bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does loss of interaction of progranulin and prosaposin promote neurofibrillary tangle development?
Authors: Mendsaikhan Anarmaa , Tooyama Ikuo , Serrano Geidy E , Beach Thomas G , Walker Douglas G 
Published: December 2020

AbstractBackgroundProgranulin (PGRN) and prosaposin (PSAP) have lysosomal and neurotrophic properties. Reduced amounts of PGRN in mutant tau‐expressing Alzheimer’s disease (AD) model mice exacerbated phosphorylated tau pathology. The implication of PGRN in tangle formation in AD is not understood nor the association of PSAP with AD. Both features need further research.MethodFixed human brain tissue sections of middle temporal gyrus (MTG) from low plaque (LP)(n=4), high plaque (HP)(n=4) non‐demented (ND), and AD (n=4) cases, and superior frontal gyrus from a presenilin‐1 mutated case and frontal temporal lobar degeneration (FTLD) cases (n=3) with heterozygous granulin mutations were employed in this study. The interaction of PGRN and PSAP was identified with proximity ligation assay (PLA). The colocalization of PGRN and PSAP with tangle was identified by fluorescent immunohistochemistry and triple‐color confocal microscopy with antibodies to phosphorylated tau (p‐tau). PGRN and PSAP fluorescence intensity was measured in p‐tau positive neurons and compared to adjacent p‐tau negative neurons.ResultDifferent p‐tau positive structures were measured and related to the levels of PGRN and PSAP. Extracellular neuropil threads appeared to have no association with these proteins. Reduced levels of PGRN and PSAP were detected in p‐tau positive neurons compared to control neurons in all groups. Average levels of PGRN in control neurons were decreased as disease developed. In the AD group, reduced signals of these proteins were observed overall in neurons without p‐tau, and absent in fully matured neurofibrillary tangles. The levels of PGRN and PSAP negatively correlated with p‐tau immunoreactivity. The presenilin‐1 mutated case with numerous tangles in frontal cortex had absence of PGRN and PSAP in tangles, but colocalization of PGRN and PSAP was evident in adjacent neurons. FTLD cases showed absence of PGRN in most neurons, but continued expression of PSAP. The interaction of PGRN and PSAP in neurons was verified with a PLA assay.ConclusionP‐tau positive neurons had significantly less PGRN and PSAP even in the non‐demented groups, which suggests this could be an early event of tangle formation. The insufficiency of both PGRN and PSAP in neurons might lead to accumulation of p‐tau protein due to deficits in lysosomal activity.
The differentiation of new neurons is impaired in Alzheimer’s disease patients
Authors: Terreros‐Roncal Julia , Moreno‐Jiménez Elena P , Flor‐García Miguel , Llorens‐Martin María 
Published: December 2020

AbstractBackgroundAlzheimer´s disease (AD) is a devastating neurodegenerative disorder. The hippocampus, one of the brain areas primarily affected by disease progression, hosts one of the most unique phenomena that occur in the adult mammalian brain. This phenomenon, named adult hippocampal neurogenesis (AHN), encompasses the addition of new neurons throughout life, is crucial for hippocampal‐dependent learning, and confers an unparalleled degree of plasticity to the entire hippocampal circuitry. During AHN, in rodents, newborn dentate granule cells (DGCs) go through different maturation stages before acquiring the properties of a fully mature DGC. In this study, we aimed to determine whether immature DGCs at distinct maturation stages can be identified in the human dentate gyrus (DG) and whether the differentiation process of these cells is altered in AD patients.MethodWe used a unique collection of hippocampal samples obtained from 13 neurologically healthy control subjects and 45 AD patients distributed among the 6 neuropathological Braak‐Tau stages of the disease. These samples were obtained under tightly controlled conditions and state‐of‐the‐art tissue processing methodologies and histological protocols were applied.ResultWe studied the maturation of DGCs that expressed the gold standard marker of immature neurons, doublecortin (DCX) in the DG of these subjects. For that purpose, we co‐localized DCX with markers that characterize distinct maturation stages during AHN. These markers included calretinin for the most immature neurons or calbindin for neurons at more advanced stages of maturation. We observed remarkable morphological differences among these cell populations in control subjects, which suggested remarkable similarities between AHN in rodents and humans. Strikingly, the maturation of DCX+ DGCs was blocked at multiple levels in AD patients, as shown by the reduced percentage of DCX+ DGCs that expressed markers of mature neurons in these patients.ConclusionOur data do not only support that human AHN exhibits remarkable similarities with that of rodents, but also demonstrate that this process is blocked at different levels during AD. Given that AHN is regulated by lifestyle habits in rodents and these manipulations have a positive impact on cognition, modulating AHN in humans emerges as a potential therapeutic target for AD or other neurodegenerative diseases.
The development of appropriate care pathways for older prisoners with mild cognitive impairment and dementia
Authors: Heathcote Leanne , Forsyth Katrina , Senior Jane , Shaw Jenny , Domone Rachel 
Published: December 2020

AbstractBackgroundNo standardised specialised services or care pathways exist for older prisoners with mild cognitive impairment or dementia in England and Wales. Current service provision is suboptimal and ad hoc. Aim: Identify service needs and appropriate care pathways for older prisoners with cognitive impairment throughout custody and on release into the community;MethodTo identify service needs and develop an appropriate care pathway for older prisoners with dementia/mild cognitive impairment we adopted a Balance of Care approach. Data from the quantitative aspects of the study was used to create sub‐groups of people with similar care needs, from which were developed a series of representative case studies. Each case study was presented to multidisciplinary staff from prison and community settings at a series of workshops. Staff were asked to design an appropriate care package for each case study. Feedback notes from workshops were collated and summarised using a care plan template. Key themes were identified which formed an initial draft of as assessment and treatment care pathway. A further workshop was held with professionals to adjust and further develop the final pathway.FindingsThe final pathway (figures 1 & 2) outlines the steps to be taken within prison and community services to streamline the diagnostic process. Additional guidance is provided around environmental modifications in prison, the development of adapted, specialist wings and circumstances under which care out of the prison setting, for example release on temporary license or some type of secure nursing home/hospital accommodation should be considered.
Factors associated with cognitive performance in elderly caregivers of the community
Authors: Ottaviani Ana Carolina , Brigola Allan Gustavo , Oliveira Nathalia Alves , Luchesi Bruna Moretti , Pavarini Sofia Cristina Iost 
Published: December 2020

AbstractBackgroundThe loss of cognitive health of older caregivers can even become a risk to their own self‐care, functionality, autonomy, and independence.MethodCross‐sectional study carried out with 351 older caregivers attending primary healthcare services in Brazil. Sociodemographic, care variables and Addenbrooke's Cognitive Examination‐Revised (ACE‐R). The data were analyzed using the STATA / MP12 software and the ACER domains were used as dependent variables in the Tobit model with a cross section. All ethical aspects were respected.ResultMost older caregivers were women (n = 267; 76.1%), with a mean age of 69.5 (± 7.0) years and who provided care to their spouse (n = 298; 84.9%). Higher levels of education were significantly associated with better cognitive scores in all domains of ACE‐R. Male sex was significantly associated with worse orientation scores and older age was significantly associated with worse scores on memory, language and visuospatial tests. Also, days per week spent caregiving, was associated with worse on memory and verbal fluency scores and having emotional help was associated with higher memory scores.ConclusionAge, education, male gender, days of care per week and emotional help were associated with the cognitive performance of the older caregivers. In this perspective, scalable interventions that aim to reduce the time spent on care and increase emotional support may be the most effective in preventing cognitive impairment in public policies.
Misconceptions in acquired brain injury
Authors: Tabernero Maria Eugenia , Gallo Maria Fernanda , Cores Evangelina Valeria , Deschle Florencia , Pavon Hernan Marcelo , Cancino Jorge Jose 
Published: December 2020

