Robert Perneczky

• Professor (Full) at Ludwig-Maximilians-Universität in Munich

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 amyloid-beta...

Purpose Clinical staging in individuals with Alzheimer’s disease (AD) typically relies on neuropsychological testing. Recognizing the imperative for an objective measure of clinical AD staging, regional perfusion in early-phase β-amyloid-PET may aid as a cost-efficient index for the assessment of neurodegeneration severity in patients with Alzheime...

Depressive symptoms are common in mild cognitive impairment (MCI), dementia caused by Alzheimer’s disease (AD dementia) and in cognitively unimpaired older adults. However, it is unclear whether they could contribute to the identification of cognitive impairment in ageing. To assess the potential utility of depressive symptoms to distinguish betwee...

Background Studies comparing cerebrospinal fluid (CSF) and plasma complement proteins in Alzheimer’s disease (AD) patients versus healthy controls (HC) have yielded inconsistent results. Discrepancies in the preanalytical sample handling could contribute to the heterogeneity in the reported findings. Objective Using qualified immunoassays, we aime...

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 participant...

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. the locus coeruleus, the main source of noradrenal...

In Alzheimer’s disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperact...

Patients with Alzheimer’s disease (AD) and clinically overlapping neurodegenerative diseases are classified molecularly using the A/T/N classification system. Apart from fluid biomarkers and structural MRI, the three-dimensional A/T/N system incorporates characteristic features from β-amyloid-PET (A), tau-PET (T), and FDG-PET (N). We evaluated if d...

BACKGROUND: Many dementia and Alzheimers disease (AD) registries operate at local or national levels without standardization or comprehensive real-world data (RWD) collection. This initiative sought to achieve consensus among experts on priority outcomes and measures for clinical practice in caring for patients with symptomatic AD, particularly in...

Numerous drugs (including disease‐modifying therapies, cognitive enhancers and neuropsychiatric treatments) are being developed for Alzheimer’s and related dementias (ADRD). Emerging neuroimaging modalities, and genetic and other biomarkers potentially enhance diagnostic and prognostic accuracy. These advances need to be assessed in real‐world stud...

Background There is a strong link between tau and progression of Alzheimer’s disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial hetero...

Background Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. Method To unco...

Background Analysis of neuroimaging data based on convolutional neural networks (CNNs) can improve detection of clinically relevant characteristics of patients with Alzheimer’s disease (AD). Previously, our group developed a CNN‐based approach for detecting AD via magnetic resonance imaging (MRI) scans and for identifying features that are relevant...

Background Differences in task‐fMRI activation have recently been found to be related to neuropathological hallmarks of AD. However, the evolution of fMRI‐based activation throughout AD disease progression and its relationship with other biomarkers remains elusive. Applying a disease progression model (DPM) to a multicentric cohort with up to four...

Background In Alzheimer’s disease, Aß triggers tau spreading which drives neurodegeneration and cognitive decline. However, the mechanistic link between Aß and tau remains unclear, which hinders therapeutic efforts to attenuate Aß‐related tau accumulation. Preclinical research could show that tau spreads across connected neurons in an activity‐depe...

Background Inadequate glymphatic clearance through perivascular spaces (PVS) is hypothesized to contribute to the formation of white matter hyperintensities (WMH). However, longitudinal evidence for such a mechanistic link in aging remains limited. Using multivariate modelling, we investigated the interrelationship between PVS and WMH over time to...

Background Coronary heart disease (CHD) is a well‐known risk factor for cognitive impairment and dementia, and blood biomarkers of neurodegenerative diseases may be utilised to identify people at higher risk of cognitive decline. Here, we aimed to investigate prospective associations between these biomarkers and mild neurocognitive disorder (MiND)...

Background Analysis of neuroimaging data based on convolutional neural networks (CNNs) can improve detection of clinically relevant characteristics of patients with Alzheimer’s disease (AD). Previously, our group developed a CNN‐based approach for detecting AD via magnetic resonance imaging (MRI) scans and for identifying features that are relevant...

