bluuebunny/crossref_metadata_2025_split huggingface dataset:
The apolipoprotein E ε4 allele‐dependent relationship between serum lipid levels and cognitive function: A population‐based cross‐sectional study
Authors: Wei Shan , Gao Ling , Jiang Yu , Shang Suhang , Chen Chen , Dang Liangjun , Wang Jin , Huo Kang , Wang Jingyi , Qu Qiumin 
Published: December 2020

AbstractBackgroundTill now, the effect of serum lipid levels on cognitive function is still controversial. The apolipoprotein E ε4 (APOE) allele is the most critical genetic risk factor for Alzheimer’s disease and cognitive impairment. Additionally, APOE ε4 allele has a major impact on lipid metabolism. The aim of this study was to investigate the APOE genotype‐dependent relationship between peripheral serum lipid levels and cognitive impairment.Method1273 subjects aged 40‐86 years participated in this cross‐sectional study. Serum lipid levels and the APOE genotype were detected. Mini‐mental state examination was used to diagnose the cognitive impairment or not. Univariate and multivariate analyses were used to analyze the relationships between APOE genotype, serum lipid levels and cognition function.ResultAfter controlling for all possible covariates, a significant interaction between low serum high density lipoprotein and the APOE ε4 allele on cognitive impairment (Wald's chi‐square=4.269, df=1, OR=20.094, p=0.039) (Table 1) was found in the total participants. In APOE ε4 carriers, low serum high density lipoprotein was positively associated with cognitive impairment (Wald's chi‐square=8.200, df=1, OR=60.335, p=0.004) (Table 2), and serum high density lipoprotein levels were positively correlated with Mini‐mental state examination score (r=0.217, df=176, p=0.004). There was no significant correlation between serum total cholesterol, low‐density lipoprotein, triglycerides levels and cognitive impairment in either the total participants or APOE ε4 carriers/non‐carriers. (Figure 1).ConclusionAPOE ε4 carriers, but not non‐carriers, with lower serum high‐density lipoprotein had a higher prevalence of cognitive impairment and a lower Mini‐mental state examination score. These results suggest that the APOE ε4 allele may affect the relationship between serum lipid levels and cognitive impairment. However, the specific mechanism needs to be further elucidated.
Scoping review of current state of the literature on the impact of music on symptoms of Alzheimer’s disease
Authors: Colverson Aaron 
Published: December 2020

AbstractBackgroundAcross the globe, researchers, clinicians, and caregivers are continuing to search for solutions to the myriad problems caused by Alzheimer’s disease and related dementias (ADRDs). Music is an area of focus receiving considerable attention for its potential benefits to help manage the effects of neuropsychiatric symptoms upon individuals living with ADRDs. However, attention is lacking on the potential social value of music to positively influence quality of life for both individuals living with dementias and their surrounding communities. This scoping review compiles recent reports on this potential, highlighting the social nature of music and its various uses (e.g. listening, making) to change the often tense and reactive atmosphere surrounding both the individuals living with ADRDs and their surrounding communities into comparatively joyous living environments. Databases used included PubMed, EBSCOhost’s CINAHL and PsychINFO, Cochrane Library (sub‐search conducted using ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG)), ProQuest’s Biological Science Collection, the Journal of Music Therapy and Nordic Journal of Music Therapy, and Google Scholar. After screening for eligibility and inclusion, 26 documents were identified, including review articles, experimental studies, recommendations, pilot studies, conference proceedings, book chapters, and executive summaries. Overall, this review concludes that music can facilitate prosocial engagement between persons living with ADRDs and their surrounding communities, due to a complex interplay of neurobiological mechanisms largely preserved in the ADRD population. More well designed and well controlled empirical studies are necessary to clarify contexts in which music and its various uses may be helpful to improve quality of life for both the individuals suffering from ADRDs and their surrounding communities. Such results would provide further evidence‐based support for the use of music to strengthen both formal and informal patient‐centered care models.
Entorhinal tau is associated with increased hippocampal activation and memory deficits in Alzheimer’s disease
Authors: Richter Nils , Bischof Gerard N. , Dronse Julian , Nellessen Nils , Neumaier Bernd , Langen Karl‐Josef , Drzezga Alexander , Fink Gereon R. , van Eimeren Thilo , Kukolja Juraj , Onur Oezguer A. 
Published: December 2020

