Publications by authors named "Eric Westman"

272 Publications

Deep learning from MRI-derived labels enables automatic brain tissue classification on human brain CT.

Neuroimage 2021 Sep 25;244:118606. Epub 2021 Sep 25.

Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Psychiatry and Neurochemistry, Institute of Physiology and Neuroscience, University of Gothenburg, Gothenburg, Sweden; Dementia Research Centre, Institute of Neurology, University College London, London, UK; Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address:

Automatic methods for feature extraction, volumetry, and morphometric analysis in clinical neuroscience typically operate on images obtained with magnetic resonance (MR) imaging equipment. Although CT scans are less expensive to acquire and more widely available than MR scans, their application is currently limited to the visual assessment of brain integrity and the exclusion of co-pathologies. CT has rarely been used for tissue classification because the contrast between grey matter and white matter was considered insufficient. In this study, we propose an automatic method for segmenting grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), and intracranial volume (ICV) from head CT images. A U-Net deep learning model was trained and validated on CT images with MRI-derived segmentation labels. We used data from 744 participants of the Gothenburg H70 Birth Cohort Studies for whom CT and T1-weighted MR images had been acquired on the same day. Our proposed model predicted brain tissue classes accurately from unseen CT images (Dice coefficients of 0.79, 0.82, 0.75, 0.93 and 0.98 for GM, WM, CSF, brain volume and ICV, respectively). To contextualize these results, we generated benchmarks based on established MR-based methods and intentional image degradation. Our findings demonstrate that CT-derived segmentations can be used to delineate and quantify brain tissues, opening new possibilities for the use of CT in clinical practice and research.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118606DOI Listing
September 2021

Atrial Fibrillation, Stroke, and Silent Cerebrovascular Disease: A Population-based MRI Study.

Neurology 2021 10 14;97(16):e1608-e1619. Epub 2021 Sep 14.

From the Institute of Neuroscience and Physiology (L.R., S.Sacuiu, H.W., J.N., X.G., S.K., A.Z., I.S.), Sahlgrenska Academy, Centre for Ageing and Health at the University of Gothenburg; Department of Psychiatry Cognition and Old Age Psychiatry (L.R., S.S., J.N., S.K., I.S.), Sahlgrenska University Hospital, Region Västra Götaland, Mölndal; Department of Mood Disorders (X.G.), Sahlgrenska University Hospital, Region Västra Götaland, Göteborg; Division of Clinical Geriatrics (S.Shams, J.B.P., L.-O.W., E.W.), Centre for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden; Department of Radiology (S.S.), Stanford, CA; and Clinical Memory Research Unit (J.B.P.), Department of Clinical Sciences, Malmö, Lund University, Sweden.

Background And Objectives: Atrial fibrillation (AF) has been associated with cognitive decline and dementia. However, the mechanisms behind these associations are not clear. Examination of cerebrovascular pathology on MRI may shed light on how AF affects the brain. This study aimed to determine whether AF is associated with a broad range of cerebrovascular diseases beyond the well-known association with symptomatic stroke, including silent infarcts and markers of small vessel disease, i.e., cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and lacunes, in a population-based sample of 70-year-olds.

Methods: Data were obtained from the Gothenburg H70 Birth Cohort Studies, in which individuals are invited based on birthdate. This study has a cross-sectional design and includes individuals born in 1944 who underwent structural brain MRI in 2014 to 2017. AF diagnoses were based on self-report, ECG, and register data. Symptomatic stroke was based on self-report, proxy interviews, and register data. Brain infarcts and CMBs were assessed by a radiologist. WMH volumes were measured on fluid-attenuated inversion recovery images with the Lesion Segmentation Tool. Multivariable logistic regression was used to study the association between AF and infarcts/CMBs, and multivariable linear regression was used to study the association between AF and WMHs.

Results: A total of 776 individuals were included, and 65 (8.4%) had AF. AF was associated with symptomatic stroke (odds ratio [OR] 4.5, 95% confidence interval [CI] 2.1-9.5) and MRI findings of large infarcts (OR 5.0, 95% CI 1.5-15.9), lacunes (OR 2.7, 95% CI 1.2-5.6), and silent brain infarcts (OR 3.5; 95% CI 1.6-7.4). Among those with symptomatic stroke, individuals with AF had larger WMH volumes (0.0137 mL/total intracranial volume [TIV], 95% CI 0.0074-0.0252) compared to those without AF (0.0043 mL/TIV, 95% CI 0.0029-0.0064). There was no association between AF and WMH volumes among those without symptomatic stroke. In addition, AF was associated to CMBs in the frontal lobe.

Discussion: AF was associated with a broad range of cerebrovascular pathologies. Further research is needed to establish whether cerebrovascular MRI markers can be added to current treatment guidelines to further personalize anticoagulant treatment in patients with AF and to further characterize the pathogenetic processes underlying the associations between AF and cerebrovascular diseases, as well as dementia.
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http://dx.doi.org/10.1212/WNL.0000000000012675DOI Listing
October 2021

The carbohydrate-insulin model: a physiological perspective on the obesity pandemic.

Am J Clin Nutr 2021 Sep 13. Epub 2021 Sep 13.

New Balance Foundation Obesity Prevention Center, Boston Children's Hospital, Boston, MA, USA.

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body-resulting from the hormonal responses to a high-glycemic-load diet-drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.
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http://dx.doi.org/10.1093/ajcn/nqab270DOI Listing
September 2021

Effects of a Highly Challenging Balance Training Program on Motor Function and Brain Structure in Parkinson's Disease.

