Search

BackgroundCerebral blood flow (CBF) is critical for brain metabolism and overall function. Age-related changes in CBF have been associated with cognitive deficits and increased risk of neurocognitive disorders and vascular events such as stroke. Exercise is considered among the protective factors for age-related brain and cognitive impairment, but how different lifestyle characteristics, such as low or moderate-to-vigorous physical activity or frequency of everyday activities, relate to cross-sectional and longitudinal measures of CBF has not been established.ObjectiveWith the main aim of identifying potential targets for interventions, our objective was to examine associations between cortical and subcortical CBF and frequency of diverse everyday activities in healthy community-dwelling adults aged 65-89 years, and assess to which degree activity level at baseline is associated with longitudinal changes in CBF across a one-to-two years interval.MethodOne hundred nineteen (N = 119) adults underwent brain magnetic resonance imaging (MRI), neurocognitive, physical, and activity assessment at baseline. CBF was obtained using pseudo-continuous arterial spin labelling (ASL) MRI. Frequency of everyday activities were measured using Frenchay Activities index, while minutes of low and moderate-to-vigorous intensity physical activity were measured using a StepWatch Activity Monitor. Eighty-six participants completed a follow-up ASL MRI, on average 506 (SD = 113) days after the baseline scan.ResultsBayesian multilevel modelling revealed positive associations between baseline cortical and subcortical CBF and various everyday activities. Higher baseline accumbens, putamen and pallidum CBF was associated with more time spent on low intensity (> 0 steps/minute to < 100 steps/minute) physical activity, higher accumbens and caudate CBF with more moderate to vigorous intensity (≥ 100 steps/minute) physical activity, higher cerebral cortical CBF with more participation in social activity, higher cortical and thalamic CBF with more reading, and higher baseline pallidum CBF with more actively pursuing hobbies. We did not find evidence for an association between baseline activity level and longitudinal changes in CBF.ConclusionThe identified associations between everyday activity measures and CBF provide new knowledge on malleable lifestyle factors that may indicate or contribute to healthy brain aging. In addition to the relevance for prioritizing targets for public health guidelines, our findings contribute to disclose parts of the intricate connection between brain metabolism and everyday activities in aging.

Frailty is a dementia risk factor commonly measured by a frailty index (FI). The standard procedure for creating an FI requires manually selecting health deficit items and lacks criteria for selection optimization. We hypothesized that refining the item selection using data-driven assessment improves sensitivity to cognitive status and future dementia conversion, and compared the predictive value of three FIs: a standard 93-item FI was created after selecting health deficit items according to standard criteria (FI

Sequalae following stroke represents a significant challenge in current rehabilitation. The location and size of focal lesions are only moderately predictive of the diverse cognitive outcome after stroke. One explanation building on recent work on brain networks proposes that the cognitive consequences of focal lesions are caused by damages to anatomically distributed brain networks supporting cognition rather than specific lesion locations. To investigate the association between post-stroke structural disconnectivity and cognitive performance, we estimated individual level whole-brain disconnectivity probability maps based on lesion maps from 102 stroke patients using normative data from healthy controls. Cognitive performance was assessed in the whole sample using Montreal Cognitive Assessment, and a more comprehensive computerized test protocol was performed on a subset (n=82). Multivariate analysis using Partial Least Squares on the disconnectome maps revealed that higher disconnectivity in right insular and frontal operculum, superior temporal gyrus and putamen was associated with poorer MoCA performance, indicating that lesions in regions connected with these brain regions are more likely to cause cognitive impairment. Furthermore, our results indicated that disconnectivity within these clusters was associated with poorer performance across multiple cognitive domains. These findings demonstrate that the extent and distribution of structural disconnectivity following stroke are sensitive to cognitive deficits and may provide important clinical information predicting post stroke cognitive sequalae.

