bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of the MIITRA T1‐weighted and DTI templates of the older adult brain in a common space at 0.5mm resolution
Authors: Wu Yingjuan , Ridwan Abdur Raquib , Niaz Mohammad Rakeen , Bennett David A , Arfanakis Konstantinos 
Published: June 2023

AbstractBackgroundHigh resolution multimodal MRI templates of the older adult brain have the potential to facilitate template‐based studies of aging. As part of the Multichannel Illinois Institute of Technology & Rush university Aging (MIITRA) atlas, the present work developed high quality 0.5mm isotropic resolution T1‐weighted (T1w) and diffusion tensor imaging (DTI) templates in common space using data from a large, diverse, community cohort of non‐demented older adults.Method
Data
T1w and DTI data were collected using two 3T MRI scanners on 400 non‐demented older adults (50% male;64.9‐98.9 yrs;54% white,43% black) (Bennett et al.,2018; Barnes et al.,2012).
Template construction
Step1: An unbiased initial T1w template was created by pairwise affine registration (Ridwan et al.,2021).Step2: Spatial normalization was driven by T1w and DTI data alternatively (Wu et al., 2019). All transformations were combined to minimize interpolations and applied to both modalities. A patch‐based tissue‐guided sparse‐representation approach was employed to compute the template (Ridwan et al.,2021).Step3: High spatial resolution templates were created based on principles of super‐resolution (Niaz et al.,2022)The resulting templates are referred to as MIITRA_0.5mm templates.
Evaluation
T1w and DTI data from 202 ADNI3 non‐demented older adults were used for evaluation.The MIITRA_0.5mm templates were compared to other high resolution templates and the templates including older adults in terms of image sharpness and spatial normalization accuracy of ADNI3 data when each template was used as a reference for normalization.ResultMIITRA_0.5mm templates exhibited higher image sharpness (Fig.1,2). MIITRA_0.5mm templates allowed the highest inter‐subject spatial normalization accuracy across spatially normalized ADNI3 data and required less deformation than other high‐resolution templates (Fig.3,4). It should be noted that 1mm templates require on average less deformation than high‐resolution templates because larger voxels limit local deformations. Finally, the MIITRA_0.5mm templates allowed higher inter‐modality spatial matching of normalized older adult data (Fig.5).ConclusionThis work developed high resolution T1w and DTI multimodal templates of the older adult brain for the MIITRA atlas. The new templates exhibited higher image quality, were more representative of the older adult brain, and allowed higher spatial normalization accuracy compared to other templates. The new templates will be available for download at www.nitrc.org/projects/miitra.
Frailty in Relation to Cognition in Community‐Dwelling Older Adults: Validating the Electronic Frailty Index based on the Comprehensive Geriatric Assessment (eFI‐CGA) in Primary Care
Authors: Song Xiaowei , Park Grace , Clarke Barry , Rockwood Kenneth 
Published: June 2023

AbstractBackgroundFrailty can be screened using the Clinical Frailty Scale (CFS) and quantified using a Frailty Index (FI) based on deficit accumulation. Higher degrees of frailty have been associated with greater risks of adverse outcomes, including dementia. Comprehensive Geriatric Assessment (CGA, allows development of individualized care plans for older adults’) has been used to derive an FI‐CGA. To promote effective assessment of frailty outside specialized geriatric services, we developed and are validating an electronic CGA with an automated electronic FI‐CGA (eFI‐CGA). The goal is early detection and management of frailty in home‐living older adults. Here, we examined the characteristics and robustness of the eFI‐CGA assessed by primary‐care physicians and investigated the relationship between the eFI‐CGA and cognition.MethodData were collected as part of the collaborative effort between Fraser Health and Nova Scotia Health to validate the eFI‐CGA. Baseline assessments were conducted at primary care clinics using eFI‐CGA software tools with the eFI‐CGA created following standard procedures. Dementia diagnoses on no cognitive impairment (NCI), mild cognitive impairment (MCI), and dementia were made following DSM‐IV criteria. For robustness testing, multiple interactions of the eFI‐CGA were generated, excluding cognitive measures. Data were analyzed employing regression and descriptive statistics.ResultThe sample (n = 137; age = 79.2±7.6 years, women = 67.9%; CFS = 3.7±1.3) contained 82.5% NCI and 17.5% MCI/dementia cases. Participants with MCI/dementia were slightly older, less educated, more likely to live alone and take 7+ medications, compared to those with NCI. Sores of the various integrations of the eFI‐CGA were highly correlated. These showed consistent distributions, age relationships, and the maximum values <0.70. The NCI group showed the lowest mean eFI‐CGA scores consistently across the iterations. Close correlations of the eFI‐CGA with the CFS (p<0.001) and the mini‐cog (p<0.010) were observed.ConclusionThe characteristics of the eFI‐CGA in primary care were consistent with those widely reported for the FI. A clear association between the eFI‐CGA and cognition was found, even when cognitive measurements were excluded from the eFI‐CGA. Ongoing work will test the generalizability of these findings, with a larger sample size and follow‐up assessments and outcomes, as well as examine how primary care CGA data compared with geriatrician assessments.
Meta‐analysis of high‐clearance anti‐amyloid immunotherapies trials in early Alzheimer’s disease: A significant clinical effect but a low benefit/risk ratio
Authors: Villain Nicolas , Planche Vincent 
Published: June 2023