J Parkinsons Dis 2021 ;11(4):2057-2071

Division of Physiotherapy, Department of Neurobiology, Care sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Background: Parkinson's disease (PD) is characterized by motor deficits and brain alterations having a detrimental impact on balance, gait, and cognition. Intensive physical exercise can induce changes in the neural system, potentially counteracting neurodegeneration in PD and improving clinical symptoms.

Objective: This randomized controlled trial investigated effects of a highly challenging, cognitively demanding, balance and gait training (HiBalance) program in participants with PD on brain structure.

Methods: 95 participants were assigned to either the HiBalance or an active control speech training program. The group-based interventions were performed in 1-hour sessions, twice per week over a 10-week period. Participants underwent balance, gait, cognitive function, and structural magnetic resonance imaging assessments before and after the interventions. Voxel-based morphometry was analyzed in 34 HiBalance and 31 active controls. Additionally, structural covariance networks were assessed.

Results: There was no significant time by group interaction between the HiBalance and control training in balance, gait, or brain volume. Within-HiBalance-group analyses showed higher left putamen volumes post-training. In repeated measures correlation a positive linear, non-significant relationship between gait speed and putamen volume was revealed. In the HiBalance group we found community structure changes and stronger thalamic-cerebellar connectivity in structural covariance networks. Neither brain volume changes nor topology changes were found for the active controls after the training.

Conclusion: Thus, subtle structural brain changes occur after balance and gait training. Future studies need to determine whether training modifications or other assessment methods lead to stronger effects.
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http://dx.doi.org/10.3233/JPD-212801DOI Listing
January 2021

Assessment of Tau Pathology as Measured by 18F-THK5317 and 18F-Flortaucipir PET and Their Relation to Brain Atrophy and Cognition in Alzheimer's Disease.

J Alzheimers Dis 2021 Sep 9. Epub 2021 Sep 9.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Background: In Alzheimer's disease (AD), the abnormal aggregation of hyperphosphorylated tau leads to synaptic dysfunction and neurodegeneration. Recently developed tau PET imaging tracers are candidate biomarkers for diagnosis and staging of AD.

Objective: We aimed to investigate the discriminative ability of 18F-THK5317 and 18F-flortaucipir tracers and brain atrophy at different stages of AD, and their respective associations with cognition.

Methods: Two cohorts, each including 29 participants (healthy controls [HC], prodromal AD, and AD dementia patients), underwent 18F-THK5317 or 18F-flortaucipir PET, T1-weighted MRI, and neuropsychological assessment. For each subject, we quantified regional 18F-THK5317 and 18F-flortaucipir uptake within six bilateral and two composite regions of interest. We assessed global brain atrophy for each individual by quantifying the brain volume index, a measure of brain volume-to-cerebrospinal fluid ratio. We then quantified the discriminative ability of regional 18F-THK5317, 18F-flortaucipir, and brain volume index between diagnostic groups, and their associations with cognition in patients.

Results: Both 18F-THK5317 and 18F-flortaucipir outperformed global brain atrophy in discriminating between HC and both prodromal AD and AD dementia groups. 18F-THK5317 provided the highest discriminative ability between HC and prodromal AD groups. 18F-flortaucipir performed best at discriminating between prodromal and dementia stages of AD. Across all patients, both tau tracers were predictive of RAVL learning, but only 18F-flortaucipir predicted MMSE.

Conclusion: Our results warrant further in vivo head-to-head and antemortem-postmortem evaluations. These validation studies are needed to select tracers with high clinical validity as biomarkers for early diagnosis, prognosis, and disease staging, which will facilitate their incorporation in clinical practice and therapeutic trials.
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http://dx.doi.org/10.3233/JAD-210614DOI Listing
September 2021

The Cognitive Connectome in Healthy Aging.

Front Aging Neurosci 2021 18;13:694254. Epub 2021 Aug 18.

Department of Clinical Psychology, Psychobiology and Methodology, Faculty of Psychology, University of La Laguna, La Laguna, Spain.

: Cognitive aging has been extensively investigated using both univariate and multivariate analyses. Sophisticated multivariate approaches such as graph theory could potentially capture unknown complex associations between multiple cognitive variables. The aim of this study was to assess whether cognition is organized into a structure that could be called the "cognitive connectome," and whether such connectome differs between age groups. : A total of 334 cognitively unimpaired individuals were stratified into early-middle-age (37-50 years, = 110), late-middle-age (51-64 years, = 106), and elderly (65-78 years, = 118) groups. We built cognitive networks from 47 cognitive variables for each age group using graph theory and compared the groups using different global and nodal graph measures. : We identified a cognitive connectome characterized by five modules: verbal memory, visual memory-visuospatial abilities, procedural memory, executive-premotor functions, and processing speed. The elderly group showed reduced transitivity and average strength as well as increased global efficiency compared with the early-middle-age group. The late-middle-age group showed reduced global and local efficiency and modularity compared with the early-middle-age group. Nodal analyses showed the important role of executive functions and processing speed in explaining the differences between age groups. : We identified a cognitive connectome that is rather stable during aging in cognitively healthy individuals, with the observed differences highlighting the important role of executive functions and processing speed. We translated the connectome concept from the neuroimaging field to cognitive data, demonstrating its potential to advance our understanding of the complexity of cognitive aging.
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http://dx.doi.org/10.3389/fnagi.2021.694254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416612PMC
August 2021

Type 2 Diabetes Mellitus: A Pathophysiologic Perspective.

Authors:
Eric C Westman

Front Nutr 2021 10;8:707371. Epub 2021 Aug 10.

Department of Medicine, Duke University, Durham, NC, United States.

