LRP10 and α-synuclein transmission in Lewy body diseases.

Autosomal dominant variants in LRP10 have been identified in patients with Lewy body diseases (LBDs), including Parkinson's disease (PD), Parkinson's disease-dementia (PDD), and dementia with Lewy bodies (DLB). Nevertheless, there is little mechanistic insight into the role of LRP10 in disease pathogenesis. In the brains of control individuals, LRP10 is typically expressed in non-neuronal cells like astrocytes and neurovasculature, but in idiopathic and genetic cases of PD, PDD, and DLB, it is also present in α-synuclein-positive neuronal Lewy bodies.

What's in a score: A longitudinal investigation of scores based on item response theory and classical test theory for the Amsterdam Instrumental Activities of Daily Living Questionnaire in cognitively normal and impaired older adults.

Objective: We aimed to investigate whether item response theory (IRT)-based scoring allows for a more accurate, responsive, and less biased assessment of everyday functioning than traditional classical test theory (CTT)-based scoring, as measured with the Amsterdam Instrumental Activities of Daily Living Questionnaire.

Method: In this longitudinal multicenter study including cognitively normal and impaired individuals, we examined IRT-based and CTT-based score distributions and differences between diagnostic groups using linear regressions, and investigated scale attenuation. We compared change over time between scoring methods using linear mixed models with random intercepts and slopes for time.

Effects of the DICE Method to Improve Timely Recognition and Treatment of Neuropsychiatric Symptoms in Early Alzheimer's Disease at the Memory Clinic: The BEAT-IT Study.

Background: Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD) and are associated with negative outcomes. However, NPS are currently underrecognized at the memory clinic and non-pharmacological interventions are scarcely implemented.

Objective: To evaluate the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) method™ to improve the care for NPS in AD at the memory clinic.

Biweekly fluctuations of neuropsychiatric symptoms according to the Neuropsychiatric Inventory: Erratic symptoms or scores?

Objectives: This study investigates the stability of neuropsychiatric symptoms (NPS) assessed biweekly using the Neuropsychiatric Inventory (NPI) in a memory clinic population during a 6 week period.

Methods: Twenty-three spousal caregivers (mean [SD] age = 69.7 [8.

Anterior insular network disconnection and cognitive impairment in Parkinson's disease.

Background: The insula is a central brain hub involved in cognition and affected in Parkinson's disease (PD). The aim of this study was to assess functional connectivity (FC) and betweenness centrality (BC) of insular sub-regions and their relationship with cognitive impairment in PD.

Methods: Whole-brain 3D-T1, resting-state functional MRI and a battery of cognitive tests (CAMCOG) were included for 53 PD patients and 15 controls.

Clinical and Pathological Phenotypes of LRP10 Variant Carriers with Dementia.

Background: Rare variants in the low-density lipoprotein receptor related protein 10 gene (LRP10) have recently been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB).

Objective: We searched for LRP10 variants in a new series of brain donors with dementia and Lewy pathology (LP) at autopsy, or dementia and parkinsonism without LP but with various other neurodegenerative pathologies.

Methods: Sanger sequencing of LRP10 was performed in 233 donors collected by the Netherlands Brain Bank.

Identification of novel cerebrospinal fluid biomarker candidates for dementia with Lewy bodies: a proteomic approach.

Background: Diagnosis of dementia with Lewy bodies (DLB) is challenging, largely due to a lack of diagnostic tools. Cerebrospinal fluid (CSF) biomarkers have been proven useful in Alzheimer's disease (AD) diagnosis. Here, we aimed to identify novel CSF biomarkers for DLB using a high-throughput proteomic approach.

LRP10 variants in progressive supranuclear palsy.

The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort.

The Cognitive-Functional Composite is sensitive to clinical progression in early dementia: Longitudinal findings from the Catch-Cog study cohort.

Introduction: In an attempt to capture clinically meaningful cognitive decline in early dementia, we developed the Cognitive-Functional Composite (CFC). We investigated the CFC's sensitivity to decline in comparison to traditional clinical endpoints.

Methods: This longitudinal construct validation study included 148 participants with subjective cognitive decline, mild cognitive impairment, or mild dementia.

Family History is Associated with Phenotype in Dementia with Lewy Bodies.

It is currently unknown whether patients with dementia with Lewy bodies (DLB) with relatives with dementia or Parkinson's disease (familial DLB patients) have a different phenotype than sporadic DLB patients. In this study, we aimed to examine disease onset, rate of cognitive decline, survival, and Alzheimer's disease (AD) biomarkers in patients with familial DLB (n = 154) and sporadic DLB (n = 137), using linear mixed model analysis and Cox regression analysis, among others. Familial patients had a shorter survival (8.

Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study.

Background: Neurofilament light chain (NfL) is a promising blood biomarker in genetic frontotemporal dementia, with elevated concentrations in symptomatic carriers of mutations in GRN, C9orf72, and MAPT. A better understanding of NfL dynamics is essential for upcoming therapeutic trials. We aimed to study longitudinal NfL trajectories in people with presymptomatic and symptomatic genetic frontotemporal dementia.

Normative brain volumetry derived from different reference populations: impact on single-subject diagnostic assessment in dementia.

Brain imaging data are increasingly made publicly accessible, and volumetric imaging measures derived from population-based cohorts may serve as normative data for individual patient diagnostic assessment. Yet, these normative cohorts are usually not a perfect reflection of a patient's base population, nor are imaging parameters such as field strength or scanner type similar. In this proof of principle study, we assessed differences between reference curves of subcortical structure volumes of normal controls derived from two population-based studies and a case-control study.

