bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retinal hyperspectral imaging biomarker for Alzheimer’s disease: Preliminary study of the influence of eye diseases on imaging scores
Authors: van Wijngaarden Peter , Hui Flora , Dang Darvy , Ha Jason , Fowler Christopher J , Villemagne Victor LL , Rowe Christopher C , Masters Colin L , Williamson Robert , Crowston Jonathan G , Hadoux Xavier 
Published: December 2020

AbstractBackgroundWe and others have demonstrated that in vivo retinal hyperspectral imaging may serve as a non‐invasive biomarker of brain amyloid beta (Aβ) levels (Hadoux, 2019; More, 2019). We next sought to determine whether individuals with a range of common eye diseases have imaging scores distinct from those of people known to have high Aβ burden on brain PET imaging.MethodRetinal hyperspectral imaging was performed on people presenting to ophthalmology outpatient clinics with visually significant cataracts (n=10), glaucoma (n=18) or diabetic retinopathy (n=14). Hyperspectral imaging scores were calculated for each participant using image processing methods described previously (Hadoux, 2019). Scores were compared with those of participants with high Aβ burden on brain PET imaging (n=15) and age‐matched PET‐negative controls (n = 20) (Hadoux, 2019).ResultParticipants in each group were similar for gender and age. Significant differences in hyperspectral imaging scores were found between PET+ participants and all other groups (Figure 1). Post‐hoc analysis demonstrated that PET‐ control participants had lower hyperspectral imaging scores than PET+ participants with normal (≥24, n=7; p=0.01) or reduced (<24, n=8; p=0.035) MMSE scores.ConclusionWe have shown that individuals presenting to outpatient ophthalmology clinics with a range of eye diseases including cataract, diabetic retinopathy and glaucoma have retinal hyperspectral imaging scores that are distinct from those of individuals with high Aβ burden on brain PET imaging. Further studies are warranted to establish the influence these eye diseases on hyperspectral imaging scores in PET+ individuals. We also provide evidence that retinal hyperspectral scores may be elevated in PET+ individuals with normal MMSE scores, indicating that the method may have a role in identifying those with pre‐symptomatic Alzheimer’s disease. Prospective studies are underway to test this hypothesis. References: Hadoux, X, et al. Nature Communications; 2019; More, SS, et al. ACS Chem Neurosci. 2019.
Childhood head injury, control beliefs, and later life cognitive function in the Health and Retirement Study
Authors: Turner Robert 
Published: December 2020

AbstractBackgroundMild traumatic brain injury earlier in life is a risk for dementia later in life. While research has rightly focused attention on strategies for reducing the risk of incurring brain injury in youth, less attention has been paid to potentially modifiable risk factors for dementia in the context of a sustained childhood brain injury. Psychosocial resources may play an important role in mitigating the risk of dementia associated with early life brain injury. We investigated the role of control beliefs in the relationship between early life brain injury and cognitive functioning in the Health and Retirement Study.MethodData were from four biennial waves of HRS, combining 2006 and 2008 (time 1) and 2010 and 2012 (time 2) (n=5,999). A linear regression model evaluated the relationship between self‐reported head injury ("Before you were 16 years old, did you have a blow to the head, a head injury or head trauma that was severe enough to require medical attention, to cause loss of consciousness or memory loss for a period of time") and perceived control at time 1. A second examined the relationship between self‐reported head injury at time 1 and working memory (immediate and delayed recall) at time 2, controlling for working memory at time 1. A final model examined control beliefs as a potential mediator. Controls included age, race, gender, depression, health conditions, education, and income.ResultMean age was 65.4 years, 78.2% White, 10.1% Black, 5% Latino, 6.5% other, and 10.1 percent reported early head injury. Those with a history of head injury in childhood reported lower personal control beliefs at time 1 (p<.001). History of childhood head injury (time 1) were modestly associated with working memory at time 2, after controlling for baseline working memory (p<.05). Control beliefs partially mediated this relationship.ConclusionHRS respondents with a self‐reported history of head injury in childhood reported lower personal control beliefs. In turn, control beliefs mediated the relationship between early head injury and later life working memory. Personal control beliefs may be an important modifiable risk for cognitive decline among those with a history of childhood head injury.
