Biomarkers.

Background: As global populations age, both Alzheimer's Disease (AD) and diabetes mellitus (DM) incidence are projected to increase tremendously over the coming 20-30 years. Studies have found that having DM is associated with increased risk of developing AD dementia. It remains unclear however whether DM impacts underlying AD pathology.

Alzheimer's disease-specific transcriptomic and epigenomic changes in the tryptophan catabolic pathway.

Background: Neurodegenerative disorders, including Alzheimer's disease (AD), have been linked to alterations in tryptophan (TRP) metabolism. However, no studies to date have systematically explored changes in the TRP pathway at both transcriptional and epigenetic levels. This study aimed to investigate transcriptomic, DNA methylomic (5mC) and hydroxymethylomic (5hmC) changes within genes involved in the TRP and nicotinamide adenine dinucleotide (NAD) pathways in AD, using three independent cohorts.

Linking human cerebral and ocular waste clearance: Insights from tear fluid and ultra-high field MRI.

Impaired cerebral waste clearance (i.e., glymphatics) is evident in aging and neurodegenerative disorders, such as Alzheimer's disease, where an impaired waste clearance system could be related to the accumulation of pathological proteins (e.

Small vessel disease burden and functional brain connectivity in mild cognitive impairment.

Background: The role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing.

Relation of the kynurenine pathway with normal age: A systematic review.

Background: The kynurenine pathway (KP) is gaining more attention as a common pathway involved in age-related conditions. However, which changes in the KP occur due to normal ageing is still largely unclear. The aim of this systematic review was to summarize the available evidence for associations of KP metabolites with age.

The role of the kynurenine pathway in cognitive functioning after stroke: A prospective clinical study.

Background: The kynurenine pathway is the main metabolic pathway of tryptophan degradation and has been associated with stroke and impaired cognitive functioning, but studies on its role in post-stroke cognitive impairment (PSCI) are scarce. We aimed to investigate associations between metabolites of the kynurenine pathway at baseline and post-stroke cognitive functioning over time.

Methods: Baseline plasma kynurenines were quantified in 198 stroke patients aged 65.

Tear biomarkers for Alzheimer's disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study.

Background: Alzheimer's disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers.

Determinants of quality of life in family caregivers in MCI: a comparison with mild dementia.

Objectives: The aim of the current study was to investigate the health-related quality of life (HRQol) of the family caregiver in MCI, explore possible determinants and study possible differences with mild dementia.

Methods: This secondary data analysis included 145 persons with MCI and 154 persons with dementia and their family caregivers from two Dutch cohort studies. HRQoL was measured with the VAS of the EuroQol-5D-3L version.

Correlations between kynurenines in plasma and CSF, and their relation to markers of Alzheimer's disease pathology.

Introduction: Altered levels of kynurenines in blood and cerebrospinal fluid (CSF) have been reported in Alzheimer's disease (AD). However, it is still largely unknown whether peripheral kynurenine concentrations resemble those found in CSF and how they relate to AD pathology. We therefore studied correlations between kynurenines in plasma and CSF and their associations with CSF amyloid-beta (Aβ) and tau levels in patients from the memory clinic spanning the whole cognitive spectrum.

Novel developments in non-contrast enhanced MRI of the perivascular clearance system: What are the possibilities for Alzheimer's disease research?

The cerebral waste clearance system (i.e, glymphatic or intramural periarterial drainage) works through a network of perivascular spaces (PVS). Dysfunction of this system likely contributes to aggregation of Amyloid-β and subsequent toxic plaques in Alzheimer's disease (AD).

A comparison of two approaches for modeling dementia progression in a changing patient context.

Objectives: To explain the heterogeneity in dementia disease trajectory, we studied the influence of changing patient characteristics on disease course by comparing the association of dementia progression with baseline comorbidity and frailty, and with time-varying comorbidity and frailty.

Methods: We used individual growth models to study baseline and time-varying associations in newly diagnosed dementia patients (n = 331) followed for 3 years. We measured cognition using the Mini-Mental State Examination (MMSE), daily functioning using the Disability Assessment for Dementia (DAD), frailty using the Fried criteria and comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G).

The Role of Vascular Risk Factors in Biomarker-Based AT(N) Groups: A German-Dutch Memory Clinic Study.

Background: The relation between vascular risk factors (VRFs) and Alzheimer's disease (AD) is important due to possible pathophysiological association.

Objective: To assess the prevalence of VRFs in biomarker-based AT(N) groups and the associations between VRFs, AD cerebrospinal fluid (CSF) biomarkers, brain magnetic resonance imaging (MRI), and cognition in clinical context.

Methods: We included patients from two memory clinics in University Hospital Aachen (Germany) and Maastricht University Medical Centre (The Netherlands).

Association of tear fluid amyloid and tau levels with disease severity and neurodegeneration.

There has been increasing interest in finding non-invasive biomarkers for neurodegenerative diseases such as Alzheimer's disease (AD). This observational study investigated AD-specific biomarkers in tear fluid. Tear fluid was collected from a total of 65 subjects, including 23 patients with subjective cognitive decline (SCD), 22 patients with mild cognitive impairment (MCI), 11 dementia patients and 9 healthy controls (HC).

