bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between an abbreviated CAIDE score and amyloid chronicity
Authors: Erickson Claire M , Koscik Rebecca L , Cody Karly Alex , Mueller Kimberly D , Chin Nathaniel A , Clark Lindsay R , Christian Bradley T , Betthauser Tobey J , Johnson Sterling C 
Published: December 2020

AbstractBackgroundEfforts to quantify dementia risk have led to the development of indices that include health factors, like the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) index. Prior studies demonstrate that higher CAIDE is associated with cognitive decline and neurodegeneration. Few studies have analyzed the association between CAIDE and Alzheimer’s disease (AD)‐related pathophysiology, like beta‐amyloid. Recent studies suggest that duration of beta‐amyloid positivity (amyloid chronicity) is associated with cognitive decline. It is unclear whether health factors contribute to the onset of beta‐amyloid accumulation. This study examines the relationship between the three cardiovascular components of the CAIDE score and amyloid chronicity as assessed by [C‐11]PiB PET imaging.MethodParticipants (n=272; Table 1) from the Wisconsin Registry for Alzheimer’s Prevention were included in this study based on the availability of PiB‐PET imaging data, APOE information, and cardiovascular CAIDE components (total cholesterol, BMI, and systolic blood pressure; CAIDE range 0‐3). Based on observed stability of CAIDE scores (Figure 1), a within‐person average was used in linear regression models assessing whether average CAIDE was associated with amyloid chronicity (calculated as last CAIDE assessment age – estimated age PiB(+)) or estimated age of PiB(+) onset (sensitivity analysis).ResultThe median average CAIDE was 0.4 (1st and 3rd quartiles = 0 and 1 CAIDE, respectively). The mean(SD) age of last PiB scan and last CAIDE ages were 66.55(6.74) and 66.53(6.45), respectively. After adjusting for covariates (education, sex, APOE status, last scan age), CAIDE score was not associated with amyloid chronicity (beta=‐0.47; p=0.74). Sensitivity analyses examining amyloid onset and amyloid positivity since last scan were consistent with our primary analysis. In secondary analyses, we found that CAIDE did not modify associations between APOE status and amyloid chronicity at time of last CAIDE (beta=‐0.28; p=0.87; see Table 2 for full model output).ConclusionOur results suggest that peripheral measures of vascular health do not relate to beta‐amyloid duration in a relatively healthy sample. These results add to recent findings suggesting the independent pathways leading to cognitive decline for vascular factors and amyloid. In the future, we will probe the relationship between health factors, AD‐related pathology, and cognition.
Agents of change: Establishment of quality improvement collaboratives to improve the quality of dementia care in Australia
Authors: Laver Kate , Cations Monica , de la Perrelle Lenore , Radisic Gorjana 
Published: December 2020

AbstractIntroductionThe quality of dementia care in Australia is dependent on the clinician involved and the extent to which they apply best available evidence. The Clinical Practice Guidelines for Dementia in Australia (the Guidelines) provided comprehensive guidance for clinicians about best practice for people with dementia and their care partners. Dissemination of guidelines is generally insufficient alone to achieve tangible improvements in practice.MethodThe Agents of Change project is an implementation research study that aims to improve clinician adherence to three key recommendations from the Guidelines. The clinicians participated in a training program and were supported to develop a quality improvement plan unique to their service context. Clinicians met regularly with their QIC to facilitate benchmarking and problem‐solving, and updated their plan iteratively using plan‐do‐study‐act cycles. The primary outcome was guideline adherence which was tracked over a period of 18 months.ResultsThe majority of the participating clinicians were highly experienced and leaders within their service. Adherence to the specified guidelines increased steadily over time with an overall increase of 42% adherence. Increases in adherence over time were steady suggesting that each element of the quality collaborative intervention contributed to increased guideline adherence. There was great interest in joining the collaborative and few withdrawals over the duration suggesting an appetite from clinicians to be involved in this type of initiative.ConclusionsAgents of Change is an innovative translational research project highlighting key elements of collaborative quality improvement efforts among clinicians working with people with dementia and their supporters.
Frailty trajectory related to Alzheimer’s dementia after controlling for neuropathological burden
Authors: Wallace Lindsay MK , Theou Olga , Godin Judith , Andrew Melissa K , Bennett David A , Rockwood Kenneth 
Published: December 2020

