Brain networks in aging and dementia

  This thesis describes neuroimaging techniques to investigate brain networks in healthy aging and dementia. Functional and structural brain networks change with healthy and pathological aging, with differences in network degeneration between different types of dementia. These disease-specific network differences suggest the potential of brain networks to improve diagnostic accuracy. However, at this moment, our findings are only applicable for groups of patients and not yet suitable as a diagnostic tool on an individual basis.  Printing of this thesis was funded by Alzheimer Nederland, ChipSoft B.V., InfoCortex UG, Internationale Stichting Alzheimer Onderzoek, Nutricia Advanced Medical Nutrition, Sectra Benelux, TauRx Therapeutics Ltd., and Leiden University.Multivariate analysis of psychological dat

An understanding of (mis)understanders: exploring the underlying mechanisms of concept learning using functional magnetic resonance imaging

Obtaining adequate understanding of scientific concepts is considered challenging due to learners' misconceptions about natural phenomena. Misconceptions may coexist with scientific knowledge in the brain. Therefore, misconceptions must be cognitively inhibited in order to select the scientific knowledge. There is, however, lack of substantial neuroscientific evidence supporting this hypothesis. In this study, we sought for this evidence by investigating medical students who solved a cardiovascular conceptual problem in a magnetic resonance imaging scanner. Brain activation was compared between understanders who had the scientific knowledge, and misunderstanders who held a misconception. No significant activation was found in brain areas related to cognitive inhibition in understanders compared with misunderstanders. Therefore, we could not confirm the idea that cognitive inhibition is involved in overcoming a misconception. Instead, we found that the putamen was significantly activated in misunderstanders compared with understanders, suggesting a role for episodic memory in learners holding a misconception.Medical Education Researc

The psychological burden of an initially unexplained illness: patients with sternocostoclavicular hyperostosis before and after delayed diagnosis

<p>Abstract</p> <p>Background</p> <p>Sternocostoclavicular hyperostosis (SCCH) is a rare, debilitating, chronic inflammatory disorder of the anterior chest wall due to a chronic sterile osteomyelitis of unknown origin. SCCH is largely underdiagnosed and often misdiagnosed. In individual cases it can remain unrecognized for years. The purpose of this study is twofold. Firstly, to evaluate the psychological condition of SCCH patients, both in the sometimes quite extended pre-diagnostic period between first manifestations and confirmed diagnosis of the disease, and in the current situation. Secondly, to investigate the relationships between the pre-diagnostic and the current psychological conditions of confirmed SCCH patients.</p> <p>Methods</p> <p>Structured interviews were held with 52 confirmed SCCH patients. Questionnaires were included to assess posttraumatic stress symptoms, social support, aspects of pain, illness perceptions, self-reported health status, and quality of life.</p> <p>Results</p> <p>SCCH patients reported stronger posttraumatic stress symptoms, more unfavorable illness perceptions, lower health status, and poorer quality of life than healthy individuals and patients with other diseases or traumatic experiences. Psychological distress in the pre-diagnostic period was associated with unfavorable conditions in the current situation.</p> <p>Conclusion</p> <p>SCCH is an illness with serious psychological consequences. Psychological monitoring of patients with unexplained complaints is recommended as long as a diagnosis has not been reached.</p

Does EMDR Therapy Have an Effect on Memories of Emotional Abuse, Neglect and Other Types of Adverse Events in Patients with a Personality Disorder? Preliminary Data

Background: Little is known about the effectiveness of trauma-focused therapies for memories of events not meeting the A-criterion of post-traumatic stress disorder (PTSD). Objective: Determining the effect of EMDR therapy on memories of emotional abuse, neglect and other types of adverse events in patients with a personality disorder (PD). Method: We conducted a secondary analysis of the data from our study, which aimed to determine the effectiveness of five sessions of EMDR therapy in 49 patients with a PD. Patients were divided into three different groups depending on their most prevalent type of adverse event. Data were analyzed with Generalized Estimating Equations. Results: Of all patients, 49% reported emotional neglect, 22.4% emotional abuse and 26.5% other types. Only one patient reported memories that predominantly fulfilled the A-criterion of PTSD. After five sessions of EMDR therapy, medium to large treatment effects for memories related to neglect (ds between 0.52 and 0.79), medium treatment effects for memories involving emotional abuse (ds between 0.18 and 0.59) and other types of adverse events were found (ds between 0.18 and 0.53). No significant differences in symptom reduction associated with the application of EMDR therapy among memories involving these three different types of adverse events could be revealed. Conclusions: The results support the notion that EMDR therapy is not only an effective therapy for memories related to A-criteria-worthy events, but that it also has a symptom-reducing effect on memories involving other types of adverse events. This suggests that EMDR might be a valuable addition to the treatment of PD without PTS

Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease

Neuro Imaging Researc

Aging effect, reproducibility, and test-retest reliability of a new cerebral amyloid angiopathy MRI severity marker-cerebrovascular reactivity to visual stimulation

