Temporal stability of optimism and pessimism (LOT-R) over 6 years in the general population.

Objective: The aims of this study were to examine changes in habitual optimism over a six-year period and to analyze the relationship between changes in optimism and changes in other quality of life-related variables. Method: A randomly selected community sample of the German adult general population (N = 4,965) was surveyed twice, with a time interval of 6.04 years. Results: During the course of the 6 years, the mean score of the LOT-R total scale improved (effect size d = 0.11). The temporal stability in terms of the test-retest correlation was r = 0.61 for the total sample. There were only marginal gender differences in this temporal stability, however, the stability in the oldest age group ≥70 years (r = 0.50) was lower than the stability of the other age groups. The cross-sectional correlations showed clear relationships between optimism on the one hand and quality of life, life satisfaction, social support, and low levels of anxiety and physical complaints on the other. The corresponding longitudinal correlations between changes in optimism and changes in the other variables were less pronounced, but in the same direction. Conclusion: The study confirmed the applicability of the LOT-R in longitudinal studies. In samples with participants of 70 years and above, the limited stability in the optimism assessments needs to be considered in clinical practice and epidemiologic research.

Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration - A transdiagnostic study cross-validating atrophy and fluid biomarkers.

INTRODUCTION: Frontotemporal lobar degeneration (FTLD) encompasses behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy, corticobasal syndrome/degeneration, and primary progressive aphasias (PPAs). We cross-validated fluid biomarkers and neuroimaging. METHODS: Seven fluid biomarkers from cerebrospinal fluid and serum were related to atrophy in 428 participants including these FTLD subtypes, logopenic variant PPA (lvPPA), Alzheimer's disease (AD), and healthy subjects. Atrophy was assessed by structural magnetic resonance imaging and atlas-based volumetry. RESULTS: FTLD subtypes, lvPPA, and AD showed specific profiles for neurofilament light chain, phosphorylated heavy chain, tau, phospho-tau, amyloid beta1-42 from serum/cerebrospinal fluid, and brain atrophy. Neurofilaments related to regional atrophy in bvFTD, whereas progranulin was associated with atrophy in semantic variant PPA. Ubiquitin showed no effects. DISCUSSION: Results specify biomarker and atrophy patterns in FTLD and AD supporting differential diagnosis. They identify neurofilaments and progranulin in interaction with structural imaging as promising candidates for monitoring disease progression and therapy. HIGHLIGHTS: Study cross-validated neuroimaging and fluid biomarkers in dementia. Five kinds of frontotemporal lobar degeneration and two variants of Alzheimer's disease. Study identifies disease-specific fluid biomarker and atrophy profiles. Fluid biomarkers and atrophy interact in a disease-specific way. Neurofilaments and progranulin are proposed as biomarkers for diagnosis and therapy.

Improved Tau PET SUVR Quantification in 4-Repeat Tau Phenotypes with [18F]PI-2620.

We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclear palsy or cortical basal syndrome. The study found that SUV ratios calculated using the identified reference regions (i.e., fusiform gyrus and crus-cerebellum) were significantly associated with symptom severity and disease duration. This establishes, for the first time to our knowledge, the suitability of [18F]PI-2620 for tracking disease progression in this 4-repeat disease population. This is an important step toward increased clinical utility, such as patient stratification and monitoring in disease-modifying treatment trials. Additionally, the applied methodology successfully optimized reference regions for automated detection of brain imaging tracers. This approach may also hold value for other brain imaging tracers.

Tau accumulation is associated with dopamine deficiency in vivo in four-repeat tauopathies.

PURPOSE: We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [18F]PI-2620 tau-positron-emission-tomography (PET) imaging with [123I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability. METHODS: Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.0 ± 8.5 years) and 15 patients with clinically diagnosed α-synucleinopathies (8 male; 66.1 ± 10.3 years) who underwent [18F]PI-2620 tau-PET and DaT-SPECT imaging with a time gap of 3 ± 5 months were evaluated. Regional Tau-PET signals and DaT availability as well as their principal components were correlated in patients with 4R-tauopathies and α-synucleinopathies. Both biomarkers and the residuals of their association were correlated with clinical severity scores in 4R-tauopathies. RESULTS: In patients with 4R-tauopathies, [18F]PI-2620 binding in basal ganglia and midbrain regions was negatively associated with striatal DaT availability (i.e. globus pallidus internus and putamen (ß = - 0.464, p = 0.006, Durbin-Watson statistics = 1.824) in a multiple regression model. Contrarily, [18F]PI-2620 binding in the dentate nucleus showed no significant regression factor with DaT availability in the striatum (ß = 0.078, p = 0.662, Durbin-Watson statistics = 1.686). Patients with α-synucleinopathies did not indicate any regional associations between [18F]PI-2620-binding and DaT availability. Higher DaT-SPECT binding relative to tau burden was associated with better clinical performance (ß = - 0.522, p = 0.011, Durbin-Watson statistics = 2.663) in patients with 4R-tauopathies. CONCLUSION: Tau burden in brain regions involved in dopaminergic pathways is associated with aggravated dopaminergic dysfunction in patients with clinically diagnosed primary tauopathies. The ability to sustain dopamine transmission despite tau accumulation may preserve motor function.

Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems.

Background: Aside to clinical changes, behavioral variant frontotemporal dementia (bvFTD) is characterized by progressive structural and functional alterations in frontal and temporal regions. We examined if there is a selective vulnerability of specific neurotransmitter systems in bvFTD by evaluating the link between disease-related functional alterations and the spatial distribution of specific neurotransmitter systems and their underlying gene expression levels. Methods: Maps of fractional amplitude of low-frequency fluctuations (fALFF) were derived as a measure of local activity from resting-state functional magnetic resonance imaging for 52 bvFTD patients (mean age = 61.5 ± 10.0 years; 14 females) and 22 healthy controls (HC) (mean age = 63.6 ± 11.9 years; 13 females). We tested if alterations of fALFF in patients co-localize with the non-pathological distribution of specific neurotransmitter systems and their coding mRNA gene expression. Furthermore, we evaluated if the strength of co-localization is associated with the observed clinical symptoms. Results: Patients displayed significantly reduced fALFF in frontotemporal and frontoparietal regions. These alterations co-localized with the distribution of serotonin (5-HT1b and 5-HT2a) and γ-aminobutyric acid type A (GABAa) receptors, the norepinephrine transporter (NET), and their encoding mRNA gene expression. The strength of co-localization with NET was associated with cognitive symptoms and disease severity of bvFTD. Conclusions: Local brain functional activity reductions in bvFTD followed the distribution of specific neurotransmitter systems indicating a selective vulnerability. These findings provide novel insight into the disease mechanisms underlying functional alterations. Our data-driven method opens the road to generate new hypotheses for pharmacological interventions in neurodegenerative diseases even beyond bvFTD. Funding: This study has been supported by the German Consortium for Frontotemporal Lobar Degeneration, funded by the German Federal Ministry of Education and Research (BMBF; grant no. FKZ01GI1007A).

The different areas of chronic stress and food addiction: Results from the LIFE-Adult-Study.

There is an empirical association between stress and symptoms of food addiction (FA), but it is still not clear which domains of stress are the most relevant when it comes to FA, limiting the ability of researchers and practitioners to address problematic eating-related health outcomes. In order to address this gap in the literature, we analysed how different domains of chronic stress are related to FA. We used data from a subsample of the LIFE-Adult-Study (N = 1172), a German cohort study. We conducted a linear regression analysis with stress domains (Trier Inventory for Chronic Stress, TICS) as predictors of FA (Yale Food Addiction Scale, YFAS). In the second regression analysis we included sociodemographic variables, personality, and smoking as control variables. There was a significant and positive association between Social Overload, Work Discontent, Excessive Demands from Work, and Chronic Worrying and FA. After adding control variables, only Social Overload, Excessive Demands from Work, and Chronic Worrying remained significant predictors. Connections between stress domains and FA can serve as starting points for the development of meaningful interventions that support individuals self-care strategies (Social Overload), complexity management (Excessive Demands from Work), and coping with negative emotions (Chronic Worrying).

Changes in anxiety in the general population over a six-year period.

BACKGROUND: Anxiety is a frequent condition in patients and in the general population. The aim of this study was to investigate changes in anxiety over time and to test several psychometric properties of the Generalized Anxiety Disorder Screener (GAD-7) from a longitudinal perspective. METHODS: The GAD-7 was included in an examination with two waves, six years apart. The study sample (n = 5355) was comprised of representatively selected adults from the general population with a mean age of 57.3 (SD = 12.3) years. RESULTS: During the 6-year time interval, anxiety increased significantly from 3.28 ± 3.16 (t1) to 3.66 ± 3.46 (t2). Confirmatory factor analyses proved the longitudinal measurement invariance of the GAD-7. Reliability of the GAD-7 was established both for the cross-sectional and the longitudinal perspective. The test-retest correlation was r = 0.53, and there were no substantial sex or age differences in these coefficients of temporal stability. The mean changes in anxiety were similar for males and females, and there was no linear age trend in the changes measured by the GAD-7. Changes in anxiety over the 6-year period were correlated with changes in satisfaction with life (r = -0.30), bodily complaints (r = 0.31), and the mental component of quality of life (r = -0.48). CONCLUSION: The GAD-7 is a suitable instrument for measuring changes in anxiety. Age and gender have only minor significance when interpreting change scores.

