bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gerocovid 19 and implications for territorial management of old people affected with dementia
Authors: Gareri Pietro , Cotroneo Antonino Maria , Nisticò Michelangelo , Perrone Rosalia , Signore Susanna Del , Incalzi Raffaele Antonelli 
Published: December 2020

AbstractBackgroundThis study is part of a wider observational project addressed to old people in different care settings. To assess the suitable strategies to deal with the lockdown created by the Covid‐19 emergency, to better care for the elderly outpatient and home patients suffering from cognitive disorders. Medical, social and psychological conditions will be evaluated for identifying the effects of Covid‐19 pandemics on older patients with dementia.MethodThe present study is retrospective and in part prospective and will involve 100 older adults. They will be administered MMSE for assessing cognitive functions, ADL, and IADL for functional status, CIRS for assessing comorbidities, 5‐items GDS for mood evaluation, and SF‐36 for detecting the perceived quality of life. Contacts with both outpatients and home patients will be managed either by phone, preferably by video call (Whatsapp, Facetime) or, in a few cases, via Skype.ResultsThe results of tests, the prescription of aids, and treatment plans are recorded on an electronic registry as anonymized clinical data. Moreover, a general questionnaire about the clinical investigation site focusing on the specific preventive measures and the change of the operating methods at home was compiled on a dedicated Information Technology platform by all participating centers. Changes in blood pressure, use of personal protective equipment, the need for operators or patients to quarantine in the event of suspected/full‐blown infection will be reported. Other information will be requested on the effects of social distancing, the presence of formal/informal caregivers, and the methods of procurement. Psychological reactions to the effects of isolation at the baseline and three months (anxiety, depression, acceptance, denial), changes in sleep, and bowel function and differences according to housing conditions will be assessed as well.ConclusionThe Gerocovid 19 could be a remarkable study for the management of outpatient and home patients affected with cognitive disorders.
Synergistic toxicity between tau and amyloid drives neuronal dysfunction and neurodegeneration in transgenic Caenorhabditis elegans
Authors: Benbow Sarah J , Strovas Timothy J , Darvas Martin , Saxton Aleen , Kraemer Brian C 
Published: December 2020

AbstractBackgroundAggregates of Aβ peptide and the microtubule‐associated protein tau are key molecular hallmarks of Alzheimer's disease (AD). However, the interaction between these two pathologies and the mechanisms underlying disease progression have remained unclear. Numerous failed clinical trials suggest the necessity for greater mechanistic understanding in order to refine strategies for therapeutic discovery and development.MethodTo this end, we have generated a transgenic Caenorhabditis elegans model expressing both human Aβ1‐42 peptide and human tau protein pan‐neuronally. We used behavioral, morphological and biochemical assays to assess pathological progression.ResultsWe observed exacerbated behavioral dysfunction and age‐dependent neurodegenerative changes in the Aβ;tau transgenic animals. Further, these changes occurred in the Aβ;tau transgenic animals at greater levels than worms harboring either the Aβ1‐42 or tau transgene alone and interestingly without changes to the levels of tau expression, phosphorylation or aggregation. Functional changes were partially rescued with the introduction of a genetic suppressor of tau pathology.ConclusionTaken together, the data herein support a synergistic role for both Aβ and tau in driving neuronal dysfunction seen in AD. Additionally, we believe that the utilization of the genetically tractable C. elegans model will provide a key resource for dissecting mechanisms driving AD molecular pathology.
Preventing Loss of Independence through Exercise (PLIÉ) improves behavioral outcomes and increases default mode network connectivity in people with mild cognitive impairment
Authors: Martinez Steven , Barnes Deborah E , Mehling Wolf , Chesney Margaret A , Lee Jennifer Ann , Lee Amanda , Chao Linda L 
Published: December 2020

