抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Objectives: To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia.

Design: Validation study.

Setting: A community clinic and an academic center.

Participants: Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score≥17), and 90 healthy elderly controls (NC).

Measurements: The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD.

Results: Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively).

Conclusion: MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.

/pdf/the-montreal-cognitive-assessment-moca-a-brief-screening-4w06t9e7qy.pdf

The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

/pdf/the-diagnosis-of-dementia-due-to-alzheimer-s-disease-w5k0egjbz5.pdf

The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2796.2004.01388.x

Mild cognitive impairment as a diagnostic entity

IC-P-190 AN AMYLOID LIGAND-FREE OPTICAL RETINAL IMAGING METHOD TO PREDICT CEREBRAL AMYLOID PET STATUS Jean-Paul Soucy, Claudia Chevrefils, Jean-Philippe Sylvestre, Jean Daniel Arbour, Marc-Andr e Rh eaume, Sylvain Beaulieu, C eline Chayer, Alain Robillard, Pedro Rosa-Neto, Sulantha Mathotaarachchi, Ziad S. Nasreddine, Serge Gauthier, Fr ed eric Lesage, McConnell Brain Imaging Centre, McGill University, Montr eal, QC, Canada; Optina Diagnostics, Montreal, QC, Canada; Clinique Ophtalmologique 2121, Montreal, QC, Canada; Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada; Translational Neuroimaging Laboratory, McGill University, Verdun, QC, Canada; Institut et Clinique MoCA, Greenfield Park, QC, Canada; McGill University Research Centre for Studies in Aging, Verdun, QC, Canada; 8 Ecole Polytechnique de Montr eal, Montr eal, QC, Canada. Contact e-mail: jean-paul.soucy@mcgill.ca

Ic‐p‐190: an amyloid ligand‐free optical retinal imaging method to predict cerebral amyloid pet status

Fronto-temporal dementia (FTD) is a neurodegenerative disease characterized by focal atrophy of the gray matter (GM), especially in the frontal and temporal regions. Recent studies suggest a framework where white matter (WM) atrophy plays an important role in FTD pathophysiology. However, these studies often overlook the fact that WM tracts bridging different brain regions may have different vulnerabilities to the disease and the relative contribution of GM atrophy to this WM model, resulting in a less comprehensive understanding of the relationship between clinical symptoms and pathology. Here, by leveraging the sensitivity of advanced diffusion MRI modelling and metrics to precise white matter microstructural properties, we aim to clarify the relative contributions of WM fibers and GM atrophy to the cognitive symptoms typically found in FTD. A total of 155 participant from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) were analysed, including 68 normal elderly controls (CN), 28 behavioral variants (BV), 26 sematic variants (SV) and 30 progressive non fluent aphasia variants (PNFA) of FTD. Diffusion MRI analysis was performed using two complementary techniques: whole brain fixel-based analysis (FBA) and structural connectivity based on probabilistic tractography. Whole brain GM atrophy was assessed using voxel-based morphometry (VBM). Using a common factor analysis to extract a semantic and an executive factor, we aim to test the relative contribution of WM and GM of specific tracts in predicting cognition. We found that semantic symptoms were mainly dependent on short-range WM fiber disruption, while damage to long-range WM fibers was preferentially associated to executive dysfunction with the GM contribution to cognition being predominant for local processing. Our results support the importance of the disruption of specific WM tracts to the core cognitive symptoms associated with FTD. As large-scale WM tracts, which are particularly vulnerable to vascular disease, were highly associated with executive dysfunction, our findings highlight the importance of controlling for risk factors associated with deep white matter disease, such as vascular risk factors, in patients with FTD in order not to potentiate underlying executive dysfunction.

https://biorxiv.org/content/10.1101/2020.05.01.064576v1.full.pdf

Impact of long- and short-range fiber depletion on the cognitive deficits of fronto-temporal dementia

Cholinesterase inhibitors in Alzheimer's disease: A consensus view on managing treatment failure

Emmanuelle Levy1, Howard C Margolese2 and Serge Gauthier3 1Douglas Institute of Mental Health, Department of Psychiatry, McGill University, Montreal, 2Clinical Psychopharmacology Unit, McGill University Health Centre and Department of Psychiatry, McGill University, Montreal, 3Professor of Neurology, Neurosurgery and Medicine, McGill University, and Director of the Alzheimer’s disease Research Unit, McGill Centre for Studies in Aging, Montreal, Canada

/pdf/antipsychotics-versus-cholinesterase-inhibitors-for-the-3k4wcvlv0f.pdf

Serge Gauthier

Papers

Ic‐p‐190: an amyloid ligand‐free optical retinal imaging method to predict cerebral amyloid pet status

Impact of long- and short-range fiber depletion on the cognitive deficits of fronto-temporal dementia

Cholinesterase inhibitors in Alzheimer's disease: A consensus view on managing treatment failure

Antipsychotics Versus Cholinesterase Inhibitors for the Treatment of Psychosis in Alzheimer's : A Critical Review

Pharmacological treatment of Alzheimer's disease