Type 2 Diabetes Mellitus (T2DM) is characterized by chronically elevated blood glucose (hyperglycemia) and elevated blood insulin (hyperinsulinemia). When the blood glucose concentration is 100 milligrams/deciliter the bloodstream of an average adult contains about 5-10 grams of glucose. Carbohydrate-restricted diets have been used effectively to treat obesity and T2DM for over 100 years, and their effectiveness may simply be due to lowering the dietary contribution to glucose and insulin levels, which then leads to improvements in hyperglycemia and hyperinsulinemia. Treatments for T2DM that lead to improvements in glycemic control and reductions in blood insulin levels are sensible based on this pathophysiologic perspective. In this article, a pathophysiological argument for using carbohydrate restriction to treat T2DM will be made.
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http://dx.doi.org/10.3389/fnut.2021.707371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384107PMC
August 2021

The interplay between gray matter and white matter neurodegeneration in subjective cognitive decline.

Aging (Albany NY) 2021 08 25;13(16):19963-19977. Epub 2021 Aug 25.

Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society (NVS), Karolinska Institutet (KI), Stockholm, Sweden.

Aims: To investigate the interplay between gray matter (GM) and white matter (WM) neurodegeneration in subjective cognitive decline (SCD), including thickness across the whole cortical mantle, hippocampal volume, and integrity across the whole WM.

Methods: We included 225 cognitively unimpaired individuals from a community-based cohort. Subjective cognitive complaints were assessed through 9 questions covering amnestic and non-amnestic cognitive domains. In our cohort, 123 individuals endorsed from one to six subjective cognitive complaints (i.e. they fulfilled the diagnostic criteria for SCD), while 102 individuals reported zero complaints. GM neurodegeneration was assessed through measures of cortical thickness across the whole mantle and hippocampal volume. WM neurodegeneration was assessed through measures of mean diffusivity (MD) across the whole WM skeleton. Mediation analysis and multiple linear regression were conducted to investigate the interplay between the measures of GM and WM neurodegeneration.

Results: A higher number of complaints was associated with reduced hippocampal volume, cortical thinning in several frontal and temporal areas and the insula, and higher MD across the WM skeleton, with a tendency to spare the occipital lobe. SCD-related cortical thinning and increased MD were associated with each other and jointly contributed to complaints, but the contribution of cortical thinning to the number of complaints was stronger.

Conclusions: Neurodegeneration processes affecting the GM and WM seem to be associated with each other in SCD and include brain areas other than those typically targeted by Alzheimer's disease. Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.
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http://dx.doi.org/10.18632/aging.203467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436909PMC
August 2021

Carbohydrate-restricted diets and Type 1 diabetes mellitus: research considerations.

Curr Opin Endocrinol Diabetes Obes 2021 10;28(5):437-440

Duke University, Durham, North Carolina, USA.

Purpose Of Review: Type 1 diabetes mellitus (T1DM) is managed via careful control of blood glucose, exogenous insulin, diet, exercise, and other physiologic factors. Interestingly, the dietary recommendations for T1DM have had very little systematic research. Many clinical observations, as well as emerging research studies, have noted that a carbohydrate-restricted diet can lead to normalization of blood glucoses with reduction in hypoglycemic reactions among motivated individuals.

Recent Findings: In this paper, we review observations of carbohydrate restriction and propose a series of studies to test two levels of dietary carbohydrate intake for the management of individuals affected by T1DM. We recommend that the studies start in otherwise healthy adults with hemoglobin A1c > 8%, and then progress to more complicated populations including children, those with secondary complications and/or good glycemic control. Larger, long-term studies would then address growth in children, and diabetic complications including cardiovascular outcomes.

Summary: Due to the clinical observations of improvements using carbohydrate-restricted nutrition for T1DM, we recommend that these types of studies addressing the level of dietary carbohydrate be urgently conducted.
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http://dx.doi.org/10.1097/MED.0000000000000669DOI Listing
October 2021

Cerebrovascular Disease and Depressive Symptomatology in Individuals With Subjective Cognitive Decline: A Community-Based Study.

Front Aging Neurosci 2021 27;13:656990. Epub 2021 Jul 27.

Department of Neurobiology, Care Sciences, and Society, Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institutet (KI), Stockholm, Sweden.

Subjective cognitive decline (SCD) may be the first sign of Alzheimer's disease (AD), but it can also reflect other pathologies such as cerebrovascular disease or conditions like depressive symptomatology. The role of depressive symptomatology in SCD is controversial. We investigated the association between depressive symptomatology, cerebrovascular disease, and SCD. We recruited 225 cognitively unimpaired individuals from a prospective community-based study [mean age (SD) = 54.64 (10.18); age range 35-77 years; 55% women; 123 individuals with one or more subjective cognitive complaints, 102 individuals with zero complaints]. SCD was assessed with a scale of 9 memory and non-memory subjective complaints. Depressive symptomatology was assessed with established questionnaires. Cerebrovascular disease was assessed with magnetic resonance imaging markers of white matter signal abnormalities (WMSA) and mean diffusivity (MD). We combined correlation, multiple regression, and mediation analyses to investigate the association between depressive symptomatology, cerebrovascular disease, and SCD. We found that SCD was associated with more cerebrovascular disease, older age, and increased depressive symptomatology. In turn, depressive symptomatology was not associated with cerebrovascular disease. Variability in MD was mediated by WMSA burden, presumably reflecting cerebrovascular disease. We conclude that, in our community-based cohort, depressive symptomatology is associated with SCD but not with cerebrovascular disease. In addition, depressive symptomatology did not influence the association between cerebrovascular disease and SCD. We suggest that therapeutic interventions for depressive symptomatology could alleviate the psychological burden of negative emotions in people with SCD, and intervening on vascular risk factors to reduce cerebrovascular disease should be tested as an opportunity to minimize neurodegeneration in SCD individuals from the community.
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http://dx.doi.org/10.3389/fnagi.2021.656990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353130PMC
July 2021

Editorial: Carbohydrate restriction: from the 'bedside' to the 'bench'.