The development of a valid, reliable, harmonized segmentation protocol for hippocampal subfields and medial temporal lobe cortices: A progress update
Authors: La Joie Renaud , Olsen Rosanna , Berron David , Amunts Katrin , Augustinack Jean , Bakker Arnold , Bender Andrew , Boccardi Marina , Bocchetta Martina , Chakravarty M. Mallar , Chetelat Gael , de Flores Robin , DeKraker Jordan , Ding Song‐Lin , Insausti Ricardo , Kedo Olga , Mueller Susanne G , Ofen Noa , Palombo Daniela , Raz Naftali , Stark Craig E. , Wang Lei , Yushkevich Paul A. , Yu Qijing , Carr Valerie A , Wisse Laura , Daugherty Ana M. 
Published: December 2020

AbstractBackgroundThe medial temporal lobe (MTL, i.e. hippocampus and adjacent cortices) is particularly vulnerable to age‐related diseases: Alzheimer’s disease, other age‐related proteinothies (TDP‐43, AGD, etc) and vascular injury. Yet, the subregional pattern of vulnerability is thought to differ across etiologies; characterizing these differences using high‐resolution MRI may provide more insight in disease processes and better biomarkers. However, substantial differences in subfield definition has hindered the ability to compare results across laboratories or draw robust conclusions (Figure 1). The Hippocampal Subfields Group (HSG) is an international group seeking to remedy this problem by developing a histologically‐valid, reliable, and freely available segmentation protocol for high‐resolution T2‐weighted 3T MRI (http://www.hippocampalsubfields.com)MethodOur workflow consists of five steps: 1) collecting histology samples labeled by multiple expert neuroanatomists to form a novel reference dataset to guide the development of the MRI segmentation protocol, 2) developing boundary definitions for each segment of the hippocampus, (head, body, and tail) and MTL cortices), 3) assessing HSG community agreement with boundary rules via online questionnaires and revising boundary rules based on questionnaire responses, and 4) testing reliability of the protocol definitions on multiple MRI datasets.ResultFor both the hippocampal body and head, we have developed a preliminary subfield segmentation protocol (i.e. completed steps 1‐2, see Figure 2 for a histology slice segmented by three anatomists). Step 3 was piloted for the outer boundaries of the body (i.e., the anterior/posterior, medial/lateral, and superior/inferior boundaries) using an online questionnaire describing each of the proposed rules. 29 labs participated and consensus agreement was reached for all rules, with only minor changes being made to improve comprehension and clarity. We are now creating and administering additional questionnaires for assessing agreement of the hippocampal body and head inner boundary rules (e.g., between the CA fields and dentate gyrus). Upon completion of the assessment/revision process for each set of rules, the final phase – reliability testing of the protocol – should begin mid 2020 for the body.ConclusionOnce completed, the harmonized protocol will significantly facilitate cross‐study comparisons thus advancing insight in the role of hippocampal subfields across the lifespan in aging and disease.
Sex and cognition: Relationships with tau PET across the Alzheimer’s disease spectrum
Authors: Banks Sarah Jane , Andrews Murray J , Digma Leonardino A , Caldwell Jessica ZK , Sundermann Erin E , Brewer James B 
Published: December 2020

AbstractBackgroundRecent evidence suggests that tau accumulates differently in the brains of men and women with Alzheimer’s disease (AD), with greater neurofibrillary tangles in women especially in the MCI stage. Women show a reserve in verbal memory but then more rapid decline in this domain once they are symptomatic. Since regional tau deposition is closely tethered to cognitive symptoms, we were interested in how relationships between tau distribution and cognition might differ by sex.MethodData were extracted from the AD Neuroimaging Initiative database for participants (136 women, 139 men) who were amyloid PET positive and had flortaucapir (“tau”) PET, across clinical diagnoses of normal cognition (NC), mild cognitive impairment (MCI) and AD. Vertex‐wise analyses were conducted in FreeSurfer, quantifying the vertices with above‐threshold SUVR and assessing regional distribution. We compared overall burden in men and women, and further investigated results by ApoE status and diagnosis and assessed how regional tau burden related to different cognitive scores.ResultsWomen and men did not differ on overall amount of tau PET uptake, but there was a sex by diagnosis interaction on overall tau SUVr. On further analysis (figure 1) this was driven by higher SUVr in women in the MCI stage (F(1, 85) = 7.313, p = .008). Furthermore, women with a higher tau burden scored worse across verbal memory measures, whereas men with higher tau burdens demonstrated worse performance on processing speed and executive measures. This was reflected in topological representation of the tau burden by cognitive test (figure 2).ConclusionSex differences in the expression of AD correspond to differences in tau especially at the MCI stage. Higher tau in women is reflected in reduced performance in verbal memory, while higher tau in men reflects worse performance on executive measures. These findings point to the differences in trajectories of tau deposition in men and women and the relationship of tau to sex differences in cognitive findings.
