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October 2005 - present
Publications
Publications (667)
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...
Background
Patients with Progressive Supranuclear Palsy (PSP) suffer from several neuropsychological impairments. These mainly affect the frontal lobe and subcortical brain structures. However, a scale for the assessment of cognitive and neuropsychiatric disability in PSP is still missing.
Objectives
To create and validate a new scale for cognitiv...
Inferior frontal sulcal hyperintensities (IFSH) observed on fluid-attenuated inversion recovery (FLAIR) MRI have been proposed as indicators of elevated cerebrospinal fluid waste accumulation in cerebral small vessel disease (CSVD). However, to validate IFSH as a reliable imaging biomarker, further replication studies are required. The objective of...
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...
Background
Timely diagnosis of mild cognitive impairment (MCI) in Alzheimer’s disease (AD) is crucial for early interventions, but its implementation is often challenging due to the complexity and time burden of required cognitive assessments. Remote unsupervised self‐testing of cognition can potentially addres this health care challenge. We conduc...
Background
Environmental factors account for a considerable percentage of dementia cases. Studies in animal models have shown that environmental enrichment (EE; i.e., stimuli‐rich housing conditions) has positive effects on brain structure, including the memory system. In humans, EE as measured by the engagement in a variety of leisure activities h...
Background
Training studies report beneficial effects of physical (PP) on cognitive performance (COG) in older adults, but are often accompanied by potentially biased parameters, conclusions, and lack of directionality. To address these issues, we used a dynamic Bayesian approach to analyse the dynamic session‐to‐session change and coupling of PP a...
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
While some memory decline in old age is “normal”, there are some older individuals with maintained high cognitive performance. Using a multimodal approach including neuroimaging, fitness, genetic and questionnaire data (Fig1A), we aimed to identify factors that are related to successful cognitive aging and whether these differ between se...
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
Previous studies have examined the impact of post‐traumatic stress disorder and chronic stress on the Locus Coeruleus‐Noradrenergic System (LC‐NA) revealing significant neurobiological alterations (Aston‐Jones & Cohen, 2005; McCall et al., 2015). However, while animal studies have yielded valuable insights regarding the effects of trauma...
Background
Memory decline, which is especially prevalent in Alzheimer’s disease (AD), has been studied via fMRI, primarily focusing on the prefrontal cortex and hippocampus. However, emerging evidence suggests that the brainstem, alongside various midbrain regions, is an initial target for pathological processes like hyperphosphorylated TAU protein...
Background
Alzheimer’s Disease (AD), a progressively worsening neurodegenerative disorder, impacts millions globally. Understanding its progression is crucial for developing effective interventions and management strategies. However, high variability in disease progression amongst individuals and the complexity of neuroimaging data pose significant...
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
Episodic memory declines in old age. Successful memory relies on the process of mnemonic discrimination (MD) to establish distinct representations. However, the scope for improvement in older adults’ cognitive performance using cognitive training is poorly understood. Here we investigated whether cognitive training leads to improvement i...
Background
The Locus Coeruleus (LC) is prominently affected by neuronal loss in the earliest stages of Alzheimer’s disease (AD). Assessing LC integrity can serve as an important early biomarker for assessing AD progression. Neuromelanin (NM) accumulates in LC neurons and NM imaging has therefore been proposed as a means of imaging the LC. As signal...
Background
Locus coeruleus (LC) is a primary source of noradrenalin in the brain and plays a complex role in human behavior. In healthy aging and Alzheimer’s disease (AD), LC cell loss has been linked to a decline in overall cognitive function. This study aimed to explore age‐ and AD‐related differences in a proxy measure of LC activity. Using pupi...
Background
The timely diagnosis of mild cognitive impairment (MCI) in Alzheimer’s disease is challenging in routine care due to the complexity and time burden of required cognitive assessments. New unsupervised digital remote assessment tools could adress this challenge.
Method
The multicentric healthcare study “re.cogni.ze” evaluated usability, a...
Background
Mnemonic discrimination tasks (MDTs) hold potential for early detection of memory changes in Alzheimer’s disease (AD). Object and scene processing tasks differently tap into memory networks vulnerable to early tau and amyloid pathology, respectively. We used an object and scene MDT to assess longitudinal effects of AD on distinct functio...
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
Drugs with desirable and undesirable anticholinergic effects influence cognitive performance and increase the risk of dementia later in life. MRI imaging studies showed structural effect of these substances on basal forebrain and hippocampus, key regions of Alzheimer’s disease pathology.
Methods
We analyzed data from 787 participants of...
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
Training studies report beneficial effects of physical (PP) on cognitive performance (COG) in older adults, but are often accompanied by potentially biased parameters, conclusions, and lack of directionality. To address these issues, we used a dynamic Bayesian approach to analyse the dynamic session‐to‐session change and coupling of PP a...
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
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
Speech abnormalities are increasingly recognized as a manifestation of cognitive deficits in Alzheimer's disease (AD) and its preclinical and prodromal stages. Here, we investigated whether MRI measures of brain atrophy, specifically in the basal forebrain and cortical language areas, can predict cognitive decline and speech difficulties...
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...
Mnemonic discrimination (MD) is the ability to distinguish current experiences from similar memories. Research on the brain correlates of MD has focused on how regional neural responses are linked to MD. Here we go beyond this approach to investigate inter-regional functional connectivity patterns related to MD, its inter-individual variability and...
