bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cortical glucose metabolism signatures of cognitive resilience in amyloid positive cognitively unimpaired elderly adults
Authors: Liu Lin , Sun Pan , Lan Guoyu , Cai Yue , Li Anqi , Zhu Yalin , Ma Shaohua , Guo Tengfei 
Published: December 2023

AbstractBackgroundβ‐amyloid (Aβ) positive (A+) cognitively unimpaired (CU) individuals who maintain normal cognitive function at follow‐up may have good cognitive resilience (CR). A+/CU Individuals with high CR may have hypermetabolism. In this study, we explored the cortical glucose metabolism features of CR in A+/CU elderly adults.MethodWe analyzed 855 ADNI participants with Aβ PET (18F‐florbetapir (FBP) or 18F‐florbetaben (FBB)), CSF p‐Tau181, 18F‐fluorodeoxyglucose (FDG) PET and longitudinal residual hippocampal volume (rHCV) and cognitive assessments. A+/T+/N+ were defined as AD summary cortical standardized uptake value ratio (SUVR) for FBP ≥1.11 or FBB ≥1.08, CSF p‐Tau≥23pg/ml, and rHCV≤‐0.67 respectively. We compared intensity‐ and spatial‐normalized FDG SUVR images between 96 A‐/T‐/N‐/CU individuals (Reference group) and 68 A+/CU individuals who maintained CU at follow‐up regardless of T+ or N+ (CR group). Cortical regions with higher FDG SUVR in the CR group were identified as the CR_metaROI. Baseline CR_metaROI FDG‐SUVRs were compared between different stages of AD. Finally, we determined whether CR_metaROI FDG‐SUVR can modulate the association of Aβ PET and CSF p‐Tau with longitudinal changes of cognition, controlling for age, sex, and education.ResultCR_metaROI was primarily located in the precentral and postcentral regions (Fig. 1). AD dementia patients had lower CR_metaROI FDG SUVRs than the CU (standardized β (βstd) = ‐0.326[95% confidence interval (ci): ‐0.534, ‐0.119], p = 0.002) and MCI (βstd = ‐0.303[95%ci: ‐0.496, ‐0.111], p = 0.002) groups (Fig. 2A), and A+/CU group had higher (βstd = 0.605[95%ci: 0.352, 0.859], p<0.001) CR_metaROI FDG SUVRs than the A‐/CU group (Fig. 2B). A‐/T+ and A+/T‐ individuals had lower (βstd = ‐0.248[95%ci: ‐0.4474, ‐0.022], p = 0.031) and higher (βstd = 0.305[95%ci: 0.093, 0.516], p = 0.005) CR_metaROI FDG SUVRs than the A‐/T‐ group respectively (Fig. 2C). The A+/T‐/N+ group had higher (βstd = 0.466[95%ci: 0.153, 0.779], p = 0.004) CR_metaROI FDG SUVRs than the A‐/T‐/N‐group (Fig. 2D). Moreover, higher baseline metaROI FDG‐SUVRs were associated with slower rates of decline in memory, executive function and preclinical Alzheimer cognitive composite scores upon the same levels of Aβ PET (Fig. 3A‐C) and CSF p‐Tau (Fig. 3D‐F).ConclusionWe identified a metabolism signature of CR in A+/CU elderly adults. These findings may provide novel insights into understanding the hypermetabolism patterns of CR in aging people.
Longitudinal sleep, pain interference, and depressive symptoms in cognitively impaired older adults
Authors: Dimitrov Theodore , Monroe Todd B , Failla Michelle D , Bruehl Stephan , Romestan Rachel , Moss Karen O , Cowan Ronald L , Anderson Alison R 
Published: December 2023