AbstractBackgroundFrailty is an established risk factor for cognitive decline and Alzheimer’s disease. Changes in frailty have been associated with adverse health outcomes including mortality, health service use, institutionalization, and disability. Few studies have examined the longitudinal relationship between frailty and cognition. Here, we use data from a longitudinal clinical‐pathologic cohort study to extend this work and examine longitudinal change in frailty, how it is influenced by sex, neuropathology, and Alzheimer’s dementia.MethodParticipants of the Rush Memory and Aging project (n=443, 69.3% female, 83.1±5.9 years of age at baseline) underwent annual clinical evaluations (average 5.3±3.5 years of follow‐up) followed by post‐mortem neuropathologic assessment. A frailty index was constructed from 41 health variables at each annual study evaluation. Alzheimer’s dementia was determined (blinded to neuropathological data) at time of death. Age, sex, and education, and neuropathological burden (10‐item index including amyloid load, neurofibrillary tangle density, TDP‐43, hippocampal sclerosis, cerebral amyloid angiopathy, gross infarcts, gross chronic infarcts, atherosclerosis, arteriolosclerosis, and presence of Lewy bodies) were evaluated as covariates. Frailty trajectories were calculated using a mixed effects model.ResultFrailty increased linearly at a rate of 3% per year on average. Higher baseline frailty was associated with being female (F(1)=22.45, p<0.0001), but not with neuropathological burden (p=0.25) or having Alzheimer’s dementia at death (p=0.142). Frailty trajectories differed as a function of sex, neuropathological index, and Alzheimer’s dementia status; specifically, female sex (p=0.04), higher neuropathological burden (p<0.0001), and Alzheimer’s dementia (p<0.0001) were associated with accumulating deficits at a significantly faster rate.ConclusionFindings suggest a strong link between health status as measured by a frailty index and Alzheimer’s dementia, after controlling for neuropathology. Frailty trajectories over 18 years in older adults predicted dementia risk, underscoring the importance of frailty intervention and management in later life.
Hippocampal subfield volumes on 7T MRI in normal cognition, subjective memory impairment, and early Alzheimer’s disease
Authors: Blom Kim , Koek Huiberdina L , Zwartbol Maarten H.T. , Biessels Geert Jan , Geerlings Mirjam I. 
Published: December 2020

AbstractBackgroundThe hippocampal formation is considered to be one of the first brain structures affected in Alzheimer’s disease. High resolution brain MRI has made it possible to visualize the subfields of the hippocampal formation in greater detail. We estimated volumes of hippocampal subfields on 7T MRI in normal aging and early Alzheimer’s disease. We hypothesized that the subfields were differentially affected in normal cognition, subjective memory impairment, Mild Cognitive Impairment (MCI) and Alzheimer’s disease.MethodWe included 336 participants (68±9 years; 35% women) from memory clinics and from existing cohorts (SMART‐MR study and PREDICT‐MR study), and participants without dementia and MCI recruited from medical files from general practices, all of whom had 7T brain MRI using the same scan protocol. Using ASHS, hippocampal subfields (entorhinal cortex, subiculum, CA1, CA2, CA3, CA4/dentate gyrus, and tail) were segmented. Participants were categorized as having normal cognition (n=175), subjective memory impairment (n=66), cognitive impairment or MCI (n=75), and Alzheimer’s disease (n=20). General linear models with multivariate outcomes (Z‐scores of hippocampal subfield volumes) were estimated across cognitive groups, and adjusted for age, sex and intracranial volume.ResultIn the total study sample, subfield volumes (left and right hemisphere summed) (mm3) were 817±167 for entorhinal cortex, 1143±181 for subiculum, 2923±382 for CA1, 117±23 for CA2, 195±47 for CA3, 1547±245 for CA4/DG, and 284±69 for the tail. Compared to all other groups, Alzheimer’s disease patients had significantly smaller subfield volumes (p<0.05 for all subfields). Participants with cognitive impairment or MCI had smaller CA1 and CA4/dentate gyrus (p<0.05), compared to normal cognition, but not other subfields. Participants with subjective memory impairment did not differ significantly from the group with normal cognition (Figure 1).ConclusionThis study suggests that in MCI the CA1 and CA4/dentate gyrus are primarily affected, and that all hippocampal subfields are progressively affected in Alzheimer’s disease. No volume loss was observed in participants with subjective memory impairment, potentially due to inclusion of participants with etiologies other than Alzheimer’s disease.
Results from a pilot study: The effects of nicotinamide riboside on mild cognitive impairment
Authors: Orr Miranda E. , Kotkowski Eithan , Bair‐Kelps Darcy , Romo Terry , Espinoza Sara , Musi Nicolas , Powers Becky ,   San Antonio Claude D. Pepper Center
Published: December 2020