AbstractBackgroundPreventing Loss of Independence through Exercise (PLIÉ) is an integrative group movement program developed to improve quality of life and daily function in people with mild‐to‐moderate dementia. We performed a single‐arm pre‐post pilot trial to examine the impact of PLIÉ in people with mild cognitive impairment (MCI) on behavioral and neuroimaging outcomes.MethodsStudy participants, recruited from the community, had received MCI diagnoses or reported subjective memory complaints plus Montreal Cognitive Assessment (MoCA) scores ≤ 26. PLIÉ classes were 1‐hour, 2 days/week over 12 weeks with 8‐12 participants per class. Pre‐post outcomes included validated measures of cognitive function, physical performance, self‐rated quality of life, mood, affect, mobility, social isolation, attention regulation, self‐regulation, and well‐being. Neuroimaging measures included structural magnetic resonance images (MRIs) and resting state fMRIs. Participants also completed PLIÉ satisfaction surveys. Standardized effect sizes (ES) were calculated based on pre‐post change divided by the baseline standard deviation, and paired t‐tests were used to compare pre‐post scores. Changes in functional connectivity of the Default Mode Network (DMN) were examined using two nodes, the anterior medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), as seeds.ResultsEighteen participants completed the 12‐week program. Participants were 74.9±9.1 years old (11 men, 7 women) and predominately white. Half were US‐veterans. We observed pre‐post improvement on measures of cognitive function (ES=0.33, p=0.001), physical performance (ES=0.39, p=0.047), social isolation (ES=0.62, p=0.009), and self‐regulation (ES=0.55, p=0.006). Though not statistically significant, most other measures suggested improvement with clinically meaningful effect sizes. Neuroimaging revealed increased functional connectivity between nodes of the DMN, specifically between the hippocampus and the mPFC (p=.03) and between the PCC and bilateral parietal cortex after PLIÉ. Satisfaction ratings among participants were high (mean 3.95±.07; range 1‐4).ConclusionThese preliminary findings provide proof‐of‐concept for the PLIÉ intervention in people with MCI and suggest that it may enhance cognitive function, physical performance, mood and well‐being, and increase DMN functional connectivity. Additional studies with a control group are warranted.
Role of gait and speed performance in predicting cognitive decline and dementia in people with Down syndrome: Preliminary findings
Authors: Gonçalves Aline Souza , Carvalho Claudia Lopes , Ramos Andressa Souza , de Fátima Rebouças da Silva Maria , Rigoleto Soares Cristiane Nogueira , Sant´Ana Livea Carla Fidalgo , da Costa Maria Lucia Gurgel , Fonseca Luciana Mascarenhas , Forlenza Orestes Vicente 
Published: December 2020

AbstractBackgroundThe longevity of people with DS has increased substantially in recent decades. This population shows signs of premature aging in many organs and systems. The neuropathology of Alzheimer's disease (AD) is overexpressed in DS. Cognitive and functional losses, such as decline in executive function and apraxia, interfere with the sequencing of movements and the integrity of gait. There is evidence that a decrease in gait may precede other clinical symptoms of dementia in AD in the general population, but we found no studies investigating gait performance and decline in DS. The aim of this study is to characterize gait and speed performance in a sample of adults with DS divided into three groups by diagnosis: stable cognition, prodromal dementia and AD.MethodsWe used the Performance Oriented Mobility Assessment (POMA) to address balance, gait and the risk of falls and the Timed “Up and Go” test (TUG) to assess gait speed in a sample of 35 individuals with DS over 35 years of age. Dementia diagnosis was based on the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX‐DS). The 1‐factor, 3‐level ANOVA model was used in the 3 groups.Results9 participants (25.7%) had AD (mean POMA 12.0 ± 7.1; mean TUG 18.0 ±5.8), 8 (22.9%) were classified as prodromal dementia (mean POMA 19.0 ± 5.6; mean TUG 21.0± 6.1) and 18 (51.4%) were in the stable cognition group (mean POMA score 20 ± 4.5; mean TUG 17.0 ±5.5). Mean POMA scores were significant different among the groups (p<0.05) with higher impairment in the group with AD relative to those with prodromal dementia and stable cognition. We did not find difference for the TUG scores among the groups.ConclusionsPOMA results indicates that those with AD have worse balance, gait performance and higher risk of falls relative to those with prodromal dementia and stable cognition, suggesting that gait performance may be more affected in later stages of neurodegeneration. Gait speed does not seem to be useful differentiating the groups. Further longitudinal studies with bigger samples are needed to confirm our results.
Saffron for mild cognitive impairment and dementia: A systematic review and meta‐analysis of randomised clinical trials
Authors: Ayati Zahra 
Published: December 2020

