Clinical Manifestations.

Background: Alzheimer's disease (AD) causes increasing cognitive and functional impairments, and both are therefore important outcome measures for intervention studies. Cognition and everyday functioning are often used interchangeably, yet the extent of their relationship is still unclear. We therefore aim to assess the relationship between different cognitive domains and everyday functioning across the AD spectrum.

Clinical Manifestations.

Background: Verbal fluency, especially semantic fluency, may hold promise to predict clinical progression in the preclinical Alzheimer's disease (AD) stage, where patients show no objective cognitive impairment. We examined verbal fluency trajectories in amyloid-negative and amyloid-positive individuals with subjective cognitive decline (SCD), as well as whether baseline fluency characteristics (total scores and item-level) predicted progression to MCI or AD dementia.

Method: We retrospectively selected data of 471 Dutch individuals with SCD, with at least 1 follow-up fluency assessment, from the Amsterdam Dementia Cohort (Follow-up years = 4.

Clinical Manifestations.

Background: It remains unclear to what extent global cognition translates to everyday functioning, although this is essential to interpreting the clinical meaningfulness of cognitive deficits. Here, we investigate potential linking between the Mini-Mental State Examination (MMSE) and the proxy-based Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q).

Methods: Cross-sectional data from 1228 amyloid-positive participants (age = 64±7yrs; 51.

Charge of karyopherins and nuclear FG-Nups are key ingredients of nucleocytoplasmic transport.

The nuclear pore complex (NPC) is responsible for the selective transport of biomolecules in and out of the nucleus. This selective feature is achieved through intrinsically disordered proteins, FG-Nups, that are anchored to the inner wall of the NPC. Cargo smaller than approximately 5 nm can rapidly diffuse through the NPC whereas larger cargo is increasingly slowed down.

Survey among experts on the future role of tau-PET in clinical practice and trials.

Background: Recent advancements in Alzheimer's disease (AD) biomarker research and clinical trials prompt reflection on the value and consequently appropriate use of tau positron emission tomography (tau-PET) in the future.

Methods: We conducted an online survey among dementia and PET experts worldwide to investigate the anticipated future role of tau-PET in clinical practice and trials.

Results: Two hundred sixty-eight dementia experts, comprising 143 clinicians and 121 researchers, covering six continents participated.

Longitudinal Assessment of Retinal Microvasculature in Preclinical Alzheimer's Disease.

Purpose: To investigate if changes in vessel density (VD) and the foveal avascular zone (FAZ) occur in the preclinical phase of Alzheimer's disease (pAD) over time.

Methods: Optical coherence tomography angiography (OCTA) was used to image VD and FAZ at baseline and for a follow-up period of 2 years. Positron emission tomography (PET) was used to determine the amyloid beta (Aβ) status of participants.

C9orf72 polyPR interaction with the nuclear pore complex.

The C9orf72 gene associated with amyotrophic lateral sclerosis/frontotemporal dementia is translated to five dipeptide repeat proteins, among which poly-proline-arginine (PR) is the most toxic in cell and animal models, contributing to a variety of cellular defects. It has been proposed that polyPR disrupts nucleocytoplasmic transport (NCT) through several mechanisms including accumulation in the nuclear pore complex (NPC), accumulation in the nucleolus, and direct interactions with transport receptors. The NPC, which is the key regulator of transport between the cytoplasm and nucleus, plays a central role in these suggested mechanisms.

Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.

Background: Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups.

[Precision psychiatry and neuroimaging: Towards improved treatment success in psychosis].

Background: In the future, clinicians might use information about neurobiological processes, obtained through imaging techniques, to guide personalized prevention and intervention strategies for psychosis and related disorders. However, this requires more knowledge about these individuals’ brain function.

Aim: To advance the current knowledge on neurobiological processes in patients with schizophrenia spectrum disorders (SSD) and individuals at increased risk of these disorders.

The Early Perfusion Image Is Useful to Support the Visual Interpretation of Brain Amyloid-PET With 18F-Flutemetamol in Borderline Cases.

Purpose: Visual interpretation of brain amyloid-β (Aβ) PET can be difficult in individuals with borderline Aβ burden. Coregistration with individual MRI is recommended in these cases, which, however, is not always available. This study evaluated coregistration with the early perfusion frames acquired immediately after tracer injection to support the visual interpretation of the late Aβ-frames in PET with 18F-flutemetamol (FMM).

Digital remote assessment of speech acoustics in cognitively unimpaired adults: feasibility, reliability and associations with amyloid pathology.