Assessment of Visual Association Memory in Low-Educated, Non-Western Immigrants with the Modified Visual Association Test.

Background: Neuropsychological tests are influenced by culture, language, level of education, and literacy, but there are few cognitive tests of which the applicability in ethnic minority populations has been studied.

Objectives: The aim of this study was to assess the reliability and validity of the Visual Association Test (VAT), a test of visual association memory, in a non-Western, low-educated memory clinic population. Additionally, a modified version of the VAT using colored photographs instead of line drawings was studied (mVAT).

Trajectories and Determinants of Quality of Life in Dementia with Lewy Bodies and Alzheimer's Disease.

Background: Quality of Life (QoL) is an important outcome measure in dementia, particularly in the context of interventions. Research investigating longitudinal QoL in dementia with Lewy bodies (DLB) is currently lacking.

Objective: To investigate determinants and trajectories of QoL in DLB compared to Alzheimer's disease (AD) and controls.

LRP10 variants in Parkinson's disease and dementia with Lewy bodies in the South-West of the Netherlands.

Objective: To analyse LRP10 variants, recently associated with the development of Parkinson's disease (PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), in a series of patients and controls from the South-West of the Netherlands (Walcheren).

Methods: A series of 130 patients with PD, PDD or DLB were clinically examined, and a structured questionnaire used to collect information about family history of PD and dementia. The entire LRP10 coding region was sequenced by Sanger methods in all patients, and haplotype analysis was performed for one recurrent LRP10 variant.

Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia.

Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD.

Early recognition and treatment of neuropsychiatric symptoms to improve quality of life in early Alzheimer's disease: protocol of the BEAT-IT study.

Background: Neuropsychiatric symptoms (NPS) are very common in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and are associated with various disadvantageous clinical outcomes including a negative impact on quality of life, caregiver burden, and accelerated disease progression. Despite growing evidence of the efficacy of (non)pharmacological interventions to reduce these symptoms, NPS remain underrecognized and undertreated in memory clinics. The BEhavioural symptoms in Alzheimer's disease Towards early Identification and Treatment (BEAT-IT) study is developed to (1) investigate the neurobiological etiology of NPS in AD and (2) study the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) approach to structure and standardize the current care of NPS in AD.

Assessing cognition and daily function in early dementia using the cognitive-functional composite: findings from the Catch-Cog study cohort.

Background: The cognitive-functional composite (CFC) was designed to improve the measurement of clinically relevant changes in predementia and early dementia stages. We have previously demonstrated its good test-retest reliability and feasibility of use. The current study aimed to evaluate several quality aspects of the CFC, including construct validity, clinical relevance, and suitability for the target population.

Dementia With Lewy Bodies: A Clinicopathologic Series of False-positive Cases.

Diagnosing dementia with Lewy bodies (DLB) is challenging as symptoms are heterogenous and not specific to the disease. Here we present a clinicopathologic series of false-positive DLB cases. Patients were enrolled retrospectively from the Netherlands Brain Bank when they met the clinical criteria of probable DLB, but with a pathologic diagnosis other than DLB or Parkinson's disease dementia.

Differential insular cortex sub-regional atrophy in neurodegenerative diseases: a systematic review and meta-analysis.

The insular cortex is proposed to function as a central brain hub characterized by wide-spread connections and diverse functional roles. As a result, its centrality in the brain confers high metabolic demands predisposing it to dysfunction in disease. However, the functional profile and vulnerability to degeneration varies across the insular sub-regions.

The Pentagon Copying Test and the Clock Drawing Test as Prognostic Markers in Dementia with Lewy Bodies.

Aims: To determine whether the pentagon copying test (PCT) and the clock drawing test (CDT) are associated with nursing home admission or survival in dementia with Lewy bodies (DLB).

Methods: The PCT and/or the CDT were retrospectively collected from 103 clinically diagnosed probable DLB patients at a university medical center and general hospital. Patients with high versus low scores on these tests were compared.

LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study.

Background: Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders.

Methods: Our study was done in three stages.

A novel cognitive-functional composite measure to detect changes in early Alzheimer's disease: Test-retest reliability and feasibility.

Introduction: To improve the detection of changes in Alzheimer's disease (AD), we designed the cognitive-functional composite (CFC). As a first validation step, we investigated its test-retest reliability and feasibility of use.

Methods: We performed a test-retest study with 2-3 weeks between assessments, including patients with mild cognitive impairment (MCI) or mild AD dementia and cognitively healthy participants.

Clinical value of neurofilament and phospho-tau/tau ratio in the frontotemporal dementia spectrum.

Objective: To examine the clinical value of neurofilament light chain (NfL) and the phospho-tau/total tau ratio (p/t-tau) across the entire frontotemporal dementia (FTD) spectrum in a large, well-defined cohort.

Methods: CSF NfL and p/t-tau levels were studied in 361 patients with FTD: 179 behavioral variant FTD, 17 FTD with motor neuron disease (FTD-MND), 36 semantic variant primary progressive aphasia (PPA), 19 nonfluent variant PPA, 4 logopenic variant PPA (lvPPA), 42 corticobasal syndrome, and 64 progressive supranuclear palsy. Forty-five cognitively healthy controls were also included.

A composite measure of cognitive and functional progression in Alzheimer's disease: Design of the Capturing Changes in Cognition study.

Introduction: Cognitive testing in Alzheimer's disease (AD) is essential for establishing diagnosis, monitoring progression, and evaluating treatments. Assessments should ideally be brief, reliable, valid, and reflect clinically meaningful changes. There is a lack of instruments that meet all these criteria.