Repurposing of existing vaccines for personalized prevention of Alzheimer’s disease: Vaccination against pneumonia may reduce AD risk depending on genotype
Authors: Ukraintseva Svetlana , Yashkin Arseniy , Duan Matt , Akushevich Igor , Arbeev Konstantin , Wu Deqing , Stallard Eric , Tropsha Alex , Yashin Anatoliy 
Published: December 2020

AbstractBackgroundRepurposing of existing vaccines could be a promising approach to Alzheimer’s disease (AD) prevention, exploiting potential heterologous effects of such vaccines. Adult vaccinations against pneumonia and the flu showed beneficial off‐target effects on mortality and morbidity in some studies, including on dementia‐related outcomes, suggesting that respective vaccines may be evaluated as repurposing candidates for prevention of AD and/or other dementias.MethodWe investigated associations between pneumococcal vaccine, with and without an accompanying flu shot, and the risk of AD among 5,146 elderly participants (65+) of the Cardiovascular Health Study, using covariates including sex, race, birth cohort, education, smoking, and rs2075650, a known genetic risk factor for AD in TOMM40 gene that may also be involved in brain vulnerability to infection through its connection to NECTIN2 (Yashin et al. 2018).ResultBeing vaccinated against pneumonia between ages 65‐75 was associated with a reduction in the risk of AD afterwards (OR = 0.70; P < 0.04) in logistic model with all covariates. A largest reduction in the risk of AD (OR = 0.62; P < 0.04) was observed in the vaccinated against pneumonia non‐carriers of rs2075650 G allele (risk factor for AD). Total count of vaccinations against pneumonia and the flu between ages 65 and 75 was also associated with a lower risk of AD occurrence later in life (OR = 0.88; P < 0.01); however, the effect was not seen for the flu alone.ConclusionVaccination against pneumonia before the age 75 may reduce AD risk later in life, especially in people without genetic risk factor for AD (rs2075650, G allele). These results suggest that pneumococcal vaccine may be a promising candidate for repurposing for personalized AD prevention in carriers of particular genotypes. Validation of these effects in higher power datasets is warranted. The study was in part supported by NIH grants R56AG059428, 1R01AG062623, and 2R01AG046860.
Predictive value of visually rated tau PET imaging for amyloid status, atrophy, and syndromic diagnosis across a spectrum of neurodegenerative phenotypes
Authors: McGinnis Scott , Collins Jessica A. , Eckbo Ryan , Brickhouse Michael , Gomperts Stephen , Johnson Keith A. , Dickerson Brad C. 
