Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid.

Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis.

Computerized decision support to optimally funnel patients through the diagnostic pathway for dementia.

Background: The increasing prevalence of dementia and the introduction of disease-modifying therapies (DMTs) highlight the need for efficient diagnostic pathways in memory clinics. We present a data-driven approach to efficiently guide stepwise diagnostic testing for three clinical scenarios: 1) syndrome diagnosis, 2) etiological diagnosis, and 3) eligibility for DMT.

Methods: We used data from two memory clinic cohorts (ADC, PredictND), including 504 patients with dementia (302 Alzheimer's disease, 107 frontotemporal dementia, 35 vascular dementia, 60 dementia with Lewy bodies), 191 patients with mild cognitive impairment, and 188 cognitively normal controls (CN).

The CSF lipid profile in patients with probable idiopathic normal pressure hydrocephalus differs from control but does not differ between shunt responders and non-responders.

Idiopathic normal pressure hydrocephalus is a common form of hydrocephalus in the elderly, characterized by enlarged ventricles combined with clinical symptoms presenting as gait impairment, urinary incontinence, and dementia. Idiopathic normal pressure hydrocephalus may be difficult to differentiate clinically from other neurodegenerative disorders, and up to 80% of cases may remain unrecognized and thus untreated. Consequently, there is a pressing demand for biomarkers that can confirm the diagnosis of idiopathic normal pressure hydrocephalus.

Diagnostic performance of light reflex pupillometry in Alzheimer's disease.

Unlabelled: Easily applied diagnostic tools such as digital biomarkers for Alzheimer's disease (AD) are urgently needed due to the recent approval of disease-modifying therapies. We aimed to determine the diagnostic performance of hand-held, quantitative light reflex pupillometry (qLRP) in patients with AD in a proof-of-concept, cross-sectional study. Participants underwent qLRP at a university memory clinic from August 2022 to October 2023.

Cerebrospinal fluid synaptic biomarker changes in bipolar disorder - A longitudinal case-control study.

Background: This exploratory study investigated cerebrospinal fluid (CSF) synaptic protein biomarkers in bipolar disorder (BD), aiming to highlight the neurobiological basis of the disorder. With shared cognitive impairment features between BD and Alzheimer's disease, and considering increased dementia risk in BD patients, the study explores potential connections.

Methods: Fifty-nine well-characterized patients with BD and thirty-seven healthy control individuals were examined and followed for one year.

Neurofilament light chain is elevated in patients with newly diagnosed idiopathic intracranial hypertension: A prospective study.

Background: Idiopathic intracranial hypertension is a secondary headache disorder potentially causing visual loss. Neurofilament light chain is a candidate, prognostic biomarker, but further studies of neuronal biomarkers are needed. Our objective was to investigate neurofilament light chain in cerebrospinal fluid (cNfL) and plasma (pNfL), amyloid-beta 42 (Aβ-42), total-tau and phosphorylated-tau in cerebrospinal fluid in new-onset idiopathic intracranial hypertension.

Subclinical epileptiform discharges in Alzheimer's disease are associated with increased hippocampal blood flow.

Background: In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF).

The cingulate island sign in a mixed memory clinical cohort: Prevalence and diagnostic accuracy.

Introduction: Visual rating of the cingulate island sign (CIS) on [F]fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) has a high specificity for dementia with Lewy bodies (DLB) in selected cohorts such as DLB versus Alzheimer's disease (AD). In a mixed memory clinical population this study aimed to uncover the prevalence of CIS, the diagnostic accuracy for DLB, and the relationship between CIS and disease severity.

Methods: CIS on [F]FDG-PET was retrospectively assessed with the visual CIS rating scale (CISRs) in 1000 patients with a syndrome diagnosis of mild cognitive impairment (MCI) or dementia with no restrictions in etiological diagnosis.

Cholinergic changes in Lewy body disease: implications for presentation, progression and subtypes.

