Volume 3, Issue 2, 2021

Tosun et al. report a systematic comparison of β-amyloid positivity detection models, identifying effective combinations of demographics, APOE genotype, global cognitive measures, MRI and plasma biomarkers as promising minimally invasive and low-cost assessments to detect the β-amyloid positivity using florbetapir PET status as the ground-truth.

Accurate early prognostication is vital for appropriate long-term care decisions after traumatic brain injury. O’Donnell et al. observe a link between alpha band power in the resting-state electroencephalogram of patients in acute post-traumatic unresponsive states and outcome at 3 months post-injury, indicating the value of electroencephalography for augmenting prognoses.

Cercignani et al. report significantly reduced functional connectivity of noradrenaline transporter-related circuits in multiple sclerosis patients with high as compared to low cognitive fatigue. This result, obtained with a novel multimodal analysis approach, suggests that imbalances in catecholaminergic functional circuits might underlie fatigue in multiple sclerosis.

The brain vital signs framework is a portable, neurophysiological evaluation of brain function. Fickling et al. observed a strong, significant linear relationship between changes in brain vital signs and the total number of subconcussive head impacts sustained over the course of a playing season in male ice hockey players.

Muhammed et al. investigate the link between motivation and motor output and its association with apathy and dopamine in patients with Parkinson’s disease and healthy controls. Using an oculomotor reward task, links between pupillary responses to rewards and motor action in differing dopaminergic states was explored.

Ceyzériat et al. demonstrate dysfunction in serotonin/dopamine connectivity and functional hypersensitivity of dopamine receptors in the TgF344-AD rat model of Alzheimer’s disease aged 6 months. Neurochemical alterations in serotonin receptor were also reported at an advanced age. Consequently, these results suggest dopamine and serotonin systems as new early-diagnostic and therapeutic avenues.

Bonthrone et al. assessed individualized brain growth in infants with congenital heart disease compared with a large normative sample to determine atypicality indices in the patient group. Low cerebral oxygen delivery was associated with impaired grey matter development and resulted in poor cognitive outcome in this population.

In models of neuronal ceroid lipofuscinoses, preventively targeting neuroinflammation attenuates neurodegeneration. Here Groh et al. show that in a model for infantile neuronal ceroid lipofuscinosis also complex clinical phenotypes like visual acuity, can be ameliorated by immunomodulation. Importantly, treatment after disease onset also mitigates disease, albeit less robustly than preventive treatment.

Abbreviated summary

Martinez Oeckel et al. report that aphasia after stroke is associated with lesions of the extreme capsule fibres and not with lesions of the arcuate fascicle. They use a new promising method of anatomy-based lesion-symptom mapping, mapping lesions of either tract on the occurrence of aphasia in acute stroke patients.

Perra et al. detected α-synuclein aggregates in olfactory mucosa and CSF samples of patients with dementia with Lewy bodies, using real-time quaking-induced conversion assay. Positivity in unpaired olfactory mucosa and CSF samples was significantly concordant with the clinical diagnosis and nearly 100% in participants in whom paired samples were tested.

Boutet and Germann et al. examined whether machine learning could predict clinical benefits in specific Parkinsonian signs when informed by the precise location of stimulation. They report that machine learning modelling using distinct brain areas could predict sign-specific clinical changes in Parkinson’s disease patients with subthalamic nucleus deep brain stimulation.

Cserpan et al. report the impact of age on high-frequency oscillations recorded in the scalp EEG of children with epilepsy. Children <7 years had higher rates of high-frequency oscillations when compared with older children. EEG intervals of ≥10 min were required for the reliable estimation of these rates.

Transient epileptic amnesia is a distinctive syndrome of late-onset limbic epilepsy occurring in late middle age and is a treatable cause of memory loss in older people. Here, Baker et al. describe 65 cases, comparing these to their previous cohort of 50 patients and to 102 literature cases.