AbstractBackgroundNicotinamide adenine dinucleotide (NAD+) is a critical coenzyme in cellular metabolism. NAD(+) levels decrease with aging. Experimentally boosting NAD(+) improves cognitive function and synaptic plasticity in Alzheimer's disease mouse models. NAD(+) can be synthesized from dietary intake of its precursors, including nicotinamide riboside (NR), a readily available non‐prescription nutritional supplement. Recent studies have demonstrated that dietary NR increases blood NAD(+) levels in healthy older adults. We hypothesize that NR supplementation will positively affect brain function in older adults with mild cognitive impairment (MCI).MethodPhase 2 randomized, double‐blind, placebo‐controlled trial with a 10‐week treatment period. Adults aged ≥65‐years‐old with a prior diagnosis of normal cognition [Montreal Cognitive Assessment (MoCA) score 26‐30] or MCI (MoCA score of 21‐25) participated at UT Health San Antonio. Dose escalation with NR over a 4‐week period was used to reach 1g/day, or maximum tolerated dose, for the final 6 weeks of the study. The primary outcomes were change from baseline on the MoCA and hippocampal blood flow as assessed by functional MRI (fMRI). Secondary outcomes included psychometric and frailty measures. Levels of blood NAD(+) and metabolites were determined at baseline and at the end of the study.ResultBaseline levels of NAD(+) did not significantly differ between MCI and control groups (21.4 ± 0.75 versus 19.3 ± 2.04μM, mean ± SEM, MCI and control, respectively; p = 0.24). NR was well tolerated and significantly increased blood NAD(+), NAAD, and Me4PY (log2fold change: 1.2, 2.6, 3.3, respectively; p < 0.0001). NR treatment was associated with positive functional changes in the brain and frailty measures, but changes in cognitive measures were not observed.ConclusionA 10‐week supplementation of NR was well tolerated and significantly increased NAD(+) and associated metabolites in the blood of older adults with MCI. NR improved fMRI and physical function, our primary and secondary outcome measures, respectively. However, differences in cognition were not achieved in this small pilot study. Our results provide supporting evidence for further testing of NR as a method to maintain brain structure and function in older adults with MCI.
An RCT to identify best practices for disclosure of amyloid imaging results in mild cognitive impairment: The ABIDE simulation study
Authors: Fruijtier Agnetha D , van Maurik Ingrid S , Scheltens Philip , Bouwman Femke , Pijnenburg Yolande AL , Ebenau Jarith , Van Berckel Bart NM , Smets Ellen M , van Der Flier Wiesje , Visser Leonie NC 
Published: December 2020

AbstractIntroductionConcerns about Mild Cognitive Impairment (MCI) patients’ understanding of disclosure of amyloid‐positive status and the emotional impact of this complex message have resulted in disclosure‐frameworks based on expert opinion. To date, evidence lacks which communication strategy works best. Our study aimed to empirically study the effectivity of six different communication strategies on patients’ understanding, and emotional state when receiving a positive amyloid status.MethodsWe performed a Randomized Controlled Trial with an online video‐vignette design [3,4]. Communication strategies were varied across otherwise standardized, enacted videotaped consultations. Healthy individuals aged > 50, instructed to imagine themselves in the situation of the video‐patient [5], were randomly assigned to one of seven conditions: 1) Control, 2) Non‐specified risk, 3) Explicit PET‐scan and Alzheimer’s disease information, 4) Showing the PET‐scan, 5) Risk best‐practice, 6) Emotional response, and 7) The teach‐back. Questionnaires measuring emotional state (PANAS) and anxiety (STAI) were administered prior to‐ (T0) and directly after viewing the vignette (T1). The T1 questionnaire contained questions assessing information recall (coding of open‐ended questions is currently ongoing), information recognition (multiple‐choice), behavioral intentions, uncertainty, trust in the clinician, and satisfaction.ResultsWe included 1017 participants (table 1). We found differences between conditions on information recognition (P=.001, figure 1A), uncertainty (P=.000, figure 1B), trust in the physician (P=.008, figure 1C), and satisfaction (P=.000, figure 1D). Information recognition (P=.046), and satisfaction (P=.013) were highest in the emotional response condition. Risk‐best practice led to higher uncertainty (P=.000), yet trust in the clinician was higher when risk‐estimate was mentioned (control‐condition), compared to no mention of a specified risk‐estimate (P=.017). Satisfaction was best in the emotional response condition (P=.013).ConclusionThis is the first study to provide empirical evidence of best strategies for disclosure of amyloid PET to MCI patients. Disclosing a positive amyloid PET result with risk information does not increase negative emotions and anxiety, although it enhances feelings of uncertainty. Actively attending to emotions after providing risk information results in enhanced recognition of information, trust in the clinician, and satisfaction. We can use these results to inform an evidence‐based practice recommendation for amyloid disclosure in a clinical setting.
The association between white matter hyperintensity shape and cognitive functioning: The SMART‐MR study
Authors: Zwartbol Maarten H.T. , Ghaznawi Rashid , Jaarsma‐Coes Myriam , Kuijf Hugo J. , Hendrikse Jeroen , de Bresser Jeroen , Geerlings Mirjam I. 
Published: December 2020

