Reduced expression of fMRI subsequent memory effects with increasing severity across the Alzheimer's disease risk spectrum.

In functional magnetic resonance imaging (fMRI) studies, episodic memory is commonly investigated with the subsequent memory paradigm in which brain activity is recorded during encoding and analyzed as a function of subsequent remembering and forgetting. Impaired episodic memory is common in individuals with or at risk for Alzheimer's disease (AD), but only few studies have reported subsequent memory effects in AD or its risk states like mild cognitive impairment (MCI). One reason for this might be that subsequent memory responses may be blunted in AD or MCI and thus less likely to manifest in fMRI signal differences.

Disease stage-specific atrophy markers in Alzheimer's disease.

Introduction: Structural magnetic resonance imaging (MRI) often lacks diagnostic, prognostic, and monitoring value in Alzheimer's disease (AD), particularly in early disease stages. To improve its utility, we aimed to identify optimal atrophy markers for different intended uses.

Methods: We included 363 older adults; cognitively unimpaired individuals who were negative or positive for amyloid beta (Aβ) and Aβ-positive patients with subjective cognitive decline, mild cognitive impairment, or dementia of the Alzheimer type.

Associations between digital speech features of automated cognitive tasks and trajectories of brain atrophy and cognitive decline in early Alzheimer's disease.

BackgroundSpeech-based features extracted from telephone-based cognitive tasks show promise for detecting cognitive decline in prodromal and manifest dementia. Little is known about the cerebral underpinnings of these speech features.ObjectiveTo examine associations between speech features, brain atrophy, and longitudinal cognitive decline in individuals at risk for Alzheimer's disease (AD).

The economic burden of subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia: excess costs and associated clinical and risk factors.

Background: With the availability of first disease-modifying treatments, evidence on costs across the entire Alzheimer's Continuum, especially for early disease stages, becomes increasingly important to inform healthcare planning, resource allocation, and policy decisions. This study assessed costs and cost-associated factors in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and Alzheimer's Disease (AD) dementia compared to healthy controls.

Methods: The German DELCODE cohort study assessed clinical data, healthcare resource use, and informal care provision.

Mini social cognition and emotional assessment: Diagnostic performance and neural correlates in behavioural-variant frontotemporal dementia.

We aimed at validating the Mini Social Cognition and Emotional Assessment (Mini-SEA) in a German cohort of mildly impaired behavioural-variant frontotemporal dementia (bvFTD) patients and healthy controls. The Mini-SEA comprises the Facial Emotion Recognition Test (FERT) and the Faux Pas Test (FPT) measuring Theory of Mind (ToM) abilities in social norm-related real-life stories. We examined the diagnostic performance of the Mini-SEA alongside other neuropsychological assessments and investigated its structural neural correlates.

Speech-based digital cognitive assessments for detection of mild cognitive impairment: Validation against paper-based neurocognitive assessment scores.

BackgroundCognitive decline in Alzheimer's disease (AD) often includes speech impairments, where subtle changes may precede clinical dementia onset. As clinical trials focus on early identification of patients for disease-modifying treatments, digital speech-based assessments for scalable screening have become crucial.ObjectiveThis study aimed to validate a remote, speech-based digital cognitive assessment for mild cognitive impairment (MCI) detection through the comparison with gold-standard paper-based neurocognitive assessments.

Application of IVDr NMR spectroscopy to stratify Parkinson's disease with absolute quantitation of blood serum metabolites and lipoproteins.

The challenge of early detection and stratification in Parkinson's disease (PD) is urgent due to the current emergence of mechanism-based disease-modifying treatments. In here, metabolomic and lipidomic parameters obtained by a standardized and targeted in vitro diagnostic research (IVDr) platform have a significant potential to address therapy-related questions and generate improved biomarker panels. Our study aimed to use IVDr nuclear magnetic resonance (NMR) spectroscopy to quantify metabolites and lipoproteins in PD blood serum from different cohorts to stratify metabolically driven subtypes of idiopathic and genetic PD.

A computational ontology framework for the synthesis of multi-level pathology reports from brain MRI scans.