AbstractBackgroundSaffron (stigma of Crocus sativus L.) from Iridaceae family is a well‐known traditional herbal medicine that has been used for hundreds of years to treat several diseases such as depressive mood, cancer and cardiovascular disorders. Recently, anti‐dementia property of saffron has been indicated. However, the effects of saffron for the management of dementia remain controversial. The aim of the present study is to explore the effectiveness and safety of saffron in treating mild cognitive impairment and dementia.MethodAn electronic database search of some major English and Chinese databases was conducted until 31th May 2019 to identify relevant randomised clinical trials (RCT). The primary outcome was cognitive function and the secondary outcomes included daily living function, global clinical assessment, quality of life (QoL), psychiatric assessment and safety. Rev‐Man 5.3 software was applied to perform the meta‐analyses.ResultA total of four RCTs were included in this review. The analysis revealed that saffron significantly improves cognitive function measured by the Alzheimer’s Disease Assessment Scale‐cognitive subscale (ADAS‐cog) and Clinical Dementia Rating Scale‐Sums of Boxes (CDR‐SB), compared to placebo groups. In addition, there was no significant difference between saffron and conventional medicine, as measured by cognitive scales including ADAS‐cog, CDR‐SB and SCIRS. Saffron improved daily living function, but the changes were not statistically significant. Adverse events were mild.ConclusionSaffron has the potential to improve cognitive function and activities of daily living in patients with Alzheimer’s disease and mild cognitive impairment (MCI). However due to limited high quality studies there is insufficient evidence to make any recommendations for clinical use. Further clinical trials on larger sample sizes are warranted to shed more light on its efficacy and safety.
Novel regulation of death‐associated protein kinase 1 in Alzheimer’s disease
Authors: Chen Dongmei , Mei Yingxue , Lan Guihua , Gan Chen‐Ling , Zhang Tao , Xia Yongfang , Wang Long , Lee Tae Ho 
Published: December 2020

AbstractBackgroundDeath‐associated protein kinase 1 (DAPK1) is a serine/threonine kinase that plays an important role in regulating neuronal function and is genetically linked to Alzheimer’s disease (AD). We previously showed that DAPK1 expression is markedly increased in 75% of human AD brains. Moreover, we found that DAPK1 promotes tau protein accumulation and its phosphorylation at multiple AD‐related sites. However, it is not known whether and how DAPK1 expression or activity is regulated in AD, including tau hyperphosphorylation and functions.MethodWe investigated the effects of melatonin on DAPK1 regulation by examining DAPK1 protein stability, and tau hyperphosphorylation and functions using comprehensive approaches in cell culture models, ex vivo mouse models, and human patient tissues. We synthesized biotin‐melatonin to demonstrate direct binding of melatonin and DAPK1. Moreover, we assessed the correlation of melatonin‐regulated DAPK1 expression and Pin1 phosphorylation because DAPK1 increases tau hyperphosphorylation through inhibiting the catalytic activity of Pin1.ResultWe discovered that melatonin critically regulates DAPK1 by reducing its protein stability, thereby attenuating tau hyperphosphorylation in AD. Melatonin decreases DAPK1 expression in a dose‐ and time‐dependent manner in primary neurons and neuronal cell lines. Moreover, the regulation of DAPK1 by melatonin is not dependent on DAPK1 transcription because DAPK1 mRNA levels are not affected by melatonin. Melatonin promotes the ubiquitination of DAPK1 and decreases its protein stability through a proteasome‐dependent pathway. Furthermore, melatonin directly interacts with the ankyrin repeat domain of DAPK1. Inhibition of DAPK1 by melatonin and a pharmacological DAPK1 inhibitor synergistically reduces tau expression and phosphorylation at multiple AD‐related sites. Melatonin and a DAPK1 inhibitor promote neurite outgrowth and microtubule assembly, which are disrupted by tau hyperphosphorylation. Mechanistically, melatonin‐mediated DAPK1 degradation increases the activity of Pin1, a prolyl isomerase known to play a protective role against tau hyperphosphorylation and AD. Finally, DAPK1 and melatonin levels are inversely correlated in the brains of human AD patients.ConclusionOur study demonstrates a novel role of melatonin in the direct regulation of DAPK1, and that synergistic targeting of DAPK1 by melatonin and DAPK1 inhibitors offers an attractive approach to block tau hyperphosphorylation in AD.
Theta‐gamma coupling and ApoE genotype in patients at risk for Alzheimer’s dementia
Authors: Patterson Rachel A , Brooks Heather J , Zomorrodi Reza , Kumar Sanjeev , Blumberger Daniel M , Graff‐Guerrero Ariel , Fischer Corinne E , Flint Alastair , Herrmann Nathan , Kennedy James L , Lanctot Krista L , Mah Linda , Mulsant Benoit H , Pollock Bruce G , Rajji Tarek K ,   PACt‐MD Study Group
Published: December 2020