The present study investigated the neuromodulatory substrates of salience processing and its impact on memory encoding and behaviour, with a specific focus on two distinct types of salience: reward and contextual unexpectedness. 46 Participants performed a novel task paradigm modulating these two aspects independently and allowing for investigating...
Background
Previous findings evaluating longitudinal cognition in relation to the MeDi diet are inconsistent, and few studies have examined it in relation to the presence/absence of subjective cognitive decline (SCD). Our current aims are to test whether adherence to the MeDi diet is associated with the risk of clinical progression, future cognitiv...
Background
Frequent and remote cognitive assessment may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer’s disease (AD). Our objective was to evaluate the feasibility, reliability, and construct validity of repeated remote memory assessment in late middle‐aged and older adults.
Method
Participants were recruite...
Background
Timely diagnosis of mild cognitive impairment (MCI) in Alzheimer’s disease (AD) is crucial for early interventions, but its implementation is often challenging due to the complexity and time burden of required cognitive assessments. Remote unsupervised self‐testing of cognition can potentially addres this health care challenge. We conduc...
Background
Anosognosia is a frequent phenomenon in Alzheimer’s dementia. Both heightened and decreased awareness of cognitive decline (AoCD) have been observed in mild cognitive impairment (MCI) and subjective cognitive decline (SCD). Despite some studies, the association between altered awareness and clinical conversion remained unclear. This stud...
Background
The identification of cognitively unimpaired individuals at risk of short‐term cognitive decline is a critical task for Alzheimer´s disease (AD) research. Cognitively normal individuals with amyloid and/or tau pathology have a high risk for short‐term cognitive decline. However, not all of these individuals show clinical progression. Ind...
Background
Frequent and remote cognitive assessment may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer’s disease (AD). However, repeated testing can result in unintended inflation of scores, due to practice effects. The objective of this study is to evaluate the extent of sessions with non‐identical stimuli on...
Background
Speech and language impairments are associated with cognitive decline in neurodegenerative dementias, particularly Alzheimer’s Disease (AD), where subtle speech changes may precede clinical dementia onset. As clinical trials prioritize early identification for disease‐modifying treatments, digital biomarkers for timely screening become i...
Background
Remote unsupervised cognitive assessments have the potential to complement and facilitate cognitive assessment in clinical and research settings.
Method
Here we evaluate the usability, validity and reliability of unsupervised remote memory assessments via mobile devices (see Figure 1) in individuals without dementia from the Swedish Bio...
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 m...
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...
Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-di...
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
While some memory decline in old age is “normal”, there are some older individuals with maintained high cognitive performance. Using a multimodal approach including neuroimaging, fitness, genetic and questionnaire data (Figure 1A), we aimed to identify factors that are related to successful cognitive aging and whether these differ betwee...
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...
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...
Alzheimer's disease (AD) is a major cause of dementia and cognitive decline. Here we assessed how episodic memory circuit dysfunction, a hallmark of AD, is related to the longitudinal cascade of AD biomarkers, neurodegeneration and cognition using data from the DZNE Longitudinal Cognitive Impairment and Dementia study. This data set is unique by in...
Individuals with Alzheimer′s disease dementia postmortem show Alzheimer′s disease pathology in and heterogeneous degeneration of the Substantia Nigra (SN). However, it is unclear how the SN degeneration is related to cognitive dysfunction across the Alzheimer′s disease dementia continuum. In this study, using data from a prospective dementia study...
INTRODUCTION
While incident ischemic lesions (IILs) are not unusual on follow‐up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown.
METHODS
In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing ris...
The efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation effects. Therefore, a taVNS setup was establi...
Introduction
We investigated the agreement between automated and gold‐standard manual transcriptions of telephone chatbot‐based semantic verbal fluency testing.
Methods
We examined 78 cases from the Screening over Speech in Unselected Populations for Clinical Trials in AD (PROSPECT‐AD) study, including cognitively normal individuals and individual...
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...
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 ac...
Background
While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse set...
Training studies typically investigate the cumulative rather than the analytically challenging immediate effect of exercise on cognitive outcomes. We investigated the dynamic interplay between single‐session exercise intensity and time‐locked recognition speed‐accuracy scores in older adults with Alzheimer's dementia (N = 17) undergoing a 24‐week d...
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),...
Background
Blood-brain barrier (BBB) alterations may contribute to AD pathology through various mechanisms, including impaired amyloid-β (Aβ) clearance and neuroinflammation. Soluble platelet-derived growth factor receptor beta (sPDGFRβ) has emerged as a potential biomarker for BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DC...
The efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation effects. Therefore, a taVNS setup was establi...
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,...
INTRODUCTION: The Locus Coeruleus (LC) is linked to the development and pathophysiology of neurodegenerative diseases such as Alzheimer's Disease (AD). Magnetic Resonance Imaging based LC features have shown potential to assess LC integrity in vivo.
METHODS: We present a Deep Learning based LC segmentation and feature extraction method: ELSI-Net an...
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
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...
The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution f...
Mnemonic discrimination (MD), the ability to distinguish between similar experiences in memory, is essential for memory precision. We hypothesized that training mnemonic discrimination should improve memory precision by increasing the neural activity differences between a new experience and a similar familiar experience (repeat). Participants perfo...
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...
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),...
INTRODUCTION
Remote unsupervised cognitive assessments have the potential to complement and facilitate cognitive assessment in clinical and research settings.
METHODS
Here, we evaluate the usability, validity, and reliability of unsupervised remote memory assessments via mobile devices in individuals without dementia from the Swedish BioFINDER‐2 s...