Long-term Course of Alzheimer Disease in Patients Treated According to the Dutch Dementia Guideline at a Memory Clinic: A "Real-Life" Study.

Introduction: There is little knowledge of the long-term course of Alzheimer disease (AD) in light of current pharmacological and nonpharmacological interventions provided in a "real-life" setting.

Methods: The Frisian Alzheimer's Disease Cohort study is a "real-life" study of the course of AD in patients (n=576) treated with pharmacological (ie, cholinesterase inhibitors) and nonpharmacological (ie, case management, respite care) interventions. Disease course was described by changes in cognition (Mini Mental State Examination, clock-drawing test) and number of types of professional care applying a repeated-measures analysis using a marginal model (population-based average model).

The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer's disease.

Introduction: Depression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies between both neurodegenerative conditions, given the lack of an efficient pharmacological treatment until present.

Overdiagnosing Vascular Dementia using Structural Brain Imaging for Dementia Work-Up.

Hypothesizing that non-significant cerebrovascular lesions on structural brain imaging lead to overdiagnosis of a vascular etiology of dementia as compared to autopsy-confirmed diagnosis, we set up a study including 71 patients with autopsy-confirmed diagnoses. Forty-two patients in the population (59%) appeared to have definite Alzheimer's disease (AD), whereas 29 (41%) had a non-AD dementia form. The panel clinically diagnosed possible or probable vascular dementia (VaD) in 27 (38%) patients, whereas only five (19%) patients (p = 0.

Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis.

Background: Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis.

Objective: To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P).

Serum NGAL is Associated with Distinct Plasma Amyloid-β Peptides According to the Clinical Diagnosis of Dementia in Down Syndrome.

Background: The majority of people with Down syndrome (DS) develop dementia due to Alzheimer's disease (AD). Neuropathological features are characterized by an accumulation of amyloid-β (Aβ) deposits and the presence of an activated immune response. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a newly identified (neuro)inflammatory constituent in AD.

Acute modulation of the cholinergic system in the mouse brain detected by pharmacological resting-state functional MRI.

Introduction: The cholinergic system is involved in learning and memory and is affected in neurodegenerative disorders such as Alzheimer's disease. The possibility of non-invasively detecting alterations of neurotransmitter systems in the mouse brain would greatly improve early diagnosis and treatment strategies. The hypothesis of this study is that acute modulation of the cholinergic system might be reflected as altered functional connectivity (FC) and can be measured using pharmacological resting-state functional MRI (rsfMRI).

Association of cerebrospinal fluid prion protein levels and the distinction between Alzheimer disease and Creutzfeldt-Jakob disease.

Importance: Although typical forms of Alzheimer disease (AD) and Creutzfeldt-Jakob disease (CJD) are clinically distinguishable, atypical AD phenotypes may pose a diagnostic challenge. The major biological diagnostic biomarker for identifying CJD, 14-3-3 protein in cerebrospinal fluid (CSF), unfortunately lacks specificity when confronting a rapid dementia presentation.

Objective: To assess the relevance of total CSF prion protein (t-PrP) levels in the differential biological diagnosis between atypical AD phenotypes and CJD.

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

Background: The Parelsnoer Institute 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. The objective of this paper is to describe the design and methods of the Pearl Neurodegenerative Diseases, as well as baseline descriptive variables, including their biomarker profile.

Impaired gait pattern as a sensitive tool to assess hypoxic brain damage in a novel mouse model of atherosclerotic plaque rupture.

Apolipoprotein E deficient (ApoE(-/-)) mice with a heterozygous mutation in the fibrillin-1 gene (Fbn1(C1039G+/-)) show spontaneous atherosclerotic plaque ruptures, disturbances in cerebral flow and sudden death when fed a Western-type diet (WD). The present study focused on motor coordination and spatial learning of ApoE(-/-) Fbn1(C1039G+/-) mice on WD for 20 weeks (n=21). ApoE(-/-) mice on WD (n=24) and ApoE(-/-) Fbn1(C1039G+/-) mice on normal diet (ND, n=21) served as controls.

Diagnostic value of MIBG cardiac scintigraphy for differential dementia diagnosis.

Objective: Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy has shown the potential to discriminate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). However, these studies did not reflect clinical practice, as patients with ischemic heart disease, heart failure, diabetes mellitus, arterial hypertension, and hyperlipidemia and patients treated with antidepressants like trazodone were excluded.

Methods: This study aimed to evaluate the use of MIBG cardiac scintigraphy to diagnose DLB in clinical practice.

Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease.

Objectives: The objective of this study is to clarify the role of (G4C2)n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson's Disease (GEO-PD) cohort.

Methods: C9orf72 (G4C2)n repeats were assessed in a GEO-PD cohort of 7,494 patients diagnosed with PD and 5,886 neurologically healthy control individuals ascertained in Europe, Asia, North America, and Australia.

Results: A pathogenic (G4C2)n>60 expansion was detected in only 4 patients with PD (4/7,232; 0.

Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer's dementia.

Objectives: The aim of this study is to determine the prevalence of psychosis in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia, and to characterize the associated behavioral and psychological signs and symptoms of dementia (BPSD).