Leptin, but not ghrelin, is associated with food addiction scores in a population-based subject sample.

Background: Ghrelin and leptin are both peptide hormones and act as opposing players in the regulation of hunger, satiety and energy expenditure. Leptin reduces appetite and feelings of hunger and is secreted mainly by adipocytes, while ghrelin increases appetite and food intake and reduces metabolic rate. Both hormones have been implicated in addictive disorders. Ghrelin was shown to have pro-addictive effects while leptin's role in addiction yields more conflicting results. Their involvement in the regulation of both food intake and addictive behaviors make them interesting candidates when investigating the regulation of food addiction. However, only few human studies have been performed and large-scale studies are lacking to date. We aimed to investigate the association between total ghrelin and leptin serum levels with scores in the Yale Food Addiction Scale (YFAS). Methods: Subjects were recruited in the LIFE Adult cohort. 909 subjects were included in the analysis and we performed univariate multiple linear regression models, adjusted for age, sex (in total group analyses only), alcohol consumption, smoking status, BMI scores, cortisol concentrations, Center for Epidemiological Studies Depression Scale (CES-D) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) sum scores. The dependent variable was the YFAS score. Results: In men, leptin serum levels showed a significant positive association (standardized ß = 0.146; p = 0.012) with the YFAS score. This finding was confirmed in an extreme-group comparison: men in the highest quartile of leptin levels had significantly higher YFAS sum scores than men in the lowest quartile (1.55 vs. 1.18; p = 0.00014). There was no association with YFAS sum score in the total group (standardized ß = -0.002; p = 0.974) or in women (standardized ß = -0.034; p = 0.674). Total serum ghrelin showed no association with YFAS sum score neither in the total group (standardized ß = -0.043; p = 0.196) nor in men (n = 530; standardized ß = -0.063; p = 0.135) or women (n = 379; standardized ß = -0.035; p = 0.494). Conclusion: Our findings are in line with previous literature and suggest that total ghrelin serum levels are not associated with food addiction scores. Leptin had been previously shown to be associated with food addiction and we confirmed this finding for men in a large, population-based approach.

Brain dysconnectivity with heart failure.

Structural brain damage associated with heart failure is well described; however, little is known about associated changes in various specific brain functions that bear immediate clinical relevance. A satisfactory pathophysiological link between heart failure and decline in cognitive function is still missing. In the present study, we aim to detect functional correlates of heart failure in terms of alterations in functional brain connectivity (quantified by functional magnetic resonance imaging) related to cognitive performance assessed by neuropsychological testing. Eighty patients were post hoc grouped into subjects with and without coronary artery disease. The coronary artery disease patients were further grouped as presenting with or without heart failure according to the guidelines of the European Society of Cardiology. On the basis of resting-state functional magnetic resonance imaging, brain connectivity was investigated using network centrality as well as seed-based correlation. Statistical analysis aimed at specifying centrality group differences and potential correlations between centrality and heart failure-related measures including left ventricular ejection fraction and serum concentrations of N-terminal fragment of the pro-hormone brain-type natriuretic peptide. The resulting correlation maps were then analysed using a flexible factorial model with the factors 'heart failure' and 'cognitive performance'. Our core findings are: (i) A statistically significant network centrality decrease was found to be associated with heart failure primarily in the precuneus, i.e. we show a positive correlation between centrality and left ventricular ejection fraction as well as a negative correlation between centrality and N-terminal fragment of the pro-hormone brain-type natriuretic peptide. (ii) Seed-based correlation analysis showed a significant interaction between heart failure and cognitive performance related to a significant decrease of precuneus connectivity to other brain regions. We obtained these results by different analysis approaches indicating the robustness of the findings we report here. Our results suggest that the precuneus is a brain region involved in connectivity decline in patients with heart failure, possibly primarily or already at an early stage. Current models of Alzheimer's disease-having pathophysiological risk factors in common with cerebrovascular disorders-also consider reduced precuneus connectivity as a marker of brain degeneration. Consequently, we propose that heart failure and Alzheimer's disease exhibit partly overlapping pathophysiological paths or have common endpoints associated with a more or less severe decrease in brain connectivity. This is further supported by specific functional connectivity alterations between the precuneus and widely distributed cortical regions, particularly in patients showing reduced cognitive performance.