Background Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test-retest reliability of these parameters should be assessed. Purpose Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test-retest reliability of these parameters. Study Type Prospective-observational. Population Eighty-six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D-CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D-CAA mutation carriers (mean age 54 years, 70% female). Field Strength/Sequence 3-T, three-dimensional (3D) T1-weighted MRI and gradient echo BOLD fMRI. Assessment To assess test-retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3-week interval for each subject. Statistical Tests Linear regression analyses and two-way mixed absolute agreement intra-class correlation approach. Results Healthy aging was associated with decreased BOLD amplitude (beta = -0.711) and prolonged time to baseline (beta = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test-retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856-0.910) and presymptomatic D-CAA mutation carriers (ICC 0.959-0.981). In symptomatic D-CAA mutation carriers, test-retest reliability was poor for all parameters (ICCs < 0.5). Data Conclusion Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D-CAA mutation carriers, but not in symptomatic D-CAA mutation carriers.Multivariate analysis of psychological dat

Cerebral blood flow in presymptomatic MAPT and GRN mutation carriers: A longitudinal arterial spin labeling study

Objective Frontotemporal dementia (FTD) is characterized by behavioral disturbances and language problems. Familial forms can be caused by genetic defects in microtubule-associated protein tau (MAPT), progranulin (GRN), and C9orf72. In light of upcoming clinical trials with potential disease-modifying agents, the development of sensitive biomarkers to evaluate such agents in the earliest stage of FTD is crucial. In the current longitudinal study we used arterial spin labeling MRI (ASL) in presymptomatic carriers of MAPT and GRN mutations to investigate early changes in cerebral blood flow (CBF). Methods Healthy first-degree relatives of patients with a MAPT or GRN mutation underwent ASL at baseline and follow-up after two years. We investigated cross-sectional and longitudinal differences in CBF between mutation carriers (n = 34) and controls without a mutation (n = 31). Results GRN mutation carriers showed significant frontoparietal hypoperfusion compared with controls at follow-up, whereas we found no cross-sectional group differences in the total study group or the MAPT subgroup. Longitudinal analyses revealed a significantly stronger decrease in CBF in frontal, temporal, parietal, and subcortical areas in the total group of mutation carriers and the GRN subgroup, with the strongest decrease in two mutation carriers who converted to clinical FTD during follow-up. Interpretation We demonstrated longitudinal alterations in CBF in presymptomatic FTD independent of grey matter atrophy, with the strongest decrease in individuals that developed symptoms during follow-up. Therefore, ASL could have the potential to serve as a sensitive biomarker of disease progression in the presymptomatic stage of FTD in future clinical trials

Resting state functional connectivity differences between behavioral variant frontotemporal dementia and Alzheimer's disease

Introduction: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of early-onset dementia. Early differentiation between both types of dementia may be challenging due to heterogeneity and overlap of symptoms. Here, we apply resting state functional magnetic resonance imaging (fMRI) to study functional brain connectivity differences between AD and bvFTD. Methods: We used resting state fMRI data of 31 AD patients, 25 bvFTD patients, and 29 controls from two centers specialized in dementia. We studied functional connectivity throughout the entire brain, applying two different analysis techniques, studying network-to-region and region-to-region connectivity. A general linear model approach was used to study group differences, while controlling for physiological noise, age, gender, study center, and regional gray matter volume. Results: Given gray matter differences, we observed decreased network-to-region connectivity in bvFTD between (a) lateral visual cortical network and lateral occipital and cuneal cortex, and (b) auditory system network and angular gyrus. In AD, we found decreased network-to-region connectivity between the dorsal visual stream network and lateral occipital and parietal opercular cortex. Region-to-region connectivity was decreased in bvFTD between superior temporal gyrus and cuneal, supracalcarine, intracalcarine cortex, and lingual gyrus. Conclusion: We showed that the pathophysiology

Brain activity and connectivity changes in response to glucose ingestion

Objectives: The regulatory role of the brain in directing eating behavior becomes increasingly recognized. Although many areas in the brain have been found to respond to food cues, very little data is available after actual caloric intake. The aim of this study was to determine normal whole brain functional responses to ingestion of glucose after an overnight fast.Methods: Twenty-five normal weight, adult males underwent functional MRI on two separate visits. In a single-blind randomized study setup, participants received either glucose solution (50 g/300 ml of water) or plain water. We studied changes in Blood Oxygen Level Dependent (BOLD) signal, voxel-based connectivity by Eigenvector Centrality Mapping, and functional network connectivity.Results: Ingestion of glucose led to increased centrality in the thalamus and to decreases in BOLD signal in various brain areas. Decreases in connectivity in the sensory-motor and dorsal visual stream networks were found. Ingestion of water resulted in increased centrality across the brain, and increases in connectivity in the medial and lateral visual cortex network. Increased BOLD intensity was found in the intracalcarine and cingulate cortex.Discussion: Our data show that ingestion of glucose leads to decreased activity and connectivity in brain areas and networks linked to energy seeking and satiation. In contrast, drinking plain water leads to increased connectivity probably associated with continued food seeking and unfulfilled reward.Trail registration: This study combines data of two studies registered at clinicaltrails.gov under numbers NCT03202342 and NCT03247114.Multivariate analysis of psychological dat