concepts were compared with the items of the four measures. Relevance of the concepts included in the four measures was evaluated by patients with mild AD in a survey and follow-up interviews. Results: The four measures assessed few of the symptoms/impacts of mild AD identified within the literature. Measured items addressing emotional impacts were deemed most relevant by participants but were included in the measures only superficially. Discussion: The four assessment measures do not appear to capture the concepts most relevant to/important to patients with mild/mild-moderate AD. © 2018 The Author

Generation and quality control of lipidomics data for the alzheimers disease neuroimaging initiative cohort.

Alzheimers disease (AD) is a major public health priority with a large socioeconomic burden and complex etiology. The Alzheimer Disease Metabolomics Consortium (ADMC) and the Alzheimer Disease Neuroimaging Initiative (ADNI) aim to gain new biological insights in the disease etiology. We report here an untargeted lipidomics of serum specimens of 806 subjects within the ADNI1 cohort (188 AD, 392 mild cognitive impairment and 226 cognitively normal subjects) along with 83 quality control samples. Lipids were detected and measured using an ultra-high-performance liquid chromatography quadruple/time-of-flight mass spectrometry (UHPLC-QTOF MS) instrument operated in both negative and positive electrospray ionization modes. The dataset includes a total 513 unique lipid species out of which 341 are known lipids. For over 95% of the detected lipids, a relative standard deviation of better than 20% was achieved in the quality control samples, indicating high technical reproducibility. Association modeling of this dataset and available clinical, metabolomics and drug-use data will provide novel insights into the AD etiology. These datasets are available at the ADNI repository at http://adni.loni.usc.edu/

Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and dementia pugilistica in retired boxers1-3, CTE has since been identified in former participants of other contact sports, ex-military personnel and after physical abuse4-7. No disease-modifying therapies currently exist, and diagnosis requires an autopsy. CTE is defined by an abundance of hyperphosphorylated tau protein in neurons, astrocytes and cell processes around blood vessels8,9. This, together with the accumulation of tau inclusions in cortical layers II and III, distinguishes CTE from Alzheimer's disease and other tauopathies10,11. However, the morphologies of tau filaments in CTE and the mechanisms by which brain trauma can lead to their formation are unknown. Here we determine the structures of tau filaments from the brains of three individuals with CTE at resolutions down to 2.3 Å, using cryo-electron microscopy. We show that filament structures are identical in the three cases but are distinct from those of Alzheimer's and Pick's diseases, and from those formed in vitro12-15. Similar to Alzheimer's disease12,14,16-18, all six brain tau isoforms assemble into filaments in CTE, and residues K274-R379 of three-repeat tau and S305-R379 of four-repeat tau form the ordered core of two identical C-shaped protofilaments. However, a different conformation of the β-helix region creates a hydrophobic cavity that is absent in tau filaments from the brains of patients with Alzheimer's disease. This cavity encloses an additional density that is not connected to tau, which suggests that the incorporation of cofactors may have a role in tau aggregation in CTE. Moreover, filaments in CTE have distinct protofilament interfaces to those of Alzheimer's disease. Our structures provide a unifying neuropathological criterion for CTE, and support the hypothesis that the formation and propagation of distinct conformers of assembled tau underlie different neurodegenerative diseases

Space-centred information management approach to improve CAD-based healthcare building design

This study focuses on developing a space-centred CAD tool to enable designers to effectively manage and implement the information of design guidance information and user requirements during design processes, especially for the stages of design briefing and conceptual design. It aims to structure and store design guidance and user requirements for healthcare building design into a relational database, and link them to relevant space entities in design plans. The tool is developed on the platform of Autodesk Architecture Desktop (ADT). It also enables users to store and retrieve pictures associated with textual information, because pictures have been always used by designers as an effective medium to represent and deliver design information and knowledge. This can give users directly visual and more understandable perceptions of the design guidance. The tool is fully embedded with Autodesk AutoCAD systems to ensure the application of this tool being fully merged with CAD-based design process. A set of design guidance about Alzheimer clinic built environments are adopted as a sample to demonstrate and validate the tool. Moreover, the scenario of expanding this application to more broad areas has also been foreseen

The Alzheimer conundrum

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Vascular neurocognitive disorders and the vascular risk factors

Dementias are clinical neurodegenerative diseases characterized by permanent and progressive transformation of cognitive functions such as memory, learning capacity, attention, thinking, language, passing judgments, calculation or orientation. Dementias represent a relatively frequent pathology, encountered at about 10% of the population of 65-year olds and 20% of the population of 80-year olds. This review presents the main etiological forms of dementia, which include Alzheimer form of dementia, vascular dementia, dementia associated with alpha-synucleionopathies, and mixed forms. Regarding vascular dementia, the risk factors are similar to those for an ischemic or hemorrhagic cerebrovascular accident: arterial hypertension, diabetes mellitus, dyslipidemia, smoking, obesity, age, alcohol consumption, cerebral atherosclerosis/ arteriosclerosis. Several studies show that efficient management of the vascular risk factors can prevent the expression and/ or progression of dementia. Thus, lifestyle changes such as stress reduction, regular physical exercise, decreasing dietary fat, multivitamin supplementation, adequate control of blood pressure and serum cholesterol, and social integration and mental stimulation in the elderly population are important factors in preventing or limiting the symptoms of dementia, a disease with significant individual, social, and economic implications

The Alzheimer variant of Lewy body disease: A pathologically confirmed case-control study

The objective of the study was to identify clinical features that distinguish patients with dementia with Lewy bodies (DLB), who were classified as Alzheimer's disease ( AD) patients, from patients with AD. We examined a group of 27 patients from our memory clinic, originally diagnosed with AD, of whom 6 were postmortem found to have DLB. For the present study, we compared cognitive, noncognitive and neurological symptoms between the two groups. We found that there were no differences on ratings of dementia and scales for activities of daily living. Patients with DLB performed better on the MMSE and the memory subtest of the CAMCOG, but there was no difference in any other cognitive domain. Furthermore, genetic risk factors, including family history of dementia or allele frequency of the apolipoprotein epsilon 4, did not discriminate between the two groups, and there were no differences on CCT scans. Taken together, our findings suggest that Lewy body pathology may be present in patients who do not show the typical clinical features which distinguish DLB from AD. Copyright (C) 2005 S. Karger AG, Basel