BackgroundConvolutional neural network (CNN) based volumetry of MRI data can help differentiate Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD) as causes of cognitive decline and dementia. However, existing CNN-based MRI volumetry tools lack a structured hierarchical representation of brain anatomy, which would allow for aggregating regional pathological information and automated computational inference.ObjectiveDevelop a computational ontology pipeline for quantifying hierarchical pathological abnormalities and visualize summary charts for brain atrophy findings, aiding differential diagnosis.

Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease.

Subjective cognitive decline (SCD) is proposed as an indicator of transitional disease stage 2 in the Alzheimer's disease (AD) continuum. However, molecular and particularly longitudinal fluid biomarker data for this stage are still limited. This study aimed to determine whether blood-based biomarkers in amyloid-positive individuals with SCD (A + SCD) support the notion of stage 2 as a distinct stage between stages 1 and 3 of AD and to identify those at high risk for clinical progression.

Disease stage-specific atrophy markers in Alzheimer's disease.

Introduction: Structural MRI often lacks diagnostic, prognostic, and monitoring value in Alzheimer's disease (AD), particularly in early disease stages. To improve its utility, we aimed to identify optimal MRI readouts for different use cases.

Methods: We included 363 older adults; healthy controls (HC) who were negative or positive for amyloidbeta (Aβ) and Aβ-positive patients with subjective cognitive decline (SCD), mild cognitive impairment, or dementia of the Alzheimer type.

Perivascular space and white matter hyperintensities in Alzheimer's disease: associations with disease progression and cognitive function.

Background: Alzheimer's disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and neurofibrillary tangles. Recent studies emphasize the role of vascular factors, including the glymphatic system, in AD pathogenesis, particularly in Aβ clearance. The diffusion tensor image analysis along the perivascular space (DTI-ALPS; ALPS-Index) has emerged as a novel, non-invasive method to evaluate the glymphatic system in vivo, showing glymphatic insufficiency in AD.

CSF biomarkers are differentially linked to brain areas high and low in noradrenaline, dopamine and serotonin across the Alzheimer's disease spectrum.

Neurotransmitter systems of noradrenaline, dopamine, serotonin and acetylcholine are implicated in cognitive functions such as memory, learning and attention and are known to be altered in neurodegenerative diseases like Alzheimer's disease. Specific brain structures involved in these systems, e.g.

Linking higher amyloid beta 1-38 (Aβ(1-38)) levels to reduced Alzheimer's disease progression risk.

Introduction: The beneficial effects of amyloid beta 1-38, or Aβ(1-38), on Alzheimer's disease (AD) progression in humans in vivo remain controversial. We investigated AD patients' cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.

Methods: Cognitive function and diagnostic change were assessed annually for 3 years in 177 Aβ-positive participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia from the German Center for Neurodegenerative Diseases (DZNE) longitudinal cognitive impairment and dementia study (DELCODE) cohort using the Mini-Mental State Examination (MMSE), Preclinical Alzheimer's Cognitive Composite (PACC), Clinical Dementia Rating (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer's disease.

Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.

Environmental enrichment is associated with favorable memory-related functional brain activity patterns in older adults.

Background: In humans, environmental enrichment (EE), as measured by the engagement in a variety of leisure activities, has been associated with larger hippocampal structure and better memory function. The present cross-sectional study assessed whether EE during early life (13-30 years) and midlife (30-65 years) is associated with better preserved memory-related brain activity patterns in older age.

Methods: In total, 372 cognitively unimpaired older adults (aged ≥60 years old) of the DZNE-Longitudinal Study on Cognitive Impairment and Dementia (DELCODE; DRKS00007966) were investigated.

Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.

Background: Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components.

Methods: In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma.

Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation.

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding.

Perivascular space enlargement accelerates in ageing and Alzheimer's disease pathology: evidence from a three-year longitudinal multicentre study.

Background: Perivascular space (PVS) enlargement in ageing and Alzheimer's disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD.

Methods: We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; mean = 70.

Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults.

Background: For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce.

Methods: We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period.

GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA).

Background: Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

Introduction: Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies.

Methods: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers.

Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.

Introduction: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline.

Methods: We measured levels of amyloid beta (Aβ)X-40 and AβX-42 in immunoprecipitated eluates from the DELCODE cohort.

Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases.