bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOE ε4 predicts amyloid PET positive in amnesic subjective cognitive decline
Authors: Yang Dong Won , Hong Yun Jeong , Ho SeongHee , Jeong Jee Hyang , Park Kee Hyung , Kim Sangyun , Wang Minjung , Choi Seong Hye , Han SeungHyun , Kang Seung Wan 
Published: February 2022

AbstractBackgroundSubjective cognitive decline (SCD) has been considered as at risk state to progress to mild cognitive impairment(MCI) or Alzheimer's disease(AD). Apolipoprotein E e4 allele is a well‐known genetic risk for rapid deterioration of cognitive and dementia development. We investigated the effect of APOE ε4 on the brain amyloid pathology and other clinical features in the elderly with SCD.MethodOne hundred and nineteen elderly subjects, 60 or older, complaining of persistent cognitive decline, with 7% to 50% of the memory test score and over 7% of the other tests score were included through neuropsychological tests(Seoul neuropsychological battery, SNSB). Brain magnetic resonance imaging (MRI) volumetry, visual and standardized uptake value ratio (SUVR) analysis of 18F‐Florbetaben brain amyloid‐beta Positron Emission Tomography (PET) were performed. Demographics, physical data, social and physiological functions were also obtained.ResultOf the 119 SCD subjects, 26 (21.8%) had APOE ε4 and 26 (21.8%) had amyloid PET positive. Age was not different between two groups (70.9 V.S. 70.9, p=0.880). Test Z‐score was only marginally lower in Digit span test‐forward (p=0.053) in SCD with APOE ε4. Amyloid PET SUVR value was higher in SCD with APOE ε4 (1.2±0.2 V.S. 1.5±0.3, p=0.001). Regional brain volume including hippocampus and entorhinal cortex were not different in SPM based volumetric ananlysis. Korean_Everyday Cognition subscores, depression scores measured with Patient Health Questionnaire 9, sleep quality measured with Pittsburgh Sleep Quality Index total score, Body Mass Index, and gait speed were not different between two groups.ConclusionWith the baseline data, APOE ε4 was associated with decreased attention and higher brain amyloid accumulation in amnestic SCD. Longitudinal data will be needed to clarify whether APOE ε4 is associated with progression of cognitive dysfunction in SCD. This study was supported by a grant from the Ministry of Health and Welfare, HI18C0530.
The persistence and longitudinal impacts of sleep disturbances in nursing home residents with dementia
Authors: Webster Lucy A , Gonzalez Sergi Costafreda , Barber Julie , Livingston Gill 
Published: February 2022

AbstractBackgroundSleep disturbances are common in people living with dementia, with a prevalence of 40%. These disturbances may be the reason people with dementia move into a nursing or residential care home. However, there is little research into the persistence and long‐term impacts of sleep disturbances in this population, and this has practical implications on if and how these disturbances should be treated, and we aimed to investigate this.MethodWe used data from the MARQUE (Managing Agitation and Raising QUality of lifE) cohort study, with data collected from 1483 care home residents with dementia every four months for 16 months; the largest care home study in England, UK. Outcomes collected at every time point included quality of life, hospital admissions, mortality, medication, and sleep disturbances; which were defined as either any symptoms or clinically significant cases when the symptoms were more frequent and severe (defined as score ≥4 on the Neuropsychiatric Inventory sleep item).ResultMost participants were female (69%), with a median age 86 years. Nearly a third of residents (31%) had a clinically significant case and nearly half (47%) of residents had symptoms of sleep disturbance across the study. Of those with clinically significant cases at baseline, 16% remained persistent cases, 46% fluctuated, and 38% did not have a clinically significant case again. Furthermore, residents with clinically significant cases longitudinally had a lower quality of life (regression coefficient ‐3.94, 95% confident intervals (CI) ‐4.82–‐3.06), and were significantly more likely to be prescribed sleep medications (odds ratio (OR) 1.57, CI 1.02–2.42). Residents who had a clinically significant case at baseline were more likely to have a hospital admission at follow‐up (OR 1.52, CI 1.07–2.14), but were not more likely to die during follow‐up (hazards ratio 0.93, CI 0.71–1.22).ConclusionAs sleep disturbances fluctuate or persist in most residents who have them, this highlights the importance of treatment for these disturbances, as they mostly will not resolve without it. As these disturbances also negatively impact people with dementia’s quality of life and increase the likelihood of hospital admissions, they are therefore a priority for treatment.
At‐homeness: A novel psycho‐socio‐environmental construct for an eMental Health controlled trial to prevent loneliness and cognitive decline among older adults with multimorbidity
Authors: Gan Daniel RY , Chaudhury Habib , Best John R , Rowles Graham , Wister Andrew 
Published: February 2022