Fatigue and emotional distress rank high among self-reported unmet needs in stroke survivors. Currently, few treatment options exist for post stroke fatigue, a condition frequently associated with depression. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have shown promise in alleviating fatigue and depression in other patient groups, but the acceptability and effects for chronic phase stroke survivors are not established. Here, we used a randomized sham-controlled design to evaluate the added effect of tDCS combined with computerized cognitive training to alleviate symptoms of fatigue and depression. 74 patients were enrolled at baseline (mean time since stroke = 26 months) and 54 patients completed the intervention. Self-report measures of fatigue and depression were collected at five consecutive timepoints, spanning a period of two months. While fatigue and depression severity were reduced during the course of the intervention, Bayesian analyses provided evidence for no added effect of tDCS. Less severe symptoms of fatigue and depression were associated with higher improvement rate in select tasks, and study withdrawal was higher in patients with more severe fatigue and younger age. Time-resolved analyses of individual symptoms by a network-approach suggested overall higher centrality of fatigue symptoms (except item 1 and 2) than depression symptoms. In conclusion, the results support the notion of fatigue as a significant stroke sequela with possible implications for treatment adherence and response, but reveal no effect of tDCS on fatigue or depression.

Key summary points Aim To assess impact of frailty screening and two markers of illness severity on survival following discharge from the hospital. Findings Independently of age, ward (acute geriatric and general medical) and comorbidity, both higher degree of frailty and illness severity associated with reduced survival probability following discharge. The impact of frailty on survival was higher in those experiencing high clinical and laboratory illness severity. Message The prognostic value of frailty screening increased when performed in conjunction with two markers of illness severity. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00555-8., Purpose Study associations between frailty, illness severity and post-discharge survival in older adults admitted to medical wards with acute clinical conditions. Methods Prospective cohort study of 195 individuals (mean age 86; 63% females) admitted to two medical wards with acute illness, followed up for all-cause mortality for 20 months after discharge. Ward physicians screened for frailty and quantified its degree from one to eight using Clinical Frailty Scale (CFS), while clinical illness severity was estimated by New Early Warning Score 2 (NEWS2) and laboratory illness severity was calculated by a frailty index (FI-lab) using routine blood tests. Results CFS, NEWS2 and FI-lab scores were independently associated with post-discharge survival in an adjusted Cox proportional hazards model with age, ward category (acute geriatric and general medical) and comorbidity as covariates. Adjusted hazard ratios and 95% confidence intervals were 1.54 (1.24–1.91) for CFS, 1.12 (1.03–1.23) for NEWS2, and 1.02 (1.00–1.05) for FI-lab. A frailty × illness severity category interaction effect (p = 0.003), suggested that the impact of frailty on survival was greater in those experiencing higher levels of illness severity. Among patients with at least moderate frailty (CFS six to eight) and high illness severity according to both NEWS2 and FI-lab, two (13%) were alive at follow-up. Conclusion Frailty screening aided prognostication of survival following discharge in older acutely ill persons admitted to medical wards. The prognostic value of frailty increased when combined with readily available illness severity markers acquired during admission. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-021-00555-8.

Stroke patients commonly suffer from post stroke fatigue (PSF). Despite a general consensus that brain perturbations constitute a precipitating event in the multifactorial etiology of PSF, the specific predictive value of conventional lesion characteristics such as size and localization remain unclear. The current study represents a novel approach to assess the neural correlates of PSF in chronic stroke patients. While previous research has focused primarily on lesion location or size, with mixed or inconclusive results, we targeted the extended structural network implicated by the lesion, and evaluated the added explanatory value of a disconnectivity approach with regards to the brain correlates of PSF. To this end, we estimated individual brain disconnectome maps in 84 stroke survivors in the chronic phase (≥ 3 months post stroke) using information about lesion location and normative white matter pathways obtained from 170 healthy individuals. PSF was measured by the Fatigue Severity Scale (FSS). Voxel wise analyses using non-parametric permutation-based inference were conducted on disconnectome maps to estimate regional effects of disconnectivity. Associations between PSF and global disconnectivity and clinical lesion characteristics were tested by linear models, and we estimated Bayes factor to quantify the evidence for the null and alternative hypotheses, respectively. The results revealed no significant associations between PSF and disconnectome measures or lesion characteristics, with moderate evidence in favor of the null hypothesis. These results suggest that symptoms of post-stroke fatigue are not simply explained by lesion characteristics or brain disconnectome measures in stroke patients in a chronic phase, and are discussed in light of methodological considerations.

