bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yoga prevents grey matter volume decline in women at risk for Alzheimer’s Disease: A randomized controlled trial
Authors: Lavretsky Helen 
Published: June 2023

AbstractBackgroundFemale sex, subjective cognitive decline (SCD), and cardiovascular risk factors (CVRF) are known risk factors for developing Alzheimer’s disease (AD). We previously demonstrated that yoga improved depression, resilience, memory and executive functions, increased hippocampal choline concentrations and modulated brain connectivity in older adults with mild cognitive impairment. In this study (NCT03503669), we investigated brain gray matter volume (GMV) changes in older women with SCD and CVRF following three months of yoga compared to memory training (MET).MethodsEleven women (mean age = 61.45, SD = 6.58) with CVRF and SCD completed twelve weeks of Kundalini yoga (KY) and Kirtan Kriya (KK), while eleven women (mean age = 64.55, SD = 6.41) underwent MET. T1‐weighted MRI scans were acquired at baseline and follow‐up using a Siemens 3T Prisma scanner. We used Freesurfer 6 and longitudinal two‐step models to test group differences in symmetrized percent change in GMV. Resulting clusters were corrected and Monte‐Carlo simulations applied at an alpha level of 0.05. Region‐of‐interest analysis was performed for hippocampus and amygdala.ResultsCompared to KY+KK, MET showed reductions in GMV in left prefrontal, pre‐ and post‐central, supramarginal, superior temporal and pericalcarine cortices, right paracentral, postcentral, superior and inferior parietal cortices, the banks of the superior temporal sulcus, and the pars opercularis. Right hippocampal volume increased after yoga but did not survive corrections.ConclusionYoga training may offer neuroprotective effects compared to MET in preventing neurodegenerative changes and cognitive decline, even over short time intervals. Future analyses will address changes in functional connectivity in both groups.
Multimodal, longitudinal digital brain health platform using participant‐driven study design
Authors: Popp Zachary T , Low Spencer , Kolachalama Vijaya B. , Lin Honghuang , Rahman Md Salman , Prabhu Meha , Chan Cameron , Salgado Maria , Au Rhoda 
Published: June 2023

AbstractBackgroundLongitudinal studies that embrace digital data collection offer a low cost, time‐efficient solution compared to traditional methods. As such, ongoing advances in data science combined with the wealth of data produced by digital technologies can enable a pragmatic shift from investigator‐ to participant‐driven protocols. A participant‐driven study design might bring major efficiencies across the life course of longitudinal studies.MethodWe recruited participants from the Boston University Alzheimer’s Disease Research Center to a longitudinal study on brain health utilizing a multimodal, technology‐based protocol. Remote assessment technologies included active and passive engagement mobile and computer‐based applications and wearable devices to capture digital measures of cognition, voice, gait, motor activity, and activities of daily living. A full list of study technologies is shown in Table 1. Participants specify which technologies they would like to continue to use, providing a sense of ownership that promotes study participation.ResultThrough January 2022, a total of 22 participants (average age = 74.3+ 8.8 years; 68.2% women) have been recruited. The majority of participants (n = 21, 95.5%) have expressed a willingness to engage with multiple technologies. Among those enrolled for >3 months, 14 participants (87.5%) have opted to use 3 or more technologies (mean number of technologies = 4.38). Several technologies only worked on specific operating systems (NeuraMetrix, Longevity). Compatibility (n = 16, 72.7%) was the most frequent factor in leading a participant to not use a study technology, followed by concern over the burden of using an additional device or application (n = 14, 63.6%). The most common factor leading participants to select a given technology was the availability of participant‐facing data (n = 15, 68.2%), such as step counts or scores on gamified cognitive tests.ConclusionThrough the use of a participant‐driven study design, we have been able to conduct longitudinal brain health digital phenotyping with high uptake of digital technologies. Participant’s selections offer insights to investigators assessing which technologies to use in clinical research. Digital data collection opens opportunities for participant‐driven approaches that can enable longitudinal follow‐up with broader more inclusive reach with appropriate retention of data quality.
Design, docking, synthesis and biological evaluation of chromone derivatives as dual inhibitors of Interleukin‐6 and acetylcholinesterase for treatment of Alzheimer’s Disease
Authors: Kaur Sukhvir , Bansal Yogita , Mishra Shivam 
Published: June 2023

