bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperspectral retinal imaging as a biomarker for Alzheimer’s disease
Authors: Thach Michelle , de Ruyter Frederique J. Hart , Curro‐Tafili Katie R. , van de Giessen Elsmarieke , Collij Lyduine E. , den Braber Anouk , Tan H. Stevie , Visser Pieter Jelle , Verbraak Frank D. , Osseiran Sam , Grondin Jean‐Sébastien , Orellina Julie Antonelle , Campbell Shannon , Chevrefils Claudia , Sylvestre Jean‐Philippe , Bouwman Femke H. 
Published: December 2023

AbstractBackgroundCurrently, Alzheimer’s disease (AD) diagnosis relies on biomarkers that are either expensive, invasive or time‐consuming. The retina is easily accessible and may be used as a patient‐friendly and cost‐effective diagnostic tool. Optina Diagnostics’ Mydriatic Hyperspectral Retinal Camera (MHRC) may improve diagnostic abilities of the retina by using rich datasets and artificial intelligence. Here we aim to explore diagnostic possibilities of the MHRC by identifying image features associated with the cerebral amyloid status.MethodSix cognitively healthy participants with a negative amyloid‐PET scan and twenty‐five participants with a positive amyloid‐PET scan (clinical AD n = 4, preclinical AD n = 21, MMSE ≥17) were recruited from the EMIF‐AD PreclinAD Twin60++ study and Amsterdam Dementia Cohort (Table 1). Retinal imaging was performed using the MHRC that acquires 92 retinal images in an ∼1 second exposure, in steps of 5 nm increments across a spectral range of 450‐905 nm (visible and near‐infrared) on a 31° field‐of‐view (Figure 1). Spatial‐spectral features (n = 2304) were extracted from two or three hyperspectral cubes per participant using different combinations of anatomical masks, spectral regions and texture measures. Morphological features (n = 935) related to the blood vessels (diameter, tortuosity, density and fractal dimension) were also extracted from different retinal zones. Features were assessed with a Tukey’s test for statistical significance to classify the cerebral amyloid status determined by amyloid‐PET scans. Features were considered significant if their p‐value was below 0.05 simultaneously for both our present cohort and an independent cohort of 499 subjects.ResultExplorative analysis identified thirty significant spatial‐spectral features (p‐value range 0.0033‐0.049) for the classification of the cerebral amyloid‐PET status. Examples of such features covering different spectral ranges and retinal anatomic regions are presented in Figure 2. In contrast, only three morphological features were identified (p‐value range 0.017‐0.049).ConclusionPhenotypic features extracted from hyperspectral retinal images hold promise to discriminate between amyloid‐PET positive and negative individuals, beyond morphological features available with conventional retinal imaging. More data are collected from several centers to build a classifier of features with the aim to discriminate amyloid‐PET positive from negative subjects. This would yield a patient‐friendly and non‐invasive retinal biomarker for AD.
Preserved absolute pitch and musical working memory in posterior cortical atrophy
Authors: Jiang Jessica , Brotherhood Emilie V , Hardy Chris JD , Yong Keir X X , Foulkes Alexander JM , Warren Jason D 
Published: December 2023

AbstractBackgroundThe cognitive organisation of working memory for nonverbal sounds and the unusual musical ability of absolute pitch is poorly understood. We recently had the opportunity to investigate this in a musician with absolute pitch who developed posterior cortical atrophy (PCA), the canonical ‘visual variant’ of Alzheimer’s disease.MethodWe studied a 59 year old professional pianist, PA, known premorbidly to have absolute pitch and fulfilling diagnostic criteria for PCA, in comparison to five healthy age‐matched female musicians (three with absolute pitch, two without). Each participant completed the melodic organisation (scale, contour, interval) and rhythm subtests of the Montreal Battery for Evaluation of Amusia (MBEA), an assessment of absolute pitch ability, a standard test of auditory verbal working memory (digit span), an equivalent working memory test for spoken letters and a series of bespoke musical working memory tasks assessing forward and reverse span for pitch sequences, rhythmic sequences and sequences combining these two dimensions.ResultPA had reduced digit span and letter span relative to healthy musician controls, as anticipated from her diagnosis. However, she had retained absolute pitch and performed normally on MBEA subtests assessing pitch and rhythm patterns and within the healthy musician range on the bespoke tests of pitch and rhythm working memory. Across musical working memory tests, PA showed a profile similar to healthy musician controls with absolute pitch: all performed better on the pitch working memory task than other musical working memory tasks. On the pitch working memory test, PA performed better than the healthy musicians without absolute pitch, all of whom performed worse on the pitch task than other musical working memory tasks.ConclusionOur findings suggest that absolute pitch may be preserved and continue to support musical working memory (despite impaired verbal working memory) in PCA. This study has implications for our understanding of the cognitive and neural mechanisms of absolute pitch and nonverbal auditory working memory.
Atlas of Retinal Imaging in Alzheimer’s Study (ARIAS): SD‐OCT in Preclinical Alzheimer’s disease
Authors: Alber Jessica , Thompson Louisa I , Arthur Edmund , Strenger Jennifer , Price Ashley N. , Sinoff Stuart , Snyder Peter J 
Published: December 2023