AbstractBackgroundSeveral studies have shown misconceptions about Acquired Brain Injury (ABI) and it's sequelae on different populations. Considering the motor, sensory, cognitive or emotional consequences of ABI, and their impact in the patient and its relatives’ life, the information offered on ABI is essential to provide adequate care. Objectives: to acknowledge the presence of misconceptions regarding ABI in our population by applying a self‐administered questionnaireMethodThree groups were formed. One for general population (GP), one for patients’ relatives with ABI (RP), and one for health workers (HW). Instrument: five questions were added to the Spanish survey about misconceptions in ABI published by Navarro Main et al. (2017). The survey includes twenty‐four mandatory true or false questions. Furthermore, demographical data was required (for e.g. age, years of education and place of residence), along with information regarding having a relative who has suffered from traumatic brain injury or a stroke. The survey was distributed virtually.Result648 surveys were obtained; 305 belonged to GP, 143 to RP, and 200 to HW. The median age of the respondents was 37, 42 and 36 years‐old respectively. Tertiary and college education have been referred by the 77,5%, 71,5% and 96,5% respectively. The highest number of errors was similar for the three populations for the questions that assessed misconceptions about the influence of cognitive symptomatology, giving the idea that only the behavior observation and physical state of a patient allows us to infer ABI, and that cognitive status is not related to functional independence. “The greater the effort, the faster the recovery” misconception was more prevalent in the RP group.ConclusionThe results showed that having a direct relative does not improve the knowledge on ABI and it's possible sequelae, and this fact stands for the need of a better communication from the rehabilitation group to the relatives in order to adequate achievement expectations and to accomplish a better symptoms management. Moreover, although HW obtained the lowest rate of misconception, the lack of knowledge on ABI’s cognitive component was solid evidence.
Dysfunctional microglial phenotype in the hippocampus of aged amyloidogenic Alzheimer's model
Authors: Nuñez‐Diaz Cristina , Sanchez‐Mejias Elisabeth , Arboledas Angela Gomez , Mejias‐Ortega Marina , Sanchez‐Varo Raquel , Davila Jose Carlos , Vitorica Javier , Gutierrez Antonia 
Published: December 2020

AbstractBackgroundThe accumulation of amyloid beta (Aβ), giving rise to soluble toxic oligomers and insoluble amyloid plaques, is one of the main hallmarks of Alzheimer’s disease (AD). Aβ pathology triggers an inflammatory response mediated by activated astroglia and microglia. However, the specific role of the latter in the progression of AD and their relationship with plaques are not fully understood yet. Here we have analyzed, at cellular and subcellular levels, the progression of amyloid pathology and the associated activated microglia in the hippocampus of the model APP750SL/PS1M146L.MethodImmunohistochemistry for light and electron microscopy were performed in hippocampal samples from 4‐ to 18‐month‐old APP750SL/PS1M146L mice. Quantifications were done by image analysis and stereology.ResultThere is an age‐dependent increase in the amyloid burden and plaques grow, increasing both the size of the core and the halo, in the hippocampus of APP/PS1 model. Besides, a correlation exists between the size of plaques and the number of neuritic dystrophies surrounding them. Amyloid plaques are surrounded by activated microglia, showing a transcriptomic DAM profile. Microglial processes intertwine with the amyloid fibrils, acting as a barrier that isolates plaques and phagocytose Aβ, which might be toxic for these cells. Therefore, microglia surrounding amyloid plaques show ultrastructural signs of dysfunction, which might lead to a worsening of amyloid pathology and neurodegeneration.ConclusionMicroglia surrounding amyloid plaques suffer a degenerative process with the progression of the pathology, which might affect their functions of phagocytosis/isolation/compaction of amyloid plaques. This could contribute to the progression of AD, with the plaques releasing highly toxic soluble Aβ oligomers to the brain parenchyma. Therefore, restoring microglial function or renewing this population might be a promising therapeutic approach for AD. Supported by: Instituto de Salud Carlos III, co‐financed by FEDER funds from European Union, projects PI18/01557 (to AG) and PI18/01556 (to JV), by CIBERNED (to AG and JV), and by Junta de Andalucia project UMA18‐FEDERJA211 (to AG).
Cerebral correlates of autobiographical memory in MCI and AD: Evidence from a positron‐emission tomography study
Authors: Frankenberg Claudia , Schröder Johannes , Haberkorn Uwe , Degen Christina , Buchsbaum Monte S. 
Published: December 2020