AbstractBackgroundTheta‐gamma coupling (TGC) is an electroencephalography (EEG) marker of working memory and depends on robust synaptic plasticity within the recurrent prefrontal cortical networks (Rajji et al. 2017, Buszaski et al. 2012). ApoE4 allele has deleterious effects on synaptic plasticity (Teter et al. 2004). Thus, the primary objective of this analysis is to determine whether there is a relationship between ApoE4 genotype and TGC during the performance of a working memory task (N‐back).MethodWe used baseline data from a large Alzheimer’s dementia prevention trial. Participants were diagnosed with Mild Cognitive Impairment (MCI), past history of Major Depressive Disorder (MDD), or both (MCI+MDD) and had completed N‐back‐EEG and ApoE genotyping. TGC was measured across right and left frontal electrodes. Participants were grouped based on E4 presence (ApoE2/E3 or ApoE3/E3 [noncarriers] vs. ApoE3/E4 or ApoE4/E4 [carriers]).ResultWe included 248 participants (MCI= 125; MDD= 44, MCI+MDD= 79; 153 females/95 males). There were 182 ApoE4 noncarriers (age= 71±6.5; Theta power= 16,290±14,764; Gamma power= 5793±5663; TGC= 0.00251±0.00227; PiB frontal amyloid=1.4371±0.32) and 66 noncarriers (age=71±5.0; Theta power= 17,235±14,312; Gamma power= 6473±5287; TGC= 0.002184±0.001622; PiB frontal amyloid= 2.09±0.78). Multiple linear regression results show that ApoE4 carriers had reduced TGC (β= 0.205, p= 0.042, Cohen’s d= 0.28) after controlling for age, sex, diagnosis, theta power, gamma power, and PiB frontal amyloid. Gamma power was also a significant predictor of TGC.ConclusionOur results suggest that presence of ApoE4 allele contributes to the modulation of TGC during a working memory task. As ApoE impacts synaptic plasticity, our findings suggest that synaptic plasticity or other ApoE‐related mechanisms underlie TGC. Rajji, T.K., et al., Ordering Information in Working Memory and Modulation of Gamma by Theta Oscillations in Humans. Cerebral Cortex, 2017. 27(2): p. 1482‐1490. Buzsaki, G. and X.J. Wang, Mechanisms of Gamma Oscillations, in Annual Review of Neuroscience, Vol 35, S.E. Hyman, Editor. 2012. p. 203‐225. Teter, B., ApoE‐dependent plasticity in Alzheimer's disease. Journal of Molecular Neuroscience, 2004. 23(3): p. 167‐179.
Time‐frequency analysis in a working memory task in pre‐clinical stage and symptomatic stage of Alzheimer’s disease
Authors: Doval Sandra , Serrano Noelia , Sanz David López , Fernández Ricardo Bruña , Losada María Luisa Delgado , Higes Ramón López , Dolado Alberto Marcos , Maestú Fernando 
Published: December 2020