In their study, Wiese et al. found that pharmacological inhibition of acid sphingomyelinase with antidepressants such as sertraline or amitriptyline increased the proportion of Foxp3⁺ regulatory T cells among human CD4⁺ T cells both in cell culture in vitro as well as in vivo in patients treated for major depression.

Mukherjee et al. report more than 80% of amyloid β N-terminus accumulating in sporadic Alzheimer’s disease is isomerized at Asp-1 and Asp-7 using ion mobility mass spectrometry. The discovery has implications for drug discovery, particularly immunotherapeutic strategies that often target the N-terminus of the peptide.

Kawano et al. report that the elevated neutrophil-to-lymphocyte ratio at cancer diagnosis is associated with the incidence of ischaemic stroke within 2 years after cancer diagnosis, suggesting that neutrophil-to-lymphocyte ratio at cancer diagnosis might be useful for identifying patients at high risk of ischaemic stroke.

Elevated cortical inflammation and defective choroid plexus activity associate with high-risk atherosclerosis in cynomolgus monkeys. Using diet-induced atherosclerosis, in-vivo imaging and gene analysis, Di Cataldo et al. showed (i) monkeys exhibit similar atherosclerosis features and vulnerable plaques-associated genes as patients, (ii) brain imaging demonstrated frontal cortex neuroinflammation and neurovascular signs.

Cerebellar hypoplasia is common in people with Down syndrome. Wu et al. decipher the spatial correspondence between cerebellar layers and diffusion MRI contrasts. The layer-specific oscillating gradient diffusion MRI at short diffusion-time shows superior sensitivity to detect microstructure alterations in both developing and mature cerebellar layers of a Down syndrome mouse model.

Geva et al. identified five lesion sites that caused verbal short-term memory impairments in a sample of 816 stroke survivors. These sites were located in left temporo-parietal and left basal ganglia structures. Sparing of these regions very rarely resulted in persistently poor verbal short-term memory.

Gerhalter et al. report the in vivo detection of ionic imbalances in mild traumatic brain injury in the form of decreased total sodium concentrations in global grey and white matter compared to controls. These changes correlated with the degree of neuropsychological impairment and differentiated non-recovered patients from controls.

Weber et al. demonstrate for the first time that vagal nerve stimulation in humans enhances reinforcement learning and decelerates extinction of learned behaviour. Behavioural modelling indicates that vagal stimulation increases reward sensitivity and shifts accuracy-speed trade-offs towards maximizing rewards.

Rostral degeneration of the spinal cord injury is an immediate process, while caudal degeneration is delayed. Ohnishi et al. reported that the glycolytic pathway is involved in the delayed caudal degeneration, while immediate rostral degeneration is exacerbated by oxidative stress in early thoracic spinal cord injury.

Bray et al. report psychotic symptom severity was associated with volumetric loss in the right hippocampal head across the chronic stages of moderate–severe traumatic brain injury. The authors propose a novel aetiological hypothesis by which this localized neurodegenerative change promotes dopaminergic network dysregulation contributing to delayed positive symptomatology post-brain injury.

Vemuri et al. report that measuring and accounting for white matter changes (vascular health-related diffusion changes and white matter hyperintensities) and microbleeds will aid in capturing vascular contributions to cognitive impairment and dementia (VCID). VCID was equivalent to the impact of amyloidosis in this population-based sample of older adults.

Stroke induces alterations in resting-state functional connectivity consisting of both hyper- and hypo-connectivity. Therapy-induced changes show a trend towards increases in contralesional intrahemispheric connectivity for both hyper- and hypo-connected regions suggesting the supportive role of the contralesional hemisphere in recovery during the early rehabilitation phase post stroke.

Cystic white matter injury is the key pathological substrate of cerebral palsy in preterm infants. Lear et al. show that in fetal sheep cystic injury after severe hypoxia evolved over many weeks, raising the tantalizing possibility that substantial white matter protection may be possible with very delayed interventions.

Harwood et al. report a transcriptome-wide association study of monocyte gene expression on two Alzheimer's disease genome-wide association studies. As immunity is important in Alzheimer’s disease, this provides a biological interpretation in immune cells, of genome-wide association studies and implicates two novel genes, PLIN2 and LACTB2, in Alzheimer’s disease.