AbstractBackgroundTo date, it remains unclear how the hallmark pathological changes of Alzheimer’s disease (AD), amyloid plaques, and neurofibrillary tangles, affect neuronal activity and, consequently, cognition. In cognitively normal aging, it appears that tau accumulation may drive hippocampal hyperactivity, however, studies investigating this association in AD are sparse.MethodPatients with mild cognitive impairment (MCI) or mild dementia due to AD (n = 15) underwent positron emission tomography with the tracer [18F]‐AV‐1451, which binds to tau accumulation, and performed a visual item memory task during functional magnetic resonance imaging.ResultEntorhinal tau accumulation was highly correlated with memory‐related hippocampal activation. Greater tau accumulation and hippocampal activation were negatively correlated with memory performance. Neural activation in other task‐related structures was not correlated with local or global tau accumulation.ConclusionSimilar to observations in cognitively healthy aging, entorhinal tau accumulation is closely associated with hippocampal hyperactivity and impaired memory performance in MCI and mild dementia. Interestingly, this association is specific for medial temporal lobe structures.
Functional connectivity is associated with tau spreading in dementia with Lewy bodies
Authors: Schumacher Julia , Gunter Jeffrey L. , Przybelski Scott A. , Jones David T. , Graff‐Radford Jonathan , Savica Rodolfo , Schwarz Christopher G. , Senjem Matthew L. , Jack Clifford R. , Lowe Val J , Knopman David S. , Fields Julie A. , Kremers Walter K. , Petersen Ronald C. , Graff‐Radford Neill R. , Ferman Tanis J. , Boeve Bradley F. , Thomas Alan J. , Taylor John‐Paul , Kantarci Kejal 
Published: December 2020

AbstractBackgroundDementia with Lewy bodies (DLB) is neuropathologically defined by the presence of α‐synuclein aggregations, but many DLB cases show significant Alzheimer’s disease (AD) pathology in the form of β‐amyloid and tau. Our first objective was to investigate the effect of AD co‐pathology on functional network failure in DLB. Secondly, we studied how the distribution of tau relates to functional connectivity in DLB.MethodTwenty‐three DLB, 23 age‐ and sex‐matched AD, and 90 cognitively unimpaired (CU) participants underwent AV1451 tau‐PET, Pittsburgh compound‐B (PiB) PET, and resting state (rs)‐fMRI scans. The rs‐fMRI data were used to calculate the Network Failure Quotient (NFQ), a marker of functional network failure within the default mode network. The NFQ was then correlated with overall cortical tau standardized uptake value ratio (SUVr). The strength of inter‐regional functional connectivity was assessed using the Schaefer100 atlas. Tau‐PET covariance was measured as the correlation in AV1451 SUVr between any two regions across participants. The association between region‐to‐region functional connectivity and tau‐PET covariance was assessed using linear regression. Additionally, we identified the region with highest and the region with lowest tau SUVrs (tau hot‐ and coldspot) and tested whether tau SUVr in all other brain regions was associated with the strength of functional connectivity to these tau hot‐ and coldspots.ResultOverall higher cortical tau‐PET uptake correlated with higher NFQ (i.e. greater functional network failure) in DLB who were PiB+ (N=14, ρ=0.60, p=0.02), but not in DLB who were PiB‐ (N=9, ρ=‐0.06, p=0.87). Higher functional connectivity between regions was associated with higher tau covariance in CU, AD, and DLB, independent of PiB status. Higher functional connectivity of a target region to the tau hotspot (i.e. inferior/medial temporal cortex) was related to higher AV1451 SUVRs in the target region whereas higher functional connectivity to the tau coldspot (i.e. sensory‐motor cortex) was related to lower AV1451 SUVr in the target region.ConclusionGreater tau burden in DLB patients with β‐amyloid co‐pathology is associated with an AD‐like functional network failure. As previously demonstrated within the AD spectrum, functional connectivity may contribute to the spreading of tau across the brain also in DLB.
Understanding metaphor comprehension in Alzheimer disease: An N400 study
Authors: Dikmen Merve , Karakulak Ece Zeynep , Aygüneş Mehmet , Hanoğlu Lutfu 
Published: December 2020