AbstractBackgroundIn the last three years, three over four phase II or III clinical trials using high‐dose anti‐amyloid immunotherapies in early Alzheimer’s disease (AD) have turned out to be positive on clinical outcomes: aducanumab (one of two), donanemab, and lecanemab. These results contrast with the previous failures of anti‐amyloid immunotherapies. Despite different pharmacodynamic properties, these drugs share a new characteristic: the high clearance of amyloid load as measured with amyloid positron emission tomography. In the meantime, the Food and Drug Administration’s conditional approval of aducanumab has led to unprecedented scientific controversies.MethodWe used the data from the highest dose group (i.e., the groups used for approval application or ongoing phase III trials) versus placebo after 18 months of the lecanemab and donanemab phase II trials and of the two aducanumab phase III trials to perform a meta‐analysis. Regarding clinical efficacy, we analyzed the CDR‐SB, ADASCog, and MMSE data. Regarding safety, we analyzed the occurrence of any Amyloid‐Related Imaging Abnormalities (ARIA), of ARIA‐edema (ARIA‐E), of ARIA‐hemorrhage (ARIA‐H), and of symptomatic and serious ARIA. The analyses were performed using RevMan 5.4.1 and a random effect model.ResultHigh‐clearance anti‐amyloid immunotherapies were shown to significantly slow down cognitive decline after 18 months as measured with CDR‐SB (weighted mean = ‐0.24 points; p = 0.04), and ADAS‐Cog (weighted mean = ‐1.25 points; p = 0.0003), but not with MMSE (weighted mean = +0.31 points; p = 0.23) when compared to placebo. In parallel, the drugs significantly increased the occurrence of any ARIA (risk ratio = 3.68; p<0.0001), of ARIA‐E (risk ratio = 13.39; p<0.0001), of ARIA‐H (risk ratio = 2.78; p = 0.0002), and of symptomatic and serious ARIA (7/1321 = 0.53% in the high dose groups versus 0/1446 in the placebo groups; risk ratio = 6.44; p = 0.04).ConclusionWhen pooled together, the data from high‐clearance anti‐amyloid immunotherapies trials confirm a significant clinical effect after 18 months. However, this effect remains below the established minimal clinically relevant values. Safety remains an issue with 0.5% of symptomatic and serious ARIA, significantly beyond chance, despite thorough in‐trial monitoring and management. The benefit/risk ratio of this class of drugs in early AD is thus questionable after 18‐months. Identifying subgroups of better responders and the perspective of combination therapies may help improve their clinical relevance.
Cognitive screening among older afro‐caribbean adults in rural areas of South Florida
Authors: Daniel E. Valerie , Wiese Lisa Ann Kirk , Galvin James E 
Published: June 2023