AbstractBackgroundPoor sleep, pain, and depression are interrelated factors in older adulthood that may impair cognition. Few studies have examined associations among sleep, pain interference (i.e., how pain interferes with daily living), and depression with cognitive status. Therefore, we investigated these associations in verbally communicative older adults with and without cognitive impairment (CI). We hypothesized that individuals with CI will be more impacted by all variables in relation to the control group.MethodSleep (Neuro‐QoL Sleep), pain interference (Brief Pain Inventory‐Short Form), depression (15‐item Geriatric Depression Scale), and cognitive function (Telephone Interview for Cognitive Status) were investigated in older adults (ages ≥ 65) with CI (N = 16) compared to age‐ and sex‐matched controls (N = 28). Sleep, pain, and depression data were collected weekly over six weeks to allow for a detailed assessment of potential changes in symptoms. Data analyses were conducted in R using linear mixed effects models and conditional growth curve analysis.ResultAcross our sample, we found that more sleep disturbances were associated with more severe depression (p<0.001), greater pain interference was associated with more severe depression (p<0.001), and more sleep disturbances were associated with greater pain interference (p<0.001). There was a significant interaction between cognitive status and sleep disturbances on depression (p = 0.0005), such that the CI group had a stronger positive relationship between sleep disturbances with depression severity. Similarly, there was a significant interaction between cognitive status and pain interference on depression (p<0.001), such that the CI group had a stronger positive relationship between pain interference and depression severity.ConclusionThe findings demonstrate that the relationship among sleep, pain, and depression remain a concern in older adults with CI. As sleep worsened, depression tended to increase across both groups, yet in those with CI, this finding was stronger. Similarly, as pain interference worsened, depression tended to worsen in both groups, but this association was stronger in those with CI. Additional attention to the assessment, prevention, and treatment of sleep disturbance, pain, and depression in people living with and without CI is warranted, especially as individuals with CI may have difficulties communicating these problems.
SPRINT MIND: Implications of Recents Findings for New Trials Focused on ADRD Prevention Through Vascular Pathways
Authors: Williamson Jeff D. 
Published: December 2023

AbstractBackgroundClinical trial proven treatments for reducing the risk of patient centered outcomes such as mild cognitive impairment (MCI) and dementia have been lacking. The impact of intensive treatment of hypertension on the incidence of Mild Cognitive Impairment (MCI) and dementia was tested in the Systolic Blood Pressure Intervention Trial (SPRINT‐MIND) by prospectively assessing the effect of intensive blood pressure control to a target systolic blood pressure of <120 mmHg versus a standard target (<140 mmHg). This presentation reviews the SPRINT results and presents more recent analyses on the reliability of the MCI classification, evidence for the impact of BP control on transition from MCI to dementia and recent evidence on the outcome trajectories after trial discontinuation.RESULTSAt one year, mean systolic blood pressure was 121.4 mmHg in the intensive‐treatment group and 136.2 mmHg in the standard‐treatment group. Participant mean age was 67.9 years (35.6% women) and 8,626 (92.1%) completed at least one follow‐up cognitive assessment. After only 3.26 years of treatment, the 5 year assessment of cognition deonstrated a significantly lower rate of adjudicated incident MCI (HR 0.81, CI 0.67‐0.97) and a non‐significant reduction in probable dementia (HR 0.83, CI 0.69‐1.04) in th intensively treated group. The combined outcome of MCI plus probable all cause dementia was significantly lower (HR 0.85, CI 0.74‐0.97) in the intensive versus standard treatment group. Most cases occurred in persons over age 70. At 2 years, MCI classification was 10X more likely to transition to dementia than normal cognition and 30% of classified as MCI reverted to normal, consistent with other large epidemiologic studies of MCI trajectory. In secondary analyses, intensive therapy also showed the greatest benefit on persons with the highest risk for cognitive decline.CONCLUSIONSAmong ambulatory adults at increased risk for CVD but without diabetes, treating to a SBP target <120 mmHg compared to a target of <140 mmHg reduces the risk of incident MCI and combined MCI/probable dementia. MCI classification in SPRINT MIND was highly predictive of transition to dementia, similar to large reputable observational studies and cognitively vulnerable persons benefitted the most.
Reconsideration of appropriate use criteria for amyloid PET based on real‐world experiences
Authors: Park Kee Hyung , Shim YongSoo , Choi Seong Hye , Youn Young Chul , Yang Dong Won , Kim SangYun 
Published: December 2023