Background Recent developments in physiological and digital biomarkers provide an opportunity to shift the first diagnostic steps to the home‐setting, thus allowing earlier detection and treatment of Alzheimer’s disease (AD). Blood‐based, magnetic resonance imaging, electrophysiological, digital and microbiome biomarkers have shown great promise an...

Background Perivascular spaces (PVS) can become large enough to be visible in magnetic resonance imaging (MRI). The exact aetiology of PVS enlargement in humans remains, however, elusive and under continuous debate [1‐5]. Here, we tracked PVS volumes longitudinally over three years in 525 individuals along AD syndromal cognitive stages, namely cogn...

Background Subjective cognitive decline (SCD), in the absence of objective cognitive impairment, may be the first symptomatic manifestation of Alzheimer's disease (AD). Previous studies have suggested that its combination with amyloid‐positivity (Aβ+) may represent stage 2 AD, and is associated with a higher risk of future cognitive decline. Here,...

Background In Alzheimer’s disease, Aβ triggers tau spreading which drives neurodegeneration and cognitive decline. However, the mechanistic link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ‐related tau accumulation. Preclinical research could show that tau spreads across connected neurons in an activity‐depe...

Background There is a strong link between tau and progression of Alzheimer’s disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial hetero...

Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussion about their coupled temporal dynamics (Garnier‐Crussard et al. 2023). Longitudinal evidence supporting this hypothesis remains nonetheless scarce (Ter Telgte et al. 2018). We integrated surface‐based morph...

Background Alzheimer's Disease (AD) is often accompanied by neuroinflammation, which manifests prior to significant cognitive decline. Reactive astrocytosis is a hallmark of such inflammation, potentially serving as an early biomarker for AD pathology. Our study employs [18F]fluorodeprenyl‐D2 ([18F]F‐DED) positron emission tomography (PET) imaging...

Background Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. Method To unco...

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...

Introduction This study evaluates the clinical value of a deep learning–based artificial intelligence (AI) system that performs rapid brain volumetry with automatic lobe segmentation and age‐ and sex‐adjusted percentile comparisons. Methods Fifty‐five patients—17 with Alzheimer's disease (AD), 18 with frontotemporal dementia (FTD), and 20 healthy...

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 com...

Background Differences in task‐fMRI activation have recently been found to be related to neuropathological hallmarks of AD. However, the evolution of fMRI‐based activation throughout AD disease progression and its relationship with other biomarkers remains elusive. Applying a disease progression model (DPM) to a multicentric cohort with up to four...

INTRODUCTION With the advent of disease‐modifying therapies, accurate assessment of biomarkers indicating the presence of disease‐associated amyloid beta (Aβ) pathology becomes crucial in patients with clinically suspected Alzheimer's disease (AD). We evaluated Aβ levels in cerebrospinal fluid (Aβ CSF) and Aβ levels in positron emission tomography...

Dementia prevention in Africa is critically underexplored, despite the continent's high prevalence of modifiable risk factors. With a predominantly young and middle‐aged population, Africa presents a prime opportunity to implement evidence‐based strategies that could significantly reduce future dementia cases and mitigate its economic impact. The m...

This study introduces the Structural MRI based Alzheimer's Disease Score (SMAS), a novel index intended to quantify Alzheimer's Disease (AD) related morphometric patterns using a deep learning Bayesian supervised Variational Autoencoder (Bayesian sVAE). SMAS index was constructed using baseline structural MRI data from the DELCODE study and evaluat...

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 func...

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 determi...

Background and objectives: CSF biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). However, AD is still diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Thus, further identification of biomarkers is required to detect related pathology...

Since it was shown that Alzheimer’s disease (AD) begins many years before the onset of symptoms with subjective cognitive decline (SCD), there has been increasing interest in the early clinical stages where disease-modifying drugs are expected to have the greatest benefit. However, at this early stage cognitive testing may yield unremarkable result...