AbstractBackgroundARIAS is a preclinical Alzheimer’s disease (AD) cohort study, with the aim of following cognitively unimpaired (CU) older adults at high and low risk for AD and studying changes in retinal biomarkers over time. Here, we share baseline Spectral Domain Optical Coherence Tomography (SD‐OCT) data from ARIAS.MethodSD‐OCT was completed using the Heidelberg SPECTRALIS on 146 CU older adults (aged 55‐80), 83 high risk (APOE E4 carriers, first degree family history of AD), 63 low risk (APOE E4 non‐carriers, no first‐degree family history of AD). We took macular (30×25‐degree) and optic disc centered (radii of 3.5, 4.1, and 4.7 mm) SD‐OCT images. Vendor software was used to segment and compute average retinal thickness and volume in the 9 ETDRS maps for the macular and 7 glaucoma fields for the optic disk. ANCOVA (with age as a covariate) was used to compare retinal layer thickness and volume between the two groups. Bonferroni correction was used for multiple comparisons.ResultThe high risk group had significantly higher thickness/volume than the low risk group in the inner temporal quadrant of the ganglion cell layer (GCL, F(2, 144) = 3.67p<.05), the central quadrant of the inner nuclear layer (INL, F(2, 144) = 3.48,p<.05), the inner nasal quadrant of the outer plexiform layer (OPL, F(2, 144) = 7.35,p<.05). The peripapillary retinal nerve fiber layer (pRNFL) showed increased global thickness (F(2, 144) = 4.30, p<.05), and thickness in the nasal (F(2, 144) = 4.23, p<.05), nasal inferior (F(2, 144) = 3.34, p<.05), and temporal inferior (F(2, 144) = 3.61,p<.05) quadrants in the high risk group compared to the low risk group.ConclusionSD‐OCT can be applied to examine retinal thickness in preclinical AD. Thickness/volume of specific quadrants of the GCL, INL, and OPL differentiated high risk CU older adults from low risk CU older adults in a large preclinical cohort. pRNFL global thickness, and thickness in the nasal, nasal inferior, and temporal inferior quadrants, was increased in the high risk group. These results confirm and extend our prior findings of increased retinal layer thickness in preclinical AD. Longitudinal data will confirm whether these layers change over time in preclinical AD.
Blood proteomics to identify AD CSF molecular subtypes
Authors: Tijms Betty M. , Teunissen Charlotte E. , Gobom Johan , Shi Liu , Zetterberg Henrik , Lovestone Simon , Visser Pieter Jelle , Blennow Kaj 
Published: December 2023