Summary Introduction Malnutrition and nutrition-related diseases are associated with hospital admissions, disability, institutionalization, and mortality in older people. Specialists in Geriatric Medicine and nutrition evaluate nutritional status as part of the comprehensive geriatric assessment; however, malnutrition still remains under-recognized and under-managed. Our survey explored nutrition assessment approaches used in daily clinical practice by geriatricians across Europe. Methods A 19-item survey on methods and instruments for malnutrition assessment in geriatric settings, and details of any national guidelines, was sent to 40 postgraduate fellows of the European Academy of Medicine of Aging (EAMA, 2017–2019 class). Results Thirty-six of the 40 eligible EAMA participants, representing 14 European countries, responded. In clinical practice, MNA and MNA-SF were most frequently used for screening (44.1%, 52.9%, respectively) and diagnosing (45.7%, 40.0%) malnutrition. Weight loss (n = 36, 100%), body mass index (n = 30, 85.7%), and low energy/food intake (n = 27, 77.1%) were the most frequent clinical variables considered. The absolute and relative amount of weight loss, and over what time period, varied widely. These routinely considered clinical factors contribute to validated GLIM, ASPEN-AND and ESPEN criteria for diagnosis of malnutrition, but these criteria were seldom used (GLIM = 0%, ASPEN = 0%; n = 9, ESPEN = 25.7%). National guidelines were available in 9 of the 14 countries, and generally recommended MNA and MNA-SF for community-dwelling and hospitalized older patients. Albumin was often suggested as a nutritional marker. Conclusions Nutritional assessment is systematically performed in geriatrics; but differs widely among geriatricians and countries. Harmonizing guidelines with the new international consensus might provide best-evidence care for older people across Europe.

Alzheimer's disease (AD) is a debilitating age-related neurodegenerative disorder. Accurate identification of individuals at risk is complicated as AD shares cognitive and brain features with aging. We applied linked independent component analysis (LICA) on three complementary measures of gray matter structure: cortical thickness, area and gray matter density of 137 AD, 78 mild (MCI) and 38 subjective cognitive impairment patients, and 355 healthy adults aged 18-78 years to identify dissociable multivariate morphological patterns sensitive to age and diagnosis. Using the lasso classifier, we performed group classification and prediction of cognition and age at different age ranges to assess the sensitivity and diagnostic accuracy of the LICA patterns in relation to AD, as well as early and late healthy aging. Three components showed high sensitivity to the diagnosis and cognitive status of AD, with different relationships with age: one reflected an anterior-posterior gradient in thickness and gray matter density and was uniquely related to diagnosis, whereas the other two, reflecting widespread cortical thickness and medial temporal lobe volume, respectively, also correlated significantly with age. Repeating the LICA decomposition and between-subject analysis on ADNI data, including 186 AD, 395 MCI and 220 age-matched healthy controls, revealed largely consistent brain patterns and clinical associations across samples. Classification results showed that multivariate LICA-derived brain characteristics could be used to predict AD and age with high accuracy (area under ROC curve up to 0.93 for classification of AD from controls). Comparison between classifiers based on feature ranking and feature selection suggests both common and unique feature sets implicated in AD and aging, and provides evidence of distinct age-related differences in early compared to late aging. The work was supported by the European Commission’s 7th Framework Programme (#602450, IMAGEMEND), Research Council of Norway (213837, 223273, 204966/F20), the South-Eastern Norway Regional Health Authority (2013123, 2014097, 2015073, 2016083), The Norwegian Health Association's Dementia Research Program, and KG Jebsen Foundation. We acknowledge the contribution of patient data from the Norwegian registry for persons being evaluated for cognitive symptoms in specialized care (NorCog) by the Norwegian National Advisory Unit on Ageing and Health. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