AbstractBackgroundAmyloid PET can detect brain abnormality at very early stages of AD. However, deciding which patients should undergo amyloid PET requires careful consideration, because of its expense and the lack of treatment options. Until now, 2013 recommendations for appropriate use of amyloid PET, by Amyloid Imaging Taskforce, have been used widely. However, anti‐amyloid treatment is becoming available, so it is an appropriate time to reconsider the optimal criteria for amyloid PET use. In Korea, amyloid PET is widely used in clinical practice due to its low cost and easy accessibility. Therefore, we conducted a survey to investigate the current status of amyloid PET use by dementia experts in Korea, and considered what would be the optimal criteria for using amyloid PET in the real world.MethodThe survey consisted of 52 questions, conducted using an online platform, in 2022. Fifty‐six dementia experts (34 neurologists and 22 psychiatrists) participated, mainly working at university hospitals in Korea.ResultExperts responded positively that they would use amyloid pet in the following situations: cognitive complaint with objectively confirmed impairment (88.5%), persistent MCI (32%), progressive unexplained MCI (84.9%), possible AD or mixed pathology (63.5%), possibility to change medication (75%), among patients age under 65 in MCI (86.5%), and in AD (82.6%). In cases of probable AD, it is recommended not to take an amyloid PET scan, but only 25% of experts answered “no”. 36.4% answered positively that they would use amyloid PET, and if the patient was under 65 years old, 30.8% responded “always”. And, to the question ‘If anti‐amyloid treatment becomes available, would you be willing to perform amyloid PET scan?’, nearly 90% of experts answered that they would consider amyloid PET in MCI and Probable AD.ConclusionUnlike previous recommendations, amyloid PET scan is widely used in actual clinical practice in Korea. In particular, in the situation where the use of anti‐amyloid based disease modifying drugs has become a reality, contrary to the recommendations, it could be used more actively in patients with probable AD. Therefore, it is necessary to reconsider what is the appropriate amyloid PET use criteria.
A Cross‐Regional and Cross‐Generational Approach to Addressing Recruitment Barriers: The Engaging Communities of Hispanics/Latinos for Aging Research (ECHAR) Network
Authors: Medina Luis Daniel 
Published: December 2023

AbstractBackgroundDespite being the largest and one of the fastest growing ethnic groups in the United States, Hispanics/Latinos (H/Ls) comprise only about 5% of NIH‐funded Alzheimer’s disease and related dementias (ADRD) research participant samples. Exclusion of H/Ls limits the generalizability of research findings and our understanding of brain health disparities. The Engaging Communities of Hispanics for Aging Research (ECHAR) Network is a collaborative, transdisciplinary network aimed at engaging, educating, and motivating H/Ls for participation in ADRD research by addressing several barriers to inclusion, including trust and ADRD‐related communication.MethodECHAR has been employing a novel, community‐engaged method – Boot Camp Translation (BCT) – to translate medical jargon into action‐based, community relevant messages by answering the questions: What are the key messages [about ADRD]? Who in my community needs to hear these messages? How do we get these messages to them? BCT was carried out in three metropolitan areas with large H/L populations: Denver, Colorado; Houston, Texas; and Las Vegas, Nevada. We also carried out BCT in groups of middle‐to‐older‐age adults as well as in younger adults. Over the course of several months, community stakeholders worked closely with the research team to co‐create ADRD communications targeted to local communities. An additional objective of ECHAR has been to invite BCT participants to form local community action boards (CABs); as members of the research infrastructure, CABs help further improve community relations and inclusion.ResultPre‐/post‐ comparisons showed significant improvement in subjective understanding (Cohen’s d = 0.75; p<0.001) and objective knowledge of Alzheimer’s disease (Cohen’s d = 0.79; p<0.001). Similarities were observed across the three sites; H/L community members identified key messages related to reducing stigma, emphasizing brain health and risk mitigation, and acknowledging the impact of Alzheimer’s disease on multi‐generational families/households. Participants also recommended sharing these messages with H/Ls across the lifespan using multi‐media avenues. Key cross‐regional and cross‐generational differences were also observed and will be described.ConclusionThe ECHAR Network has developed key, culturally responsive, ADRD‐related materials as well as dissemination strategies for H/L recruitment. Moreover, by establishing CABs in each city, we have developed sustainable research infrastructure to enhance outreach.
What do we still need to know about antihypertensives and dementia prevention?
Authors: Peters Ruth 
Published: December 2023