AbstractBackgroundWe identified three distinct molecular subtypes in Alzheimer’s disease (AD) using cerebrospinal fluid (CSF) proteomics: one subtype was characterised by neuronal hyperplasticity with increased amyloid metabolism, the second subtype was characterised by innate immune activation and the third subtype by a disrupted blood‐brain barrier. Each subtype will likely need specific treatment, but for patient selection CSF proteomics might be impractical. Here we investigated if AD molecular subtypes can also be detected in blood.MethodWe selected from EMIF‐AD MBD 149 individuals with AD across the clinical spectrum who had plasma proteomics as well as a CSF subtype definition available. We compared CSF subtypes on plasma levels using general linear models. We selected a subset of proteins that best predicted AD subtype by trying a random forest classifier on 70% of the patient sample, and computed prediction accuracy statistics on patients that were left out.ResultPlasma levels of 407 (13%) proteins differed between AD subtypes (figure). The plasma profiles specific to AD subtype showed altered levels for corresponding molecular processes: The CSF hyperplasticity subtype (n = 53) showed low plasma levels of 76 proteins associated with neuron development and axon guidance. The CSF innate immune activation subtype (n = 48) showed low plasma levels of 142 proteins related to regulation of immune response. The CSF blood‐brain barrier subtype (n = 48) showed the low plasma levels of 189 proteins associated with blood vessel morphogenesis. The random forest could classify subtypes with an overall accuracy of 77% (range 70%‐85%), and the top 5 contributing proteins were FGF10, CTCF, TCN2, PLXNA1, and EMILIN3.ConclusionIt is possible to detect distinct AD CSF molecular subtypes in blood. The next step is to validate this in independent cohorts, and to test if subtypes are related to different treatment responses.
How our emerging understanding of Alzheimer’s disease and dementia risk factors is enhanced using UK Biobank
Authors: Llewellyn David J 
Published: December 2023

AbstractWe have long known that there are large individual differences in the risk of developing Alzheimer’s disease and other dementia subtypes. Indeed, the hope is that this variation gives us clues that may provide new opportunities for targeted interventions and dementia prevention. Thousands of studies in recent decades provide compelling evidence that there are dozens of modifiable and non‐modifiable dementia risk factors. This provides cause for optimism, though critics stress several limitations that need to be addressed. The thorny issue of possible confounding remains, and the causal status of many dementia risk factors is challenging or even impossible to establish in randomized controlled trials. Most prior studies are modest in size and there is large variation in the associations observed between studies that is difficult to explain. Lastly, the window of opportunity for early intervention is difficult to assess from studies of older adults whose underlying pathologies may already be well established. UK Biobank provides us with a fundamentally different type of resource to help address these limitations and accelerate the pace of our discoveries. So, what’s new? For the first time we can investigate genetic, lifestyle and environmental risk factors for dementia in half a million middle‐aged and older adults. This has been a game changing shift in the size and richness of the data available to us, which in turn has changed the scientific questions that are possible to address. For example, we established for the first time that lifestyle factors do not interact with polygenic risk, suggesting that lifestyle interventions may decrease dementia risk regardless of genetic variation (Lourida, et al., 2019, JAMA). We can now investigate single or multiple risk factors for dementia with greater confidence. For instance, recent studies of frailty and cardiometabolic multimorbidity in combination with genetic, neuroimaging, and other rich data provide practical examples (Ward, et al., 2022, JNNP; Tai, et al., 2022, Lancet Healthy Longevity). Mendelian randomization and causal machine learning are particularly promising approaches when evaluating causality. Future enhancements to UK Biobank will facilitate even more powerful insights into the natural history of dementia, raising new possibilities for precision dementia medicine.
Extending understanding of the genetic architecture of cerebral small vessel disease using advanced imaging measures in UK Biobank
Authors: Debette Stéphanie 
Published: December 2023