A cerebral stroke is characterized by compromised brain function due to an interruption in cerebrovascular blood supply. Although stroke incurs focal damage determined by the vascular territory affected, clinical symptoms commonly involve multiple functions and cognitive faculties that are insufficiently explained by the focal damage alone. Functional connectivity (FC) refers to the synchronous activity between spatially remote brain regions organized in a network of interconnected brain regions. Functional magnetic resonance imaging (fMRI) has advanced this system-level understanding of brain function, elucidating the complexity of stroke outcomes, as well as providing information useful for prognostic and rehabilitation purposes. We tested for differences in brain network connectivity between a group of patients with minor ischemic strokes in sub-acute phase (n = 44) and matched controls (n = 100). As neural network configuration is dependent on cognitive effort, we obtained fMRI data during rest and two load levels of a multiple object tracking (MOT) task. Network nodes and time-series were estimated using independent component analysis (ICA) and dual regression, with network edges defined as the partial temporal correlations between node pairs. The full set of edgewise FC went into a cross-validated regularized linear discriminant analysis (rLDA) to classify groups and cognitive load. MOT task performance and cognitive tests revealed no significant group differences. While multivariate machine learning revealed high sensitivity to experimental condition, with classification accuracies between rest and attentive tracking approaching 100%, group classification was at chance level, with negligible differences between conditions. Repeated measures ANOVA showed significantly stronger synchronization between a temporal node and a sensorimotor node in patients across conditions. Overall, the results revealed high sensitivity of FC indices to task conditions, and suggest relatively small brain network-level disturbances after clinically mild strokes., Cerebral stroke, fMRI, Brain network connectivity, Machine learning, Behavioral Neuroscience, Cognitive Neuroscience, Systems Neuroscience, Neurology, Medical Imaging

Human brain structure topography is thought to be related in part to functional specialisation. However, the extent of such relationships is unclear. Here, using a data-driven, multi-modal approach for studying brain structure across the lifespan (n=484, 260 females), we demonstrate that numerous structural networks, covering the entire brain, follow a functionally-meaningful architecture. These grey matter networks emerge from the co-variation of grey matter volume and cortical area at the population level. We further reveal fine-grained anatomical signatures of functional connectivity. For example, within the cerebellum, a structural separation emerges between lobules that are functionally connected to distinct, mainly sensorimotor, cognitive and limbic regions of the cerebral cortex and subcortex. Structural modes of variation also replicate the fine-grained functional architecture seen in 8 well-defined visual areas in both task and resting-state fMRI. Furthermore, our study shows a structural distinction corresponding to the established segregation between anterior and posterior default-mode networks. These fine-grained grey matter networks further cluster together to form functionally-meaningful larger-scale organisation. In particular, we identify a structural architecture bringing together the functional posterior default-mode network and its anti-correlated counterpart. In summary, our results demonstrate that the relationship between structural and functional connectivity is fine-grained, widespread across the entire brain, and driven by co-variation in cortical area, i.e. likely differences in shape, depth or number of foldings. These results suggest that neurotrophic events occur during development to dictate that the size and folding pattern of distant, functionally-connected brain regions should vary together across subjects.SIGNIFICANCE STATEMENTQuestions over the relationship between structure and function in the human brain have engaged neuroscientists for centuries in a debate that continues to this day. Here, by interrogating inter-subject variation in brain structure across a large number of individuals, we reveal modes of structural variation that map onto fine-grained functional organisation across the entire brain, and specifically in the cerebellum, visual areas and default-mode network. This functionally-meaningful structural architecture emerges from the co-variation of grey matter volume and cortical folding. These results suggest that the neurotrophic events at play during development, and possibly evolution, which dictate that the size and folding pattern of distant brain regions should vary together across subjects, might also play a role in functional cortical specialisation.

In this perspective paper, we examine possible premises of plasticity in the neural substrates underlying cognitive change. We take the special role of the medial temporal lobe as an anchoring point, but also investigate characteristics throughout the cortex. Specifically, we examine the dimensions of evolutionary expansion, heritability, variability of morphometric change, and inter-individual variance in myelination with respect to the plastic potential of different brain regions. We argue that areas showing less evolutionary expansion, lower heritability, greater variability of cortical thickness change through the lifespan, and greater inter-individual differences in intracortical myelin content have a great extent of plasticity. While different regions of the brain show these features to varying extent, analyses converge on the medial temporal lobe including the hippocampi as the target of all these premises. We discuss implications for effects of training on brain structures, and conditions under which plasticity may be evoked.