Method: A cross-sectional analysis of baseline data from an ongoing, prospective, longitudinal study on BPSD was performed, including 270 MCI and 402 AD patients. BPSD assessment was performed through Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI) and Cornell Scale for Depression in Dementia (CSDD).

Subcortical vascular cognitive impairment, no dementia: EEG global power independently predicts vascular impairment and brain symmetry index reflects severity of cognitive decline.

Background And Purpose: Vascular cognitive impairment, no dementia (vCIND) is a prevalent and potentially preventable disorder. Clinical presentation of the small-vessel subcortical subtype may be insidious, and differential difficulties can arise with mild cognitive impairment. We investigated EEG parameters in subcortical vCIND in comparison with amnestic multidomain mild cognitive impairment to determine the additional diagnostic value of quantitative EEG in this setting.

Validation assessment of risk tools to predict outcome after thrombolytic therapy for acute ischemic stroke.

Objective: We evaluated the reliability of eight clinical prediction models for symptomatic intracerebral hemorrhage (sICH) and long-term functional outcome in stroke patients treated with thrombolytics according to clinical practice.

Methods: In a cohort of 169 patients, 60 patients (35.5%) received IV rtPA according to the European license criteria.

Serum MHPG strongly predicts conversion to Alzheimer's disease in behaviorally characterized subjects with Down syndrome.

Background: Down syndrome (DS) is the most prevalent genetic cause of intellectual disability. Early-onset Alzheimer's disease (AD) frequently develops in DS and is characterized by progressive memory loss and behavioral and psychological signs and symptoms of dementia (BPSD). Predicting and monitoring the progression of AD in DS is necessary to enable adaptive caretaking.

Sperm-associated antigen 16 is a novel target of the humoral autoimmune response in multiple sclerosis.

We have previously identified eight novel autoantibody targets in the cerebrospinal fluid of multiple sclerosis (MS) patients, including sperm-associated Ag 16 (SPAG16). In the current study, we further investigated the autoantibody response against SPAG16-a protein with unknown function in the CNS-and its expression in MS pathology. Using isoelectric focusing, we detected SPAG16-specific oligoclonal bands in the cerebrospinal fluid of 5 of 23 MS patients (22%).

Depression in mild cognitive impairment is associated with progression to Alzheimer's disease: a longitudinal study.

Background: Behavioral and psychological signs and symptoms of dementia (BPSD) belong to the core symptoms of dementia and are also common in mild cognitive impairment (MCI).

Objective: This study would like to contribute to the understanding of the prognostic role of BPSD in MCI for the progression to dementia due to Alzheimer's disease (AD).

Methods: Data were generated through an ongoing prospective longitudinal study on BPSD.

Monoaminergic neurotransmitter alterations in postmortem brain regions of depressed and aggressive patients with Alzheimer's disease.

Depression and aggression in Alzheimer's disease (AD) are 2 of the most severe and prominent neuropsychiatric symptoms (NPS). Altered monoaminergic neurotransmitter system functioning has been implicated in both NPS, although their neurochemical etiology remains to be elucidated. Left frozen hemispheres of 40 neuropathologically confirmed AD patients were regionally dissected.

Agitation-associated behavioral symptoms in mild cognitive impairment and Alzheimer's dementia.

Objectives: The aim of this study is to determine the prevalence of agitation in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia (AD), and to characterize the associated behavioral symptoms.

Method: A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms was performed, including 268 MCI and 393 AD patients. Behavioral assessment was performed through Middelheim Frontality Score (MFS), Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia (CSDD).

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration.

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899).

Epigenetics: the neglected key to minimize learning and memory deficits in Down syndrome.

Down syndrome (DS) is the most common genetic intellectual disability, caused by the triplication of the human chromosome 21 (HSA21). Although this would theoretically lead to a 1.5 fold increase in gene transcription, transcript levels of many genes significantly deviate.

Novel and sensitive reversed-phase high-pressure liquid chromatography method with electrochemical detection for the simultaneous and fast determination of eight biogenic amines and metabolites in human brain tissue.

A fast and simple RP-HPLC method with electrochemical detection (ECD) and ion pair chromatography was developed, optimized and validated in order to simultaneously determine eight different biogenic amines and metabolites in post-mortem human brain tissue in a single-run analytical approach. The compounds of interest are the indolamine serotonin (5-hydroxytryptamine, 5-HT), the catecholamines dopamine (DA) and (nor)epinephrine ((N)E), as well as their respective metabolites, i.e.

Nutritional interventions in community-dwelling Alzheimer patients with (risk of) undernutrition: a systematic review.

Background: Weight loss and undernutrition are common in patients with Alzheimer's disease (AD) and associated with negative health outcomes. In the current guidelines on diagnosis and treatment of AD, no recommendations for treatment of (risk of) undernutrition in community-dwelling AD patients are given.

Methods: We conducted a systematic review on the effect of nutritional interventions in community-dwelling AD patients with (risk of) undernutrition, according to the methods outlined by the Cochrane Collaboration.