Cholinergic degeneration is significant in Lewy body disease, including Parkinson's disease, dementia with Lewy bodies, and isolated REM sleep behaviour disorder. Extensive research has demonstrated cholinergic alterations in the CNS of these disorders. More recently, studies have revealed cholinergic denervation in organs that receive parasympathetic denervation.

Biomarkers for neurodegeneration impact cognitive function: a longitudinal 1-year case-control study of patients with bipolar disorder and healthy control individuals.

Background: Abnormalities in cerebrospinal fluid (CSF)-amyloid-beta (Aβ)42, CSF-Aβ40, CSF-Aβ38, CSF-soluble amyloid precursor proteins α and β, CSF-total-tau, CSF-phosphorylated-tau, CSF-neurofilament light protein (NF-L), CSF-neurogranin, plasma-Aβ42, plasma-Aβ40, plasma-total-tau, plasma-NF-L and, serum-S100B during affective episodes may reflect brain changes that could impact cognitive function in patients with bipolar disorder (BD). The study aimed to investigate the association between these biomarkers indicative of Alzheimer's disease and those reflecting neurodegeneration alongside their impact on cognitive function in patients with BD and healthy control individuals (HC). The primary hypothesis was that GL and VL would increase with increasing levels of CSF-Aβ42 based on data from T0 and T3 in BD and HC jointly.

Test-retest reliability and short-term variability of quantitative light reflex pupillometry in a mixed memory clinic cohort.

Background: Quantitative light reflex pupillometry (qLRP) may be a promising digital biomarker in neurodegenerative diseases such as Alzheimer's disease (AD), as neuropathological changes have been found in the midbrain structures governing the light reflex. Studies investigating test-retest reliability and short-term, intra-subject variability of qLRP in these patient groups are missing. Our objective was therefore to investigate the test-retest reliability and short-term, intra-subject variability of qLRP in a memory clinic setting, where patients with neurodegenerative disease are frequently evaluated.

Neurofilament light chain levels in serum among a large mixed memory clinic cohort: Confounders and diagnostic usefulness.

Introduction: Early and accurate diagnosis of neurocognitive disorders including neurodegenerative dementia remains challenging. This study explores the impact of biological factors on serum neurofilament light chain (NfL) levels and clinical usefulness for the detection of neurocognitive disorders in a mixed memory clinic.

Methods: Serum samples and clinical data were obtained from 1188 patients who underwent diagnostic investigations for memory complaints between January 2018 and September 2019.

Human Cerebrospinal Fluid Sample Preparation and Annotation for Integrated Lipidomics and Metabolomics Profiling Studies.

Cerebrospinal fluid (CSF) is a metabolically diverse biofluid and a key specimen for exploring biochemical changes in neurodegenerative diseases. Detecting lipid species in CSF using mass spectrometry (MS)-based techniques remains challenging because lipids are highly complex in structure, and their concentrations span over a broad dynamic range. This work aimed to develop a robust lipidomics and metabolomics method based on commonly used two-phase extraction systems from human CSF samples.

Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer's disease.

Background: Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for the effects of exercise in Alzheimer's disease (AD). For this purpose, we studied changes in neuroprotective proteins proBDNF, BDNF, and humanin in plasma NDEVs from patients with mild to moderate AD participating in the randomized controlled trial (RCT) of exercise ADEX.

Methods: proBDNF, BDNF, and humanin were quantified in NDEVs immunocaptured from the plasma of 95 ADEX participants, randomized into exercise and control groups, and collected at baseline and 16 weeks.

Plasma glucose is not associated with performance on standard cognitive screening tests in a mixed memory clinic cohort-An observational cross-sectional study.

Background: It has been shown under experimental conditions that cognitive performance, especially working memory, is impaired in patients with type I and type II diabetes mellitus during hyperglycemic and hypoglycemic conditions, perhaps due to altered cerebral glucose metabolism. It is not known if patients with neurodegenerative diseases, who also exhibit pathological cerebral glucose metabolism, are affected in a similar manner by their plasma glucose levels.