A large fraction of genetic risk factors for Alzheimer’s Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed a meta-analysis using GWAS results from 2,893 AD cases and 6,858 cognitively normal controls from Norway and 25,580 cases and 48,466 controls from the International Genomics of Alzheimer’s Project (IGAP), denoted the discovery sample. Second, we selected the top hits (p

As findings on the neuropathological and behavioral components of Alzheimer’s disease (AD) continue to accrue, converging evidence suggests that macroscale brain functional disruptions may mediate their association. Recent developments on theoretical neuroscience indicate that instantaneous patterns of brain connectivity and metastability may be a key mechanism in neural communication underlying cognitive performance. However, the potential significance of these patterns across the AD spectrum remains virtually unexplored. We assessed the clinical sensitivity of static and dynamic functional brain disruptions across the AD spectrum using resting-state fMRI in a sample consisting of AD patients (n = 80) and subjects with either mild (n = 44) or subjective (n = 26) cognitive impairment (MCI, SCI). Spatial maps constituting the nodes in the functional brain network and their associated time-series were estimated using spatial group independent component analysis and dual regression, and whole-brain oscillatory activity was analyzed both globally (metastability) and locally (static and dynamic connectivity). Instantaneous phase metrics showed functional coupling alterations in AD compared to MCI and SCI, both static (putamen, dorsal and default-mode) and dynamic (temporal, frontal-superior and default-mode), along with decreased global metastability. The results suggest that brains of AD patients display altered oscillatory patterns, in agreement with theoretical premises on cognitive dynamics.

Recent efforts using diffusion tensor imaging (DTI) have documented white matter (WM) alterations in Alzheimer’s disease (AD). The full potential of whole-brain DTI, however, has not been fully exploited as studies have focused on individual microstructural indices independently. In patients with AD (n = 79), mild (MCI, n = 55) and subjective (SCI, n = 30) cognitive impairment, we applied linked independent component analysis (LICA) to model inter-subject variability across five complementary DTI measures (fractional anisotropy (FA), axial/radial/mean diffusivity, diffusion tensor mode), two crossing fiber measures estimated using a multi-compartment crossing-fiber model reflecting the volume fraction of the dominant (f1) and non-dominant (f2) diffusion orientation, and finally, connectivity density obtained from full-brain probabilistic tractography. The LICA component explaining the largest data variance was highly sensitive to disease severity (AD

Although some older adults experiencing memory problems have been shown to benefit from cognitive training, evidence regarding who will improve from this type of intervention is lacking. Automated hippocampal volumetry might be used to foresee treatment outcomes. We hypothesized that larger hippocampal volumes are associated with greater memory performance changes following training, and that effects are selectively related to specific hippocampal subfields. 19 memory clinic outpatients with subjective memory impairment (mean age=60.9 years) underwent MRI-scanning and then followed an eight week training scheme aimed at improving verbal memory. We assessed verbal memory before and after training, and tested whether pretraining hippocampal volumes were related to memory improvements. To delineate regional specificity, we employed a new technique enabling automated volumetry of seven hippocampal subfields - including the cornu ammonis (CA) sectors and the dentate gyrus (DG). The results showed that larger hippocampal volumes before training were related to greater verbal recall improvements. Subfield volumetry revealed specific correlations between memory improvement and pretraining volumes of the left CA2/3 and CA4/DG. Depressive symptoms further gave a unique contribution in predicting gain of the intervention, independent of hippocampal volume. The results indicated that subjects with a stronger depressive symptom load benefited more from the training. A prediction model including baseline CA2/3-volume and depressive symptoms explained 42% of the variation in recall improvement. Our results are the first to suggest that hippocampal subfield volumetry is related to intervention outcomes in older adults experiencing memory problems. Also, previous studies have tended to exclude patients with concomitant depressive symptoms and memory complaints. The present results, however, strengthen the rationale and potential for cognitive intervention in these patients.

A growing body of research indicates benefits of cognitive training in older adults, but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored. Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our understanding of both aging‐ and training‐related neuronal plasticity. Specifically, studies using diffusion tensor imaging (DTI) suggest substantial changes in white matter (WM) in aging, but it is not known whether cognitive training might modulate these structural alterations. We used tract‐based spatial statistics (TBSS) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure. 41 participants (mean age 61 years) matched for age, sex and education were randomly assigned to an intervention or control group. All participants underwent MRI‐scanning and neuropsychological assessments at the beginning and end of the study. Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity (MD), indicating that DTI is sensitive to WM structural alterations over a 10‐week interval. Further, group analysis demonstrated positive effects of training on the short‐term changes. Participants in the training group showed a relative increase in fractional anisotropy (FA) compared with controls. Further, a significant relationship between memory improvement and change in FA was found, suggesting a possible functional significance of the reported changes. The training effect on FA seemed to be driven by a relative decrease in radial diffusivity, which might indicate a role for myelin‐related processes in WM plasticity. Hum Brain Mapp 33:2390–2406, 2012. © 2011 Wiley Periodicals, Inc.