Authors:
Eric C Westman

Curr Opin Endocrinol Diabetes Obes 2021 10;28(5):435-436

Division of General Internal Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

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http://dx.doi.org/10.1097/MED.0000000000000667DOI Listing
October 2021

A case study of overfeeding 3 different diets.

Curr Opin Endocrinol Diabetes Obes 2021 10;28(5):446-452

Division of General Internal Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.

Purpose Of Review: Quality or quantity of food has been at the heart of the diet debate for decades and will seemingly continue for many to come unless tightly controlled studies are conducted. To our knowledge, there has never been an overfeeding study comparing the effects of multiple diets.

Recent Findings: This study reports a case study of an individual who ate 5800 Calories per day of 3 different diets for 21 days at a time. The 3 different diets were low-carb, low-fat, and very-low-fat vegan. The weight gain over 21 days was 1.3 kg for low-carb, 7.1 kg for low-fat, and 4.7 kg for very-low-fat vegan.

Summary: In this n-of-1 study, consuming 5800 Calories/day of 3 different diets for 21 days did not lead to the same amount of weight gain. Further research should be conducted on how the human body gains weight with an emphasis on how different foods affect physiology. If these findings are replicated, there would be many ramifications for obesity treatment and healthcare guidelines.
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http://dx.doi.org/10.1097/MED.0000000000000668DOI Listing
October 2021

Seeing Beyond Your Nose? The Effects of Lifelong Olfactory Sensory Deprivation on Cerebral Audio-visual Integration.

Neuroscience 2021 09 24;472:1-10. Epub 2021 Jul 24.

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Monell Chemical Senses Center, Philadelphia, PA, United States; Department of Psychology, University of Pennsylvania, Philadelphia, United States; Stockholm University Brain Imaging Centre, Stockholm University, Stockholm, Sweden.

Lifelong auditory and visual sensory deprivation have been demonstrated to alter both perceptual acuity and the neural processing of remaining senses. Recently, it was demonstrated that individuals with anosmia, i.e. complete olfactory sensory deprivation, displayed enhanced multisensory integration performance. Whether this ability is due to a reorganization of olfactory processing regions to focus on cross-modal multisensory information or whether it is due to enhanced processing within multisensory integration regions is not known. To dissociate these two outcomes, we investigated the neural processing of dynamic audio-visual stimuli in individuals with congenital anosmia and matched controls (both groups, n = 33) using functional magnetic resonance imaging. Specifically, we assessed whether the previously demonstrated multisensory enhancement is related to cross-modal processing of multisensory stimuli in olfactory associated regions, the piriform and olfactory orbitofrontal cortices, or enhanced multisensory processing in established multisensory integration regions, the superior temporal and intraparietal sulci. No significant group differences were found in the a priori hypothesized regions using region of interest analyses. However, exploratory whole-brain analysis suggested higher activation related to multisensory integration within the posterior superior temporal sulcus, in close proximity to the multisensory region of interest, in individuals with congenital anosmia. No group differences were demonstrated in olfactory associated regions. Although results were outside our hypothesized regions, combined, they tentatively suggest that enhanced processing of audio-visual stimuli in individuals with congenital anosmia may be mediated by multisensory, and not primary sensory, cerebral regions.
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http://dx.doi.org/10.1016/j.neuroscience.2021.07.017DOI Listing
September 2021

Functional Connectivity and Compensation of Phonemic Fluency in Aging.

Front Aging Neurosci 2021 5;13:644611. Epub 2021 Jul 5.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.

Neural compensatory mechanisms associated with broad cognitive abilities have been studied. However, those associated with specific cognitive subdomains (e.g., verbal fluency) remain to be investigated in healthy aging. Here, we delineate: (a) neural substrates of verbal (phonemic) fluency, and (b) compensatory mechanisms mediating the association between these neural substrates and phonemic fluency. We analyzed resting-state functional magnetic resonance imaging from 133 right-handed, cognitively normal individuals who underwent the Controlled Oral Word Association Test (COWAT) to record their phonemic fluency. We evaluated functional connectivity in an established and extended language network comprising Wernicke, Broca, thalamic and anti-correlated modules. (a) We conducted voxel-wise multiple linear regression to identify the brain areas associated with phonemic fluency. (b) We used mediation effects of cognitive reserve, measured by the Wechsler Adult Intelligence Scale-Information subtest, upon the association between functional connectivity and phonemic fluency tested to investigate compensation. We found that: (a) Greater functional connectivity between the Wernicke module and brain areas within the anti-correlated module was associated with better performance in phonemic fluency, (b) Cognitive reserve was an unlikely mediator in younger adults. In contrast, cognitive reserve was a partial mediator of the association between functional connectivity and phonemic fluency in older adults, likely representing compensation to counter the effect of aging. We conclude that in healthy aging, higher performance in phonemic fluency at older ages could be attributed to greater functional connectivity partially facilitated by higher cognitive reserve, presumably reflecting compensatory mechanisms to minimize the effect of aging.
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http://dx.doi.org/10.3389/fnagi.2021.644611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287584PMC
July 2021

Metabolic syndrome is associated with poor cognition: a population-based study of 70-year-olds without dementia.

