Using cerebrospinal fluid biomarkers to diagnose Alzheimer's disease: an Australian perspective.

Cerebrospinal fluid (CSF) biomarkers are currently the only clinically validated biofluid diagnostic test for Alzheimer's Disease (AD) available in Australia. Testing of CSF biomarkers via lumbar puncture (LP), including quantification of amyloid-β peptide, total tau protein, and phosphorylated tau, can give insight into underlying pathophysiological changes and provide greater certainty in confirming or excluding the presence of Alzheimer's disease changes compared to standard clinical and radiological assessments. Despite CSF analysis being a safe and cost-effective diagnostic method, the use of CSF biomarkers in the evaluation of potential AD remains limited in Australian clinical practice due to a variety of factors, including regional access challenges, concerns over the perceived invasiveness of LP and a lack of confidence among clinicians in interpreting the results.

Resolving the problem of surface dyslexia in Italian through inflection of irregular verbs.

Surface dyslexia and dysgraphia are considered diagnostic features of semantic variant primary progressive aphasia (svPPA) and are useful signs in English, a language whose attributes afford numerous opportunities to observe these phenomena. This, however, is not the case in many languages, including Italian, that have high transparency between orthography and phonology, making surface reading and spelling errors scarce. This creates a problem in applying the diagnostic recommendations for svPPA in such languages.

Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases.

A systematic review of cognitive and behavioral tools to differentiate behavioral variant frontotemporal dementia from other conditions.

The behavioral variant of frontotemporal dementia (bvFTD) is thought to be the commonest clinical presentation of frontotemporal lobar degeneration and is predominantly characterized by changes in behavior. In patients lacking unequivocal biomarker evidence of frontotemporal neurodegeneration, the clinical diagnosis of bvFTD is often unstable. In response, we conducted a systematic review and critical appraisal of cognitive and behavioral tools that have sought to differentiate bvFTD from other conditions.

Pareidolias are a function of visuoperceptual impairment.

Pareidolias, or the misperception of ambiguous stimuli as meaningful objects, are complex visual illusions thought to be phenomenologically similar to Visual Hallucination (VH). VH are a major predictor of dementia in Parkinson's Disease (PD) and are included as a core clinical feature in Dementia with Lewy Bodies (DLB). A newly developed Noise Pareidolia Test (NPT) was proposed as a possible surrogate marker for VH in DLB patients as increased pareidolic responses correlated with informant-corroborated accounts of VH.

Increased Resolution of Structural MRI at 3T Improves Estimation of Regional Cortical Degeneration in Individual Dementia Patients Using Surface Thickness Maps.

Background: Objective measurement of regional cortical atrophy in individual patients would be a highly desirable adjunct for diagnosis of degenerative dementias.

Objective: We hypothesized that increasing the resolution of magnetic resonance scans would improve the sensitivity of cortical atrophy detection for individual patients.

Methods: 46 participants including 8 semantic-variant primary progressive aphasia (svPPA), seven posterior cortical atrophy (PCA), and 31 cognitively unimpaired participants underwent clinical assessment and 3.

A Systematic Review of Fragile X-Associated Neuropsychiatric Disorders.

Objective: Fragile X premutation carriers are reported to have increased neuropsychiatric problems, and thus the term fragile X-associated neuropsychiatric disorders (FXAND) has been proposed. Unfortunately, published prevalence estimates of these phenomena are inconsistent. This systematic review clarified this issue by reviewing both fragile X premutation prevalence in patients with neurodevelopmental disorders and psychiatric disorder prevalence in premutation carriers without fragile X-associated tremor/ataxia syndrome (FXTAS).

Instant tissue field and magnetic susceptibility mapping from MRI raw phase using Laplacian enhanced deep neural networks.

Quantitative susceptibility mapping (QSM) is an MRI post-processing technique that produces spatially resolved magnetic susceptibility maps from phase data. However, the traditional QSM reconstruction pipeline involves multiple non-trivial steps, including phase unwrapping, background field removal, and dipole inversion. These intermediate steps not only increase the reconstruction time but accumulates errors.

Support vector machine learning and diffusion-derived structural networks predict amyloid quantity and cognition in adults with Down's syndrome.