Cortical thickness decreases from childhood throughout life, as estimated by magnetic resonance imaging (MRI). This monotone trajectory does not reflect the fundamentally different neurobiological processes underlying morphometric changes in development versus aging. We hypothesized that intracortical gray matter (GM) and subjacent white matter (WM) T1-weighted signal intensity would distinguish developmental and age-related changes in the cortex better than thickness. Intracortical GM and subjacent WM signal intensity and cortical thickness was measured across the brain surface in a healthy life span sample (n=429, 8-85 years). We also computed the relaxation rate of T2* (R2*) from multiecho sequences and mapped intracortical GM and subjacent WM values to the surface to delineate age-related variability in R2* and to adjust the T1 signal intensity for possible confounds of accumulated iron. While monotone age-related reductions in thickness were found, both intracortical GM and subcortical WM signal intensity showed inverted U patterns with peaks from eight to approximately 30 years of age. The spatial pattern of intracortical neurodevelopment followed a posterior-anterior gradient, with earliest maturation of occipital visual cortices and most protracted in superior frontal regions. From 50s and 60s, substantial signal reductions were observed in several regions, including the insula, cingulate, and inferior temporal gyrus. R2* showed similar patterns but peaked much later than the T1-weighted signal intensity measures. The results are presented as animations yielding detailed depictions of the dynamic regional variability in cortical neurodevelopment and aging and demonstrate that cortical thickness and T1-weighted signal intensity are sensitive to different cortical maturational and aging-related processes.

Magnetic resonance imaging volumetry studies report inverted U-patterns with increasing white-matter (WM) volume into middle age suggesting protracted WM maturation compared with the cortical gray matter. Diffusion tensor imaging (DTI) is sensitive to degree and direction of water permeability in biological tissues, providing in vivo indices of WM microstructure. The aim of this cross-sectional study was to delineate age trajectories of WM volume and DTI indices in 430 healthy subjects ranging 8-85 years of age. We used automated regional brain volume segmentation and tract-based statistics of fractional anisotropy, mean, and radial diffusivity as markers of WM integrity. Nonparametric regressions were used to fit the age trajectories and to estimate the timing of maximum development and deterioration in aging. Although the volumetric data supported protracted growth into the sixth decade, DTI indices plateaued early in the fourth decade across all tested regions and then declined slowly into late adulthood followed by an accelerating decrease in senescence. Tractwise and voxel-based analyses yielded regional differences in development and aging but did not provide ample evidence in support of a simple last-in-first-out hypothesis of life-span changes.

Subjective memory impairment (SMI) is a common risk factor for Alzheimer's disease, with few established options for treatment. Here we investigate the effects of two months episodic memory training on regional brain atrophy in 19 memory clinic patients with SMI. We used a sensitive longitudinal magnetic resonance imaging protocol and compared the patients with 42 matched healthy volunteers randomly assigned to a group performing the same training, or a no-training control group. Following intervention, the SMI sample exhibited structural gray matter volume increases in brain regions encompassing the episodic memory network, with cortical volume expansion of comparable extent as healthy training participants. Further, we found significant hippocampal volume increases in the healthy training group but not in the SMI group. Still, individual differences in left hippocampal volume change in the patient group were related to verbal recall improvement following training. The present results reinforce earlier studies indicating intact brain plasticity in aging, and further suggest that training-related brain changes can be evident also in the earliest form of cognitive impairment.