J Gerontol A Biol Sci Med Sci 2021 Jul 6. Epub 2021 Jul 6.

Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Sweden.

Background: Individual conditions of metabolic syndrome (MetS) have been related to dementia, however, their combined impact on the preclinical stage is unknown. We investigated the associations between MetS and domain-specific cognitive function as well as the role of sociodemographic, cardiovascular, and genetic factors.

Methods: Within the Gothenburg H70 Birth Cohort Study-Birth cohort 1944, 1131 dementia-free participants (aged 70 years) were examined during 2014-2016. MetS (central obesity plus at least two factors [reduced HDL-cholesterol, elevated triglycerides, blood pressure, or blood glucose]) was identified according to the International Diabetes Federation criteria. Five cognitive domains (memory, attention/perceptual speed, executive function, verbal fluency, visuospatial abilities) were generated after z-standardizing raw scores from ten neuropsychological tests. Education, heart disease, claudication (indicating peripheral atherosclerosis), and apolipoprotein (APOE) genotype were ascertained by trained staff. Data were analyzed with linear regression models.

Results: Overall, 618 participants (55%) had MetS. In multi-adjusted linear regressions, MetS was related to poorer performance in attention/perceptual speed (β -0.14 [95% CI -0.25, -0.02]), executive function (β -0.12 [95% CI -0.23, -0.01]), and verbal fluency (β -0.19 [95% CI -0.30, -0.08]). These associations were present only among individuals who did not carry any APOE-ε4 allele or were highly educated. However, among those with MetS, high education was related to better cognitive performance. MetS together with comorbid heart disease or claudication was associated with even worse cognitive performance than each alone.

Conclusions: MetS is associated with poor attention/perceptual speed, executive function, and verbal fluency performance. Education, APOE-ε4 allele, and comorbid cardiovascular disease influenced the observed associations.
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http://dx.doi.org/10.1093/gerona/glab195DOI Listing
July 2021

The Use of Magnetic Resonance Imaging Techniques in Assessing the Effects of Alcohol Consumption and Heavy Drinking on the Adolescent Brain: A Scoping Review Protocol.

Brain Sci 2021 Jun 9;11(6). Epub 2021 Jun 9.

Alcohol, Tobacco and Other Drug Research Unit, South African Medical Research Council, Cape Town 7505, South Africa.

: Alcohol consumption, specifically heavy drinking during adolescence, has been shown to be accompanied by adverse structural brain changes in adolescent drinkers. This scoping review will aim to quantify and evaluate the quality of studies in which magnetic resonance imaging (MRI) techniques are used to assess regional brain deficits among adolescents who consume alcohol. : This scoping review will be conducted following the Arksey and O'Malley scoping review methodology framework and will be reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews (PRISMA-ScR) guidelines. Literature will be searched for the period January 1999 to March 2021. Two reviewers will independently screen titles/abstracts and full-texts in two consecutive screening stages. Eligible studies will be independently reviewed to ensure that inclusion criteria are met. Cohen's Kappa (κ) will be used to calculate inter-rater agreement. A third reviewer will resolve any disagreements. The Joanna Briggs Institute (JBI) Appraisal Tools will be used for quality appraisal of the included studies. Findings will be reported by means of a narrative overview, tabular presentation of study characteristics, and quality assessment, and a thematic analysis of major themes. This scoping review has been registered with the Open Science Framework. : Scoping reviews do not require ethical approval, however, this review forms part of a larger study that has obtained approval from the Faculty of Health and Medical Sciences, Health Research Ethics Committee at Stellenbosch University (S20/04/086). Findings will be disseminated by means of peer-reviewed publications and conferences.
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http://dx.doi.org/10.3390/brainsci11060764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228161PMC
June 2021

Cerebrovascular disease, neurodegeneration, and clinical phenotype in dementia with Lewy bodies.

Neurobiol Aging 2021 09 14;105:252-261. Epub 2021 May 14.

Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address:

We investigated whether cerebrovascular disease contributes to neurodegeneration and clinical phenotype in dementia with Lewy bodies (DLB). Regional cortical thickness and subcortical gray matter volumes were estimated from structural magnetic resonance imaging (MRI) in 165 DLB patients. Cortical and subcortical infarcts were recorded and white matter hyperintensities (WMHs) were assessed. Subcortical only infarcts were more frequent (13.3%) than cortical only infarcts (3.1%) or both subcortical and cortical infarcts (2.4%). Infarcts, irrespective of type, were associated with WMHs. A higher WMH volume was associated with thinner orbitofrontal, retrosplenial, and posterior cingulate cortices, smaller thalamus and pallidum, and larger caudate volume. A higher WMH volume was associated with the presence of visual hallucinations and lower global cognitive performance, and tended to be associated with the absence of probable rapid eye movement sleep behavior disorder. Presence of infarcts was associated with the absence of parkinsonism. We conclude that cerebrovascular disease is associated with gray matter neurodegeneration in patients with probable DLB, which may have implications for the multifactorial treatment of probable DLB.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.04.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338792PMC
September 2021

Cognitive changes and neural correlates after oral rehabilitation procedures in older adults: a protocol for an interventional study.

BMC Oral Health 2021 06 9;21(1):297. Epub 2021 Jun 9.

Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, Alfred Nobels Allé 8, Box 4064, 141 04, Huddinge, Sweden.

Background: Epidemiological studies show an association between masticatory function and cognitive impairment. This has further strengthened the notion that tooth loss and impaired masticatory function may be risk factors for dementia and cognitive decline. Animal experiments have indicated a causal relationship and several possible mechanisms have been discussed. This evidence is, however, lacking in humans. Therefore, in the current interventional study, we aim to investigate the effect of rehabilitation of masticatory function on cognition in older adults.