AbstractCerebral small vessel disease (cSVD) is a leading cause of stroke and a major contributor to cognitive decline and dementia in the population (Debette JAMA Neurol 2019). Covert cSVD, which is detectable with brain MRI but does not manifest as clinical stroke, is highly prevalent in the general population, particularly with increasing age. Large collaborative genomic studies through consortia like CHARGE or ISGC have led to substantial progress in the identification of common genetic variants that are associated with cSVD. In this presentation, we will provide an overview of such collaborative studies, prominently involving the unique UK Biobank resource, that have recently extended our understanding of the genetic architecture of cSVD, revealing over 70 independent loci associated with this condition, especially with MRI‐markers of cSVD (Bordes, Nat Rev Neurol 2022; Duperron, Nat Med AIP). In silico functional explorations of the observed genetic associations point to a major role of blood pressure‐related pathways, but also mechanisms independent of vascular risk factors, such as extracellular matrix, membrane transport, vascular development, myelination, and blood‐brain barrier. Leveraging next‐generation sequencing data in UK Biobank and other resources, these studies also shed new light on the continuum between monogenic and multifactorial cSVD, with several genes (HTRA1, COLA4) harboring both rare mutations and common variants contributing to the disease (Mishra, Brain 2019). Further, we recently showed that MRI‐cSVD risk loci identified in middle‐ and older age in UK Biobank and other cohorts are associated with white matter microstructure on diffusion imaging (DTI, NODDI) and perivascular space burden already in young adults in their twenties (e.g. at VCAN, OPA1, SLC13A3) suggesting that processes contributing to cSVD may find their root much earlier in life than previously thought (Duperron, Nat Med AIP; Sargurupremraj, Nat Commun. 2020). We provide preliminary insights on how these association patterns change across the adult lifespan and discuss how this can inform dementia prevention, including, in combination with other omics resources, for proof‐of‐concept genomics‐driven drug discovery (Duperron, Nat Med AIP; Mishra, Nature. 2022; Mishra, Brain. 2022).
Annonaceae fruit consumption is associated with cognitive decline and dementia in degenerative parkinsonism
Authors: de Langavant Laurent Cleret , Flamand‐Roze Emmanuel , Petit Aimee , Tressieres Benoit , Gharbi‐Meliani Amin , Chaumont Hugo , Michel Patrick Pierre , Bachoud‐Levi Anne‐Catherine , Remy Philippe , Edragas Regine , Lannuzel Annie 
Published: December 2023

AbstractBackgroundHigh consumption of Annona muricata fruit (soursop, graviola, guanabana, corossol) has been previously identified as a risk factor for atypical parkinsonism in the French Caribbean islands. Annonaceae fruits are consumed worldwide in tropical areas. We tested whether consumption of Annonaceae products could worsen the clinical phenotype of patients with any form of degenerative parkinsonism.MethodWe analyzed neurological data from 180 Caribbean parkinsonian patients and specifically looked for dose effects of lifelong, cumulative Annonaceae consumption on cognitive performance. Using unsupervised clustering, we identified one cluster with mild/moderate symptoms (N = 102) and one with severe symptoms including cognitive impairment (N = 78).ResultWe showed that even low cumulative consumption of fruits/juices (>0.2 fruit‐years) or any consumption of herbal tea from Annonaceae worsen disease severity and cognitive deficits in degenerative parkinsonism including Parkinson’s disease (OR fruits‐juices: 3.76 [95% CI: 1.13‐15.18]; OR herbal tea: 2.91 [95% CI: 1.34‐6.56]).ConclusionWe suggest that more restrictive public health preventive recommendations should be made regarding Annonaceae products which could increase the risk cognitive impairment and dementia in tropical areas.
Functional neuroanatomy of music perception in frontotemporal dementia
Authors: Core Lucy , Warren Jason D , Agustus Jennifer L 
Published: December 2023

AbstractBackgroundDespite considerable interest in music as an index of brain function and a therapeutic modality in dementia, the neural correlates of music processing in different dementias remain poorly defined. In the frontotemporal dementia spectrum, behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) are often associated with striking changes in musical function and/or retained musical skills, suggesting frontotemporal dementia may be an instructive disease model in which to assess brain mechanisms of music processing in neurodegenerative pathologies. Here we addressed this issue using activation fMRI in patients with frontotemporal dementia.MethodNineteen patients (10 svPPA, nine bvFTD) and 26 healthy age‐matched controls underwent 3‐Tesla ‘sparse’ fMRI in which they listened passively to musical melodies. In a 2×2 factorial design, stimulus conditions were manipulated to probe two key dimensions of music processing: semantic memory (familiarity: familiar vs. novel melodies) and perceptual features (temporal structure: isochronous vs. anisochronous melodies). Post‐scan behavioral testing assessed participants’ ability to discriminate melodies under each of the two manipulated stimulus dimensions. Information about participant demographics and musical background was also collected.ResultThe healthy older control group showed separable profiles of activation in posterior superior temporal cortex for processing musical temporal structure, and in anterior temporal and inferior frontal cortices for processing musical familiarity. Compared with healthy older listeners, syndromic groups showed differential patterns of engagement of these distributed neural networks. In post‐scan behavioral testing, patients with bvFTD also exhibited significantly impaired musical familiarity judgments relative to healthy controls.ConclusionFrontotemporal dementia syndromes show distinct functional neuroanatomical signatures of music perception. Future work should explore fMRI of music processing as a probe of neural function in particular molecular pathologies and a candidate marker of therapeutic potential in dementia.
Prevalence of subjective cognitive decline and its association with physical health problems among urban community dwelling elderly population in South India
Authors: Kantipudi Suvarna Jyothi , Menon Jayakumar 
Published: December 2023

