bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and in silico investigation of cholinesterase inhibition and anti‐radical properties of Solanum macrocarpon leaf extracts: A preliminary anti‐Alzheimer's study
Authors: Idowu Gbohunmi Paul , Obuotor Efere Martins , Onajobi Funmilayo Dorcas
Published: December 2021

Background

Alzheimer's disease (AD) is an age‐associated, progressive neurodegenerative disease characterized by decline in cognitive function. There is presently no cure for AD and the currently used drugs have limited efficacy. Cholinergic enzyme inhibition, oxidative stress and neuroinflammation have been growing areas of research in the pharmacological management of AD (Simunkova et al., 2019). Furthermore, computational approaches have been instrumental in designing and discovering new drugs for several diseases (Romano & Tatonetti, 2018). Solanum macrocarpon L. (eggplant) is a specie of African ancestry reported to be an ethno‐ medicinal plant that improves memory (Ogunsuyi et al., 2018). This study therefore investigated the antioxidant and acetylcholinesterase (AChE) inhibitory potential of S. macrocarpon leaf extracts, identified active compound(s) and explored their enzyme‐ligand interactions using In silico approaches to discover new functional leads for AD.

Method

Methanol extract and fractions of S. macrocarpon leaves were subjected to phytochemical investigation of AChE inhibitory activity and cell‐free antioxidant activity. Phytochemicals were identified through the profiling of the most potent fraction using Liquid Chromatography‐Mass Spectrometry (LC‐MS) and Gas Chromatography‐Mass Spectrometry (GC‐MS). Molecular docking was performed employing AutoDock Vina. The prediction of the ADMET properties was obtained using pkCSM and SwissADME online tools. Furthermore, the compound(s) with favorable pharmacokinetic properties and interaction with key residues within the AChE active site was selected for molecular dynamics (MD) simulation studies using GROMACS 5.0.7.

Result

The S. macrocarpon leaves ethyl‐acetate fraction (SMEA) displayed the highest concentration‐dependent inhibition of AChE and highest antioxidant capacity among the fractions. Seventy‐eight (78) and sixty (60) compounds were tentatively identified from the LC‐MS and GC‐MS of SMEA respectively. A total number of 21 compounds demonstrated better docking score than the standard, eserine and interacted with key residues within the human acetylcholinesterase (PDB ID:4EY7) active site akin to Donepezil. Amongst the compounds with the least docking score, 1,1‐Biphenyl‐4‐carboxylic acid showed the most favorable pharmacokinetic properties. Also, the 10ns MD produced a trajectory which showed stable Root‐Mean‐Square‐Deviation and favorable g_mmpbsa energy calculations.

Conclusion

The current study proposes that 1,1‐Biphenyl‐4‐carboxylic acid, a constituent of S. macrocarpon is a potential lead compound for AD management.
The effect of illiteracy on performance in screening tools for dementia: A systematic review and meta‐analysis
Authors: Maher Caragh , Calia Clara
Published: December 2021

Background

Research indicates that many tools designed for screening dementia are affected by literacy level (Ardila et al., 2010; Kosmidis, 2018). However, no systemic analysis exists to evaluate the overall effects of this important confounding factor. We systematically reviewed and meta‐analytically estimated the differences in performance in dementia screening tools between literate and illiterate individuals.

Method

Electronic databases (MEDLINE, PsycINFO, and EMBASE) were searched from 1975 to February 2020 to identify empirical studies examining performance in dementia screening tools in literate and illiterate individuals over 50 years old. Data for effect sizes, participant demographic information, and study information were extracted.

Results

We identified 28 studies collectively comprising of 28,298 individuals classified as literate and 15,995 individuals classified as illiterate. Of the 28 studies, 24 included the Mini‐Mental State Examination (MMSE) or an adapted version of the MMSE. Eleven studies included a cognitive screening tool that was adapted for use in illiterate/low educated participants. Nineteen studies were methodologically suitable for meta‐analysis. Multi‐level random‐effects modelling demonstrated a significant overall effect, with literate participants scoring significantly higher than illiterate participants (g = ‐1.2962, 95% CI = ‐1.6200, ‐0.9723, p < 0.001; Figure 1). Moderator analyses indicated significant effects of test type and the presence of cognitive impairment on the extent of the difference in performance between literate and illiterate participants. The difference in performance between groups was smaller in screening tests designed or modified for illiterate individuals (p < 0.05), and in individuals with cognitive impairment (p < 0.01).

