Age-related changes in neural functional connectivity and its behavioral relevance

<p>Abstract</p> <p>Background</p> <p>Resting-state recordings are characterized by widely distributed networks of coherent brain activations. Disturbances of the default network - a set of regions that are deactivated by cognitive tasks and activated during passive states - have been detected in age-related disorders such as Alzheimer's or Parkinson's disease but alterations in the course of healthy aging still need to be explored.</p> <p>Results</p> <p>Using magnetoencephalography (MEG), the present study investigated how age-related functional resting-state brain connectivity links to cognitive performance in healthy aging in fifty-three participants ranging in age from 18 to 89 years. A beamforming technique was used to reconstruct the brain activity in source space and the interregional coupling was investigated using partial directed coherence (PDC). We found significant age-related alterations of functional resting-state connectivity. These are mainly characterized by reduced information input into the posterior cingulum/precuneus region together with an enhanced information flow to the medial temporal lobe. Furthermore, higher inflow in the medial temporal lobe subsystem was associated with weaker cognitive performance whereas stronger inflow in the posterior cluster was related to better cognitive performance.</p> <p>Conclusion</p> <p>This is the first study to show age-related alterations in subsystems of the resting state network that are furthermore associated with cognitive performance.</p

Accumulation of intraneuronal Aβ correlates with ApoE4 genotype

In contrast to extracellular plaque and intracellular tangle pathology, the presence and relevance of intraneuronal Aβ in Alzheimer’s disease (AD) is still a matter of debate. Human brain tissue offers technical challenges such as post-mortem delay and uneven or prolonged tissue fixation that might affect immunohistochemical staining. In addition, previous studies on intracellular Aβ accumulation in human brain often used antibodies targeting the C-terminus of Aβ and differed strongly in the pretreatments used. To overcome these inconsistencies, we performed extensive parametrical testing using a highly specific N-terminal Aβ antibody detecting the aspartate at position 1, before developing an optimal staining protocol for intraneuronal Aβ detection in paraffin-embedded sections from AD patients. To rule out that this antibody also detects the β-cleaved APP C-terminal fragment (β-CTF, C99) bearing the same epitope, paraffin-sections of transgenic mice overexpressing the C99-fragment were stained without any evidence for cross-reactivity in our staining protocol. The staining intensity of intraneuronal Aβ in cortex and hippocampal tissue of 10 controls and 20 sporadic AD cases was then correlated to patient data including sex, Braak stage, plaque load, and apolipoprotein E (ApoE) genotype. In particular, the presence of one or two ApoE4 alleles strongly correlated with an increased accumulation of intraneuronal Aβ peptides. Given that ApoE4 is a major genetic risk factor for AD and is involved in neuronal cholesterol transport, it is tempting to speculate that perturbed intracellular trafficking is involved in the increased intraneuronal Aβ aggregation in AD

Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease

status: publishe

Is implicit motor learning preserved after stroke? A systematic review with meta-analysis

© 2016 Kal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Many stroke patients experience difficulty with performing dual-tasks. A promising intervention to target this issue is implicit motor learning, as it should enhance patients' automaticity of movement. Yet, although it is often thought that implicit motor learning is preserved poststroke, evidence for this claim has not been systematically analysed yet. Therefore, we systematically reviewed whether implicit motor learning is preserved post-stroke, and whether patients benefit more from implicit than from explicit motor learning. We comprehensively searched conventional (MEDLINE, Cochrane, Embase, PEDro, PsycINFO) and grey literature databases (BIOSIS, Web of Science, OpenGrey, British Library, trial registries) for relevant reports. Two independent reviewers screened reports, extracted data, and performed a risk of bias assessment. Overall, we included 20 out of the 2177 identified reports that allow for a succinct evaluation of implicit motor learning. Of these, only 1 study investigated learning on a relatively complex, whole-body (balance board) task. All 19 other studies concerned variants of the serial-reaction time paradigm, with most of these focusing on learning with the unaffected hand (N = 13) rather than the affected hand or both hands (both: N = 4). Four of the 20 studies compared explicit and implicit motor learning post-stroke. Meta-analyses suggest that patients with stroke can learn implicitly with their unaffected side (mean difference (MD) = 69 ms, 95% CI[45.1, 92.9], p < .00001), but not with their affected side (standardized MD = -.11, 95% CI[-.45, .25], p = .56). Finally, implicit motor learning seemed equally effective as explicit motor learning post-stroke (SMD = -.54, 95% CI[-1.37, .29], p = .20). However, overall, the high risk of bias, small samples, and limited clinical relevance of most studies make it impossible to draw reliable conclusions regarding the effect of implicit motor learning strategies post-stroke. High quality studies with larger samples are warranted to test implicit motor learning in clinically relevant contexts