The hippocampus is an anatomically and functionally heterogeneous structure, but longitudinal studies of its regional development are scarce and it is not known whether protracted maturation of the hippocampus in adolescence is related to memory development. First, we investigated hippocampal subfield development using 170 longitudinally acquired brain magnetic resonance imaging scans from 85 participants aged 8-21 years. Hippocampal subfield volumes were estimated by the use of automated segmentation of 7 subfields, including the cornu ammonis (CA) sectors and the dentate gyrus (DG), while longitudinal subfield volumetric change was quantified using a nonlinear registration procedure. Second, associations between subfield volumes and change and verbal learning/memory across multiple retention intervals (5 min, 30 min and 1 week) were tested. It was hypothesized that short and intermediate memory would be more closely related to CA2-3/CA4-DG and extended, remote memory to CA1. Change rates were significantly different across hippocampal subfields, but nearly all subfields showed significant volume decreases over time throughout adolescence. Several subfield volumes were larger in the right hemisphere and in males, while for change rates there were no hemisphere or sex differences. Partly in support of the hypotheses, greater volume of CA1 and CA2-3 was related to recall and retention after an extended delay, while longitudinal reduction of CA2-3 and CA4-DG was related to learning. This suggests continued regional development of the hippocampus across adolescence and that volume and volume change in specific subfields differentially predict verbal learning and memory over different retention intervals, but future high-resolution studies are called for. © 2014 S. Karger AG, Basel.

Cortical surface area has tremendously expanded during human evolution, and similar patterns of cortical expansion have been observed during childhood development. An intriguing hypothesis is that the high-expanding cortical regions also show the strongest correlations with intellectual function in humans. However, we do not know how the regional distribution of correlations between intellectual function and cortical area maps onto expansion in development and evolution. Here, in a sample of 1048 participants, we show that regions in which cortical area correlates with visuospatial reasoning abilities are generally high expanding in both development and evolution. Several regions in the frontal cortex, especially the anterior cingulate, showed high expansion in both development and evolution. The area of these regions was related to intellectual functions in humans. Low-expanding areas were not related to cognitive scores. These findings suggest that cortical regions involved in higher intellectual functions have expanded the most during development and evolution. The radial unit hypothesis provides a common framework for interpretation of the findings in the context of evolution and prenatal development, while additional cellular mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and intracortical myelination, likely impact area expansion in later childhood. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Cerebral Cortex following peer review. The version of record [insert complete citation information here] is available online at: http://dx.doi.org/10.1093/cercor/bht201

The brain's ability to alter its functional and structural architecture in response to experience and learning has been extensively studied. Mental stimulation might serve as a reserve mechanism in brain aging, but macrostructural brain changes in response to cognitive training have been demonstrated in young participants only. We examined the short-term effects of an intensive memory training program on cognition and brain structure in middle-aged and elderly healthy volunteers. The memory trainers completed an 8-week training regimen aimed at improving verbal source memory utilizing the Method of Loci (MoL), while control participants did not receive any intervention. Both the memory trainers and the controls underwent magnetic resonance imaging (MRI) scans and memory testing pre and post 8 weeks of training or no training, respectively. Cortical thickness was automatically measured across the cortical mantle, and data processing and statistical analyses were optimized for reliable detection of longitudinal changes. The results showed that memory training improved source memory performance. Memory trainers also showed regional increases in cortical thickness compared with controls. Furthermore, thickness change in the right fusiform and lateral orbitofrontal cortex correlated positively with improvement in source memory performance, suggesting a possible functional significance of the structural changes. These findings demonstrate that systematic mental exercise may induce short-term structural changes in the aging human brain, indicating structural brain plasticity in elderly. The present study included short-term assessments, and follow-up studies are needed in order to assess whether such training indeed alters the long-term structural trajectories.

Neurocognitive disorders are frequent among chronic kidney disease (CKD) patients. Identifying and characterizing cognitive impairment (CI) can help to assess the ability of adherence to CKD risk reduction strategy, identify potentially reversible causes of cognitive decline, modify pharmacotherapy, educate the patient and caregiver and provide appropriate patient and caregiver support. Numerous factors are associated with the development and progression of CI in CKD patients and various conditions can influence the results of cognitive assessment in these patients. Here we review clinical warning signs that should lead to cognitive screening; conditions frequent in CKD at risk to interfere with cognitive testing or performance, including specificities of cognitive assessment in dialysis patients or after kidney transplantation; and available tests for screening and observed cognitive patterns in CKD patients., Graphical Abstract Graphical abstract

Funding: This article is published as part of a supplement financially supported by the COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT). Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research. publishersversion published