AbstractBackgroundInterleukin‐6 (IL‐6) and acetylcholinesterase (AChE) are two important targets implicated in the progression of Alzheimer’s Disease (AD). Concurrent inhibition of both IL‐6 and AChE by a molecule presents an effective strategy for the treatment of AD. In the present study, novel molecules are designed by coupling a chromone and a N,N‐disubstituted carbamoyl amine as pharmacophore for IL‐6 and AChE inhibition, respectively.MethodFour series (S1‐S4) of 40 compounds are designed by coupling the two selected pharmacophore through alkyl linkers of different lengths (1‐4 carbon atoms). All designed compounds are docked in AChE (PDB 1EVE). The compounds having docking score ±20% of donepezil (the lead molecule) are synthesised, and evaluated for AChE inhibitory activity. The compounds showing >45% inhibition of AChE are further evaluated for IL‐6 inhibitory activity.ResultTwelve best‐fit compounds (AChE docking score >8.3) among all designed compounds are selected for synthesis. The data suggests that a 1‐ or 2‐carbon atom(s) linker is conducive to orient the pharmacophore for optimum binding with AChE active site. The predicted ADME properties of the 12 selected compounds suggest that these can cross the blood brain barrier with good oral bioavailability. These compounds are synthesised and evaluated for anti‐AChE activity. Five compounds, showing >45% inhibition of AChE, are further evaluated for IL‐6 inhibitory activity. Compound S1f is found to be the most potent inhibitor of both AChE and IL‐6 (IC50 0.7 and 0.8 µM, respectively).ConclusionA chromone moiety connected to a piperidine ring through a 1‐carbon atom linker may prove as a useful template for the development of new chemical entities effective against AD.
Vitamin D intake and cognitive decline in African Americans and European Americans: The role of diet and supplements
Authors: Dhana Klodian , Barnes Lisa L. , Agarwal Puja , Liu Xiaoran , Dhana Anisa , Desai Pankaja , Aggarwal Neelum T. , Evans Denis A , Rajan Kumar B 
Published: June 2023

AbstractBackgroundVitamin D intake and supplementation has received considerable interest in dementia research because the prevalence of vitamin D deficiency is higher among older adults, particularly among older African Americans and cognitively impaired individuals. We prospectively examined the role of vitamin D intake, from both diet and supplements, in association with cognitive decline in African Americans and European Americans.MethodUtilizing data from the population‐based Chicago Health and Aging Project, we studied 2,061 African Americans and 1,329 European Americans with dietary vitamin D data and cognitive testing over 18 years of follow‐up. Multivariable linear mixed‐effects models adjusted for age, sex, education, APOE e4, body mass index, late‐life cognitive activities, physical activity, comorbidities, total energy intake, and their respective interactions with follow‐up time were used to determine the association of vitamin D intake with cognitive decline.ResultOn average, the vitamin D intake was lower in African Americans than European Americans (210.2 IU/d vs. 348.7 IU/d). In African Americans, participants in the highest tertile had a slower cognitive decline of 0.019 units/year (95%CI 0.009, 0.030) compared to those in the lowest tertile of dietary intake. The use of vitamin D supplementation was not associated with cognitive decline in African Americans (β 0.004, 95%CI ‐0.006, 0.013). In European Americans, vitamin D intake was not associated with cognitive decline.ConclusionDietary vitamin D may help slow the rate of cognitive decline in African Americans as they age.
Longitudinal association between exposure to vitamin D supplementation and incident dementia – A study of dementia‐free older adults
Authors: Ghahremani Maryam , Chen Hung‐Yu , Creese Byron , Goodarzi Zahra , Smith Eric E. , Ismail Zahinoor 
Published: June 2023