Methods: Eighty patients indicated for prosthodontic rehabilitation will be randomly assigned to an experimental or a control group. Participants will conduct neuropsychological assessments, masticatory performance tests, saliva tests, optional magnetic resonance imaging, and answer questionnaires on oral health impact profiles and hospital anxiety and depression scale before, 3 months, and 1 year after oral rehabilitation. The difference between the two groups is that the control group will be tested an additional time, (at an interval of about 3 months) before the onset of the oral rehabilitation procedure. The primary outcome is a change in measures of episodic memory performance.

Discussion: Although tooth loss and masticatory function are widespread in older people, it is still an underexplored modifiable risk factor potentially contributing to the development of cognitive impairment. If rehabilitation of masticatory function shows positive effects on the neurocognitive function, this will have great implications on future health care for patients with impaired masticatory status. The present project may provide a new avenue for the prevention of cognitive decline in older individuals.

Trial Registration: The protocol for the study was retrospectively registered in ClinicalTrials.gov Identifier: NCT04458207, dated 02-07-2020.
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http://dx.doi.org/10.1186/s12903-021-01654-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191046PMC
June 2021

Inter-Cohort Validation of SuStaIn Model for Alzheimer's Disease.

Front Big Data 2021 20;4:661110. Epub 2021 May 20.

Laboratory of Neuroinformatics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Alzheimer's disease (AD) is a neurodegenerative disorder which spans several years from preclinical manifestations to dementia. In recent years, interest in the application of machine learning (ML) algorithms to personalized medicine has grown considerably, and a major challenge that such models face is the transferability from the research settings to clinical practice. The objective of this work was to demonstrate the transferability of the Subtype and Stage Inference (SuStaIn) model from well-characterized research data set, employed as training set, to independent less-structured and heterogeneous test sets representative of the clinical setting. The training set was composed of MRI data of 1043 subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI), and the test set was composed of data from 767 subjects from OASIS, Pharma-Cog, and ViTA clinical datasets. Both sets included subjects covering the entire spectrum of AD, and for both sets volumes of relevant brain regions were derived from T1-3D MRI scans processed with Freesurfer v5.3 cross-sectional stream. In order to assess the predictive value of the model, subpopulations of subjects with stable mild cognitive impairment (MCI) and MCIs that progressed to AD dementia (pMCI) were identified in both sets. SuStaIn identified three disease subtypes, of which the most prevalent corresponded to the typical atrophy pattern of AD. The other SuStaIn subtypes exhibited similarities with the previously defined hippocampal sparing and limbic predominant atrophy patterns of AD. Subject subtyping proved to be consistent in time for all cohorts and the staging provided by the model was correlated with cognitive performance. Classification of subjects on the basis of a combination of SuStaIn subtype and stage, mini mental state examination and amyloid-β cerebrospinal fluid concentration was proven to predict conversion from MCI to AD dementia on par with other novel statistical algorithms, with ROC curves that were not statistically different for the training and test sets and with area under curve respectively equal to 0.77 and 0.76. This study proves the transferability of a SuStaIn model for AD from research data to less-structured clinical cohorts, and indicates transferability to the clinical setting.
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http://dx.doi.org/10.3389/fdata.2021.661110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173213PMC
May 2021

Cognitive dedifferentiation as a function of cognitive impairment in the ADNI and MemClin cohorts.

Aging (Albany NY) 2021 05 26;13(10):13430-13442. Epub 2021 May 26.

Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.

The cause of cognitive dedifferentiation has been suggested as specific to late-life abnormal cognitive decline rather than a general feature of aging. This hypothesis was tested in two large cohorts with different characteristics. Individuals (n = 2710) were identified in the Alzheimer's Disease Neuroimaging Initiative (ADNI) research database (n = 1282) in North America, and in the naturalistic multi-site MemClin Project database (n = 1223), the latter recruiting from 9 out of 10 memory clinics in the greater Stockholm catchment area in Sweden. Comprehensive neuropsychological testing informed diagnosis of dementia, mild cognitive impairment (MCI), or subjective cognitive impairment (SCI). Diagnosis was further collapsed into cognitive impairment (CI: MCI or dementia) vs no cognitive impairment (NCI). After matching, loadings on the first principal component were higher in the CI vs NCI group in both ADNI (53.1% versus 38.3%) and MemClin (33.3% vs 30.8%). Correlations of all paired combinations of individual tests by diagnostic group were also stronger in the CI group in both ADNI (mean inter-test r = 0.51 vs r = 0.33, p < 0.001) and MemClin (r = 0.31 vs r = 0.27, p = 0.042). Dedifferentiation was explained by cognitive impairment when controlling for age, sex, and education. This finding replicated across two separate, large cohorts of older individuals. Knowledge that the structure of human cognition becomes less diversified and more dependent on general intelligence as a function of cognitive impairment should inform clinical assessment and care for these patients as their neurodegeneration progresses.
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http://dx.doi.org/10.18632/aging.203108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202862PMC
May 2021

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

Department of Medicine and Surgery, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.

Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts.

Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives.

Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes.

Discussion: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.
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http://dx.doi.org/10.1002/alz.12365DOI Listing
May 2021

Cortical Networks Underpinning Compensation of Verbal Fluency in Normal Aging.

Cereb Cortex 2021 Jul;31(8):3832-3845

Department of Clinical Psychology, Psychobiology and Methodology, Faculty of Health Science, Section of Psychology and Speech Therapy, University of La Laguna, La Laguna, Tenerife 38 200, Spain.