Background Amyloid-targeting therapies for Alzheimer’s disease (AD) might become available in Germany soon. The combination of a large pool of prevalent cases and a complex diagnostic process to determine eligibility for these treatments is likely to challenge health systems’ capacity. Objective To analyze Germany’s healthcare system capacity to i...

INTRODUCTION Recent advances in biomarker research have improved the diagnosis and monitoring of Alzheimer's disease (AD), but in vivo biomarker‐based workflows to assess 4R‐tauopathy (4RT) patients are currently missing. We suggest a novel biomarker‐based algorithm to characterize AD and 4RTs. METHODS We cross‐sectionally assessed combinations of...

Background Microglial activation is one hallmark of Alzheimer disease (AD) neuropathology but the impact of the regional interplay of microglia cells in the brain is poorly understood. We hypothesized that microglial activation is regionally synchronized in the healthy brain but experiences regional desynchronization with ongoing neurodegenerative...

Purpose Current therapy strategies still provide only limited success in the treatment of glioblastoma, the most frequent primary brain tumor in adults. In addition to the characterization of the tumor microenvironment, global changes in the brain of patients with glioblastoma have been described. However, the impact and molecular signature of neur...

β-amyloid-targeting antibodies represent the first generation of effective causal treatment of Alzheimer’s disease (AD) and can be considered historical research milestones. Their effect sizes, side effects, implementation challenges and costs, however, have stimulated debates about their overall value. In this position statement academic clinician...

Alzheimer’s disease (AD) is often accompanied by early non-cognitive symptoms, including olfactory deficits, such as hyposmia and anosmia ¹ . These have emerged as solid predictors of cognitive decline, but the underlying mechanisms of hyposmia in early AD remain elusive ² . Pathologically, one of the brain regions affected earliest is the brainste...

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,...

Background Preclinical, postmortem, and positron emission tomography (PET) imaging studies have pointed to neuroinflammation as a key pathophysiological hallmark in primary 4‐repeat (4R) tauopathies and its role in accelerating disease progression. Objective We tested whether microglial activation (1) progresses in similar spatial patterns as the...

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 remain nonetheless scarce. Methods In this study, we applied regional and global bivariate latent growth curve modell...

Introduction: Subjective cognitive decline (SCD) is proposed to indicate transitional stage-2 in the AD continuum, yet longitudinal fluid biomarker data for this stage is scarce. We investigated if blood-based biomarkers in amyloid-positive individuals with SCD (A+SCD) support stage-2 as distinct from AD stages-1 and -3 and identify those at high r...

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...

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. P...

Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and g...

Synucleinopathies such as Parkinson’s disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclei...

Background The NIA-AA Research Framework on Alzheimer’s disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS). Objective To identify participant clusters based on stage 2 features and assess their association with amyloid positivity...

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking...

Background Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. Objective This cross-sectional study investigated the association between lifetime musical activit...

Inferior frontal sulcal hyperintensities (IFSHs) on fluid-attenuated inversion recovery (FLAIR) sequences have been proposed to be indicative of glymphatic dysfunction. Replication studies in large and diverse samples are nonetheless needed to confirm them as an imaging biomarker. We investigated whether IFSHs were tied to Alzheimer’s disease (AD)...

INTRODUCTION Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. METHODS A total of 526 participants in early clinical stages of AD and controls from a longitudinal c...

Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrop...

Local therapy strategies still provide only limited success in the treatment of glioblastoma, the most frequent primary brain tumor in adults, indicating global involvement of the brain in this fatal disease. To study the impact of neuroinflammation distant of the primary tumor site on the clinical course of patients with glioblastoma, we performed...

Objectives Impaired perivascular clearance has been suggested as a contributing factor to the pathogenesis of Alzheimer disease (AD). However, it remains unresolved when the anatomy of the perivascular space (PVS) is altered during AD progression. Therefore, this study investigates the association between PVS volume and AD progression in cognitivel...

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitiv...

Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer’s disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memor...