AbstractBackgroundIn the absence of clear disease‐modifying drugs for dementia, modifiable risk factors have been explored to slow disease progression. Vitamin D deficiency is a risk factor, associated with higher risk of dementia. However, the role of vitamin D supplementation has been a subject of debate. Here we explored longitudinal associations between vitamin D supplementation and incident dementia in dementia‐free older adults from the National Alzheimer’s Coordinating Center (NACC).MethodAll participants had normal cognition (NC) or mild cognitive impairment (MCI) at baseline. Exposure to vitamin D supplementation was based on the NACC A4 medication form. Three vitamin D formulations were considered: calcium‐vitamin D, cholecalciferol, and ergocalciferol. For the primary analysis, participants with baseline exposure to any supplement were considered D+, while those without any exposure in advance of dementia diagnosis were considered D‐. Kaplan‐Meier curves were generated to compare ten‐year dementia‐free survival between D+ and D‐ groups. Cox proportional hazards models were implemented to assess the risk of dementia across vitamin D exposure groups, adjusted for baseline age, sex, years of education, race, APOE‐e4 status, cognitive diagnosis, and depression. To distinguish the associations of various vitamin D formulations with risk of dementia, sensitivity analyses were conducted to independently examine the effect of each formulation (calcium‐vitamin D, cholecalciferol, ergocalciferol).ResultThe final sample consisted of 2836 D+ (mean age = 72.1; 68.4% female) and 5075 D‐ participants (mean age = 72; 45.1% female). MCI was more prevalent in D‐ vs D+ participants (35.7% vs 26.8%; p<0.001). Similarly, depression was more prevalent in D‐ vs D+ participants (6.9% vs. 4.3%, p<0.001). Across all three vitamin D formulations, exposure was associated with longer dementia‐free survival (p<0.001) and lower adjusted hazard ratio (HR) for incident dementia compared to no exposure (calcium‐vitamin D: HR = 0.56, 95%CI: 0.47‐0.67, p<0.001; cholecalciferol: HR = 0.72, 95%CI: 0.56‐0.91, p = 0.007; ergocalciferol: HR = 0.75, 95%CI: 0.63‐0.89, p<0.001)ConclusionOur findings demonstrate that while adjusting for demographic, cognitive, behavioral, and genetic factors, exposure to vitamin D supplementation (calcium‐vitamin D, cholecalciferol, or ergocalciferol) in dementia‐free older adults was associated with lower risk of dementia, implicating vitamin D as a potential agent for dementia prevention.
Histopathologic brain age estimation via context‐aware attention‐based deep multiple instance learning
Authors: Marx Gabriel A. 
Published: June 2023

AbstractBackgroundWhile a large list of age‐related changes have been described in the human brain, the extent to which they represent the result of common pathological reactions versus signatures of underlying brain aging remains unclear. One approach to sorting out the relative importance of the myriad of changes is deep learning, which has emerged as a powerful tool for image analysis and computer vision. However, large digitized whole slide image datasets from human aging brains have not been previously available.MethodIn this study, we leveraged a large novel collection of uniformly processed digitized human post‐mortem brain tissue sections to create a histological brain age estimation model. We further investigated the effect of cognitive impairment and exogenous stress on the model. This was accomplished by developing a context‐aware attention‐based deep multiple instance learning model on 702 human brain tissues sections (age range 50‐110 yr) from the hippocampus stained with Luxol Fast Blue counterstained with hematoxylin and eosin (LH&E) on a brain age estimation task.ResultOur model estimated brain age within a mean absolute error of 6.2 years. Learned attention weights corresponded to neuroanatomical regions known to be vulnerable to age‐related change. We found that deviations from our estimated histopathologic brain age significantly correlated with the clinical marker of cognitive status (p = 0.042). In addition, we found evidence of significantly accelerated age (p = 1.12×10‐23) in a cohort of subjects with a neuropathological diagnosis of chronic traumatic encephalopathy (CTE), a neurodegenerative disease caused by mild yet repetitive traumatic brain injury, that displays features that overlap with aging.ConclusionThese data indicate that estimated histopathologic age can be used as a reliable pathologic correlate to identify factors that contribute to accelerated or decelerated brain aging.
Quantifying three types of abnormal language in semantic variant primary progressive aphasia
Authors: Jones Amelia , Hochberg Daisy , Quimby Megan , Dickerson Bradford C. 
Published: June 2023