Elucidating compensatory mechanisms underpinning phonemic fluency (PF) may help to minimize its decline due to normal aging or neurodegenerative diseases. We investigated cortical brain networks potentially underpinning compensation of age-related differences in PF. Using graph theory, we constructed networks from measures of thickness for PF, semantic, and executive-visuospatial cortical networks. A total of 267 cognitively healthy individuals were divided into younger age (YA, 38-58 years) and older age (OA, 59-79 years) groups with low performance (LP) and high performance (HP) in PF: YA-LP, YA-HP, OA-LP, OA-HP. We found that the same pattern of reduced efficiency and increased transitivity was associated with both HP (compensation) and OA (aberrant network organization) in the PF and semantic cortical networks. When compared with the OA-LP group, the higher PF performance in the OA-HP group was associated with more segregated PF and semantic cortical networks, greater participation of frontal nodes, and stronger correlations within the PF cortical network. We conclude that more segregated cortical networks with strong involvement of frontal nodes seemed to allow older adults to maintain their high PF performance. Nodal analyses and measures of strength were helpful to disentangle compensation from the aberrant network organization associated with OA.
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http://dx.doi.org/10.1093/cercor/bhab052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258442PMC
July 2021

Brain Atrophy Subtypes and the ATN Classification Scheme in Alzheimer's Disease.

Neurodegener Dis 2020 31;20(4):153-164. Epub 2021 Mar 31.

Division of Clinical Geriatrics, Department of Neurobiology, Karolinska Institutet, Center for Alzheimer Research, Care Sciences, and Society, Stockholm, Sweden.

Introduction: We investigated the association between atrophy subtypes of Alzheimer's disease (AD), the ATN classification scheme, and key demographic and clinical factors in 2 cohorts with different source characteristics (a highly selective research-oriented cohort, the Alzheimer's Disease Neuroimaging Initiative [ADNI]; and a naturalistic heterogeneous clinically oriented cohort, Karolinska Imaging Dementia Study [KIDS]).

Methods: A total of 382 AD patients were included. Factorial analysis of mixed data was used to investigate associations between AD subtypes based on brain atrophy patterns, ATN profiles based on cerebrospinal fluid biomarkers, and age, sex, Mini Mental State Examination (MMSE), cerebrovascular disease (burden of white matter signal abnormalities, WMSAs), and APOE genotype.

Results: Older patients with high WMSA burden, belonging to the typical AD subtype and showing A+T+N+ or A+T+N- profiles clustered together and were mainly from ADNI. Younger patients with low WMSA burden, limbic-predominant or minimal atrophy AD subtypes, and A+T-N- or A+T-N+ profiles clustered together and were mainly from KIDS. APOE ε4 carriers more frequently showed the A+T-N- and A+T+N- profiles.

Conclusions: Our findings align with the recent framework for biological subtypes of AD: the combination of risk factors, protective factors, and brain pathologies determines belonging of AD patients to distinct subtypes.
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http://dx.doi.org/10.1159/000515322DOI Listing
March 2021

Sex differences in CSF biomarkers for neurodegeneration and blood-brain barrier integrity.

Alzheimers Dement (Amst) 2021 17;13(1):e12141. Epub 2021 Mar 17.

Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden.

Introduction: As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (Q) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand.

Methods: Participants were derived from two Swedish samples: the population-based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, Q, n = 39252, age 0 to 95). In the population-based study, Q and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs). In the clinical cohort, Q and NfL sex differences were tested in relation to age.

Results: Men had higher Q and NfL concentrations and had higher Q and NfL concentrations from adolescence throughout life. NfL was not related to WML, but Q correlated positively with WMLs.

Discussion: The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.
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http://dx.doi.org/10.1002/dad2.12141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968119PMC
March 2021

Comparing different approaches for operationalizing subjective cognitive decline: impact on syndromic and biomarker profiles.

Sci Rep 2021 Feb 23;11(1):4356. Epub 2021 Feb 23.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

Subjective cognitive decline (SCD) has been proposed as a risk factor for future cognitive decline and dementia. Given the heterogeneity of SCD and the lack of consensus about how to classify this condition, different operationalization approaches still need to be compared. In this study, we used the same sample of individuals to compare  different SCD operationalization approaches. We included 399 cognitively healthy individuals from a community-based cohort. SCD was assessed through nine questions about memory and non-memory subjective complaints. We applied four approaches to operationalize SCD: two hypothesis-driven approaches and two data-driven approaches. We characterized the resulting groups from each operationalization approach using multivariate methods on comprehensive demographic, clinical, cognitive, and neuroimaging data. We identified two main phenotypes: an amnestic phenotype characterized by an Alzheimer's Disease (AD) signature pattern of brain atrophy; and an anomic phenotype, which was mainly related to cerebrovascular pathology. Furthermore, language complaints other than naming helped to identify a subgroup with subclinical cognitive impairment and difficulties in activities of daily living. This subgroup also showed an AD signature pattern of atrophy. The identification of SCD phenotypes, characterized by different syndromic and biomarker profiles, varies depending on the operationalization approach used. In this study we discuss how these findings may be used in clinical practice and research.
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http://dx.doi.org/10.1038/s41598-021-83428-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902653PMC
February 2021

Longitudinal deterioration of white-matter integrity: heterogeneity in the ageing population.

Brain Commun 2021 22;3(1):fcaa238. Epub 2021 Jan 22.

Department of Radiology, Mayo Clinic, Rochester, MN 559 05, USA.