AbstractBackgroundThe characteristic deterioration of the working memory (WM) in Alzheimer’s disease (AD), is also one of its first symptoms. Alterations of oscillatory activity have been evidenced in frequency bands in underlined neuronal processes during WM task execution; in comparison to healthy individuals; since the first clinical manifestation of the disease – in patients with mild cognitive impairment (MCI) ‐ until the lasts phases of the disease. However, those alterations in the WM have not been widely studied in individuals that refer subjective cognitive decline (SCD) without objective evidence of cognitive deterioration.MethodThe power of the underlined oscillatory activity during the maintenance period after an interruptor in a WM task was calculated by conducting a time‐frequency analysis. The results of three groups were compared: Controls (n = 46); SCD (n = 40), and MCI (n = 35).ResultStatistically significant results were found between‐group. Patients with MCI evidenced a decrease in alpha band in temporal, parietal and occipital sensors of both hemispheres in comparison to controls (clusterF = 3.22e+04, p= 4.99e‐05, η2=0.09). SCD group showed a decrease in beta band in left hemisphere in frontal and parietal sensors (clusterF=3.65e+03, p=0.02, η2=0.06) in comparison to controls. SCD evidenced a decrement in theta band in the left hemisphere in fronto‐temporals sensors (clusterF=4.05e+03, p=0.02, η2=0.06).ConclusionAs a conclusion, the subjective perception of SCD seems to have a biological correlate, assessable through alterations in the neuronal activity associated with WM maintenance.
Prevalence of neuropsychiatric symptoms related to dementia in individuals with Down syndrome
Authors: Fonseca Luciana Mascarenhas , Mattar Guilherme Prado , Haddad Glenda Guerra , Burduli Ekaterina , McPherson Sterling M , de Figueiredo Ferreira Guilhoto Laura Maria , Filho Geraldo Busatto , Yassuda Monica Sanches , Bottino Cassio M.C. , Hoexter Marcelo Queiroz , Chaytor Naomi S. 
Published: December 2020

AbstractBackgroundNeuropsychiatric symptoms (NPS) are significant manifestations of dementia, with important consequences for patients and caregivers. Despite the established genetic link between Down syndrome (DS) and Alzheimer’s disease (AD), studies investigating NPS in individuals with DS and dementia are scarce. The Neuropsychiatric Inventory (NPI) was developed to identify symptoms of dementia and while it is widely used for the assessment of individuals with dementia in the general population, we have found no studies using the NPI in those with DS. The aim of this study is to characterize NPS in a sample with DS with heterogeneous cognitive profiles using the NPIMethodParticipants (N=92) with DS, ≥30 years of age were assessed with the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX‐DS). They were classified by a psychiatrist into three categories: AD, prodromal dementia, and stable cognition. Another psychiatrist blinded to the CAMDEX‐DS dementia diagnosis, evaluated the participants using the NPI. Chi‐square tests were used to check for significant differences in frequency of symptoms.ResultThirteen participants (14.1%) had AD, 17 (18.4%) were classified as prodromal dementia and 62 (67.5%) were in the stable cognition group. Prevalence of delusion, depression, anxiety, disinhibition, irritability, appetite abnormalities and total NPI did not differ between groups. Anxiety and irritability were common across all groups (∼50% of the total), while euphoria was not present in any participant. Hallucination, agitation, apathy, aberrant motor behaviour and night‐time behaviour disturbance showed significant difference among the groups (p<0.05), with higher prevalence in the group with AD.ConclusionThe results indicate that individuals with DS and AD have some of the symptoms that are characteristically present among the general population with AD. Future studies are needed to understand if AD in DS is associated with a similar pattern of NPS observed among people with AD in the general population or may follow a specific NPS pattern. The high frequency of some NPS in individuals with DS and stable cognition should be considered in the diagnostic process in order to reduce the odds of generating a false positive.