As our knowledge about the biology of Alzheimer’s disease (AD) expands and we recognize the significance of early intervention for effective treatment, there is a shift in focus toward detecting the disease at an early stage. AD is characterized by the accumulation of misfolded amyloid-β (Aβ) and phosphorylated tau proteins in the brain, leading to...

The development of effective prevention and treatment strategies for Alzheimer’s disease (AD) and dementia is hindered by limited knowledge of the underlying biological and environmental causes. While certain genetic factors have been associated with AD, and various lifestyle and environmental factors have been linked to dementia risk, the interact...

Background Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients’ safety and management. Objectives To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients. Methods Cross-sectional data of MSA patients a...

Background and objectives 18-kDa translocator protein position-emission-tomography (TSPO-PET) imaging emerged for in vivo assessment of neuroinflammation in Alzheimer’s disease (AD) research. Sex and obesity effects on TSPO-PET binding have been reported for cognitively normal humans (CN), but such effects have not yet been systematically evaluated...

Neuroinflammation is a hallmark of Alzheimer’s disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across...

INTRODUCTION We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum. METHODS We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extens...

Background Preclinical evidence in transgenic models of Alzheimer’s disease (AD) suggests that liraglutide, a GLP1 analogue, exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and reducing insulin resistance, and increasing the proliferation of neuronal progenitor cells. ELAD is a 12‐month, multi‐centre, r...

Background Self‐ and informant‐reports of cognitive decline have been previously associated with a higher risk of cognitive decline in elderly. Yet, few studies assessed their longitudinal changes over time with regard to both incident mild cognitive impairment (iMCI) and Alzheimer’s disease (AD) pathology. This study aims at describing these links...

Background Structural MRI is frequently used to track Alzheimer’s disease (AD) progression in clinic, research, and pharmacological trials. It has been shown that established MRI‐derived measures lack diagnostic sensitivity particularly in early stages of AD. Here, we investigate if the utility of structural MRI for tracking early AD progression ca...

Background Cerebrospinal fluid (CSF) biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). Currently, AD is still mostly diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Disease‐modifying treatments should be most effective in the earliest...

Background Alzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) plaques in the brain. Blood‐brain barrier (BBB) dysfunction has been associated with AD. Aβ‐plaques have been found to disrupt the BBB, leading to increased permeability and invasion of immune cells into the CNS and triggering an inflammatory response, and...

Background Alzheimer’s Disease (AD) is difficult to diagnose and stage, often relying on burdensome clinical tests for neural protein aggregation and cognitive performance. Delays and errors in the accurate diagnosis of AD reduce patient outcomes and prevent early therapeutic intervention. The CASBA electroencephalography (EEG) system leverages a c...

Background Altered fluctuations in blood oxygen level dependent (BOLD) signal during resting‐state functional magnetic resonance imaging (rs‐fMRI) have been considered indicative of decreased cerebrovascular health. Previous studies reported changes in BOLD fluctuations associated with Alzheimer’s dementia (AD) and white matter hyperintensities (WM...

Background Highly varying cognitive abilities among individuals facing pathological alterations, e.g. in Alzheimer’s disease (AD), is conceptualized by the cognitive reserve (CR) hypothesis[1]. The growing interest in prevention and intervention methods brings many new challenges for precision medicine[2]. Hereby, studies on the residual approach f...

Background Age is the strongest risk factor for dementia, including Alzheimer’s disease (AD). However, across individuals of the same chronological age there is considerable heterogeneity in rates of cognitive decline. These differences have been attributed to individual differences in age‐related biological processes, including brain protein expre...

Background Corticobasal syndrome (CBS) with underlying 4‐repeat tauopathy is a progressive neurodegenerative disorder characterized by declining cognitive and motor functions. Biomarkers for assessing pathological brain changes in CBS including tau‐ and microglia‐PET or neurofilament light chain (NfL) have recently been evaluated for differential d...