Published: December 2020

AbstractBackgroundWe aimed to investigate the utility of qualitative visual rating of 18F‐flortaucipir tau PET to predict amyloid status, neurodegeneration and syndromic diagnosis across a range of phenotypes associated with underlying Alzheimer disease (AD) and non‐AD neuropathologies.MethodFTP PET, PiB PET, and high resolution T1 MRI scans were rated independently by visual inspection by two raters blinded to clinical diagnosis in n=118 subjects, a subset of whom had clinical diagnoses of amnesic MCI/dementia (n=26), posterior cortical atrophy (n=12), logopenic primary progressive aphasia (n=8), nonfluent PPA (n=7), semantic PPA (n=5), corticobasal syndrome (n=7), behavioral variant frontotemporal dementia (n=2), progressive supranuclear palsy (n=2), dementia with Lewy bodies (n=6), Parkinson disease (n=11), or control (n=20). Scans were classified based on level of uptake [no elevation, questionable or mild elevation, substantial elevation] and distribution of uptake [suggestive of typical AD, limbic predominant AD, hippocampal sparing AD, FTLD, or indeterminate]. PiB PET and MRI scans were rated with respect to level and distribution of uptake/atrophy.Result41/42 subjects with FTP scans classified with substantially elevated signal had PiB scans classified with elevated amyloid, versus 7/11 subjects with FTP classified as having questionable/mild elevation in a distribution suggesting AD, 1/30 with questionable/mild elevation in a distribution suggesting FTLD, 0/9 with questionable/mild elevation in an indeterminate distribution, and 1/26 classified with no elevation in FTP signal. Similarly, 41/42 subjects with FTP classified as having substantially elevated signal had MRI scans classified as having atrophy suggesting neurodegeneration, versus 44/50 subjects with FTP classified as having questionable/mild elevation and 14/26 with no elevation in signal. FTP scans were read to be suggestive of AD‐typ in 21/26 subjects with an amnesic syndrome, suggestive of AD‐hs in 16/20 subjects with lvPPA or PCA, and suggestive of FLTD in 14/23 subjects with bvFTD, nvPPA, svPPA, CBS, or PSP.ConclusionVisually rated tau PET imaging reliably predicts amyloid status and atrophy suggesting neurodegeneration in subjects with substantially elevated signal reflecting neocortical tau. Distribution helps both to determine likelihood of underlying AD neuropathology in cases with questionable/mild signal elevation, and in some cases to predict syndromic diagnosis within the spectrums of AD and FTLD.
AU‐ARROW (Australia)
Authors: Martins Ralph N , Anstey Kaarin J , Baker Laura D. , Barin Edward , Dias Cintia B , Brown Belinda M , Burnham Samantha C , Chatterjee Pratishtha , Chen Juliana , Clarnette Roger , Deang Kristine , England Tim , Fuller Stephanie , Gardener Samantha L , Gleason Andrew , Grieve Stuart , Hillebrandt Heidi , Ireland Catriona , Kenny Peter , Kivipelto Miia , Mobbs Rowena , Naismith Sharon L , Peters Ruth , Rainey‐Smith Stephanie R , Raman Rema , Savage Greg , Sohrabi Hamid , Shah Tejal M , Steiner Genevieve Z , Taddei Kevin , Thompson Belinda , Villemagne Victor L L , Yates Paul A 
Published: December 2020

AbstractBackgroundThe highly encouraging findings from the Finnish Geriatric Intervention Study (known as FINGER) led to the global initiative for dementia risk reduction known as world‐wide FINGERS (WW FINGERS). As part of the collaboration, our Australian AU‐ARROW trial will follow the general protocol of the FINGER trial, and will also be aligned with the U.S. arm of the study, US‐POINTER, though will have minor cultural and dietary modifications to determine the validity of the intervention in an Australian setting.MethodAU‐ARROW is a randomised, single‐blind 2‐year clinical trial that will recruit 600 participants aged 60‐79 satisfying specific inclusion/exclusion criteria, including normal cognition and one or more cardiovascular risk factors that place them at greater risk of cognitive decline. Participants will be distributed across two sites (a) Macquarie University Health Clinics, Sydney, NSW and (b) Sarich Neuroscience Research Institute, Edith Cowan University, Perth, WA, and will be randomised equally into either the innovative multi‐modal intervention group or the study control group, who will receive general lifestyle advice and annual health check‐ups, without treatment. Multi‐modal intervention consists of aerobic exercise, resistance training and stretching; dietary advice with monitoring to encourage adherence to the MIND diet; cognitive training sessions via the Brain HQ computerised online training system; and medical monitoring and regular health education sessions. Heart rate trackers, diet and exercise log books, and the monitoring of Brain HQ sessions will all help with adherence. Primary outcome measure is improvement in global cognitive score, measured using neurocognitive tests identical to those in the US‐POINTER protocol. Additional neurocognitive tests, physical function improvements, detailed diet monitoring and sleep monitoring will provide added data. The unique extra value of AU‐ARROW trial consists of the testing for Alzheimer’s disease (AD) blood biomarkers in all participants; as well as the AD Aβ amyloid‐specific ligand‐PET imaging, brain MRI and retinal biomarker tests that half of the participants will undergo. These tests will provide comprehensive data which have the ultimate purpose of increasing knowledge of the preclinical stages of AD, and help not only to develop preclinical AD diagnostic tests but also efficacy of AU‐ARROW’s intervention.