AbstractBackgroundIn clinical routine and research, abstract thinking difficulties are often tested by assessing the Alzheimer disease (AD) patient’s ability to understand nonliteral languages. The goal of the present study was to test more specifically the processing of metaphors in AD patients to establish links between clinical observations and measures of brain activity.MethodParticipants: Twelve right‐handed Alzheimer disease (AD) patients and eleven right‐handed healthy volunteers took part in the study. Healthy vounteers were matched with the patients on age and academic level. All of the participants were right‐handed, corrected‐to‐normal vision, and native speakers of Turkish. EEG recording; Brain Vision Analyzer 2.1 Software (Brainproducts, Munich, Germany) was used for EEG data processing. 13 channels EEG active electrodes were placed on a cap (Acticap, Germany) according to the international 10‐20 system (Fp1, Fp2, F3, Fz, F4, C3, Cz, C4, P3, Pz, P4). Electrode impedance was maintained at below 10 kΩ. EEG was amplified and digitized at a sampling frequency of 500 Hz (BrainAmp). The continuous EEG was filtered off‐line with a band pass filter of 0.01‐15 Hz filter. Epochs of interest were selected time‐locked to the target stimulus onset (−200 to 1200 ms) and baseline correction was applied ‐200 to 0 ms. We measured the amplitude of N400 time locked to the onset of critical word, which was also the sentence final‐word.ResultRepeated measure ANOVA with three repeated variables: 3(electrode site:frontal/central/parietal) 3(electrode laterality: left/middle/right) 4(condition: literal/ conventional/ novel/anormal) and one between variable (group: AS/control) revealed no significant main effect of group, F(1, 21) = 2.596, p > .05. Condition effect was significan F(3,63) = 3.193, p < .05. Moreover, condition type by group interaction was significant F(1,21) = 5.565, p < .05. The pattern of N400 elicited for the only conventional metaphor was different between the two groups.ConclusionLarge N400 amplitudes for conventional metaphors demonstrated the difficulties in metaphor comprehension in the AD participants as compared to controls. Findings suggest that differences in linguistic information processing cause difficulties in metaphor comprehension in AD. This study was supported financially by the Scientific and Technological Research Council of Turkey (TÜBİTAK; project number: 117S470).
Everyday life priorities and health care preferences of patients living with dementia or cognitive impairment: A systematic review
Authors: Wehrmann Hannah , Raedke Anika , Hoffmann Wolfgang , Michalowsky Bernhard 
Published: December 2020

AbstractBackgroundGaining knowledge about priorities and preferences of people living with dementia (PwD) might help to individualize and to increase the adherence of treatment and care, both could improve patient‐related outcomes. Therefore, the aim of this study was to systematically identify and summarize preferences of PwD or mild cognitive impairment, considering all relevant aspects of healthcare and daily living.MethodsA systematic review of patient preference studies was conducted to assess needs, priorities, and preferences of PwD or mild cognitive impairment using Pubmed and Science Direct. The inclusion criterion was that preferences were elicited directly by PwD. Of 1,103 studies, only 40 met this inclusion criterion. The ICHOM (International Consortium for Health Outcomes Management) value set for dementia was used to systematize the reported preferences of PwD as follows: (a) clinical status, (b) symptoms, functioning and quality of life, (c) and sustainability.ResultsTwelve studies revealed preferences pertaining to PwDs’ clinical status (a), highlighting that patients prefer to be informed about the diagnosis as early as possible for anticipatory planning of care. Most patients do not want to receive resuscitation, forgoing antibiotics are accepted. In addition, preferences are altruistic: PwD rank being no burden to others higher than being cured. Further, 25 studies reported preferences concerning PwDs’ symptoms, functioning and quality of life (b), demonstrating that PwD are eager to participate in health‐related decisions, especially in decisions about social life and particularly conjointly with their caregivers. Quality of life, patient self‐efficacy and emotional wellbeing were preferred most. Furthermore, institutionalized PwD prefer individualized and person‐centered care, which is commonly missing in nursing homes. Only, three studies elaborated preferences for sustainability (c), revealing that PwD less likely to prefer residential care as compared to persons without dementia.ConclusionA multiplicity of studies about patient preferences in dementia was found, that provide useful insights into the patient, which are not always taken into consideration, yet. Future interventional studies should examine whether including these preferences into treatment and care or daily living might improve their outcomes.
Understanding and improving the experience of care for people with dementia in hospital: Developing the dementia care pointers for service change
Authors: Thompson‐Coon Jo , Abbott Rebecca A , Lourida Ilianna , Gwernan‐Jones Ruth , Rogers Morwenna , Cheeseman Debbie , Moore Darren , Green Colin , Ball Sue , Clare Linda , Llewellyn David J , Hemsley Anthony , Burton Julia , Lawrence Sue , Rogers Martyn , Hussey Chrissy , Coxon George , Naldrett Tina 
Published: December 2020