Ingo et al. performed advanced diffusion complexity analyses to determine the impact of vascular health for adults at midlife. Higher burden of vascular risk factor exposure from young adulthood to midlife is associated with heterogeneous diffusion properties at midlife, which may reflect axonal disruption, increased inflammation and/or increased glial proliferation.

Lussier et al. report that plasma phosphorylated tau181 is associated cross-sectionally with CSF phosphorylated tau181 and [¹⁸F]fluorodeoxyglucose PET in 823 individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort. The authors also report a significant association between baseline plasma p-tau181 and longitudinal change in brain glucose metabolism indexed by [¹⁸F]fluorodeoxyglucose PET.

A key priority in multiple sclerosis is to uncover the neural mechanisms associated with cognitive change. Winter et al. demonstrate that the relationships between white matter pathology and the structure of specific tracts explain differences in learning and recall tasks in long-standing relapse-onset multiple sclerosis.

Guder et al. investigated FWC of diffusion-weighted imaging data in chronic stroke patients. Showing that this approach can strengthen the relationship between microstructural properties of the cortico-spinal tract, measures of cortical excitability and also behaviour suggests its potential to improve our existing models of structure-function associations after stroke.

Kuroda et al. report the results of the computational analysis of intracranial EEG data from a cohort of 135 patients with drug-resistant focal epilepsy. Both interictal HFO and phase-amplitude coupling measures were found to improve the prediction of post-operative seizure outcome.

Humans are most advanced in producing song and speech, and the dorsal and ventral laryngeal representation are hypothesized to constitute specialized parts of the speech control circuits. Here, Neef et al. find that the dorsal area has an overall stronger structural network and that only the ventral network is weakened in persistent stuttering.

Niccoli et al. report, in Drosophila, that neuronal lactate dehydrogenase, through activating transcription factor 4, is increased in response to Aβ42. Conversely, lactate dehydrogenase is reduced in inhibitory neurons, which are vulnerable to neurodegeneration in Alzheimer's disease patients. It is therefore possible that upregulation of Ldh maintains neuronal homeostasis.

Jurgiel et al. examined cortical source-resolved neural dynamics occurring during a flanker paradigm among children with and without chronic tic disorders. Attenuated spectral power within the anterior cingulate as well as atypical fronto-parietal network communication was apparent in children with tic disorders.

Alhindi et al. performed a comparative morphological analysis of terminal Schwann cells at the neuromuscular junction in mice and humans. They report significant species-specific differences that need to be taken into consideration when translating findings between species.

Gizak et al. report on a novel remitting leukodystrophy associated with a variant in the FBP2 gene coding for muscle fructose 1,6-bisphosphatase. The variant has a dominant negative effect not only on enzymatic properties and stability but also on non-canonical functions important for mitochondrial protection and regulation of nuclear processes.

Plassais et al. report a meta-analysis of gut microbiome alpha-diversity which demonstrates that richness and evenness were altered neither in Parkinson’s disease patients nor in Multiple Sclerosis patients in comparison with controls. This is the first report investigating systematically alpha-diversity and its potential link to neurological disorders.

Varatharajah et al. report that subtle abnormalities in EEG measures such as the spectral power of alpha activity may help identify (i) patients with epilepsy, and (ii) the seizure generating hemisphere in focal epilepsy, even when a routine scalp EEG is free of any epileptiform activity or other visible abnormalities.

Chou et al. propose a novel classification for cerebral small vessel disease and report the common and distinct patterns of the clinical and neuroimaging manifestations in the stratified four subgroups. It could be used in clinical and research settings to differentiate arteriosclerosis and cerebral amyloid angiopathy and also their severity.

Bohnen et al. investigated cholinergic PET correlates of cardinal motor symptoms in Parkinson's disease using complementary analysis approaches. Axial motor and tremor scores significantly associated with different and system-wide cholinergic pathways but evidence for distal limb bradykinesia scores was limited. No specific cholinergic transporter associations were found for rigidity scores.