Background: Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer's disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting.

Methods: Fifty cognitively unimpaired adults (Age 68 ± 6.

Amyloid PET disclosure in subjective cognitive decline: Patient experiences over time.

Introduction: We disclosed amyloid positron emission tomography (PET) results in individuals with subjective cognitive decline (SCD) and studied patient experiences and outcomes over a 6-month period.

Methods: Fifty-seven participants from the Subjective Cognitive Impairment Cohort (SCIENCe) (66 ± 8 years, 21 [37%] F, Mini-Mental State Examination 29 ± 1, 15 [26%] amyloid positive [A+]) completed questionnaires 1 week prior (T0), 1 day after (T1), and 6 months after amyloid PET disclosure (T2). Questionnaires addressed patient-reported experiences and outcomes.

The association of tobacco smoking and metabolite levels in the anterior cingulate cortex of first-episode psychosis patients: A case-control and 6-month follow-up H-MRS study.

Tobacco smoking is highly prevalent among patients with psychosis and associated with worse clinical outcomes. Neurometabolites, such as glutamate and choline, are both implicated in psychosis and tobacco smoking. However, the specific associations between smoking and neurometabolites have yet to be investigated in patients with psychosis.

Predicting Cognitive Decline in Amyloid-Positive Patients With Mild Cognitive Impairment or Mild Dementia.

Background And Objectives: Cognitive decline rates in Alzheimer disease (AD) vary greatly. Disease-modifying treatments may alter cognitive decline trajectories, rendering their prediction increasingly relevant. We aimed to construct clinically applicable prediction models of cognitive decline in amyloid-positive patients with mild cognitive impairment (MCI) or mild dementia.

Computerized decision support is an effective approach to select memory clinic patients for amyloid-PET.

Background: The use of amyloid-PET in dementia workup is upcoming. At the same time, amyloid-PET is costly and limitedly available. While the appropriate use criteria (AUC) aim for optimal use of amyloid-PET, their limited sensitivity hinders the translation to clinical practice.

C9orf72 polyPR directly binds to various nuclear transport components.

The disruption of nucleocytoplasmic transport (NCT) is an important mechanism in neurodegenerative diseases. In the case of C9orf72-ALS, trafficking of macromolecules through the nuclear pore complex (NPC) might get frustrated by the binding of C9orf72-translated arginine-containing dipeptide repeat proteins (R-DPRs) to the Kapβ family of nuclear transport receptors. Besides Kapβs, several other types of transport components have been linked to NCT impairments in R-DPR-expressed cells, but the molecular origin of these observations has not been clarified.

Neuromelanin-Sensitive MRI as Candidate Marker for Treatment Resistance in First-Episode Schizophrenia.

Objective: Markers for treatment resistance in schizophrenia are needed to reduce delays in effective treatment. Nigrostriatal hyperdopaminergic function plays a critical role in the pathology of schizophrenia, yet antipsychotic nonresponders do not show increased dopamine function. Neuromelanin-sensitive MRI (NM-MRI), which indirectly measures dopamine function in the substantia nigra, has potential as a noninvasive marker for nonresponders.

Validation of image-derived input function using a long axial field of view PET/CT scanner for two different tracers.

Background: Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings.

Methods: Eight [F]FDG and 10 [F]DPA-714 scans were acquired respectively during 70 and 60 min on the Vision Quadra PET/CT system.

Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol.

Introduction: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively.

Visual associative learning to detect early episodic memory deficits and distinguish Alzheimer's disease from other types of dementia.

Objective: We investigated how well a visual associative learning task discriminates Alzheimer's disease (AD) dementia from other types of dementia and how it relates to AD pathology.

Methods: 3,599 patients (63.9 ± 8.

Endocannabinoid levels in plasma and neurotransmitters in the brain: a preliminary report on patients with a psychotic disorder and healthy individuals.

Background: Interactions between the endocannabinoid system (ECS) and neurotransmitter systems might mediate the risk of developing a schizophrenia spectrum disorder (SSD). Consequently, we investigated in patients with SSD and healthy controls (HC) the relations between (1) plasma concentrations of two prototypical endocannabinoids (N-arachidonoylethanolamine [anandamide] and 2-arachidonoylglycerol [2-AG]) and (2) striatal dopamine synthesis capacity (DSC), and glutamate and y-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC). As anandamide and 2-AG might reduce the activity of these neurotransmitters, we hypothesized negative correlations between their plasma levels and the abovementioned neurotransmitters in both groups.