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) disproportionately affects communities of color with older black Americans performing worse than Whites on cognitive tests and facing higher ADRD risks.1,2 Contributors to low diagnostic rates include inadequate knowledge, cultural norms, low health literacy, and an unwillingness to discuss early signs of disease. 1,3‐5 Older Afro‐Caribbeans are a growing subset of the population, particularly in rural South Florida, but best practices to screen for ADRD are unknown.6 Many instruments, including the Montreal Cognitive Assessment (MoCA) have not been assessed within this population. We report on the use of the MoCA 5‐minute test/telephone (Mini‐MoCA) as a screening tool in older, rural‐dwelling Afro‐Caribbeans.7
MethodWe conducted survey interviews with 53 Afro‐Caribbean participants. Participants were assessed with the 5‐minute Mini‐MoCA, which included tests of language fluency, orientation and recall. Linear regression models were used to investigate the association between different components of the Mini‐MoCA its effects on age, sex, and education.ResultA total of 53 Afro‐Caribbean participants (67.2 +10.8y (Mean ± SD), 68% with 10y or less of education) residing in rural South Florida within the last 20 years were included. Participants were largely from Haiti (66%) with 34% from other Caribbean countries including Cuba, Jamaica, Puerto Rico, and Barbados. About 80% of participants reported not having their memory tested prior to the study. The Mini‐MoCA demonstrated good reliability in this sample (α = 0.734). We found that 53% had a total score of 11 or lower on the Mini‐MoCA. Linear regression suggested a significant association between Mini‐MoCA score and education (p = .001).ConclusionWhile the Mini‐MoCA showed good reliability in low‐educated older Afro‐Caribbeans, scores were strongly dependent on years of education. Disparities in educational attainment may contribute to disparities in performance and affect true detection on cognitive impairment in these communities. Social and cultural factors must be considered when interpreting the Mini‐MoCA, given the high error rates on items that depend on the ability to read and write. Study results highlight the need to use a language‐neutral test to accurately measures cognitive impairment among this specific population.
Testing for acceptance of an assistive social robot for dementia and caregiving
Authors: Mitchell Kimberly M , Zhao Xiaopeng 
Published: June 2023

AbstractBackgroundApproximately 5.8 million older adults in the U.S. are living with AD and it is estimated that by 2060, this number is projected to triple. People with AD often require high levels of care and assistance to maintain daily activities. The majority of care provided to a person living with AD or other forms of dementia is from a family caregiver, representing 18.6 billion hours of unpaid care valued at $244 billion. The long duration, time‐intensive nature of caregiving imposes high burdens on caregivers. There is a great need for assistive technologies and innovative solutions for the future of dementia care because of the increasing rise in adults with dementia.MethodA multidisciplinary team of faculty and undergraduate and graduate students was created to design a low‐cost social robot to serve as assistive companions for people with AD. Focus group meetings with caregivers and those with beginning stages of dementia were held, where the team worked in identifying the audience’s needs and robot’s responsibilities. Initial sketches were formulated before being brought to life in Fusion 360 as 3D CAD objects and printed using a 3D printer. Several rounds of iterations of the social robot’s body and user interfaces were created and two final robot designs were tested with undergraduate students (N = 15) for general attitudes of acceptance and feelings of overall experience.ResultResults from our user testing showed that users preferred one design more than another. Users wanted options in their interactions – having the ability to have speech conversation and touch‐screen abilities. Overall, the results from the user testing were positive, and the team is currently working on a final robot design before testing at nursing homes and assisted living facilities.ConclusionEstimated to be less than $300, our socially assistive robot holds promise to help address the disparity issues in the underserved.
Peripapillary retinal nerve fiber layer and macular outer retinal layers are reduced in cognitively unimpaired older adults at high risk of AD. Preliminary results from a five ‐year longitudinal study
Authors: Arthur Edmund , Alber Jessica , Thompson Louisa I , Strenger Jennifer , Montgomery Catrina , Sinoff Stuart , Salloway Stephen P. , Snyder Peter J 
Published: June 2023