Differences in white matter hyperintensities in socioeconomically deprived groups: results of the population-based LIFE Adult Study.

OBJECTIVE: Previous studies have shown that socioeconomically deprived groups exhibit higher lesion load of the white matter (WM) in aging. The aim of this study was to (i) investigate to what extent education and income may contribute to differences in white matter hyperintensities (WMHs) and (ii) identify risk profiles related to a higher prevalence of age-associated WMH. DESIGN AND SETTING: Population-based adult study of the Leipzig Research Centre for Civilization Diseases (LIFE) in Leipzig, Germany. PARTICIPANTS: Dementia-free sample aged 40-80 years (n = 1,185) derived from the population registry. MEASUREMENTS: Information was obtained in standardized interviews. WMH (including the derived Fazekas scores) were assessed using automated segmentation of high-resolution T1-weighted anatomical and fluid-attenuated inversion recovery (FLAIR) MRI acquired at 3T. RESULTS: Despite a significant association between income and WMH in univariate analyses, results from adjusted models (age, gender, arterial hypertension, heart disease, and APOE e4 allele) indicated no association between income and WMH. Education was associated with Fazekas scores, but not with WMH and not after Bonferroni correction. Prevalence of some health-related risk factors was significantly higher among low-income/education groups. After combining risk factors in a factor analysis, results from adjusted models indicated significant associations between higher distress and more WMH as well as between obesity and more deep WMH. CONCLUSIONS: Previously observed differences in WMH between socioeconomically deprived groups might stem from differences in health-related risk factors. These risk factors should be targeted in prevention programs tailored to socioeconomically deprived individuals.

Improving fMRI in Parkinson's disease by accounting for brain region-specific activity patterns.

In functional magnetic imaging (fMRI) in Parkinson's disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients' tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure's temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop's structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.

Structural correlates of language processing in primary progressive aphasia.

Understanding the relationships between brain structure and language behaviour in primary progressive aphasia provides crucial information about these diseases' pathomechanisms. However, previous investigations have been limited from providing a statistically reliable view of broad language abilities by sample size, variant focus and task focus. In this study, the authors aimed to determine the relationship between brain structure and language behaviour in primary progressive aphasia, to determine the degree to which task-associated regions were atrophied across disease variants and to determine the degree to which task-related atrophy overlaps across disease variants. Participants were 118 primary progressive aphasia patients and 61 healthy, age-matched controls tested from 2011 to 2018 in the German Consortium for Frontotemporal Lobar Degeneration cohort. Diagnosis of primary progressive aphasia required progressive deterioration of mainly speech and language for ≥ 2 years, and variant was diagnosed by the criteria of Gorno-Tempini et al. (Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014). Twenty-one participants not fulfilling a specific subtype were classified as mixed-variant and excluded. Language tasks of interest included the Boston naming test, a German adaptation of the Repeat and Point task, phonemic and category fluency tasks and the reading/writing subtest of the Aachen Aphasia Test. Brain structure was measured by cortical thickness. We observed networks of language task-associated temporal, frontal and parietal cortex. Overlapping task-associated atrophy was observed in the left lateral, ventral and medial temporal lobes, middle and superior frontal gyri, supramarginal gyrus and insula. Some regions, primarily in the perisylvian region, were associated with language behaviour despite showing no significant atrophy. The results crucially extend less powerful studies associating brain and language measures in primary progressive aphasia. Cross-variant atrophy in task-associated regions suggests partially shared underlying deficits, whereas unique atrophy reinforces variant-specific deficits. Language task-related regions that are not obviously atrophied suggest regions of future network disruption and encourage understanding of task deficits beyond clearly atrophied cortex. These results may pave the way for new treatment approaches.

Speech Motor Profiles in Primary Progressive Aphasia.