Smith et al. used the Opera Phenix high-content screening system and R Studio to automate the quantification of viral transduction efficiency in the mouse brain. They show that the systemic delivery of AAV-PHP.B viruses results in widespread and even transduction throughout the brain and brain regions.

Neurological deficits following stroke are traditionally described as syndromes related to damage of a specific area or vascular territory. Bisogno et al. show that post-stroke neurological impairment can be described by robust, reproducible components of correlated deficits across functional domains with a bedside, clinically suitable, neurobehavioural assessment.

Zrafi et al. report inter-individual topographic variability in the Circle of Willis structure in a paediatric population. Their work shows a remarkably low variability of the typical Circle of Willis and provide data that have potential benefit for retrospective dosimetric studies in children developing cerebrovascular diseases after radiotherapy.

Lin, Kim and colleagues use MRI to appreciate changes in TDP-43^Q331K knock-in mice akin to those seen in presymptomatic human amyotrophic lateral sclerosis-frontotemporal dementia. A histological survey implicates parvalbumin interneuron loss, impaired neurogenesis, microglial activation and aberrant neurodevelopment in disease pathogenesis. They confirm reduced parvalbumin interneurons in human amyotrophic lateral sclerosis.

In a lesion-behaviour mapping study, Graessner et al. found dissociable contributions of left-hemispheric brain regions to basic semantic composition: While the anterior inferior frontal gyrus is relevant for task accuracy, the anterior temporal lobe is crucial for efficient semantic processing.

Kirsch et al. developed a novel task to manipulate the temporal (prospective and retrospective) and spatial context of motor belief-updating under a Bayesian modelling framework, finding that salience-related, right hemisphere disconnections affect individual’s ability to evaluate the relevance of context-dependent sensorimotor errors to more abstract (context-independent) beliefs about the self.

When patients with left spatial neglect are in an acoustic environment with frequent left-side tones, they are unable to catch and exploit statistical regularities in the omissions of tones and in the occurrence of tones in the right side of space. This deficit affects both pre-attentive processing and contextual updating.

Intrathecal contrast-enhanced MRI provided evidence for impaired glymphatic function in many brain regions, including both grey and white matter, of patients with idiopathic intracranial hypertension, a brain disease characterized by CSF disturbance and increased intracranial pressure of unknown cause.

Pires, Leitner et al. present a comprehensive characterization of the human epileptic proteome. The results reveal extensive protein alterations common across diverse epilepsies, providing insights on pathogenesis and potential novel drug targets.

Bernardi et al. report that complete resection of the corpus callosum does not affect the interhemispheric synchronization of sleep spindles, while it significantly reduces the spatial association between spindles and temporally coupled slow waves. These results are consistent with the dependence of spindle synchronization on thalamocortical rather than cortico-cortical connections.

Zhai et al. identify three dorsolateral prefrontal cortex (dlPFC)-centric circuits that predict cocaine relapse with high accuracy, providing insights into the multiple roles of the dlPFC in brain functioning that affects treatment outcome, and suggesting the dlPFC loci as potential neuromodulation targets for addiction treatment.

Kleine-Levin syndrome is a rare relapsing-remitting disease with no biological marker. Dudoignon et al. found that 70% of 138 patients had brain hypometabolism in FDG-PET/CT during remitting periods, affecting the posterior associative cortex and the hippocampus. This hypometabolism provides a trait marker for diagnosis.

Wang et al. report that APOEε4 potentiates tau burden in medial temporal regions including hippocampus, entorhinal and parahippocampal cortices in women, but not in men. The results suggest that APOE-by-sex interactive effect, rather than their main effects, modulates regional vulnerability to tau accumulation.

Bonkhoff et al. integrate machine learning and Bayesian hierarchical modelling to enable hemisphere-aware analysis of 1080 stroke patients. They quantify lateralization effects of cortical and subcortical regions, such as the pallidum and hippocampus, of middle and posterior cerebral artery vascular territories to the left for naming/memory and to the right for visuospatial functions.