Deterioration in white-matter health plays a role in cognitive ageing. Our goal was to discern heterogeneity of white-matter tract vulnerability in ageing using longitudinal imaging data (two to five imaging and cognitive assessments per participant) from a population-based sample of 553 elderly participants (age ≥60 years). We found that different clusters (healthy white matter, fast white-matter decliners and intermediate white-matter group) were heterogeneous in the spatial distribution of white-matter integrity, systemic health and cognitive trajectories. White-matter health of specific tracts (genu of corpus callosum, posterior corona radiata and anterior internal capsule) informed about cluster assignments. Not surprisingly, brain amyloidosis was not significantly different between clusters. Clusters had differential white-matter tract vulnerability to ageing (commissural fibres > association/brainstem fibres). Identification of vulnerable white-matter tracts is a valuable approach to assessing risk for cognitive decline.
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http://dx.doi.org/10.1093/braincomms/fcaa238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884606PMC
January 2021

Data-driven FDG-PET subtypes of Alzheimer's disease-related neurodegeneration.

Alzheimers Res Ther 2021 02 19;13(1):49. Epub 2021 Feb 19.

German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Rostock, Germany.

Background: Previous research has described distinct subtypes of Alzheimer's disease (AD) based on the differences in regional patterns of brain atrophy on MRI. We conducted a data-driven exploration of distinct AD neurodegeneration subtypes using FDG-PET as a sensitive molecular imaging marker of neurodegenerative processes.

Methods: Hierarchical clustering of voxel-wise FDG-PET data from 177 amyloid-positive patients with AD dementia enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used to identify distinct hypometabolic subtypes of AD, which were then further characterized with respect to clinical and biomarker characteristics. We then classified FDG-PET scans of 217 amyloid-positive patients with mild cognitive impairment ("prodromal AD") according to the identified subtypes and studied their domain-specific cognitive trajectories and progression to dementia over a follow-up interval of up to 72 months.

Results: Three main hypometabolic subtypes were identified: (i) "typical" (48.6%), showing a classic posterior temporo-parietal hypometabolic pattern; (ii) "limbic-predominant" (44.6%), characterized by old age and a memory-predominant cognitive profile; and (iii) a relatively rare "cortical-predominant" subtype (6.8%) characterized by younger age and more severe executive dysfunction. Subtypes classified in the prodromal AD sample demonstrated similar subtype characteristics as in the AD dementia sample and further showed differential courses of cognitive decline.

Conclusions: These findings complement recent research efforts on MRI-based identification of distinct AD atrophy subtypes and may provide a potentially more sensitive molecular imaging tool for early detection and characterization of AD-related neurodegeneration variants at prodromal disease stages.
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http://dx.doi.org/10.1186/s13195-021-00785-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896407PMC
February 2021

Effects of amyloid pathology and the APOE ε4 allele on the association between cerebrospinal fluid Aβ38 and Aβ40 and brain morphology in cognitively normal 70-years-olds.

Neurobiol Aging 2021 05 12;101:1-12. Epub 2021 Jan 12.

Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry Cognition and Old Age Psychiatry Clinic, Mölndal, Sweden; Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Mölndal, Sweden.

The association between cerebrospinal fluid (CSF) amyloid beta (Aβ) Aβ38 or Aβ40 and brain grey- and white matter integrity is poorly understood. We studied this in 213 cognitively normal 70-year-olds, and in subgroups defined by presence/absence of the APOE ε4 allele and Aβ pathology: Aβ-/APOE-, Aβ+/APOE-, Aβ-/APOE+ and Aβ+/APOE+. CSF Aβ was quantified using ELISA and genotyping for APOE was performed. Low CSF Aβ42 defined Aβ plaque pathology. Brain volumes were assessed using Freesurfer-5.3, and white matter integrity using tract-based statistics in FSL. Aβ38 and Aβ40 were positively correlated with cortical thickness, some subcortical volumes and white matter integrity in the total sample, and in 3 of the subgroups: Aβ-/APOE-, Aβ+/APOE- and Aβ-/APOE+. In Aβ+/APOE+ subjects, higher Aβ38 and Aβ40 were linked to reduced cortical thickness and subcortical volumes. We hypothesize that production of all Aβ species decrease in brain regions with atrophy. In Aβ+/APOE+, Aβ-dysregulation may be linked to cortical atrophy in which high Aβ levels is causing pathological changes in the gray matter of the brain.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.10.033DOI Listing
May 2021

The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer's disease.

Alzheimers Dement 2021 07 25;17(7):1145-1156. Epub 2021 Jan 25.

Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Introduction: This study investigated the diagnostic and disease-monitoring potential of plasma biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and cognitively unimpaired (CU) individuals.

Methods: Plasma was analyzed using Simoa assays from 99 CU, 107 MCI, and 103 AD dementia participants.

Results: Phosphorylated-tau181 (P-tau181), neurofilament light, amyloid-β (Aβ42/40), Total-tau and Glial fibrillary acidic protein were altered in AD dementia but P-tau181 significantly outperformed all biomarkers in differentiating AD dementia from CU (area under the curve [AUC] = 0.91). P-tau181 was increased in MCI converters compared to non-converters. Higher P-tau181 was associated with steeper cognitive decline and gray matter loss in temporal regions. Longitudinal change of P-tau181 was strongly associated with gray matter loss in the full sample and with Aβ measures in CU individuals.

Discussion: P-tau181 detected AD at MCI and dementia stages and was strongly associated with cognitive decline and gray matter loss. These findings highlight the potential value of plasma P-tau181 as a non-invasive and cost-effective diagnostic and prognostic biomarker in AD.
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http://dx.doi.org/10.1002/alz.12283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359457PMC
July 2021
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