AbstractBackgroundWhite matter hyperintensities (WMHs) are associated with cognitive decline and increased risk of dementia, including Alzheimer’s disease. However, the association between WMH and cognitive functioning is weak, presumably due to heterogeneity of the underling WMH pathology. Recently, WMH shape has been related to the severity of the underlying pathology and, compared to volume, may provide a novel metric for WMH burden. We examined the relationship between WMH volume, shape and cognitive functioning in patients with arterial disease. We hypothesized that WMH shape was related to cognitive functioning, independent of WMH volume.MethodsIn the SMART‐MR study, we performed cross‐sectional analyses in 563 patients (58±10 years) with available brain MRI and data on cognitive functioning. WMH volume and shape were automatically determined on MRI data. Linear regression analyses were used to estimate the association between Z‐scores of WMH volume, WMH shape features (concavity index, solidity, convexity, fractal dimension and eccentricity) and Z‐scores of cognitive functioning, adjusted for age, sex, education, and reading ability.ResultsA larger WMH volume was associated with poorer executive functioning (b=0.09; 95% CI ‐0.17 to ‐0.01; p=0.02), but not memory functioning. A more complex shape of periventricular/confluent WMH was associated with poorer executive functioning (concavity index: [b=‐0.13; 95% CI ‐0.20 to ‐0.06; p <0.0001]; solidity: [b=0.09; 95% CI 0.02 to 0.17; p=0.014) and poorer memory scores (fractal dimension: b=‐0.10; 95% CI ‐0.18 to ‐0.02; p=0.02). Moreover, the association between WMH shape measured by the concavity index and executive functioning was independent of WMH volume (b=‐0.12; 95% CI ‐0.19 to ‐0.04; p=0.003). Figure 1 presents an example of two patients with similar WMH volume but a 2.7 standard deviation difference in concavity index.ConclusionsA more complex shape of WMH shape was associated with poorer cognitive functioning. Our results suggest that WMH shape contains additional information about WMH burden, not otherwise captured by WMH volume.
Diabetes can increase risk for developing abnormal cognition
Authors: Li Wei , Wang Ge 
Published: December 2020

AbstractBackgroundDiabetes has been shown as a risk factor for cognitive impairments. However, it is still not clear about the time course of developing abnormal cognition in these with diabetes especially if the morbidity accelerates the cognitive deterioration process.MethodA retrospective analysis was performed using data collected by the National Alzheimer’s Coordinating Center. Incidence, prevalence and age at onset (AAO) of either mild cognitive impairment (MCI) or dementia were compared between participants with and without diabetes.ResultDuring a follow‐up period of more than 10 years, the diabetic group had a higher incidence and prevalence of MCI or dementia than the non‐diabetic group. However, the AAO of either MCI or dementia was independent of the diagnosis of diabetes.ConclusionAlthough diabetic patients have a higher incidence and prevalence of abnormal cognition than those without diabetes, diabetes does not accelerate the cognitive deterioration process.
BSI whole‐brain volume change estimation initialised with fully automatic LEAP segmentation
Authors: Joules Richard , Wolz Robin 
Published: December 2020