Down's syndrome results from trisomy of chromosome 21, a genetic change which also confers a probable 100% risk for the development of Alzheimer's disease neuropathology (amyloid plaque and neurofibrillary tangle formation) in later life. We aimed to assess the effectiveness of diffusion-weighted imaging and connectomic modelling for predicting brain amyloid plaque burden, baseline cognition and longitudinal cognitive change using support vector regression. Ninety-five participants with Down's syndrome successfully completed a full Pittsburgh Compound B (PiB) PET-MR protocol and memory assessment at two timepoints.

What's "up"? Impaired Spatial Preposition Processing in Posterior Cortical Atrophy.

This study seeks to confirm whether lesions in posterior regions of the brain involved in visuo-spatial processing are of functional relevance to the processing of words with spatial meaning. We investigated whether patients with Posterior Cortical Atrophy (PCA), an atypical form of Alzheimer's Disease which predominantly affects parieto-occipital brain regions, is associated with deficits in working memory for spatial prepositions. Case series of patients with PCA and matched healthy controls performed tests of immediate and delayed serial recall on words from three lexico-semantic word categories: number words (), spatial prepositions () and function words (e.

Metabolic derangements are associated with impaired glucose delivery following traumatic brain injury.

Metabolic derangements following traumatic brain injury are poorly characterized. In this single-centre observational cohort study we combined 18F-FDG and multi-tracer oxygen-15 PET to comprehensively characterize the extent and spatial pattern of metabolic derangements. Twenty-six patients requiring sedation and ventilation with intracranial pressure monitoring following head injury within a Neurosciences Critical Care Unit, and 47 healthy volunteers were recruited.

Traumatic brain injury fast-forwards Alzheimer's pathology: evidence from amyloid positron emission tomorgraphy imaging.

Purpose: Traumatic brain injury (TBI) has been proposed as a risk factor for Alzheimer's disease (AD), although the mechanisms underlying the putative association are poorly understood. We investigated elderly individuals with a remote history of TBI, aiming to understand how this may have influenced amyloidosis, neurodegeneration, and clinical expression along the AD continuum.

Methods: Total of 241 individual datasets including amyloid beta (Aβ) positron emission tomography ([F]-AV45), structural MRI, and neuropsychological measures, were obtained from the Alzheimer's Disease Neuroimaging Initiative.

A Systematic Review of Apathy and Depression in Progressive Supranuclear Palsy.

Depression and apathy can be significant problems in progressive supranuclear palsy (PSP). Using PRISMA guidelines, this systematic review examined prevalence estimates for depression and apathy in PSP, and, how different methods of definition may influence results. 29 studies meeting inclusion/exclusion criteria were identified: 12 on depression, 9 on apathy, and 8 on both.

Measuring cerebral perfusion with [C]-PiB R1 in Down syndrome: associations with amyloid burden and longitudinal cognitive decline.

Positron emission tomography imaging of glucose hypometabolism and amyloid deposition are two well-established methods to evaluate preclinical changes in Alzheimer's disease and people with Down syndrome. However, the use of both imaging modalities may overburden participants, particularly those with intellectual disabilities and cognitive impairment. The relative tracer delivery of the [C]-Pittsburgh Compound B has been proposed as a viable surrogate for cerebral perfusion.

Sonographic and 3T-MRI-based evaluation of the tongue in ALS.

A few systematic imaging studies employing ultrasound (HRUS) and magnetic resonance imaging (MRI) have suggested tongue measures to aid in diagnosis of amyotrophic lateral sclerosis (ALS). The relationship between structural tongue alterations and the ALS patients' bulbar and overall motor function has not yet been elucidated. We here thus aimed to understand how in-vivo tongue alterations relate to motor function and motor function evolution over time in ALS.

The upper cervical spinal cord in ALS assessed by cross-sectional and longitudinal 3T MRI.

The upper cervical spinal cord is measured in a large longitudinal amyotrophic lateral sclerosis (ALS) cohort to evaluate its role as a biomarker. Specifically, the cervical spinal cord´s cross-sectional area (CSA) in plane of the segments C1-C3 was measured semi-automatically with T1-weighted 3T MRI sequences in 158 ALS patients and 86 controls. Six-month longitudinal follow-up MRI scans were analyzed in 103 patients.

Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type.

Background: Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sporadic adult-onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA-C when compared with SAOA.