AbstractBackgroundAutobiographical memory (AM) changes are the hallmark of Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI). In recent neuroimaging studies, AM changes were associated with numerous cerebral sites, such as the frontal cortices, the mesial temporal lobe, or the cingulum. Factor analysis provides statistical methods for evaluating patterns of cerebral changes in regional glucose uptake.MethodIn 109 patients with MCI or mild AD cerebral metabolic rates were determined using positron‐emission tomography with [18F] deoxyglucose. According to the analyses of the scree plot factor analysis with VARIMAX rotation was used to identify underlying dimensions in 34 cerebral sites involved in AM deterioration. Subsequently, the respective factor scores were correlated with AM performance of 22 patients, which was measured with a structured inventory assessing memories from primary school, early adulthood, and recent years.ResultFactor analysis identified seven factors explaining 69 % of the variance (“frontal cortex,” “mesial temporal substructures”, “cingulum”, “occipital cortex”, “left temporo‐prefrontal areas”, “anterior cingulum”, “right temporal cortex”). Relative to controls, AD patients showed significantly lower values on the factors “frontal cortex” and “mesial temporal substructures”. The factor “mesial temporal substructures” was significantly correlated with both, episodic memories and personal semantic knowledge.ConclusionInterestingly, changes of the mesial temporal substructures were correlated with both semantic and episodic AM. These findings don’t necessarily contradict the multiple trace hypothesis as our sample only comprised patients with MCI or very mild AD for whom the relative preservation of semantic relative to episodic AM may not apply. In conclusion, our findings underline the importance of functional mesial temporal lobe changes in AD associated AM deficits.
A community‐based approach to advance care planning for lower socioeconomic status African Americans living with dementia
Authors: Hurst Laurel Myers , Moss Karen , Grieff Abigail M , Wills Celia 
Published: December 2020

AbstractBackgroundDespite multiple decades of research on advance care planning and existing evidence‐based national models, there remains a persistent lack of effective interventions to facilitate this process among lower socioeconomic status older African Americans living with dementia. African Americans are less likely than Caucasians to complete advance directive. This lack of advance directive documentation results in a higher likelihood of unwanted, costly, and often‐futile healthcare near the end of life that reduces quality‐of‐life. The purpose of this research study is to describe key stakeholder perspectives regarding needs and preferences for advance care planning, including desired intervention content and delivery format to assist caregivers of lower socioeconomic status African American older adults living with dementia, using the novel corona virus pandemic as an exemplar.MethodsFor this qualitative descriptive study, up to n=40 family caregivers (n=20 current) and (n=20 former) of lower socioeconomic status African American older adults living with dementia, healthcare providers (n=10), and community organization stakeholders (n=10) are being recruited. These stakeholders will complete up to two audio‐recorded interviews about needs and preferences for advance care planning, including desired intervention content and delivery format. SPSS software will be used for demographic data analysis and Dedoose software will be used to enhance thematic content analysis of transcribed interview data.ResultsStudy findings will be used to develop a decision support prototype intervention that is ready for efficacy testing. We anticipate that it will fill essential gaps in existing advance care planning interventions for lower socioeconomic status African American older adults with dementia and their caregivers. This co‐created prototype will go beyond education only and will include culturally‐tailored psychosocial and problem‐solving approaches to advance care planning through processes such as storytelling (an effective and culturally acceptable‐to‐the‐population process) as a narrative form of advance care planning through communication. Study results will be provided to participants at study completion.ConclusionsBy engaging with this population to develop and test a co‐created culturally‐focused intervention, we expect to improve advance care planning outcomes for lower socioeconomic status African American older adults living with dementia and their caregivers.
Depression and increased risk of Alzheimer’s dementia: Longitudinal analyses of modifiable risk and sex‐related factors
Authors: Kim Doyoung , Wang Ruoding , Kiss Alex , Bronskill Susan E , Lanctot Krista L , Herrmann Nathan , Gallagher Damien 
Published: December 2020