AbstractBackgroundBeing in hospital can be particularly confusing and challenging not only for people living with dementia, but also for their carers and the staff that care for them.MethodWe undertook three systematic reviews of quantitative and qualitative evidence according to best practice guidelines. The reviews explored: 1) experience of care in hospital; 2) experience of interventions to improve care in hospital; and 3) effectiveness and cost ‐effectiveness of interventions to improve the experience of care in hospital for people living with dementia, their carers and staff. Links between the findings from the three reviews were explicitly identified through the creation of a conceptual map. The overarching messages and their implications were discussed with key stakeholders. An advisory group of dementia specialists, hospital staff, commissioners and family carers advised us throughout the project. PROSPERO registration CRD42018086013ResultOur reviews show that the experience of care in hospital for people living with dementia is a dynamic process, being impacted by a complex range of personal, institutional and environmental factors. Despite the intent to deliver person centred care, and armed with the knowledge of how important this is, person centred care is still not happening consistently within hospitals. The effect of this is not only a poorer experience of care for people living with dementia and their carers, but also has a detrimental effect on staff emotional well‐being as a result of not being able to give the care they strive to provide. We highlight 12 institutional and environment practices and processes (Pointers for Service Change) that warrant consideration for those aiming to improve the experience of care in hospital for people living with dementia, their carers and staff.ConclusionEvidence suggests that although people living with dementia can have a good experience of care in hospital, this is still not happening for many. When staff cannot provide the care they would like to give, this has a negative effect on people living with dementia, their carers and the staff themselves. Further research needs to identify how best to change ward cultures, and how to maintain these changes in the long‐term.
Synaptic vesicle protein SV2A imaging with [11C]UCB‐J as a novel biomarker of neurodegeneration in Alzheimer's disease
Authors: Bendlin Barbara B , DiFilippo Alexandra H , Betthauser Tobey J , Chin Nathaniel A , Murali Dhanabalan , Vogt Nicholas M , McKinney Grace , Davenport Nancy J , Barnhart Todd E , Engle Jonathan W , Johnson Sterling C , Christian Bradley T 
Published: December 2020

AbstractBackgroundSynaptic loss is a known feature of symptomatic Alzheimer’s disease (AD). Conversely, abundance of synapses may confer resilience to cognitive decline in the presence of AD pathology. Currently, the extent and distribution of synapse loss during the asymptomatic stages of AD is unknown. Synaptic vesicle glycoprotein 2A (SV2A) is found on synaptic vesicles and recent developments in PET imaging provide the capability of assessing SV2A in vivo. [C‐11]UCB‐J is a high‐affinity ligand for SV2A currently being tested as a biomarker of neurodegeneration in AD. In this project, we are testing the extent to which loss of synaptic density tracks with cognitive decline, as well as determining the temporal course of synaptic loss in relation to development of regional amyloid and tau pathology, particularly in the asymptomatic phase of AD.MethodApproximately 120 participants from the Wisconsin Alzheimer’s Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer’s Prevention study will be imaged in this study. Participants include cognitively unimpaired biomarker negative, unimpaired biomarker positive, mild cognitive impairment (MCI), and dementia due to AD. Amyloid (A) and tau (T) status are determined via [C‐11]PiB and [F‐18]MK6240 PET imaging, while synaptic density is determined with [C‐11]UCB‐J.ResultEarly results indicate lower synapse density in AD dementia and among A+T+ even in the asymptomatic phase of AD (Figure). However, participants with dementia show greater regional loss of synapses compared to cognitively unimpaired A+T+.ConclusionOngoing analyses will test the extent to which severity of amyloid and tau accumulation are associated with synapse loss, and whether synaptic abundance is a correlate of preserved cognition in the context of lesion burden. Imaging with [C‐11]UCB‐J may provide improved prognostic precision in the context of AD.
[11C]MPC‐6827, a microtubule‐based PET imaging tracer: A potential early imaging biomarker for AD and other ADRDs
Authors: Sai Kiran Solingapuram , Damuka Naresh , Mintz Akiva , Whitlow Christopher T. , Craft Suzanne , Macauley‐Rambach Shannon 
Published: December 2020