PURPOSE: Previous research on motor speech disorders (MSDs) in primary progressive aphasia (PPA) has largely focused on patients with the nonfluent/agrammatic variant of PPA (nfvPPA), with few systematic descriptions of MSDs in variants other than nfvPPA. There has also been an emphasis on studying apraxia of speech, whereas less is known about dysarthria or other forms of MSDs. This study aimed to examine the qualitative and quantitative characteristics of MSDs in a prospective sample of individuals with PPA independent of subtype. METHOD: We included 38 participants with a root diagnosis of PPA according to current consensus criteria, including one case with primary progressive apraxia of speech. Speech tasks comprised various speech modalities and levels of complexity. Expert raters used a novel protocol for auditory speech analyses covering all major dimensions of speech. RESULTS: Of the participants, 47.4% presented with some form of MSD. Individual speech motor profiles varied widely with respect to the different speech dimensions. Besides apraxia of speech, we observed different dysarthria syndromes, special forms of MSDs (e.g., neurogenic stuttering), and mixed forms. Degrees of severity ranged from mild to severe. We also observed MSDs in patients whose speech and language profiles were incompatible with nfvPPA. CONCLUSIONS: The results confirm that MSDs are common in PPA and can manifest in different syndromes. The findings emphasize that future studies of MSDs in PPA should be extended to all clinical variants and should take into account the qualitative characteristics of motor speech dysfunction across speech dimensions. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22555534.

Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia.

Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.

The Behavioural Dysfunction Questionnaire discriminates behavioural variant frontotemporal dementia from Alzheimer's disease dementia and major depressive disorder.

BACKGROUND AND OBJECTIVES: Early-stage behavioural variant frontotemporal dementia (bvFTD) is often misdiagnosed, highlighting the need for new diagnostic instruments. Based on the revised diagnostic criteria for bvFTD, we developed the Behavioural Dysfunction Questionnaire (BDQ). In this explorative study, we aimed to determine the best scoring and analytical method for the BDQ to discriminate between bvFTD and non-bvFTD patients. MATERIALS AND METHODS: 34 patients with early-stage bvFTD, 56 with early-stage Alzheimer's disease dementia (ADD) and 41 with major depressive disorder (MDD) were recruited. We calculated BDQ-items with or without inclusion of a time criterion: (a) without time criterion, (b) with 10 years' time criterion (symptom presence less than 10 years), and (c) with 3 years' time criterion (symptom presentation within the first 3 years). Using these three differently calculated items, we generated six variables, i.e. 3*2 [BDQ-Global Score (BDQ-GS; domains average score); BDQ-Global Domain Score (BDQ-GDS; domains categorical score)]. Then, we performed univariate and bivariate (BDQ-GS and BDQ-GDS combined) ROC analyses. RESULTS: Models including BDQ-GS, BDQ-GDS or both variables combined discriminated similarly between groups. In contrast, models without time criterion or with 10 years' time criterion discriminated better than models including variables with 3 years' time criterion. These models discriminated highly (AUC = 85.98-87.78) between bvFTD and MDD and bvFTD and ADD, respectively. CONCLUSION: BDQ-scores without any time criterion discriminated highly between early-stage bvFTD and non-bvFTD groups, which could improve the early diagnosis of bvFTD. With its standardised procedure, the BDQ is also appropriate for repeated assessments.

Longitudinal changes in surface based brain morphometry measures in amnestic mild cognitive impairment and Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is associated with marked brain atrophy. While commonly used structural MRI imaging methods do not account for the complexity of human brain morphology, little is known about the longitudinal changes of cortical geometry and their relationship with cognitive decline in subjects with AD. METHODS: Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used to perform two-sample t-tests to investigate longitudinal changes of cortical thickness (CTh) and three surface-based morphometry measures: fractal dimension (i.e. cortical complexity; FD), gyrification index (GI), and sulcal depth (SD) in subjects with AD, amnestic mild cognitive impairment (aMCI) in comparison to cognitively unimpaired controls (CU) in baseline and 2-year follow-up sMRI scans. In addition, correlations of the morphological measures with two-year cognitive decline as assessed by the modified AD Assessment Scale-Cognitive Subscale (ADAS-Cog 11) were calculated via regression analyses. RESULTS: Compared to CU, both AD and aMCI showed marked decreases in CTh. In contrast, analyses of FD and GI yielded a more nuanced decline of the respective measures with some areas showing increases in FD and GI. Overall changes in FD and GI were more pronounced in AD as compared to aMCI. Analyses of SD yielded widespread decreases. Interestingly, cognitive decline corresponded well with CTh declines in aMCI but not AD, whereas changes in FD corresponded with AD only but not aMCI, whereas GI and SD were associated with cognitive decline in aMCI and AD. CONCLUSION: Patterns of longitudinal changes in FD, GI and SD were only partially overlapping with CTh reductions. In AD, surface-based morphometry measures for brain-surface complexity showed better correspondence than CTh with cognitive decline over a two-year period of time. Being drawn from measures reflecting changes in more intricate aspects of human brain morphology, these data provide new insight into the complexity of AD-related brain atrophy and its relationship with cognitive decline.