Raghavan et al. report that advanced diffusion MRI can provide specific information about synaptic density, organization, and free water content of white matter microstructure. Age and white matter hyperintensities but not Alzheimer’s disease are key drivers of these changes. Corpus callosum white matter health is fundamental for better cognitive performance.

Szczupak et al. report that patients born with developmental corpus callosum malformations have abnormal structural brain connections. While acallosal patients have a scant number of inter-hemispheric connections, they preserve functional integrity and have a better prognosis than hypoplasic patients, which have atypical structural connections leading to abnormal functional connectivity patterns.

In a rodent model of synucleinopathy, Ferreira et al., delineate the spatiotemporal progression of incipient α-synuclein pathology (of peripheral origin) in the CNS. The authors show early affection of brainstem reticular nuclei in non-paralyzed mice, and pathological white matter lesions in relation to the neuronal pathology.

Docosahexaenoic acid’s neuroprotective effect may be concentrated in the entorhinal cortex and hippocampus. Here, we show that docosahexaenoic acid’s association with entorhinal volume and spatial navigation ability is modulated by the APOE genotype, with non-significant or inverse associations found in APOE ε4 carriers who are genetically-at-risk of Alzheimer’s disease.

Piras et al. compared highly localized callosal characteristics in four mental disorders (obsessive-compulsive disorder, schizophrenia, bipolar disorder and major depression). They showed that the corpus callosum is highly changed in obsessive-compulsive disorder, selectively changed in schizophrenia and not changed in bipolar disorder and major depression.

Pardilla-Delgado et al. studied individuals with autosomal-dominant Alzheimer’s disease and found that lower medial and posterior thalamic subregional volumes were associated with greater amyloid and tau burden, years before clinical onset. Findings suggest that studying thalamic sub-regions could improve our understanding of the role of this structure in Alzheimer’s disease.

Valencia-Sanchez et al. reviewed the spectrum of cases referred to their Autoimmune Neurology Clinic with suspected Hashimoto encephalopathy, and found that almost three-quarters had an alternative non-autoimmune CNS diagnosis. They conclude that thyroid antibodies are of little utility in the evaluation of autoimmune encephalopathy in contemporary clinical practice.

There are various methods to assess white-matter damage after traumatic brain injury, including neurite orientation and dispersion imaging. Bourke et al. found that volumetric differences were the most sensitive to group differences between patients and controls. However, diffusion measures provide greater specificity in relation to cognitive performance after moderate–severe brain injury.

This study documents how key tACS parameters, namely the intensity, the frequency and the stimulation site, modulate alpha power via a within-subject paradigm involving four stimulation conditions. tACS after effects on alpha power were measured at fixed time points up to 120 minutes post-stimulation.

Mallach et al. investigated the effect of the R47H TREM2 variant in human induced pluripotent stem cell microglia-derived cells on exosome secretion and content. They found decreased exosome secretion rate from TREM2 variants, linked to decreased energy availability and differences in exosomal protein content, which influenced the viability of neuron-like cells.

By distinguishing different levels of memory performance, Tracy et al. isolate the brain network characteristics uniquely associated with intact memory in epilepsy. They highlight two forms of cognitive reorganization (computational primacy; computational support) and show that intact memory requires adaptive abnormalities, and impaired memory involves failure to generate compensatory, supportive brain responses.

Next-generation sequencing on 870 patients with Dravet syndrome identified nine variants in GABRA1, GABRB2 and GABRG2 genes, which encode the most common α1β2γ2 GABA_A receptor in the CNS. Hernandez et al. report that mutations in multiple genes (GABRA1, GABRB2 and GABRG2) have a common target (α1β2γ2) to cause Dravet syndrome.

Loreto et al. assess the cognitive profiles, measured by standard neuropsychological testing, of memory clinic patients undergoing clinical amyloid PET imaging. In this study, visuospatial and working memory impairment, rather than episodic memory, best differentiated patients with Alzheimer’s disease from those with non-Alzheimer’s disease neurodegenerative and non-Alzheimer’s disease non-neurodegenerative conditions.