AbstractBackgroundThe retina, an extension of the central nervous system, shows promise for development of non‐invasive, low cost AD risk screening biomarkers. Most studies do not answer the question of whether retinal biomarkers are useful in the pre‐symptomatic phase of AD for assessment of early disease risk. In this study1, we investigated structural changes in the retinal neural layers between low and high risk cognitively unimpaired (CU) older adults using Spectral Domain Optical Coherence tomography (SD‐OCT).MethodThese data were provided from an ongoing trial that will conclude enrolment in the summer of 2022.1 Macular (30×25‐degree) and optic disc centered (radii of 3.5, 4.1, and 4.7 mm) SD‐OCT images of 13 CU low risk (age mean: 67 years; range: 56‐75 years) and 60 CU older adults at high risk for AD (age mean: 66 years; range: 55‐81 years; no significant difference in age between the two groups, p = 0.43) were acquired using the Spectralis imaging device. Participants had MoCA score ≥ 26, and RBANS‐U DMI score ≥ 85. Vendor software was used to segment and compute average retinal thickness in the 9 ETDRS maps for the macular and 7 glaucoma fields for the optic disk. Independent sample t test was used to compare retinal layer thickness between the two groups. A p‐value < 0.05 assessed statistical significance. Cohen’s d served as effect size measure.ResultIn the macular region, there were reduced retinal volume/thickness measurements for high risk vs. low risk CU older adults (outer plexiform layer volume in the inner inferior region; 0.054 vs. 0.062 mm3, p = 0.047, d = 0.62; central outer nuclear layer, ONL thickness; 97 vs. 102 µm, p = 0.041, d = 0.64; central ONL volume; 0.076 vs. 0.16 mm3, p = 0.023, d = 0.71). In the peripapillary region, there was reduced retinal nerve fiber layer (RNFL) thickness in the temporal region for high risk vs. low risk CU older adults (3.5 mm radius; 66.7 vs. 75.6 µm, p = 0.011, d = 0.80; 4.1 mm radius; 59.7 vs. 68.3 µm, p = 0.006, d = 0.87; 4.7 mm radius; 54.2 vs. 62.2 µm, p = 0.006, d = 0.87).ConclusionOur initial analysis shows reduced peripapillary RNFL and macular outer retinal layers in CU high risk vs. low risk group.
Modelling the developmental trajectories of cognitive reserve in children
Authors: Irani Zubin , Sheridan Andrew , Silk Tim , Weinborn Michael , Gavett Brandon E 
Published: June 2023

AbstractBackgroundCognitive reserve (CR) is thought to protect cognitive ability against neurodegenerative conditions, such as Alzheimer’s disease, or other neurological insults. Because past research has studied the construct extensively in older adult populations, little is known about its development across the lifespan. The current study generated a dynamic CR index based on a modified residual approach utilised successfully in older adults (Reed et al., 2010; Bettcher et al., 2019), and examined its criterion and construct validity in a paediatric cohort comprising children both with and without ADHD.MethodArchived longitudinal data collected across 2011‐2019 from N = 115 children (MAge = 10.48, SDAge = 0.61, n = 72 [63%] male, n = 43 [37%] with ADHD) was obtained from the Murdoch Children’s Research Institute. Static and dynamic CR were operationalised based on residual variance in (change in) fluid intellect (Matrix Reasoning) not explained by demographics (i.e., sex and age) or MRI‐based brain variables (i.e., grey matter volumes, white matter hypointensities [WMH], and hippocampal volumes). This index was subsequently used to predict relevant outcome variables (i.e., sustained attention, working memory, inhibition, word reading, and mathematical computation) to assess criterion validity at baseline and across time, while construct validity was assessed via interaction effects between CR, brain, and baseline/longitudinal outcomes.ResultsApproximately 8% of the variance in fluid intellect was predicted by selected brain and demographics at baseline, with 14% predicted in the longitudinal model. CR at baseline predicted mathematical computation (p<.001), word reading (p = .012), and working memory ability (p<.001) at baseline. CR change only predicted change in word reading ability (p<.001); it was also found to moderate relationships between WMH volume change and word reading trajectory, and between WMH volume change and change in sustained attention performance.ConclusionOur results suggest that CR can be modelled in children using a residual index, but with less validity than in older adults; weak criterion and construct validity were evident, although this should be tempered by the fact that there was minimal variance explained in the residualised variable. An adjusted model optimised for a paediatric cohort will form the basis of further inquiry into the study of CR in a developmental context.
Prediction of vascular injury and the impact of physical activity on the association between Primary ALdosteronism and cerebral Microbleeds (PALM)
Authors: Lee Sun Min , Jeon Ja Young , Park Sun Ah , Choi Jin Wook , Chung Seung Ah , Han Seung Jin , Moon So Young 
Published: June 2023