AbstractBackgroundApproximately two‐thirds of older adults’ experience multimorbidity in Canada and the US. Challenges of symptoms management and reduced mobility often coincide with late‐life depression which is associated with a 2 to 5‐fold increased dementia risk. Loneliness and depression are connected in the prodromal phases. Loneliness is distinct from social isolation and has direct neurological impact on the brain (Cacioppo et al., 2014). Yet, recent umbrella review of RCTs on loneliness reported “limited effects” (Jarvis et al., 2020). Following recommendations for theory‐based non‐pharmacological interventions (Sikkes et al., 2020), this paper develops a novel construct as an antidote to loneliness for eMental Health intervention among MMOA.MethodFindings from three sequential studies were combined to examine the preventive potential of a measurable construct. (1) Systematic review identified 28 studies on the experiences people living with dementia in the community. Comparative synthesis was conducted ethnographic data (e.g., in‐depth interviews) since Chaudhury (2001). (2) Primary qualitative data were extracted to generate items for a preliminary scale. Factor analysis was conducted to examine construct validity. (3) An index was constructed using comprehensive data from the Canadian Longitudinal Study on Aging (CLSA). Path analysis was conducted to examine direct and indirect effects on loneliness, depression, and cognition, controlling for baseline. Social environment (e.g., social support) was included for comparison.Result(1) Understanding behavioral symptoms as non‐verbal expressions and employing Deweyan person‐place integration, at‐homeness emerged as a psychological construct that could address prodromal loneliness. (2) Factor analysis (n=212) reduced 28 items to 20 items (α=.920) At‐homeness includes three factors: identity‐stability(α=.886), social experiences (α=.887), self‐expression (α=.767)(SRMR=.075). Convergent validity with neighborhood factors was found (B=.43, p<.001). (3) Measures of housing, neighborhood, and life satisfaction were used. Path analysis (n=15,087) showed good model fit indexes (TLI=.989; CFI=.999; RMSEA=.026; SRMR=.006). At‐homeness (B=‐.20, p<.001) rivals the effect of social environment (B=‐.19, p<.001) on loneliness. Structural equation modelling showed that, together, at‐homeness and loneliness have as much effect on cognition as depression.ConclusionAt‐homeness is a promising novel psycho‐socio‐environmental construct to reduce loneliness and cognitive decline among MMOA. Its factors may be influenced through customized activity suggestions. A pilot study is underway.
Multimodal assessment of locus coeruleus integrity is associated with late‐life memory performance
Authors: Dahl Martin J , Bachman Shelby L , Dutt Shubir , Düzel Sandra , Lindenberger Ulman , Kühn Simone , Werkle‐Bergner Markus , Mather Mara 
Published: February 2022