Conclusion

Our findings confirm the unsuitability of many dementia screening tools for individuals who are illiterate. The results of this systematic review and meta‐analysis emphasise the need for the development, validation, and use of tools that are suitable for individuals of all literacy abilities. References: Ardila, Bertolucci, P. H., Braga, L. W., Castro‐Caldas, A., Judd, T., Kosmidis, M. H., Rosselli, M. (2010). Illiteracy: the neuropsychology of cognition without reading. Arch Clin Neuropsychol, 25(8), 689‐712. doi:10.1093/arclin/acq079. Kosmidis, M. H. (2018). Challenges in the neuropsychological assessment of illiterate older adults. Language, Cognition and Neuroscience, 33(3), 373‐386. doi:10.1080/23273798.2017.1379605
Monitoring physical parameters from wearable sensors for detection of cognitive decline in routine care
Authors: Goerss Doreen , Amaefule Chimezie O. , Kowe Antonia , Köhler Stefanie , Teipel Stefan J.
Published: December 2021

Background

Wearable sensors offer the chance to measure activity and vital signs continuously and unobtrusively in elderly people living in domesticity or stationary care. To derive meaningful features from raw data and transform sensor data into clinically relevant information it is necessary to develop efficient algorithms and validate the results, e.g. with synchronized observational data. Only then sensor data bear the potential to detect functional changes or specific behaviors that are linked to Alzheimer’s disease and allow the complementation of the diagnostic process with sensor data.

Method

International data point to a potential role of serious games applications to detect early signs of cognitive decline. Along this line a study of the DZNE uses a comprehensive memory paradigm examining age sensitive decline in a citizen science study performed with digital platforms. Complementary approaches include non‐intrusive assessment of everyday behaviour. We performed several studies to examine the feasibility and potential of mobile sensors in detection of challenging behaviors, spatial disorientation and gait changes to classify people with MCI or dementia and detect situations with need for help.

Result

In a study with dementia‐patients that were wearing mobile sensors continuously over several weeks, we could show that multimodal sensors can be applied long‐term in the setting of PwD living in stationary care. Accelerometry can be used to detect behavioral patterns in dementia patients. We extended the set of sensor data with vital signs (e.g. heart rate, electrodermal activity) and indoor tracking to detect spatial disorientation in an ongoing wayfinding study to classify MCI /dementia based on sensor data.

Conclusion

Mobile sensors will be omnipresent in the following years. With complex algorithms we were able to derive features that allow information about crucial personal conditions with respect to mental health. Digital markers including sensor data won’t be a stand‐alone diagnostic tool and need to be embedded in an innovative diagnostic pathway.
An item response theory approach to clinical diagnosis of MCI and dementia: Illustrations from ADNI and NACC data
Authors: Kiselica Andrew M , Benge Jared
Published: December 2021

Background

Diagnostic labels, such as cognitively normal, mild cognitive impairment, and dementia rely on application of several different criteria and are often based at least in part on subjective clinical judgments. These factors may lead to heterogeneity in diagnostic practices across datasets. A modern psychometric technique known as item response theory (IRT) can be used to take information from many different markers of an underlying spectrum (e.g., cognitive impairment) and evaluate how diagnostic labels perform across datasets when shared items are used.

Method

In this poster, we illustrate how IRT might be used to evaluate how diagnostic labels function across two major databases of older adults that include cognitive data and diagnostic labels, the National Alzheimer’s Coordinating Center Uniform Data Set (n = 6,042) and the Alzheimer’s Disease Neuroimaging Initiative (n = 513).

Result

Taking an IRT driven Cochran‐Mantel‐Haenzel approach revealed no significant differential item functioning for the diagnostic labels among individuals from the Alzheimer’s Disease Neuroimaging Initiative and National Alzheimer’s Coordinating Center databases (Figure 2; X2
=11.79, p < .001, Class AA item characterization).

Conclusion

The current study demonstrated how IRT scoring approaches outline similarities in cognitive functioning across a group of measures, despite being diagnosed under different criteria across studies. Findings illustrate a manner of evaluating if diagnostic labels are applied correctly across participants. The utility of this approach will be tempered by the ability to identify underlying unidimensional constructs across studies, although multi‐dimensional IRT approaches have been developed.
Masitinib in mild to moderate Alzheimer’s disease: Results from study AB09004
Authors: Dubois Bruno , Hermine Olivier ,   the AB09004 study group
Published: December 2021

Background

Masitinib is a small molecule drug targeting KIT, LYN, FYN and CSF1R. Proof‐of‐concept that masitinib slowed cognitive decline in Alzheimer's disease (AD) was previously demonstrated [doi:10.1186/alzrt75; doi:10.3233/JAD‐200466]. Study AB09004 assessed oral masitinib administered as an add‐on therapy to standard care for the treatment of mild to moderate AD.

