Abstract Background The concept of mild cognitive impairment (MCI) was developed as a research to capture a group of patients with objectively measurable cognitive impairment not fulfilling the criteria for dementia but has since diffused into clinical practice in many centers. The objective of the present survey was to assess practices with regards to diagnostic procedure and disclosure including biomarker counselling and management in patients with MCI. Methods The present study was designed as an online survey of medical doctors working in European Alzheimer Disease Centers (EADC). Results A total of 34 center coordinating doctors out of 41 (80.9 %) and 110 out of 213 (50.6 %) individual doctors responded to the survey. Almost all respondents had access to MRI (98.2%; n=108) and CSF sampling (91.8%; n=101), whereas fewer had access to 18F‐FDG‐PET (74.5%; n=82) and amyloid PET (50.9%; n=56). Most, but not all respondents, always or usually discussed the decision to order biomarkers with patients with MCI (85.7%; n=90) and dementia (81.1 %; n=86). Nearly half (49.5 % n=54) of respondents found that the diagnosis of MCI was meaningful to a great extent, whereas this was 75.5 % (n=84) for dementia (z=3.77; p=0.0002). Almost all respondents reported always or usually following up MCI (95.2%; n=100) and dementia patients (90.48%; n=95). Half (50.5%; n=53) of respondents reported following MCI patients for 5 or more years and for dementia 45.3% (n=48). Conclusion We found that biomarkers are widely used in patients with MCI, but that not all patients receive adequate pre and post biomarker counselling. For a considerable proportion of practices, we found considerable variability across centers. This may indicate that clinicians lack guidance on issues related to diagnostic disclosure including biomarker sampling.
Biobanks are important resources for biomarker discovery and assay development. Biomarkers for Alzheimer's and Parkinson's Disease (BIOMARKAPD) is a European multicenter study, funded by the EU Joint Programme - Neurodegenerative Disease Research (JPND), that aims to improve the clinical use of body fluid markers for the diagnosis and prognosis of Alzheimer's disease (AD) and Parkinson's disease (PD). The objective was to standardize the assessment of existing assays and to validate novel fluid biomarkers for AD and PD. To support the validation of novel biomarkers and assays, a central and a virtual biobank for body fluids and associated data from subjects with neurodegenerative diseases have been established. In the central biobank, cerebrospinal fluid (CSF) and blood samples were collected according to the BIOMARKAPD standardized preanalytical procedures (SOP) and stored at Integrated BioBank of Luxembourg (IBBL). The virtual biobank provides an overview of available CSF, plasma, serum, and DNA samples at each site. Currently, at the central biobank of BIOMARKAPD samples are available from over 400 subjects with normal cognition, mild cognitive impairment (MCI), AD, frontotemporal dementia (FTD), vascular dementia (VaD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), PD, PD with dementia, and dementia with Lewy bodies (DLB). The virtual biobank contains information on over 8600 subjects with varying diagnoses from 21 local biobanks. A website has been launched to enable sample requests from the central biobank and virtual biobank.
DYRK1A is implicated in mental retardation and Alzheimer's disease (AD) dementia of Down syndrome (DS) individuals. The protein is associated with cytoskeleton and altered expression has been shown to impair the cytoskeletal network via dosage effect.Our original observations of marked reduction of cytoskeletal proteins associated with DYRK1A in brains and lymphoblastoid cell lines from DS and AD prompted an investigation whether cytoskeleton abnormalities could potentially be used as biomarkers of AD.Our assay relied on quantification of co-immunoprecipitated cytoskeletal proteins with DYRK1A (co-IP assay) and analysis of the profile of G- and F-actin fractions obtained by high-speed centrifugations (spin-down assay).In co-IP assay, both DS and AD samples displayed reduced abundance of associated cytoskeletal proteins. In spin-down assay, G-actin fractions of controls displayed two closely spaced bands of actin in SDS-PAGE; while in AD and DS, only the upper band of the doublet was present. In both assays, alterations of actin cytoskeleton were present in DS, sporadic and familial AD cases, and in asymptomatic persons who later progressed to confirmed AD, but not in non-AD donors. In blind testing involving six AD and six controls, the above tests positively identified ten cases. Analysis of blood samples revealed the diversity of mild cognitive impairment (MCI) cases regarding the presence of the AD biomarker allowing distinction between likely prodromal AD and non-AD MCI cases.Both brain tissue and lymphocytes from DS and AD displayed similar semi-quantitative and qualitative alterations of actin cytoskeleton. Their specificity for AD-type dementia and the presence before clinical onset of the disease make them suitable biomarker candidates for early and definite diagnosis of AD. The presence of alterations in peripheral tissue points to systemic underlying mechanisms and suggests that early dysfunction of cytoskeleton may be a predisposing factor in the development of AD.
The prevalence of dementia is reaching epidemic proportions globally, but there remain a number of issues that prevent people with dementia, their families and caregivers, from taking control of their condition. In 2008, Alzheimer’s Disease International (ADI) launched a Global Alzheimer’s Disease Charter, which comprises six principles that underscore the urgency for a more ambitious approach to diagnosis, treatment and care. This review highlights some of the most important aspects and challenges of dementia diagnosis and treatment. These issues are reviewed in light of the six principles of the recent ADI Charter: promoting dementia awareness and understanding; respecting human rights; recognizing the key role of families and caregivers; providing access to health and social care; stressing the importance of optimal diagnosis and treatment; and preventing dementia through improvements in public health. The authors continue to hope that, one day, a cure for Alzheimer’s disease will be found. Meanwhile, healthcare professionals need to unite in rising to the challenge of managing all cases of dementia, using the tools available to us now to work toward improved patient care.
Summary Introduction. Mild Cognitive Impairment (MCI) is a syndrome defined as cognitive decline greater than expected for an individual's age and education level but that does not interfere notably with activities of daily life. The main criterion of MCI is memory impairment, and the most common method of diagnosis is Clinical Dementia Rating (CDR), scored in MCI as 0.5. Aim. We tried to estimate the utility of particular CDR's boxes scores in dementia risk estimation. Material and methods. Boxes of CDR (Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, Personal Care) baseline scores of 103 MCI persons (mean age 69.32; 80 females and 23 males) were analyzed in 2 groups: non demented - ND (n = 80; mean age 68.71; 56 females and 24 males), and demented - D (n = 23; mean age 71.82; 14 females and 9 males) after 3-year follow up. Results. Any significant difference weren't observed in Memory, Orientation and Judgment. The most differentiating were Community Affairs and Home & Hobbies, which were on favor in the non-demented group (p = 0.05). Conclusions. MCI subjects who later develop dementia differ from stable ones in functional domains of CDR at baseline evaluation. Analysis of particular CDR's boxes scores might be helpful in further patients' management.