AbstractBackgroundPatients with the semantic variant of Primary Progressive Aphasia (svPPA) experience a gradual loss of semantic memory, impairing word retrieval and word comprehension. As such, svPPA patients often use superordinate, vague, and empty words. These patients often use language that refers to one’s own experience (“self‐referential”), one’s language impairments (“inability”), and/or contains tangents (“tangential”). These forms of aberrant language were identified previously as distinguishing svPPA from the other canonical variants of PPA (Gallee et al., 2021).MethodSpeech samples of the WAB picnic scene from 15 svPPA patients were analyzed by counting words and categorizing three forms of aberrant language at two timepoints (30 samples total), baseline and follow‐up (at least 12 months post baseline). Words were identified as self‐referential, inability, or tangential. Quantitative analyses were conducted to look for relationships between total word count and each of the three forms of aberrant language.ResultPreliminary results showed a strong correlation (r = .97) between the total number of aberrant words and the total number of words in the picture description transcriptions. At T1, 40% (6/15) used self‐referential words, 87% (13/15) used inability words, and 53% (8/15) used tangential words. At T2, 67% (10/15) used self‐referential words, 100% (15/15) used inability words, and 67% (10/15) used tangential words. Inability is the most prominent type of aberrant language. Longitudinal analyses are ongoing to investigate consistency or inconsistency within patients and relationship to aphasia severity.ConclusionPreliminary findings suggest patients with svPPA produce distinct types of aberrant language in a picture description task. The prominent use of inability words may be due to its scripted nature in that svPPA patients use these phrases repeatedly and may be related to disinhibition. Further, it is notable that several components of language not analyzed in this study, including grammar, syntax, and content units, are potentially informative. Using this method provides an efficient way to characterize speech of svPPA patients, which may lead to early subtyping, prognostication, and targeted treatment goals.Reference: Gallée,J.;Cordella,C.; Fedorenko, E.; Hochberg, D.; Touroutoglou, A.; Quimby, M.; Dickerson, B.C. Breakdowns in Informativeness of Naturalistic Speech Production in Primary Progressive Aphasia. Brain Sci. 2021,11, 130.
Using smart supportive technology to explore nighttime rest in persons living with dementia
Authors: Hamza Myriam , Ault Laura , Tan Patrick , Wallace Bruce , Thomas Neil W. , Goubran Rafik , Knoefel Frank 
Published: June 2023

AbstractBackgroundSleep disturbances affect 60‐70% of persons living with dementia (PLWD) affecting prognosis and care burden. Sleep studies typically employ actigraphy, however, it is intrusive and lacks information on location. This study explores the use of ambient sensors, to compare nighttime rest patterns of higher and lower functioning PLWD.MethodStudy participants were recruited in a 16‐bed residential care setting for PLWD. Research ethics and consent were obtained. Pressure‐sensing bed mats, motion and door sensors were installed. The sensors were connected to a hub and the cloud.Participants were divided into lower‐ and higher‐functioning groups based on interRAI Home Care scores.An AI program created nightly summaries for each resident using the sensor: evening rest start / end time, number / duration of in room movements (iRM), and actual resting time (aRT) per night.ResultThe higher functioning residents (n = 7) had a mean age of 83.1 ± 11.0 years, as compared to the lower functioning group (n = 5): 85.0 ± 6.7 years. The lower functioning group had consistently higher mean interRAI scores and tended to have a greater number of medications.Preliminary data from 407 nights suggest that the total rest time was longer for the lower functioning group (12.3+/‐0.97 hr) than the higher functioning group (11.9 +/‐ 1.24 hrs). The lower functioning group had 1.83 +/‐ 1.86 iRMs per night, with an average duration of 13.8 +/‐ 11.0 mins. The higher functioning group had 3.34 +/‐ 2.12 iRMs per night, with an average duration of 15.2 +/‐ 9.3 mins. This resulted in an aRT of 11.8 +/‐ 1.04 hrs for the lower functioning group and 11.1 +/‐ 1.25 hrs for the higher functioning group.ConclusionAmbient sensors were used to collect longitudinal data on nighttime activities in PLWD within a communal living setting. The findings suggest evening rest differences between higher‐ and lower‐functioning PLWD. Residents with more advanced dementia appear to be resting more, and those with less impairment seem to have more and longer rest interruptions. This technology could be used to explore the usefulness of various interventions on rest quality.
Higher proportion of visceral adipose tissue is associated with smaller regional brain volumes in older adults with type 2 diabetes: Triglycerides may be in the pathway
Authors: Boccara Ethel , Ganmore Ithamar , Ravona‐Springer Ramit , Golan Sapir , Ben‐Meir Mery , Livny Abigail , Lesman‐Segev Orit H. , Inbar Yael , Heymann Anthony , Beeri Michal Schnaider 
Published: June 2023

