The Dutch Parelsnoer Institute - Neurodegenerative diseases; methods, design and baseline results

Background: The is a collaboration between 8 Dutch University Medical Centers in which clinical data and biomaterials from patients suffering from chronic diseases (so called "Pearls") are collected according to harmonized protocols. The Pearl Neurodegenerative Diseases focuses on the role of biomarkers in the early diagnosis, differential diagnosis and in monitoring the course of neurodegenerative diseases, in particular Alzheimer's disease. Methods: The Pearl Neurodegenerative Diseases is a 3-year follow-up study of patients referred to a memory clinic with cognitive complaints. At baseline, all patients are subjected to a standardized examination, including clinical data and biobank materials, e.g. blood samples, MRI and cerebrospinal fluid. At present, in total more than 1000 patients have been included, of which cerebrospinal fluid and DNA samples are available of 211 and 661 patients, respectively. First descriptives of a subsample of the data (n = 665) shows that patients are diagnosed with dementia (45%), mild cognitive impairment (31%), and subjective memory complaints (24%). Discussion: The Pearl Neurodegenerative Diseases is an ongoing large network collecting clinical data and biomaterials of more than 1000 patients with cognitive impairments. The project has started with data analyses of the baseline characteristics and biomarkers, which will be the starting point of future specific research questions that can be answered by this unique dataset

The copper catalysed reaction of sodium methoxide with aryl bromides. A mechanistic study leading to a facile synthesis of anisole derivatives

The copper catalysed reaction of unactivated aryl bromides with sodium methoxide has been investigated by studying a number of parameters (copper catalyst, cosolvent, concentration and relative ratio of the reactants, additives and aryl bromide substituents) which influence this reaction. The ipso-substitution reaction was found to proceed via an intimate electron transfer mechanism involving a cuprate-like intermediate, Na[Cu(OMe){2}]. A convenient synthesis of methyl aryl ethers from aryl bromides and concentrated sodium methoxide solutions in dimethyl formamide and methanol is presented. Also an attempt to extend this reaction to the use of chlorine derivatives was made

The predictive value of memory strategies for Alzheimer's disease in subjects with mild cognitive impairment

Subjects with Alzheimer's disease (AD) show impaired learning strategies. Whether impaired learning strategies are already present in subjects with prodromal AD remains unknown. The aim of the present study was to investigate the predictive accuracy of learning strategies for AD in subjects with Mild Cognitive Impairment (MCI). Subjects with MCI (n = 202) were selected from the Maastricht Memory Clinic. Subjects were reassessed over a period of 10 years. Fifty-five of the 202 subjects converted to AD. Learning strategies investigated were subjective organization and serial clustering. Lower scores of subjective organization were associated with a higher risk for AD (OR = 2.1, p =. 002). Serial clustering did not predict AD. Prodromal AD is characterized by a decreased use of effortful learning strategies. This finding may have implications for the early detection of AD in MCI subjects and for the development of cognitive training programs

The Association Between Biomarkers and Neuropsychiatric Symptoms Across the Alzheimer's Disease Spectrum

Objectiv(e): To investigate the relationship between Alzheimer's disease biomarkers and neuropsychiatric symptoms. Methods: Data from two large cohort studies, the Dutch Parelsnoer Institute - Neurodegenerative Diseases and the Alzheimer's Disease Neuroimaging Initiative was used, including subjects with subjective cognitive decline (N= 650), mild cognitive impairment (N = 887), and Alzheimer's disease dementia (N = 626). Cerebrospinal fluid (CSF) levels of A beta(42), t-tau, p-tau, and hippocampal volume were associated with neuropsychiatric symptoms (measured with the Neuropsychiatric Inventory) using multiple logistic regression analyses. The effect of the Mini-Mental State Examination (as proxy for cognitive functioning) on these relationships was assessed with mediation analyses. Results: Alzheimer's disease biomarkers were not associated with depression, agitation, irritability, and sleep disturbances. Lower levels of CSF A beta(42), higher levels of t- and p-tau were associated with presence of anxiety. Lower levels of CSF A beta(42) and smaller hippocampal volumes were associated with presence of apathy. All associations were mediated by cognitive functioning. Conclusion: The association between Alzheimer's disease pathology and anxiety and apathy is partly due to impairment in cognitive functioning.Neurological Motor Disorder