Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world This conclusion is in keeping with the position of the United States' Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient's right The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline

Brain health: the importance of recognizing cognitive impairment: an IAGG consensus conference

Lumbar puncture (LP), also known as spinal tap, is the most frequently used technique through which the restricted compartment of the subarachnoid space is accessed to sample cerebrospinal fluid. An LP can have both diagnostic and therapeutic indications. To perform an LP, the optimal length, size, and type of needle should be used, depending on the medical indication. Needles used for LP can differ in length, diameter, and design. Head-to-head studies are in favor of atraumatic-type and small-diameter needles given the lower incidence of post-lumbar puncture headache (PLPH), and consensus-based guidelines recommend to use 25G atraumatic needles.

Techniques, Contraindications, and Complications of CSF Collection Procedures

A molecular imaging probe to fluorescently image the β-site of the amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) and cathepsin D (CatD) enzymes associated with Alzheimer's disease (AD) was designed and synthesized. This imaging probe was built upon iron oxide nanoparticles (cross-linked dextran iron oxide nanoparticles, or CLIO). Peptide substrates containing a terminal near-infrared fluorochrome (fluorophore emitting at 775 nm for CatD or fluorophore emitting at 669 nm for BACE1) were conjugated to the CLIO nanoparticles. The CatD substrate contained a phenylalanine-phenylalanine cleavage site more specific to CatD than BACE1. The BACE1 substrate contained the sequence surrounding the leucine-asparagine cleavage site of the BACE1 found in the Swedish mutation of APP, which is more specific to BACE1 than CatD. These fluorescently-labeled peptide substrates were then conjugated to the nanoparticle. The nanoparticle probes were purified by gel filtration, and their fluorescence intensities were determined using a fluorescence plate reader. The CatD peptide substrate demonstrated a 15.5-fold increase in fluorescence when incubated with purified CatD enzyme, and the BACE1 substrate exhibited a 31.5-fold increase in fluorescence when incubated with purified BACE1 enzyme. Probe specificity was also demonstrated in the human H4 neuroglioma cells and the H4 cells stably transfected with BACE1 in which the probe monitored enzymatic cleavage. In the H4 and H4-BACE1 cells, BACE1 and active CatD activity increased, an occurrence that was reflected in enzyme expression levels as determined by immunoblotting. These results demonstrate the applicability of this probe for detecting potential Alzheimer's enzyme biomarkers.

https://www.mdpi.com/1420-3049/25/2/274/pdf

A Novel Dual Fluorochrome Near-Infrared Imaging Probe for Potential Alzheimer’s Enzyme Biomarkers-BACE1 and Cathepsin D

La non-conscience de ses propres symptomes est un phenomene frequemment retrouve dans la maladie d'Alzheimer (MA). Ce phenomene appele anosognosie, principalement reporte dans la forme typique de la MA, implique une absence de conscience de ses propres difficultes cognitives pouvant conduire d'une part, a des situations de mise en danger de la part du patient, et d'autre part, a un retard de diagnostic. L'origine de ce phenomene etant encore debattue, trois etudes se sont ici portees sur l'etude des substrats cognitifs et neuronaux de ce phenomene dans la forme typique de la maladie d'Alzheimer. Les investigations menees en imagerie structurelle et metabolique ont pu mettre en evidence une alteration du cortex cingulaire anterieur dorsal en lien avec ce phenomene d'anosognosie. L'etude fonctionnelle a, quant a elle, pu mettre en evidence une diminution de la connectivite entre le precuneus et le cortex cingulaire anterieur pregenual. Ces regions cles du reseau par defaut permettent la mise a jour du soi, maintenant ainsi un sentiment de continuite au cours du temps. Au sein d'une quatrieme etude, le lien entre la meconnaissance des troubles et le retard de diagnostic a ete investigue dans l'atrophie corticale posterieure. Nous avons ainsi pu mettre en evidence que la plainte visuelle et gestuelle emise par le patient ne serait pas le reflet exact de ses deficits, tant sur le plan cognitif que sur le plan metabolique. Il semblerait que dans cette forme atypique de la maladie d'Alzheimer, les patients aient egalement des difficultes a caracteriser pleinement leurs deficits.

Substrats cognitifs et neuronaux de l'anosognosie dans la maladie d'Alzheimer typique et atypique : étude en neuropsychologie et imagerie multimodale

/pdf/optimizing-use-of-diagnostic-tests-in-memory-clinics-the-500icwnbhr.pdf

Optimizing use of diagnostic tests in memory clinics; the next step

Introduction: Proposed diagnostic criteria (international working group and National Institute on Aging and Alzheimer’s Association) for Alzheimer’s disease (AD) include markers of amyloidosis (abnormal cerebrospinal fluid [CSF] amyloid beta [Ab]42) and neurodegeneration (hippocampal atrophy, temporo-parietal hypometabolism on [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and abnormal CSF tau). We aim to compare the accuracy of these biomarkers, individually and in combination, in predicting AD among mild cognitive impairment (MCI) patients. Methods: In 73 MCI patients, followed to ascertain AD progression, markers were measured. Sensitivity and specificity, positive (LR1) and negative (LR2) likelihood ratios, and crude and adjusted hazard ratios were computed. Results: Twenty-nine MCI patients progressed and 44 remained stable. Positivity to any marker achieved the lowest LR2 (0.0), whereas the combination Ab42 plus FDG-PETachieved the highest LR1 (6.45). In a survival analysis, positivity to any marker was associated with 100% conversion rate, whereas negativity to all markers was associated with 100% stability. Discussion: The best criteria combined amyloidosis and neurodegeneration biomarkers, whereas the individual biomarker with the best performance was FDG-PET. 2015 The Alzheimer’s Association. Published by Elsevier Inc. All rights reserved.

Featured Article Prediction of AD dementia by biomarkers following the NIA-AA and IWG diagnostic criteria in MCI patients from three European memory clinics

36 died while demented. These groups were compared on age, gender, and education adjusted trajectories by cognitive domain using linear mixed models (LMMs) adjusted for confounders. Neuropathological findings were compared in a cross sectional manner. Results:While the two groups had comparable cognitive test scores at enrolment and the time of the first declaration of a complaint, the demented group has steeper slopes of decline in episodic memory and naming but not fluency or sequencing. Autopsy results show the latter group has more severe Alzheimer pathology and a higher proportion of subjects with hippocampal sclerosis whereas a more complex relationship was observed in the cerebrovascular pathology subtypes in each group. Conclusions: While memory complaints are common among the elderly not all progress to dementia. This study shows that better biomarkers are needed to determine whether a complaint will lead to a dementia if this is used as enrolment criteria in future prevention trials.

Consensus guidelines to perform lumbar puncture for CSF sampling in patients with neurological conditions.

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Featured Article Prediction of AD dementia by biomarkers following the NIA-AA and IWG diagnostic criteria in MCI patients from three European memory clinics

Consensus guidelines to perform lumbar puncture for CSF sampling in patients with neurological conditions.