AbstractBackgroundOlder adults with depression are at increased risk of Alzheimer’s dementia (AD). Most adults with AD are women. Women have two‐fold lifetime risk of depression. It is not known how sex influences the risk of depression upon AD.MethodWe used the longitudinal case series dataset from National Alzheimer’s Coordinating Center for analysis. Older adults (age 50+) with normal cognition, who visited memory clinics across the United States from September/2005 to December/2019, were followed from initial visit until first diagnosis of AD or loss to follow up. Multivariable survival analyses were conducted to determine if 1) recent and remote depression were independently predictive of AD, 2) this risk differed between the sexes, and 3) sex modifies this risk.Result652 of 10,739 enrolled subjects developed AD over a median follow‐up of 55.3 months. Only recently active depression (within the last 2 years) was associated with increased risk of AD (HR=2.0; 95%CI, 1.5‐2.6) independently of other significant risk factors. After stratification by sex, recent depression was an independent predictor of AD in females (HR=2.3; 95%CI, 1.7‐3.1) but not in males (HR= 1.2; 95%CI, 0.7‐2.1). No interaction between recent depression and sex in predicting the risk of AD was observed (HR=1.5; 95%CI, 0.8‐2.8).ConclusionOnly recent history of depression was associated with higher risk of AD. This risk was significant only in women. Future analyses should determine if current findings extend to other populations and may be explained by variable distribution of neurobiological or other modifiable risk factors between the sexes.
Optimizing protocols for white matter tractography in animal models of genetic AD risk
Authors: Stout Jacques Andrew , Anderson Robert BJ , Cofer Gary , Colton Carol A , Badea Alexandra 
Published: December 2020

AbstractBackgroundAlzheimer's disease (AD) has a tremendous effect on the brain structural and functional integrity. As previous research has shown, AD impacts gray matter areas, but also neuronal tracts connecting them [1]. One of the ways this neuronal impact can be evaluated is through the combined use of diffusion imaging and tractography modeling. However, due to the complex nature of 3D modeling, it is important to evaluate not only the tractography models, but also the imaging protocols. We have evaluated several diffusion acquisition schemes in a mouse model expressing the APOE4 genotype, associated with genetic risk for AD. We have focused on fimbria, in order to recommend optimized diffusion imaging protocols in a larger cohort of mice.MethodsWe acquired diffusion images at 50 µm3 isotropic with 46 different directions and an 8‐fold compressed sensing acceleration factor for fixed brain specimens using high‐field MRI. We used six different b‐value variations on this acquisition scheme, including single, two, and three‐shells acquisitions. The diffusion signal was reconstructed using a Q ball Constant Solid Angle reconstruction[2], and tracts were built using a deterministic maximum direction getter. The smaller tracts were pruned, and models were evaluated using Linear fascicle evaluation (LiFE) [3] in regions including the fimbria (Fig.1).ResultWe ranked the quality of the tractography models according to the number of tracts and their average size in the fimbria, as well as the correspondence between the diffusion model and predicted tract results using Life error evaluation (Fig.2). Our results favored Acq 1 (single shell b = 4000s/mm2) which had the most consistent and longest tracks, and lowest errors, followed by Acq 3 (three shells, b = 2000, 3000, 4000), and 5 (double‐shell, b = 2000, 4000).ConclusionWhether it was for single, dual or triple shell, the acquisitions with the greatest model error were those with at least one lower b‐value. This would indicate that for tractography models, and despite the lower signal noise levels, the use of low b‐values lead to tract distortions. Other considerations, such as reducing bias should also be introduced so as to better estimate diffusion scalar parameters.