AbstractThere is a substantial evidence base linking higher blood pressures to an increased risk of cognitive decline and dementia and an increasingly strong evidence base showing reduced dementia risk with blood pressure lowering. Several clinical trials including SPRINT‐MIND have strongly suggested that antihypertensive treatment to lower blood pressure reduces dementia risk. Furthermore, a recent individual participant data meta‐analysis combining data from 5 large double‐blind placebo‐controlled trials of antihypertensives in a late‐mid to early‐late life population (N = 28008) found a 13% reduction in incident dementia cases (OR0.87 (95%CI: 0.75,0.99))(1). The blood pressure difference between the two combined trial arms was ∼10mmHg in systolic blood pressure and there was no clear U shape indicating no increase in risk at lower pressures. This is supported by numerous earlier meta‐analyses of published trial and epidemiological data. Blood pressure lowering is acknowledged as one of the most promising ways in which we might reduce the risk of dementia and cognitive decline.Despite this substantial progress and although we are arguably closer than ever before to answering the question of whether blood pressure lowering reduces dementia risk, there have been no double‐blind placebo‐controlled trials that have definitively shown dementia risk reduction with antihypertensive use. In the absence of strong results, recommendations for antihypertensive use inevitably remain cautious. Furthermore, not only do we still lack a definitive blood pressure dementia risk reduction trial, such a trial would need to be large and complex. Uncertainties also exist about how to deliver treatment against the backdrop of widespread antihypertensive use to reduce cardiovascular risks such as stroke or heart attack. Research is also still progressing on key practical questions. For example, whether we should have a goal blood pressure for brain health, how far we should lower blood pressure to reduce dementia risk, what is the ideal treatment package and how much do factors such as age and frailty matter? We present the key evidence so far and an ongoing pilot trial designed to answer the leading questions in the field.(1)Peters et al Eur Heart J 2022
Frailty and mild behavioral impairment: A longitudinal study of pre‐dementia markers
Authors: Isaza Juan C Uribe , Guan Dylan X. , Ismail Zahinoor 
Published: December 2023

AbstractBackgroundFrailty and mild behavioral impairment (MBI) are non‐cognitive markers of dementia and have been associated with one another cross‐sectionally. Better understanding the association between frailty, MBI, and dementia is necessary to determine whether dementia prognostication could be improved by assessing for both frailty and MBI. This study investigated the longitudinal associations between frailty, MBI, and incident dementia.MethodWe analyzed data from 20,010 dementia‐free older adults from the National Alzheimer’s Coordinating Center. Frailty was operationalized using a previously published 44‐item frailty index (FI). MBI was derived from the Neuropsychiatric Inventory Questionnaire using a published algorithm; participants were classified as MBI+ if MBI symptoms were present for ≥2 consecutive visits. We used Cox proportional hazards regression to model the association between: (1) baseline FI and incident MBI; (2) baseline MBI and the incident severe frailty (FI≥0.20). We also examined whether MBI+ older adults with higher FI were more likely to develop dementia than those with lower FI. All models were adjusted for age, sex, education, and cognitive status (cognitively normal or mild cognitive impairment).ResultParticipant characteristics are described in Table 1. The hazard of developing MBI rose by 45% for every 0.1 increase in FI (adjusted hazard ratio; aHR = 1.45, 95%CI: 1.36‐1.55, p<.001) [Table 2]. Likewise, the hazard of developing severe frailty (FI≥0.20) was 97% greater in MBI+ participants compared to MBI‐ participants (aHR = 1.97, 95%CI: 1.85‐2.10, p<.001). Finally, although MBI alone was associated with incident dementia (aHR = 2.02, 95%CI:1.89‐2.17, p<.001), the hazard developing dementia further rose by 1.17 (95%CI: 1.08‐1.26, p <.001) for every 0.1 increase in FI within a sample of MBI+ participants.ConclusionIn dementia‐free older adults, frailty is associated with the development of MBI. Further, MBI is associated with the development of severe frailty. Understanding these relationships identifies the potential to use frailty screening as an indicator of individuals who could develop MBI, and MBI screening as an indicator of individuals at risk of accumulating more health deficits. Although, MBI alone predicts incident dementia, our findings suggest that including general health measures, i.e., frailty, in modeling may improve dementia prognostication.
Blood‐brain barrier neuropathology in individuals with Down syndrome and Alzheimer’s disease
Authors: Aguilar Lisi Flores , Du Annie , Kofler Julia , Ikonomovic Milos D , Lai Florence , Brickman Adam M. , Head Elizabeth ,   Alzheimer’s Biomarker – Down Syndrome Consortium (ABC‐DS)
Published: December 2023