AbstractBackgroundNumerous studies have identified an increased risk for Alzheimer’s dementia (AD) in Type II Diabetes (T2D). However, the T2D biological characteristics contributing to this risk are still unknown. Adiposity assessed by body mass index (BMI) is one of the main causes of T2D and has been consistently linked to higher dementia risk, faster cognitive decline, and related neural injury. However, the contribution of fat specifically cannot be derived from BMI, which encompasses different adipose tissues, bone, and muscle mass. In this study we examined whether regional abdominal adiposity contributes to AD‐related regional brain volume and mechanism underlying it, in older adults with T2D participating in the Israel Diabetes and Cognitive Decline (IDCD) study.MethodRegional abdominal adiposity was measured so far in 60 participants, including hepatic and pancreatic adiposity and abdominal adipose tissue (AAT), composed of subcutaneous and visceral adipose tissues (SAT and VAT). Brain volumes were assessed for regions associated with cognitive decline (hippocampus, cingulate gyrus, amygdala, and ventromedial prefrontal cortex (vmPFC)). Linear regressions examined associations of regional abdominal adiposity with regional brain volumes adjusting for sociodemographics, BMI and intracranial volume. We also tested if triglycerides, the main components of fat and associated with dementia risk, mediated these associations.ResultGreater VAT:AAT ratio was associated with smaller volumes of the vmPFC (r = ‐0.38; p = 0.026) and hippocampal (r = ‐0.44; p = 0.005) volumes but not with amygdala and cingulate gyrus volumes. The SAT:AAT ratio was associated with greater volumes of the vmPFC (r = 0.40; p = 0.026) and hippocampus (r = 0.48; p = 0.004) but not with amygdala and cingulate. No associations were found between hepatic and pancreatic adiposity with brain volumes. Higher VAT:AAT ratio was associated with higher triglyceride levels (r = 0.38; p = 0.036) which in turn were associated with lower hippocampal volume (r = ‐0.45, p = 0.05). Triglycerides partially mediated the association between VAT:AAT ratio and hippocampal volume (r = ‐0.36; p = 0.03). Triglycerides did not mediate any other associations.ConclusionIn older adults with T2D, a higher proportion of visceral fat may have a detrimental impact on brain regions relevant to cognitive functioning. Higher proportions of subcutaneous fat may have a protective role. Triglycerides, implicated in insulin resistance and chronic systemic inflammation may mediate the VAT‐hippocampus link.
Cognitive and emotional theory of mind in dementia. Impact on real life behaviors
Authors: Zegarra‐Valdivia Jonathan Adrian , Rijpma Myrthe Gwen , Shany‐Ur Tal , Kramer Joel H. , Miller Bruce L. , Rankin Katherine P 
Published: June 2023

AbstractBackgroundTheory of mind (ToM) is a core cognitive process that allows regular socioemotional interaction in everyday life. ToM deficits may explain some essential behavior alterations in dementia, particularly in Alzheimer’s disease (AD) and frontotemporal dementia (FTD). This study aimed to (1) identify ToM differences across dementia syndromes and (2) determine if ToM scores predict neuropsychiatric function.MethodWe evaluated 304 participants (age 64.07±9.2) divided into six groups (healthy control, NC = 41; AD = 34; behavioral variant FTD = 96; semantic aphasia; svPPA = 38, nonfluent aphasia; nfvPPA = 47, and progressive supranuclear palsy; PSP = 48) using the UCSF Emotional and Cognitive ToM Test on the TabCAT platform and comprehensive neuropsychological and neuropsychiatric testing. Pa Patients were early in their disease (Clinical Dementia Rating: 0.80±0.53). We compared ToM between groups and used regression models controlling by age and sex to determine if ToM predicted neuropsychiatric symptoms.ResultCognitive ToM was impaired in AD, bvFTD, svPPA, and PSP (p<0.0001), and all groups had impaired emotional ToM (p<0.0001). Both cToM and eToM performance predicted a real‐life neuropsychiatric behavior syndrome, including anxiety, apathy, disinhibition, and aberrant motor subscales scores on the Neuropsychiatric Inventory questionnaire, even after controlling for the influence of bvFTD diagnosis.ConclusionCognitive and Emotional ToM are affected early in diverse dementia syndromes, and impaired ToM test performance can predict a real‐life neuropsychiatric behavior. Assessment of ToM and other aspects of social cognition can be beneficial for the early identification of behavioral alterations in dementia cases.