AbstractBackgroundPrimary aldosteronism(PA) induces hypertension and vascular injury. Cerebral microbleed(CMB) is a representative form and can cause cognitive decline over the long term. This study is to investigate vascular damage in PA. Regarding physical activity, a preventive factor for vascular damage and known to increase aldosterone itself, we evaluated difference between aldosteronism and CMB depending on level of usual physical activity.MethodWe recruited PA diagnosed patients aged 13 years or older, who visited Endocrinology clinic in the past 3 years. We excluded patients with other causes of hypertension and major brain lesion. Brain magnetic resonance imaging(MRI), and physiological tests were performed: transcranial doppler(TCD), peak wave velocity(PWV), and sonographic endothelial function test(SEFT). In addition, we performed funduscopy for detecting retinal microhemorrhage, and Korean version of Montreal Cognitive Assessment(K‐MoCA), Clinical Dementia Rating(CDR), Clinical Dementia Rating sum of boxes(CDR‐SOB) for cognitive assessment. Physical activity was investigated using global physical activity questionnaire.ResultTotal 41 participants (age, 46.0±13.4years; 46.3% of male; BMI, 25.8±3.4kg/m2; education, 13.8±2.2years) were enrolled. The mean duration of PA was 1.7±1.7years, and serum findings at diagnosis were as follows: renin (0.5±0.4ng/ml/hr), aldosterone concentration (318.6±203.3pg/mL), potassium (3.6±0.8mMol/L), aldosterone‐to‐renin ratio (91.5±73.7). In 30 of 41 patients, adrenal masses were observed on abdominal Computed Tomography(number, 1.3±0.6; size, 14.8±5.0mm). There were participants with vascular risk factors: hypertension(38, 8.1±6.4), diabetes mellitus(3, 2.5±1.8), and dyslipidemia(2, 7.7±5.8). 1 participant each had been diagnosed with myocardial infarction and cerebrovascular disease. 10 participants had a smoking history (7.8±12.3pack years), and 24 had a drinking history, with the average frequency of drinking per week was 1.2±1.4. Cognitive status was assessed by K‐MoCA(26.8±2.5), CDR(0.2±0.2) and CDRSOB(0.2±0.2). Moderate‐to‐vigorous physical activity was 192.2±246.7 minutes per week. CMB was confirmed in 10 and lacune in 7 cases. There were 9 participants who showed white matter change in Fazekas grade 1‐2. Physiological tests showed abnormality in 1 patient in TCD, 7 in PWV(baPWV, 14.1±1.9 m/s), and 6 in SEFT(flow mediated dilation, 6.6±1.3%).ConclusionIt is expected that more data will be collected through additional participant recruitment and evaluation. It remains to be seen that the analysis with additional data will yield results to test the hypothesis.
Role of neurofilament light chain to reduce diagnosis and improve outcomes for patients in a real‐world cognitive neuropsychiatry service: A retrospective MiND study
Authors: Kang Matthew , Eratne Dhamidhu , Dobson Hannah , Keem Michael H , Li Qiao‐Xin , Loi Samantha M , Tsoukra Paraskevi , Masters Colin L. , Collins Steven J , Velakoulis Dennis 
Published: June 2023

AbstractBackgroundIt is common for patients presenting with neuropsychiatric symptoms to endure significant diagnostic odyssey. Neurofilament light chain (NfL) has shown promise in being able to differentiate between neurodegenerative and psychiatric disorders. This study aimed to assess the clinical utility of NfL in avoiding misdiagnosis.MethodIn this retrospective study, we conducted file review of patients assessed at Neuropsychiatry, Royal Melbourne Hospital between 2009 to 2020. We included all patients (n = 212) who had a CSF NfL level at their baseline assessment. Investigators blinded to NfL levels extracted clinical information including diagnoses from the initial and follow‐up assessments using documentation available. In addition, we collected follow‐up data from external services where available. Initial and follow‐up/final diagnoses were categorised as neurodegenerative disorder (ND), psychiatric disorder (PSY), mild cognitive impairment (MCI), unclear, and not‐neurodegenerative (Not‐ND). Not‐ND were individuals who did not meet the diagnosis for PSY or MCI, and did not have worsening symptoms. Based on our previous findings, we defined an NfL>582pg/mL as a positive test result for ND.ResultSo far, we have collected information from 135 patients. Of these, 14/89 (16%) patients initially diagnosed with ND were re‐diagnosed as PSY or Not‐ND. 2/30 (7%) patients initially diagnosed with PSY were re‐diagnosed as having ND. Including MCI and unclear, 32/135 (24%) had a delayed diagnosis, which could have been reduced to 14% based on baseline CSF NfL predicting ND or Not‐ND/MC/PSY. Data analysis is ongoing and full results will be presented at the conference.ConclusionBaseline CSF NfL could have aided clinicians in a real‐world clinical setting, to reduce misdiagnosis, and increase diagnostic accuracy from 76% to 86%. An elevated level could prompt assertive investigations for neurological and neurodegenerative causes. Conversely, a low NfL, could reassure against a neurodegenerative disorder, preventing unnecessary assessments. Timely and accurate diagnosis will improve outcomes and precision care for patients and families.