AbstractBackgroundAbnormally phosphorylated tau, an indicator of Alzheimer’s disease, accumulates in the first decades of life in the locus coeruleus, the brain’s main norepinephrine supply. Recent advances in brainstem magnetic resonance imaging (MRI) suggest an association between in‐vivo locus coeruleus integrity and Alzheimer’s‐related neuropathology. However, while MR sequences have demonstrated their sensitivity for the locus coeruleus, a complete understanding of the underlying contrast mechanisms is still lacking.MethodTo investigate whether common locus coeruleus imaging approaches measure the same construct, younger and older participants of the Berlin Aging Study‐II (n ∼ 320) underwent 3T‐MRI. The imaging protocol included three scans sensitive for the locus coeruleus—a Fast‐Spin‐Echo [FSE] sequence focused on the brainstem, and a Magnetization‐Transfer sequence, acquired once with a dedicated magnetic saturation pulse [MT] and once without, resulting in a proton‐density like image [noMT]. Participants moreover completed a comprehensive cognitive battery, including tests of fluid intelligence, episodic and working memory, to assess whether different imaging protocols relate to similar aspects of late‐life cognition.Locus coeruleus MR‐intensity ratios, a non‐invasive proxy for neuronal density, were semi‐automatically extracted from FSE, MT, and noMT scans in standard space. We integrated locus coeruleus ratios across imaging modalities to derive a latent, multimodal factor expressing locus coeruleus integrity. Similarly, we used a previously established cognitive factor structure to integrate performance across multiple cognitive tasks to retrieve latent measures of fluid intelligence, episodic and working memory.ResultLocus coeruleus‐related hyperintensities were reliably detected across imaging modalities (see Figure 1). Crucially, locus coeruleus ratios derived from different imaging modalities were strongly interrelated in younger and older adults (see Figure 2), indicating a common construct. However, age‐group differences in locus coeruleus ratios were modality‐specific, warranting caution in cross‐study comparisons. Merging neural and cognitive models, we found that higher locus coeruleus ratios were related to better episodic memory performance in later life. This association was observed for multimodal locus coeruleus integrity and was replicated for each imaging modality (see Figure 3).ConclusionOur findings support the utility of brainstem MRI as proxy for locus coeruleus integrity and highlight a role of the noradrenergic system in late‐life memory decline.
The Brain Health Champion (BHC) Study, COVID‐19 sub‐study: The impact of COVID‐19 on behaviors adopted following interventions to promote brain‐healthy activities
Authors: McFeeley Brittany , Krivanek Taylor , Nicastri Casey M , Daffner Kirk R , Gale Seth A 
Published: February 2022

AbstractBackgroundEvidence suggests that brain‐healthy behaviors, such as exercise, a Mediterranean diet, and cognitive/social stimulation, help protect against the risk of cognitive decline and dementia. We have been studying two interventions (health coach vs. physician education) that promote brain‐healthy behaviors in patients with mild dementia (MD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and those at‐risk. When COVID‐19 occurred, we became interested in determining the extent to which the pandemic may have interfered with brain‐healthy behaviors that participants had adopted. We designed a sub‐study to investigate the pandemic’s effects on adherence to brain‐healthy behaviors in participants who completed either intervention in one of our two Brain Health Champion studies (BHC‐1, BHC‐2).MethodParticipants from BHC‐1 and BHC‐2 were emailed questionnaires in September 2020. Of the 25 respondents, 15 (SCD:2, MCI:8, MD:5) were from BHC‐1 and 10 (At‐risk:5, MCI:5) were from BHC‐2. Questionnaires measured changes from the start of the pandemic (March 2020) in self‐reported physical activity, diet, and social/cognitive activities, as well as current sleep quality and feelings of anxiety and depression.ResultResults demonstrated that the pandemic had negatively impacted physical activity (p=.009) and social interactions (p<.001), with no significant changes in diet or cognitive activities. Additional data trends show that at‐risk/SCD participants endorsed more feelings of anxiety and depression than MCI participants. At‐risk/SCD participants also reported worse sleep quality than MCI participants (p=.036) across both studies and intervention arms.ConclusionOur findings suggest that the pandemic significantly impacted activities typically done outside the home (social and physical activity), while activities that are typically done at home were less affected (Mediterranean diet adherence and cognitive activity). The pandemic seemed to diminish brain‐healthy behaviors that participants likely gained from the interventions, demonstrating that clinical/research programs aimed at promoting brain health are strongly influenced by changes in the environment. Trends also show that there may be a direct relationship between anxiety/depression symptoms and sleep disruption in at‐risk/SCD and MCI participants. More research is necessary to determine if these disruptions of behavior and sleep are temporary and will be well‐compensated when COVID‐19 restrictions are lifted.
Hypertension and race affect cerebral blood flow and cognition in older adults without dementia
Authors: Swinford Cecily G. , Risacher Shannon L. , West John D. , McDonald Brenna C. , Unverzagt Fred W. , Gao Sujuan , Farlow Martin R. , Apostolova Liana G. , Wu Yu‐Chien , Brosch Jared R. , Deardorff Rachael , Wang Sophia , Kamer Aaron P. , Wang Danny J.J. , Saykin Andrew J. 
Published: February 2022