Objective: We aimed to test if performance on two cognitive screening tests was associated with plasma glucose levels in a memory clinic cohort.

Estimation of brain amyloid accumulation using deep learning in clinical [C]PiB PET imaging.

Introduction: Estimation of brain amyloid accumulation is valuable for evaluation of patients with cognitive impairment in both research and clinical routine. The development of high throughput and accurate strategies for the determination of amyloid status could be an important tool in patient selection for clinical trials and amyloid directed treatment. Here, we propose the use of deep learning to quantify amyloid accumulation using standardized uptake value ratio (SUVR) and classify amyloid status based on their PET images.

Clinical validation of the cingulate island sign visual rating scale in dementia with Lewy bodies.

Introduction: The cingulate island sign (CIS) is a metabolic pattern on [F]fluorodeoxyglucose ([F]FDG) positron emission tomography (PET) associated with dementia with Lewy bodies (DLB). The aim of this study was to validate the visual CIS rating scale (CISRs) for the diagnosis of DLB and to explore the clinical correlates.

Methods: This single-center study included 166 DLB patients and 161 patients with Alzheimer's disease (AD).

Progression of Blood-Brain Barrier Leakage in Patients with Alzheimer's Disease as Measured with the Cerebrospinal Fluid/Plasma Albumin Ratio Over Time.

Background: Studies have found a disruption of the blood-brain barrier (BBB) in patients with Alzheimer's disease (AD), but there is little evidence of the changes in the BBB over time. The cerebrospinal fluid's (CSF) protein concentration can be used as an indirect measurement for the permeability of the BBB using the CSF/plasma albumin quotient (Q-Alb) or total CSF protein.

Objective: In the current study, we wanted to investigate the changes in Q-Alb in patients with AD over time.

Aerobic exercise does not affect serum neurofilament light in patients with mild Alzheimer's disease.

Introduction: Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration.

Objective: To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer's disease (AD).

Methods: This is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer's disease: The Effect of Physical Exercise (ADEX) study.

Differential proteomic profile of lumbar and ventricular cerebrospinal fluid.

Background: Pathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue.

A zero-dose synthetic baseline for the personalized analysis of [F]FDG-PET: Application in Alzheimer's disease.

Purpose: Brain 2-Deoxy-2-[F]fluoroglucose ([F]FDG-PET) is widely used in the diagnostic workup of Alzheimer's disease (AD). Current tools for uptake analysis rely on non-personalized templates, which poses a challenge as decreased glucose uptake could reflect neuronal dysfunction, or heterogeneous brain morphology associated with normal aging. Overcoming this, we propose a deep learning method for synthesizing a personalized [F]FDG-PET baseline from the patient's own MRI, and showcase its applicability in detecting AD pathology.

Cerebrospinal fluid glucose is not altered in patients with dementia.

Background: Studies have shown that the pathological changes of many dementia disorders begin several years before clinical onset. A connection between some of these pathophysiological changes and brain hypometabolism, seen in dementia disorders, is well established. Glucose is transported from the blood into the interstitial space, and the decreased demand for glucose by the degenerating brain tissue may thereby mirror increased levels of cerebrospinal fluid (CSF) glucose.

Can preoperative brain imaging features predict shunt response in idiopathic normal pressure hydrocephalus? A PRISMA review.

Purpose: This systematic literature review aimed to identify brain computed tomography (CT) and magnetic resonance imaging (MRI) features that could be used to discriminate idiopathic normal pressure hydrocephalus (iNPH) shunt responders from non-responders.

Methods: PubMed, Embase, Web of Science, and Cochrane were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only original research articles reporting preoperative CT and/or MRI features and iNPH shunt response evaluated by changes in gait, dementia, and urinary incontinence were included.