AbstractBackgroundThe incidence of cognitive disorders is increasing in India1. Stage II of the preclinical Alzheimer’s Disease (PCAD) is characterised by subjective complaints of decline in cognition, termed Subjective Cognitive Decline (SCD)2,3. Objective assessments of cognition is normal in that stage. There are no studies from India that looked at SCD in the community. Our study aims to look at the prevalence of SCD in an urban dwelling elderly population and its correlates.Method418 individuals above the age of 60 were screened using Subjective Memory Complains Questionnaire (SMCQ) and also screened for medical and psychiatric illness. Objective measurement of cognitive functions was done using MOCA.Results372(92.5%) had reported at least 1 subjective complaint using the participant version of the Subjective Memory Complaint Questionnaire(SMCQ). Among those without any reported subjective complaints,17(56.6%) had objective cognitive impairment on assessments. In total,13 (3.49%) had normal cognition and 179(48.12%) of the evaluated subjects had pre‐MCI SCD. There is no statistically significant association between physical health parameters of Diabetes mellitus and Hypertension or any sociodemographic variables except educational attainment. The mean subjective complaints score is lesser and means objective cognition scores are higher in those with higher secondary school educational attainment (p value<0.001) when compared to those who don’t.ConclusionsThere is significant morbidity of cognitive decline in the elderly. Subjective memory complaints are present in most of the elderly(92.5%) and 179(48.12%) had pre‐MCI SCD. SCD is a complex condition that requires further longitudinal studies with biomarker assessment to understand the mechanism of progression to AD.
The Israel National Brain Repository .The establishment and uniqueness of the first brain bank in Israel
Authors: Manzali Sigalit , Ravona‐Springer Ramit , Heymann Anthony , Greenbaum Lior , Cooper Itzik , Gardner Raquel C. , Liraz‐Zaltsman Sigal , Beeri Michal S 
Published: December 2023

AbstractBackgroundPost‐mortem human brain tissue is the gold‐standard for neurodegenerative disease diagnosis and is invaluable for elucidating cellular and molecular mechanisms. Therefore, neurodegenerative disease brain banks are a critical component of research to advance diagnosis and develop effective disease modifying therapies. The Israel National Brain Repository (INBR) was established in 2018 at the Sheba Medical Center via a collaboration with the Mount Sinai Neuropathology Brain Bank in New York. Israel is a unique country with a diverse population including substantial populations of individuals of European descent, Middle‐Eastern North African (MENA) descent, and combinations of both.MethodINBR predominantly recruits from two prospective longitudinal cohort studies whose participants are at high dementia risk: older adults with type 2 diabetes (the Israel Diabetes and Cognitive Decline study) and middle‐aged offspring of people with Alzheimer’s Disease (The Israel Registry for Alzheimer’s Prevention). Participants in both cohorts are phenotyped for cognition, lifestyle, brain imaging, blood biomarkers, and genetics. Biospecimen collection and processing protocols are aligned with other Neurobiobanks in the USA (see flowchart). Additionally, all participants in both cohorts are members of the second largest healthcare provider in Israel, the Maccabi Healthcare Services, permitting linkage to longitudinal medical records dating from 1998.ResultN = 450 participants have signed intent to autopsy. Among the N = 285 with race/ethnicity data available, 30% are MENA. 14 brain and 6 spinal cord donations have been completed. At time of death, donors had an average age of 81.1 years, 10 had normal cognition, 3 had dementia, and one had amyotrophic lateral sclerosis.ConclusionThe potential strengths of the INBR is in the population characteristics of Israel, the ethnic diversity and admixture, the linkage to 25‐years of medical records data, and the small size of the country allowing donations to be received from anywhere in the country. The main challenge we face is cultural barriers to brain donation that exist among some segments of Israeli society. The ultimate goal is to capitalize on the strengths and uniqueness of INBR to develop novel therapies for dementia.