AbstractBackgroundLoss of microtubule (MT) network and impairment of MT function are considered to be part of the pathophysiology of several CNS disorders, including AD, Parkinson disease and other ADRS and tauopathies. A BBB penetrating MT‐based PET ligand would permit imaging a variety of CNS disorders. Our lab reported the first brain‐penetrant PET radiotracer [11C]MPC‐6827 to image MTs in vivo, in both wild and transgenic AD mice. Here, we report a pilot longitudinal [11C]MPC‐6827 PET imaging study with early, middle and late stages of Aβ and tau progression in APP/PS1 and P301S mice respectively. PET imaging in NHP brains was performed to test translational utility.MethodDynamic brain microPET/CT imaging was performed with [11C]MPC‐6827 in APP/PS1 mice at 3, 18 and 22 months and in P301S mice (n=4) at 5, and 10 months. Regions of interest (ROIs) were drawn in whole brain, cortex, cerebellum and hippocampus and time‐activity curves (TACs) were determined. Basic distribution volume ratios (DVRs) between high‐ and low‐uptake regions were calculated. Dynamic 2h PET/CT imaging was performed in adult male vervet monkeys (n=8).ResultBased on ROIs and TACs in whole brain, cortex and hippocampus, the radioactive uptake of 3 month‐old TG APP/PS1 mice was ∼30% higher compared to the uptake at 18 months, which in turn was ∼18% higher over 22 month‐old mice. Radioactive uptake of TG P301S mice at 5 months was ∼24% higher compared to 10‐month old mice. DVRs from cortex and hippocampus to cerebellum were ∼2‐fold higher in younger APP‐PS1 and P301S mice compared to their older littermates. Radioactive changes in all experiments were statistically significant, substantiating our preliminary imaging data. NHP‐PET brain analyses indicated brain penetration and high retention of the tracer.Conclusion[11C]MPC‐6827 demonstrated decreased radioactive uptake with increased brain Aβ and tau loads. A MT‐based PET imaging tracer could be a potential early imaging biomarker for AD and other ADRDs. PET imaging studies in monkey brains showed high BBB penetration. Binding distribution is in good agreement with the known MT‐mice distribution. Next steps are to correlate radioactive uptake with tau pathologies and in an NHP model of AD.
Head direction cells in the TgF344‐AD rat model of Alzheimer's disease
Authors: Berkowitz Laura E. , Harvey Ryan E. , Clark Benjamin J. 
Published: December 2020

AbstractBackgroundSpatial navigation is impaired in the early stages of Alzheimer’s disease (AD) and may be a defining behavioral marker of preclinical AD. Head direction (HD) cells are cortical‐limbic neurons that discharge action potentials as a function of an animal’s spatial orientation in an environment. HD cells can maintain their orientation across repeated test sessions, in reference to salient landmarks, and are thought to play a critical role in guiding accurate spatial behavior. Thus, we tested the hypothesis that impairments in HD cell stability would be apparent in AD.MethodsTo test this hypothesis, we used the TgF344‐AD rat model of AD which exhibits progressive pathology in cortical‐limbic regions. Previously, we found that 10 month old TgF344‐AD rats make progressively fewer spatially and directionally precise movements during navigation. Thus, HD cells were characterized in the posterior cortex (retrosplenial, postsubiculum, and visual association area 2) and the anterior thalamus of 10 ‐ 13 month TgF344‐AD rats and age matched F344 controls. Rats performed a pellet chasing task within a cylinder fitted with a white cue card during recordings. In some sessions, the cue card was rotated to assess landmark control.ResultsHD cells were identified and were found to exhibit similar directional firing characteristics between TgF344‐AD and F344 groups. Further, we found that HD cells in TgF344‐AD rats demonstrated intact responses to cue manipulations. In contrast, we observed that HD cells exhibited more variability and instability in their directional orientation across repeated test sessions.ConclusionsThese results support the hypothesis that deficits in the stability of HD cells may underlie spatial impairments in AD.