Background Quantification of Aβ oligomers in plasma may be useful not only for early diagnosis of Alzheimer’s disease (AD), but particularly to improve our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology due to very low concentrations and possible interferences of matrix...

Background Engagement in complex leisure activities, such as playing a musical instrument, may help preserve cognitive and brain health in older age (e.g. Böttcher et al., 2022). In this study, we investigated the associations between leisure‐time musical activity and resting‐state functional connectivity (RSFC) in three higher‐order networks, the...

Background Multimodal interventions targeting modifiable disease‐associated risk factors may support large‐scale population brain health. The landmark Finnish‐Geriatric‐Intervention‐Study‐to‐Prevent‐Cognitive‐Impairment‐and‐Disability(FINGER) demonstrated improvements in cognition and health outcomes 2‐years post‐intervention. Researchers now seek...

Background Cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers of Alzheimer’s disease (AD), ß‐amyloid (Aß) and tau, can identify early disease stages with high accuracy. However, this approach is not suitable for routine clinical care because of the high costs and invasiveness. Implementation of blood‐based biomarkers (BBBM)...

Background Reliable biomarkers for detecting different abnormal tau protein isoforms between neurodegenerative diseases are currently missing. Phosphorylated tau (p‐tau) in the cerebrospinal fluid (CSF) is acknowledged as a 3/4R tau biomarker in AD but not in other tauopathies. The positron emission tomography (PET) radiotracer ¹⁸ F‐PI‐2620 has the...

Background Aß oligomers are synaptotoxic and may initiate neurodegeneration in early stages of Alzheimer´s disease (AD). Method 526 patients and controls from the DELCODE cohort were clinically diagnosed and afterwards neurobiologically classified using the ATN‐system. Aß and Tau oligomers were determined using the sFIDA technology. Result Within...

Background Perivascular spaces in the brain can become enlarged (ePVS); their temporal dynamics remain under increasing debate. We studied automatic ePVS measurements obtained from 870 subjects along the AD continuum over the course of three years. Method We measured centrum semiovale (CSO) and basal ganglia (BG) ePVS volumes computationally in th...

Background The current research consensus is that long Aβ(1‐42) peptides are neurotoxic pathological hallmarks of AD. Interestingly, short Aβ peptides, such as Aβ(1‐38), appear to be less neurotoxic and may counteract AD neuropathology. However, research on Aβ(1‐38) is scarce and their effect on AD pathophysiology in humans in vivo remains unclear....

Background The clinical relevance and longitudinal impact of minor neuropsychological deficits (MND) in cognitively normal memory clinic patients with subjective cognitive decline (SCD) is still unclear. To address this, we set out to investigate whether MND in SCD patients are related to Alzheimer´s disease (AD) pathology and future cognitive decl...

Background Independent contributions of enlarged perivascular spaces (ePVS) to cognition remain elusive due to their intertwining with white matter hyperintensities (WMH). We studied the unique and shared effects of ePVS and WMH on cognitive performance in 397 subjects along the Alzheimer’s disease (AD) continuum. Methods We quantified baseline vo...

Background Inflammation, vascular disease and Alzheimer’s Disease (AD) appear to be closely linked. We recently showed that increased vascular risk relates to certain inflammatory profiles in CSF in the DELCODE cohort (Hayek et al, AAIC 2022). Moreover, we found cerebrovascular alterations in posterior‐midline regions including precuneus in subject...

Background Self‐ and informant‐reports of cognitive decline have been previously associated with a higher risk of cognitive decline in elderly. Yet, few studies assessed their longitudinal changes over time with regard to both incident mild cognitive impairment (iMCI) and Alzheimer’s disease (AD) pathology. This study aims at describing these links...

Background Inflammation, vascular disease and Alzheimer’s Disease (AD) appear to be closely linked. We recently showed that increased vascular risk relates to certain inflammatory profiles in CSF in the DELCODE cohort (Hayek et al, AAIC 2022). Moreover, we found cerebrovascular alterations in posterior‐midline regions including precuneus in subject...