Saito et al. aimed to show that their bispectral electroencephalography (BSEEG) method can capture brain wave abnormalities indicative of delirium and predict mortality among elderly patients with and without dementia. They previously showed the usefulness of BSEEG with 274 inpatients, and this time they studied an additional 228 subjects to replicate their findings.

Multiple sclerosis is a neuroinflammatory disease of the CNS, associated with irreversible neuro-axonal loss, leading to permanent disability. Strik et al. report that advanced diffusion MRI reveals diffuse axonal loss in major sensorimotor pathways that correlate with subtle impairments in lower limb motor control and gait in minimally disabled patients.

Safar et al. show alterations in local and large-scale neural activity in children and adolescents with mild traumatic brain injury, with the majority experiencing long-term post-concussive symptoms, and establish that the functional connectome is a reliable and accurate classification marker for mild paediatric brain injury.

Brennan et al. show a rapid, low-cost blood test can identify which patients with suspected brain tumour to prioritize for diagnostic imaging, reducing time to diagnosis. The test is more than 90% sensitive for the most aggressive tumours. Earlier diagnosis can provide health and economic benefits.

Kao et al. reported that apparent diffusion coefficient parameters depicted in early period after neonatal hypoxic ischaemia are highly associated with different brain injury outcomes. The changes in intracellular ultrastructure were observed within 6 h after hypoxic ischaemia and correlated with early apparent diffusion coefficient characteristics and final severity outcome.

The hypocretin/orexin system in the brain regulates sleep and wakefulness. Aegidius et al. have developed a simple test to measure hypocretin-1 peptide in blood samples, and show that peripheral hypocretin-1 concentrations are unchanged in narcolepsy type 1 despite being absent in the brains of these patients.

The expression of human α-syn in Drosophila led to its accumulation in presynaptic terminals causing downregulation of synaptic proteins and reduction in the number of presynaptic active zones. These alterations impaired neuronal function and triggered behavioural deficits in ageing Drosophila that occurred prior to progressive degeneration of dopaminergic neurons.

Balestrini et al. report that people with focal epilepsies caused by unilateral brain lesions, especially of developmental aetiology, have increased facial asymmetry as measured by three-dimensional stereophotogrammetry and dense surface modelling. Facial asymmetry was not correlated with brain asymmetry of regional cortical thickness or surface area.

This study introduces unique method for radiological−pathological comparative research using micro-MRI. The micro-MRI was used as bridge to assess findings of in vivo MRI and neuropathology. Novel neuropathological findings of in vivo MRI-detected small vessel disease, such as cerebral microbleeds, cortical microinfarcts, and cortical superficial siderosis were described.

In the largest case series to date, Vivekananda et al. perform simultaneous magnetoencephalography and stereo-electroencephalography in refractory focal epilepsy patients. They demonstrate that for deep brain epileptogenic foci, magnetoencephalography dipoles could be derived from average stereo-electroencephalography data, thereby overcoming a traditional limitation of magnetoencephalography of reduced sensitivity for deep sources.

By screening European cohorts of individuals with genetically unsolved inherited optic neuropathies, Charif et al. report 61 new cases harbouring variants in ACO2, among whom 50 with dominant mutations, emphasizing for the first time the important contribution of ACO2 monoallelic pathogenic variants to dominant optic atrophy.

High-density EEG signals revealed abnormal brain connectivity in interictal migraine sufferers versus controls. This atypical pattern was noted during auditory and visual stimulation, and during rest. The results may aid diagnosis and treatment.

Sato et al. report the long-term associations between early neonatal nutrient intake and later white matter microstructure in children born very low birth weight. Their findings are important for understanding white matter development and for guiding early postnatal nutritional interventions in these high-risk children.

In a reporter assay, Kamath et al. report differences in the kinetics of tau aggregation accross individuals in brain samples from sporadic Alzheimer patients reflecting the properties of the initial seeds and suggesting person-specific differences in tau pathobiology even among individuals with sporadic Alzheimer disease.