Associations between plasma kynurenines and cognitive function in individuals with normal glucose metabolism, prediabetes and type 2 diabetes: the Maastricht Study.

Aims/hypothesis: Studies investigating associations between kynurenines and cognitive function have generally been small, restricted to clinical samples or have found inconsistent results, and associations in the general adult population, and in individuals with type 2 diabetes in particular, are not clear. Therefore, the aim of the present study was to investigate cross-sectional associations between plasma kynurenines and cognitive function in a cohort of middle-aged participants with normal glucose metabolism, prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes.

Methods: Plasma kynurenines were quantified in 2358 participants aged 61 ± 8 years.

Serum and cerebrospinal fluid Neutrophil gelatinase-associated lipocalin (NGAL) levels as biomarkers for the conversion from mild cognitive impairment to Alzheimer's disease dementia.

Neutrophil gelatinase-associated lipocalin (NGAL) is an acute phase protein that has been reported as a potential marker for pre-dementia stages of Alzheimer's disease (AD). Longitudinal studies for its association with the conversion of mild cognitive impairment to AD is still lacking. This study included n = 268 study participants with subjective cognitive decline (SCD) (n=82), mild cognitive impairment (MCI) (n=98) and AD dementia (n=88) at baseline and two-year follow-up clinical assessments.

Associations of increased interstitial fluid with vascular and neurodegenerative abnormalities in a memory clinic sample.

The vascular and neurodegenerative processes related to clinical dementia cause cell loss which induces, amongst others, an increase in interstitial fluid (ISF). We assessed microvascular, parenchymal integrity, and a proxy of ISF volume alterations with intravoxel incoherent motion imaging in 21 healthy controls and 53 memory clinic patients - mainly affected by neurodegeneration (mild cognitive impairment, Alzheimer's disease dementia), vascular pathology (vascular cognitive impairment), and presumed to be without significant pathology (subjective cognitive decline). The microstructural components were quantified with spectral analysis using a non-negative least squares method.

Cross-cohort generalizability of deep and conventional machine learning for MRI-based diagnosis and prediction of Alzheimer's disease.

This work validates the generalizability of MRI-based classification of Alzheimer's disease (AD) patients and controls (CN) to an external data set and to the task of prediction of conversion to AD in individuals with mild cognitive impairment (MCI). We used a conventional support vector machine (SVM) and a deep convolutional neural network (CNN) approach based on structural MRI scans that underwent either minimal pre-processing or more extensive pre-processing into modulated gray matter (GM) maps. Classifiers were optimized and evaluated using cross-validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI; 334 AD, 520 CN).

An Exploratory Study of the Development and Pilot Testing of an Interactive Visual Tool of Neuropsychological Test Results in Memory Clinics.

Background: Neuropsychological feedback is an important part of the neuropsychological assessment process. However, patients have difficulties remembering this information.

Objective: The aim of this study was to develop a web-based visual tool to improve the understanding of neuropsychological results, information retention, and psychologist-patient communication.

Obtaining EQ-5D-5L utilities from the disease specific quality of life Alzheimer's disease scale: development and results from a mapping study.

Purpose: The Quality of Life Alzheimer's Disease Scale (QoL-AD) is commonly used to assess disease specific health-related quality of life (HRQoL) as rated by patients and their carers. For cost-effectiveness analyses, utilities based on the EQ-5D are often required. We report a new mapping algorithm to obtain EQ-5D indices when only QoL-AD data are available.

Alzheimer's disease biomarkers as predictors of trajectories of depression and apathy in cognitively normal individuals, mild cognitive impairment, and Alzheimer's disease dementia.

Objectives: To examine trajectories of depression and apathy over a 5-year follow-up period in (prodromal) Alzheimer's disease (AD), and to relate these trajectories to AD biomarkers.

Methods: The trajectories of depression and apathy (measured with the Neuropsychiatric Inventory or its questionnaire) were separately modeled using growth mixture models for two cohorts (National Alzheimer's Coordinating Center, NACC, n = 22 760 and Alzheimer's Disease Neuroimaging Initiative, ADNI, n = 1 733). The trajectories in ADNI were associated with baseline CSF AD biomarkers (Aβ t-tau, and p-tau) using bias-corrected multinomial logistic regression.

Neuropsychological assessment and diagnostic disclosure at a memory clinic: A qualitative study of the experiences of patients and their family members.

Objective: The aim of this study was to gain insight into the experiences of patients and their family members regarding a neuropsychological assessment (NPA) and the diagnostic disclosure given by the medical specialist (psychiatrist, geriatrician, or their residents) at the memory clinic (MC).

Method: Patients with and without a cognitive impairment and their family members were recruited from three Dutch MCs. Four focus groups with 14 patients and 13 family members were analyzed using both inductive and deductive content analysis.

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

Objective: 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 Aβ, t-tau, p-tau, and hippocampal volume were associated with neuropsychiatric symptoms (measured with the Neuropsychiatric Inventory) using multiple logistic regression analyses.