SUPERBRAIN (South Korea)
Authors: Choi Seong Hye , Jeong Jee Hyang , Moon So Young , Park Yoo Kyoung , Hong Chang Hyung , Na Hae Ri , Song Hong‐sun , Park Hee Kyung , Lee Sun Min , Choi Muncheong , Park Kyung Won , Kim Byeong C. 
Published: December 2020

AbstractBackgroundMultidomain intervention is useful for the prevention of dementia. We have developed the programs of SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), which consists of a facility‐based (FMI) and a home‐based multidomain intervention (HMI) program suitable for elderly Koreans. We aimed to investigate the feasibility of the SUPERBRAIN programs before a large‐scale randomized controlled trial.MethodsWe recruited 152 participants from eight centers, among those without dementia aged 60‐79 years with at least one modifiable dementia risk factor. Fifty‐three were randomly assigned to the FMI arm, 53 to the HMI arm, and 52 to the control arm. The 6‐month multidomain intervention consisted of: management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The intervention program is determined feasible if the following success criteria are met: 1) a minimum retention rate of 75% at week 24; 2) a minimum adherence to the intervention program of 75%; and 3) at least no difference from the control arm on analysis of Repeatable Battery for the Assessment of Neuropsychological Status. Main secondary outcomes were disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire. For exploratory evaluation, neurotrophic, neurodegeneration and neuroinflammation factors, microbiome, telomere length, electroencephalography, and neuroimaging measures were evaluated.ResultsScreening began in May 2019 and was completed in August 2019. The study was completed in February 2020. The retention rates were 88.7%, 94.3%, and 80.8% in FMI, HMI, and control arms, respectively. The adherence rates to the program were above 95% in FMI and HMI arms, respectively.ConclusionThese multidomain intervention programs are feasible in at‐risk elderly people.
The impact of the intestinal microbiome on microglial inflammation
Authors: Frausto Dulce 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disorder associated with aging. While genetics have been shown to be important in the development of AD, environmental and lifestyle factors contribute significantly to the development and progression of AD. It is proposed that microglial inflammation leads to neuronal dysfunction in the brain and may be a driving factor promoting the development of AD. Although microglial inflammation increases with age, there are a number of lifestyle factors that can promote and/or ameliorate microglial dysfunction. These lifestyle factors include established modulators of the intestinal microbiota community structure and function, one of which is alcohol. Chronic alcohol consumption is associated with a greater risk of all types of dementia, especially vascular dementia and AD. Recently, alcohol has been found to promote AD progression in both animal and human studies. We propose alcohol influences microglial inflammation and dysfunction via a mechanism including secreted bacterial products. The objective of this study is to investigate the ability of bacterial‐derived products to influence microglial gene expression and inflammation. Specifically, we investigated the ability of bacterial products to influence alcohol‐induced microglial activation.MethodIn this study, microglia with and without alcohol exposure will be treated with supernatant from bacteria that are known to be altered following alcohol consumption or shown to be beneficial in blunting inflammation. Microglia will be analyzed for NLRP3 inflammasome activation and IL‐1 production.ResultThe results of this study demonstrate that secreted bacterial products modulate alcohol‐induced microglia activation including NLRP3 and IL‐1.ConclusionThe proposed research is significant because it suggests that bacteria found in the mammalian intestine can influence microglia in the brain and therefore may critically influence neurodegenerative disease such as AD. Identification of the intestinal microbiota as a factor that promotes microglial inflammation and dysfunction will lay the groundwork for the development of therapeutic approaches that target the microbiota (i.e., consumption of prebiotics or probiotics) to prevent and treat age‐associated diseases, such as AD.