Backhaus et al. used resting-state functional imaging of the ipsilesional parietofrontal network in severely impaired acute stroke patients and reported increased connectivity between anterior intraparietal sulcus and primary motor cortex compared to controls and an association of this connectivity with subsequent persistent disability in the late subacute stage of recovery.

In this study of reward effects in motor cortex in children with attention-deficit/hyperactivity disorder (ADHD) compared to their typically developing peers, Detrick et al. report that transcranial magnetic stimulation-evoked short-interval cortical inhibition and task-related up-modulation significantly differed between groups and may therefore represent measurable biomarkers in ADHD.

Nalls et al. report expression quantitative trait locus and colocalization data that suggests the gene, GRN, as a shared risk mechanism for multiple neurodegenerative diseases. There is an inverse relationship at GRN between gene expression level and risk of Parkinson's, Alzheimer's and amyotrophic lateral sclerosis.

Abbreviated summary

Martin et al. report lifelong persistence of sporadic Creutzfeldt–Jakob disease prions in the brain of mice lacking the endogenous prion protein gene and disease potentiation—without strain evolution—on retrotransmission to humanized mice. These findings highlight the risk of indefinite prion persistence with therapeutic strategies lowering the prion protein.

In this study, Abi Nader et al. presented a computational model of Alzheimer’s disease progression that allows to create scenarios of drug intervention. They estimated that statistically powered improvement of clinical endpoints could be obtained if amyloid was blocked at least seven years before a dementia diagnosis is made.

Using diffusion tensor imaging data, Overman et al. identified a specific relationship between white matter integrity of the splenium and memory retrieval in posterior cortical atrophy. These results fit within a framework in which memory deficits in posterior cortical atrophy are underpinned by disruption of attentional pathways.

Gellersen et al. tested object-location memory precision as a potential behavioural marker of Alzheimer’s disease risk by comparing genetic risk groups. Higher-risk apolipoprotein ε3ε4-carriers did not have poorer memory precision. Spatial navigation deficits previously identified in the same ε3ε4-carriers suggest superior early detection potential for navigation compared to object-location memory tasks.

Gadd et al. apply blood-derived epigenetic signatures of lifestyle traits to matched blood and brain samples, uncovering variability in how well blood translates across brain regions and a relationship between smoking and the prefrontal cortex. These preliminary results contribute to understanding how lifestyle-related DNA methylation affects the brain.

Abbreviated summary

Haytural et al. report that in Alzheimer’s disease, the synaptic alterations within the hippocampus are preferentially affecting the outer molecular layer of the dentate gyrus whereas other hippocampal sub-regions are preserved. The decline in synaptic proteins is restricted to the presynapse and does not correlate with the amyloid load or neuritic phosphorylated-Tau.

Gago-Dominguez et al. examined if genetic variants associated with obesity/metabolic factors and conditions were related to stroke risk in the Spanish population. SNPs rs1076173, rs2479409 and rs6511720 were found to increase risk of stroke in obese subjects, particularly among females. rs865686 increased the risk in non-obese subjects, particularly among males.

Individuals with Down syndrome show distinct deficits in cognitive processes that are mediated by the hippocampus. Using high-resolution MRI, Koenig et al. find volume reductions of select hippocampal subfields and widespread changes in synchronicity of the hippocampus in individuals with Down syndrome.

Probert et al. use an integrative analysis approach to identify novel CSF biomarkers from biochemical, proteomics, and metabolomics assays for the prediction of clinically conversion to multiple sclerosis in patients recruited at clinically isolated syndrome onset. The proposed multivariate algorithm significantly outperforms oligoclonal band status for prediction of clinical conversion.

DNA damage and deficient DNA repair are well established features of neurodegenerative diseases. This review highlights how the dysregulation of a DNA repair protein encoded by breast cancer type 1 promotes the onset of cellular senescence and contributes to brain dysfunction as it drives neurodegeneration.