AbstractBackgroundIt is known that African Americans have a higher prevalence of AD than white Americans, but it is not fully understood why this is the case. One potential explanation is that African Americans also have a higher prevalence of cardiovascular risk factors, which also confer a risk for AD. Racial differences in several AD‐specific and cardiovascular disease biomarkers have been reported, but these findings are generally not conclusive. In addition, very few papers have assessed racial differences in cerebral blood flow (CBF), an important noninvasive biomarker for AD/dementia. We investigated the relationships between cerebral blood flow (CBF), race and hypertension in a cohort of older individuals without dementia.MethodParticipants included 116 older individuals, 21 (18%) African American, who were cognitively normal (CN), had subjective cognitive decline (SCD), or had mild cognitive impairment (MCI). 3D pseudo‐continuous arterial spin label (pCASL) MRI on a Prisma 3T and cardiovascular risk factors and cognitive domain z‐scores from the time of scan were analyzed. Multiple regression was used to assess the relationships between race, hypertension, and CBF on a region‐of‐interest and voxel‐wise basis with age, sex, diagnostic group and total grey matter volume as covariates.ResultRegion‐of‐interest and voxel‐wise CBF was decreased in African Americans and in individuals with hypertension. While there was overlap between the affected regions, especially temporal lobes, hypertensive individuals also had decreased CBF in anterior brain regions, while African Americans had decreased CBF in posterior brain regions. The effect of race on CBF remained after hypertension was included as a covariate. Despite the regional overlap, there was no interaction of race and hypertension on CBF. Perfusion in affected brain regions was positively correlated with attention in all participants, as well as with visuospatial function in African Americans.ConclusionHypertensive individuals and African Americans have decreased CBF in partially overlapping brain regions. Decreased CBF in these regions was differentially associated with cognitive function according to race. Further study of CBF in larger diverse samples is warranted.
Informant measures of cognition in the Mexican Health and Aging Cognition Study
Authors: Cantu Phillip A , Wong Rebeca , Arango Silvia Mejia 
Published: February 2022

AbstractBackgroundTo describe the correlates of informant assessed cognitive functioning among older Mexican adults.MethodWe include participants in the 2016 Mexican Health and Aging Study Cognition Study Informant Questionnaire (MexCog). Cognitive functioning, measured by total Community Screening Instrument for Dementia (CSID), and CSID split into a cognition and functioning component are regressed as a function of participant characteristics, informant characteristics, and relationship characteristics.ResultsInformant measurements of cognition have distinct correlates from direct measurements. Participant education is significantly associated the total CSID and the cognition component but not the functioning component. Community size is not significantly associated with informant measures of cognition. Spousal informants reported higher total CSID scores and cognitive component but were not significantly associated with the functioning component. Other family members and other non‐family members reported fewer CSID cognition items than spouses.ConclusionSpousal informants may be more attuned to their partners cognitive functioning than other informants. Functional components and cognitive components of the CSID measure distinct domains and have different correlates.
Correspondence between cortical tau and atrophy in aged non‐demented adults with Down syndrome
Authors: Taylor Lisa , Doran Eric , Poline Jean‐Baptiste , Nguyen Dana , Krinsky‐McHale Sharon J. , Price Julie C. , Sathishkumar Mithra , Kreisl William Charles , Hom Christy , Pulsifer Margaret , Lai Florence , Rosas H. Diana , Brickman Adam M. , Schupf Nicole , Silverman Wayne , Lott Ira T. , Yassa Michael A. , Keator David 
Published: February 2022