Objectives: The objective of this study was to identify structural differences of brain gray and white matter between both patient groups.

Longitudinal trajectories of amyloid deposition, cortical thickness, and tau in Down syndrome: A deep-phenotyping case report.

Introduction: Comorbid Alzheimer disease pathologies are frequently found in people with Down syndrome (DS). We report a deep phenotyping study undertaken over 7 years in a participant with DS who was nondemented at baseline but developed dementia after 5 years.

Methods: Throughout the course of the study, the participant was seen 4 times (2010, 2013, 2015, and 2017).

7T MR neurography-ultrasound fusion for peripheral nerve imaging.

Background: We present one patient with an initial diagnosis of Guillain-Barré syndrome (GBS) and one with Charcot-Marie-Tooth disease (CMT) type 1A.

Methods: Both patients underwent ankle tibial nerve fusion-imaging of high-resolution ultrasound (HRUS) with 7T MR neurography (MRN).

Results: In GBS, the nerve was enlarged, T2-hyperintense, and showed increased vascularization 21 months after symptom onset.

The concept of regularization: Resolving the problem of surface dyslexia in semantic variant primary progressive aphasia across different languages.

Unlabelled: Surface dyslexia, a diagnostic feature of the semantic variant of primary progressive aphasia (svPPA), is difficult to observe in many languages. It can be conceptualized as one manifestation of a more general "regularization" effect-that is, with semantic impairment, patients fail to recognize exceptions and revert to default rules.

Objective: We predicted that, analogous to surface dyslexia in English, German patients with svPPA would regularize irregular verbs, especially those of lower frequency and in the less frequently used preterite tense.

Diffusion Tensor MRI to Distinguish Progressive Supranuclear Palsy from α-Synucleinopathies.

Background The differential diagnosis of progressive supranuclear palsy (PSP) and Lewy body disorders, which include Parkinson disease and dementia with Lewy bodies, is often challenging due to the overlapping symptoms. Purpose To develop a diagnostic tool based on diffusion tensor imaging (DTI) to distinguish between PSP and Lewy body disorders at the individual-subject level. Materials and Methods In this retrospective study, skeletonized DTI metrics were extracted from two independent data sets: the discovery cohort from the Swedish BioFINDER study and the validation cohort from the Penn Frontotemporal Degeneration Center (data collected between 2010 and 2018).

The atrophy pattern in Alzheimer-related PPA is more widespread than that of the frontotemporal lobar degeneration associated variants.

Objective: The three recognized variants of primary progressive aphasia (PPA) are associated with different loci of degeneration-left posterior perisylvian in logopenic variant (lvPPA), left frontal operculum in non-fluent variant (nfvPPA), and left rostroventral-temporal in semantic variant (svPPA). Meanwhile, it has become apparent that patients with lvPPA, in which Alzheimer pathology is the norm, frequently have more extensive language deficits-namely semantic and grammatical problems-than is captured in the strict diagnostic recommendations for this variant. We hypothesized that this may be because the degeneration in AD-related PPA typically extends beyond the left posterior perisylvian region.

Differential effects of Down's syndrome and Alzheimer's neuropathology on default mode connectivity.

Down's syndrome is a chromosomal disorder that invariably results in both intellectual disability and Alzheimer's disease neuropathology. However, only a limited number of studies to date have investigated intrinsic brain network organisation in people with Down's syndrome, none of which addressed the links between functional connectivity and Alzheimer's disease. In this cross-sectional study, we employed C-Pittsburgh Compound-B (PiB) positron emission tomography in order to group participants with Down's syndrome based on the presence of fibrillar beta-amyloid neuropathology.

Delineating the topography of amyloid-associated cortical atrophy in Down syndrome.

Older adults with Down syndrome (DS) often have Alzheimer's disease (AD) neuropathologies. Although positron emission tomography imaging studies of amyloid deposition (beta amyloid, Aβ) have been associated with worse clinical prognosis and cognitive impairment, their relationships with cortical thickness remain unclear in people with DS. In a sample of 44 DS adults who underwent cognitive assessments, [C]-PiB positron emission tomography, and T1-weighted magnetization-prepared rapid gradient echo, we used mixed effect models to evaluate the spatial relationships between Aβ binding with patterns of cortical thickness.