AbstractBackgroundWhole brain atrophy as measured from T1‐wieghted MR images is a key biomarker for progression in Alzheimer's disease (AD) and employed as marker for treatment efficacy in clinical trials. The Boundary Shift Integral (BSI) methodology (Freborough;IEEE;1997) is the widely established standard and well validated method for volume change. BSI requires initialisation with a whole‐brain segmentation at both timepoints, manual segmentations remain the gold standard, however the BSI approach is robust to minor segmentation, potentially facilitating the use of automatic segmentation approaches. Furthermore, to improve sensitivity to volume change and exploit the probabilistic nature of many automatic segmentations a generalised form of the BSI (gBSI) pipeline has been proposed (Prados;NeurobiolAging;2015). The use of a fully automatic pipeline to estimate volume change provides a scalable solution for clinical trial deployment without the burden of manual segmentation or edits and associated variability introduced. Here we assess the use of LEAP (Ledig;ProcISBI;2012), a fully automatic whole brain segmentation tool providing both binary and probabilistic parcellations, to initialise the BSI, as implemented in MIDAS, and gBSI pipelines.MethodWhole brain volume change over 1 year was estimated for 48 participants, acquired as part of a clinical trial, with the BSI and gBSI methods initialised with 1) manually generated whole brain segmentations and 2) automatically estimated whole brain segmentations generate with LEAP. No manual corrections were performed; all LEAP segmentations passed a visual quality control inspection.ResultFigure 1 shows the relationship between the manually initialised BSI and the fully‐automated LEAP‐BSI approach. Table 1 shows average measures of volume change across all tested methods. All measures were significantly correlated with non‐significant differences in reported mean volume change.ConclusionLEAP offers segmentations suitable for initialisation of the BSI method providing a pipeline for fully automatic volume estimation consistent with the semi‐automated BSI approach, providing a scalable solution for clinical trial deployment without the associated variability and resource burden required for fully manual segmentations. Furthermore the probabilistic output of LEAP allows for the use of the gBSI methodology with the associated potential of increased sensitivity to volume change.
Pre‐screening models for patient engagement: The MOPEAD project
Authors: Boada Mercè , Winblad Bengt , Jessen Frank , Visser Pieter Jelle , Kramberger Milica G. , Rodrigo Adrián , Simó Rafael , Rodriguez Octavio , Sannemann Lena , Bon Jaka , Zwan Marissa D. , Alegret Montserrat , Sanabria Angela , Rosende‐Roca Maitee , Krivec David , Jamilis Laura , Trigueros Paloma , Kivipelto Miia , Johansson Gunilla , Wimo Anders , Valero Sergi , Shering Craig , Glaysher Bridget , Tarraga Lluis , Dumas Annette , Georges Jean , Campo Laura 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is a devastating condition that not only impacts greatly on the patient’s health but also poses an important burden on the patient’s immediate family circle. Early detection of AD allows patients to have an active role in managing their condition, and to plan how to minimize the strain on their dear ones. Despite known benefits, a large proportion of dementia cases remains undiagnosed or receives a late stage diagnosis. The MOPEAD project aims to address this issue by exploring innovative strategies to emerge “hidden” cases of cognitive impairment.MethodMemory clinics located in five different European countries participated in the project. Four innovative pre‐screening strategies were implemented to detect cognitive decline among individuals aged 65‐85 years who had never received a dementia related diagnosis: a) a web‐based pre‐screening tool along with an online marketing campaign, b) open house initiatives where people with memory complaints were invited to receive a quick evaluation at participating memory clinics, c) a primary care‐based protocol for early detection of cognitive decline using easily administered tools, and d) a tertiary care‐based pre‐screening at diabetologist clinics specifically designed to assess risk of dementia among patients with diabetes. A positive pre‐screening result implied that individuals were at high risk of having mild cognitive impairment or AD.ResultThe number of individuals enrolled, and the proportion of those with positive pre‐screening results varied across strategies. The web‐based tool evaluated the largest number of individuals (n=1487) and yielded 547 positive results (36.8%). The Open house initiative pre‐screened 661 subjects of whom 235 (35.6%) obtained a positive result. A total of 435 patients were pre‐screened in the primary care‐based strategy and 193 of them (44.4%) were found to have a positive result. Finally, 264 patients from diabetes clinics underwent pre‐screening and 154 (58.3%) showed a positive result.ConclusionUsing innovative pre‐screening strategies, we were able to identify 1129 individuals at high risk of having dementia who had otherwise remained unnoticed. Initiatives like this, show us the way to go in order to shift the paradigm of AD towards an earlier diagnosis.