AbstractBackgroundIndividuals with Down syndrome (DS) have a higher likelihood of developing early‐onset Alzheimer’s disease which has been associated with abnormal tau proteins and atrophy in the brain [1]. Prior research has shown a spatial relationship between tau and atrophy in neurotypicals with dementia [2]. Although tau and atrophy certainly contribute independently to dementia, the synergistic relationship in a non‐demented population with DS is not well understood. This study aims to identify cortical regions with high tau and atrophy in aged, non‐demented participants with DS.MethodAnalysis included 28 non‐demented participants (49.8 +/‐ 6.4 years; 17 males) with DS from the Alzheimer’s Disease in Down Syndrome (ADDS) study. Tau PET (18F‐AV1451) and MRI scans were acquired within the same timeframe (1.8 months +/‐1.5). Gray‐matter cortical ribbons were extracted from T1 MRI segmentations with Freesurfer (RRID: SCR_001847). The cortical ribbons were used to mask the coregistered PET scan data and converted to standard uptake value ratio (SUVR) units using the cerebellar cortex reference region. The tau and gray‐matter images were converted to z‐score images using the group mean and standard deviation. We defined high tau as voxels with z‐scores >=2.0 and high atrophy as voxels with gray matter z‐scores <= ‐2.0. The z‐score images were spatially normalized into MNI space with ANTs (RRID: SCR_004757) and a voxel‐based correspondence analysis was performed. Voxels surviving the high tau and high atrophy thresholds were evaluated to determine anatomical localization using the Desikan/Killiany atlas [3].ResultWe found high correspondence between tau and atrophy in the following regions (figure 1): entorhinal cortex, insula, fusiform, pars orbitalis, paracentral, precentral, superior temporal, medial orbitofrontal, lateral orbitofrontal, temporal pole, rostral middle frontal, superior frontal, pars triangularis, lingual, and the amygdala.ConclusionOur study demonstrated a correspondence between atrophy and tau in deep cortical structures, as well as frontotemporal regions in aged, non‐demented adults with DS. Many of these regions are consistent with findings in neurotypical populations and shown in our prior work to be regions associated with increased amyloid (18F‐AV‐45) as a function of disease severity in DS [4].
Usability and functional validation of artificial intelligence‐enabled technology services in dementia care using a controlled trial in clinical practice
Authors: Savoia Sarah E , Stern Edith H , Salardini Arash , Dorai Chitra 
Published: February 2022

AbstractBackgroundMany community settings lack emotional, social, and educational resources to support persons living with dementia (PLWD) and their families, which contribute to the stressors associated with caregiving, termed "caregiver load." This paper describes the impact of artificial intelligence (AI)‐enabled personalized assistive and decision support services on improving dementia care management and reducing caregiver load. We present a study that assesses AI’s usability and functionality in the outpatient setting and is built off of two prior pilots, with each pilot expanding in its scope of technology provided, target population, and caregiving needs.Objectives: The study’s primary outcome is the functionality and usability of AI services, collectively called NeuViCare, as measured by the System Usability Scale (SUS) from caregivers. Secondary outcomes include: 1) reduction in caregiver load as measured by Oberst Caregiving Burden Scale (OCBS); and 2) increase of caregivers’ knowledge as measured by Dementia knowledge assessment scale (DKAS).MethodsThis one‐arm, open‐labeled trial is recruiting ten patients with MOCA scores of less than 26 and impaired activities of daily living and their one designated caregiver. Caregivers must have a smartphone, tablet, or laptop to access NeuViCare and to utilize all four of its HIPAA and FHIR compliant services for three months: 1) Task‐Support Service 2) Resource Advisor 3) Community; and 4) Knowledge Advisor. Periodic touchpoints with caregiver participants are in place as a safety measure.ResultsThe first pilot’s target population was aides from a national home care agency. The survey‐study reported NeuViCare's user experience to be “very positive” and “easy to use”; the quality of its information to be “clear, concise and with good depth”; and, 3) its value to be “useful for less experienced caregivers”. The second pilot focused on family caregivers from Mumbai. This study showed that Knowledge Advisor provided 97% correct answers. This third pilot study targets informal caregivers, and we hypothesize that mean SUS scores will be significantly associated with reduced OCBS scores.ConclusionEffectiveness of AI technology in reducing caregiver load will lead to a scalable, cost‐effective solution that can be made available to caregivers everywhere.