AbstractBackgroundIndividuals with Down syndrome (DS) are the largest population at genetic risk of developing early‐onset Alzheimer’s disease (AD). Throughout their lifespan, individuals with DS develop the spectrum of AD neuropathology. By 40 years of age, mature amyloid beta plaques and tau neurofibrillary tangles are present in DS brains, followed by the development of AD dementia. Despite having a low frequency of vascular risk factors (i.e., hypertension, atherosclerosis), individuals with DS display significant cerebrovascular pathology, including cerebral amyloid angiopathy, increased white matter hyperintensities, microbleeds, microinfarcts, and enlarged perivascular spaces. Such pathological changes suggest that the blood‐brain barrier (BBB) undergoes neuropathological alterations and may be associated with the development of AD pathology, in DS. Nevertheless, BBB integrity has not been studied in DS. Our main objective is to investigate BBB pathology in the brains of people with DS and AD (DSAD).MethodPost‐mortem brain tissue was obtained from the ABC‐DS study, NIH Neurobiobank, and BrightFocus Foundation. BBB components (basement membrane, endothelial cells, pericyte cell number) and BBB leakage were assessed by free‐floating immunohistochemistry in human brain tissue sections from the occipital cortex of individuals with DSAD (49‐55 years old), and their age‐matched neurotypical controls (48‐57 years old). Brain sections were digitized, and BBB components and vessel morphology were quantified using ImageJ.ResultOur preliminary data suggest that, compared to age‐matched controls, adults with DSAD have a lower number of pericytes and lower Collagen‐IV load. A proportion of DSAD cases also had lower endothelial cell coverage and shorter blood vessels. Moreover, fibrinogen leakage was observed in the brain parenchyma of DSAD brains. Interestingly, some individuals with DSAD displayed no BBB pathological changes.ConclusionIndividuals with DS have pathological alterations in the BBB. However, some people with DSAD may be resilient to such changes. Studies are ongoing to determine if BBB changes in DS are associated with the development and progression of AD neuropathology.
Dementia awareness, motivation and modifiable risk factors amongst older Australians in regional communities
Authors: Dodds Laura Eliza , Deckers Kay , Siette Joyce 
Published: December 2023

AbstractBackgroundDementia is the second leading cause of death in regional Australia. A large body of research into modifiable dementia risk factors and awareness levels has been gathered with metropolitan communities, yet this remains unexplored within regional areas. Therefore, this study aims to 1) identify awareness of modifiable dementia risk factors; 2) identify the presence/absence of modifiable dementia risk factors; and 3) explore sociodemographic and motivation characteristics associated with modifiable dementia risk in regional areas of AustraliaMethodCross‐sectional data of dementia awareness and risk levels in 180 adults >65 living in rural and remote regions within New South Wales, were collected using an online survey. Data included demographics, awareness of dementia risk factors (British Social Attitudes survey), presence/absence of modifiable dementia risk factors (LIBRA), motivation to reduce dementia risk (MCLHB‐DRR) and social connections (LSNS‐6). Descriptive analyses was used to identify awareness as well as presence/absence of risk factors and univariate associations were used to explore demographic factors and motivation characteristics, associated with dementia awareness and dementia risk.ResultParticipants had a mean age of 72.2 (SD = 5.5) years, majority were female (70%), and had less than 10 years of education (41.1%). 41.7% were from a low socio‐economic background and 97.2% were born in an English‐speaking country. A substantial proportion of participants agreed that dementia risk is modifiable (73.3%) and identified an average of 5.7 (SD = 3.1, out of 12) dementia risk factors correctly. The motivation domain of perceived susceptibility towards dementia was low (11.3 out of 20; SD = 3.4; [4‐20]), and few social connections were reported (8.2; SD = 9.3; [0‐30]).ConclusionRural and remote Australian older adults having a basic understanding that dementia is not inevitable, however, they remain unaware of more than half of the risk and protective factors for dementia. Given the consistencies in dementia risk and the inconsequential association between sociodemographic variables in regional areas, future interventions should adopt a population health approach to improve awareness and create opportunities for communities to target health risk factors contributing to dementia.