Multiclass prediction of different dementia syndromes based on multi-centric volumetric MRI imaging.

INTRODUCTION: Dementia syndromes can be difficult to diagnose. We aimed at building a classifier for multiple dementia syndromes using magnetic resonance imaging (MRI). METHODS: Atlas-based volumetry was performed on T1-weighted MRI data of 426 patients and 51 controls from the multi-centric German Research Consortium of Frontotemporal Lobar Degeneration including patients with behavioral variant frontotemporal dementia, Alzheimer's disease, the three subtypes of primary progressive aphasia, i.e., semantic, logopenic and nonfluent-agrammatic variant, and the atypical parkinsonian syndromes progressive supranuclear palsy and corticobasal syndrome. Support vector machine classification was used to classify each patient group against controls (binary classification) and all seven diagnostic groups against each other in a multi-syndrome classifier (multiclass classification). RESULTS: The binary classification models reached high prediction accuracies between 71 and 95% with a chance level of 50%. Feature importance reflected disease-specific atrophy patterns. The multi-syndrome model reached accuracies of more than three times higher than chance level but was far from 100%. Multi-syndrome model performance was not homogenous across dementia syndromes, with better performance in syndromes characterized by regionally specific atrophy patterns. Whereas diseases generally could be classified vs controls more correctly with increasing severity and duration, differentiation between diseases was optimal in disease-specific windows of severity and duration. DISCUSSION: Results suggest that automated methods applied to MR imaging data can support physicians in diagnosis of dementia syndromes. It is particularly relevant for orphan diseases beside frequent syndromes such as Alzheimer's disease.

Alterations in rhythmic and non-rhythmic resting-state EEG activity and their link to cognition in older age.

While many structural and biochemical changes in the brain have previously been associated with older age, findings concerning functional properties of neuronal networks, as reflected in their electrophysiological signatures, remain rather controversial. These discrepancies might arise due to several reasons, including diverse factors determining general spectral slowing in the alpha frequency range as well as amplitude mixing between the rhythmic and non-rhythmic parameters. We used a large dataset (N = 1703, mean age 70) to comprehensively investigate age-related alterations in multiple EEG biomarkers taking into account rhythmic and non-rhythmic activity and their individual contributions to cognitive performance. While we found strong evidence for an individual alpha peak frequency (IAF) decline in older age, we did not observe a significant relationship between theta power and age while controlling for IAF. Not only did IAF decline with age, but it was also positively associated with interference resolution in a working memory task primarily in the right and left temporal lobes suggesting its functional role in information sampling. Critically, we did not detect a significant relationship between alpha power and age when controlling for the 1/f spectral slope, while the latter one showed age-related alterations. These findings thus suggest that the entanglement of IAF slowing and power in the theta frequency range, as well as 1/f slope and alpha power measures, might explain inconsistencies reported previously in the literature. Finally, despite the absence of age-related alterations, alpha power was negatively associated with the speed of processing in the right frontal lobe while 1/f slope showed no consistent relationship to cognitive performance. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered for the comprehensive assessment of association between age, neuronal activity, and cognitive performance.

Heart failure decouples the precuneus in interaction with social cognition and executive functions.

Aging increases the risk to develop Alzheimer's disease. Cardiovascular diseases might accelerate this process. Our study aimed at investigating the impact of heart failure on brain connectivity using functional magnetic resonance imaging at resting state. Here we show brain connectivity alterations related to heart failure and cognitive performance. Heart failure decreases brain connectivity in the precuneus. Precuneus dysconnectivity was associated with biomarkers of heart failure-left ventricular ejection fraction and N-terminal prohormone of brain natriuretic peptide-and cognitive performance, predominantly executive function. Meta-analytical data-mining approaches-conducted in the BrainMap and Neurosynth databases-revealed that social and executive cognitive functions are mainly associated with those neural networks. Remarkably, the precuneus, as identified in our study in a mid-life cohort, represents one central functional hub affected by Alzheimer's disease. A long-term follow-up investigation in our cohort after approximately nine years revealed more severe cognitive impairment in the group with heart failure than controls, where social cognition was the cognitive domain mainly affected, and not memory such as in Alzheimer's disease. In sum, our results indicate consistently an association between heart failure and decoupling of the precuneus from other brain regions being associated with social and executive functions. Further longitudinal studies are warranted elucidating etiopathological mechanisms.