Method

Phase 2B/3 study AB09004 comprised two independent, double‐blinded, placebo‐controlled, sub‐studies: masitinib at 4.5mg/kg/day versus placebo (randomized 1:1), and a titrated masitinib dose of 6.0 mg/kg/day versus matched placebo (randomized 2:1). Eligible patients that had a clinical diagnosis of AD with baseline mini‐mental state examination (MMSE) score ≥12–≤25, and had received a stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine for ≥6 months, were treated for 24 weeks. Primary endpoint was overall change from baseline at week‐24 (analysis of covariance model) in the Alzheimer's Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog) or the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS‐ADL) score. The study was successful if a significant improvement was reached on either ADAS‐Cog or ADCS‐ADL at a 2.5% level of statistical significance, in either sub‐study.

Result

Masitinib (4.5mg/kg/day) (n=182, median (age=73 years, MMSE=19, ADCS‐ADL=55.0, ADAS‐Cog=25.5)) showed significant benefit over placebo (n=176, median (age=73 years, MMSE=19, ADCS‐ADL=53.5, ADAS‐Cog=24.8)) with a least‐squares mean difference in ADAS‐Cog from baseline (δCog) of ‐1.46 versus 0.69, respectively, and corresponding least‐squares mean difference between groups (ΔCog) of ‐2.15 (97.5%CI[‐3.48,‐0.81]);p=0.0003. All ADAS‐Cog sensitivity analyses were convergent with the primary outcome, including the conservative jump‐to‐reference approach with ΔCog of ‐1.89 (95%CI[‐3.06,‐0.72];p=0.0016). Considering ADCS‐ADL, δADL was 1.01 for masitinib (4.5mg/kg/day) versus ‐0.81 for placebo, with a ΔADL of 1.82 (97.5%CI[‐0.15,3.79]);p=0.038. Safety was consistent with the known profile for masitinib. The proportion of patients presenting at least one adverse event (AE) or severe AE was respectively, 87.0% and 26.5% for masitinib (4.5mg/kg/day, n=185) versus 77.5% and 19.3% for placebo (pooled, n=280). Efficacy results from the titrated masitinib 6.0 mg/kg/day sub‐study were inconclusive and no new safety signal was observed.

Conclusion

Masitinib (4.5mg/kg/day), a tyrosine kinase inhibitor targeting mast cell and microglia activity, may provide a new treatment option for mild to moderate AD.
Fully automated immunoassays for measuring beta‐amyloid peptide (1‐42) and total tau in cerebral spinal fluid
Authors: Kozo Daniel R
Published: December 2021

Background

Beta‐amyloid1‐42 (Aβ42) and tau protein are cerebral spinal fluid (CSF) biomarkers for progression to AD. The sensitivity requirements for Aβ42 and total tau assays are in the pg/mL range, a challenge for any methodology. The use of these biomarkers for clinical purposes requires assays that can reliably deliver accurate and reproducible results.

Method

New prototype immunoassays for Aβ42 and total tau on a fully automated clinical analyzer [Siemens Healthineers ADVIA Centaur® XPT Immunoassay System] are under development to enable routine testing of AD biomarkers in clinical laboratories. Each assay uses an antigen/antibody sandwich format and chemiluminescence detection. Standard curves from 0 to 4000 pg/mL and 0 to 6500 pg/mL were generated for the Aβ42 and Tau assays, respectively. Synthetic Aβ42 and recombinant tau‐441 were spiked into an immunodepleted (ID) CSF pool and tested. Precision was evaluated over 6 days by testing a CSF pool and buffer controls on two analyzers. Functional sensitivity was estimated using the precision data. Clinical utility was evaluated by testing 30 clinical CSF samples from subjects with and without AD.

Result

Recoveries of spiked Aβ42 from CSF ranged from ‐13% to +0.7% over 113 to 3179 pg/mL. Recoveries of spiked tau‐441 from CSF ranged from ‐11% to +13% over 35 to 3826 pg/mL. The repeatability and within‐laboratory precision of the Aβ42 assay ranged from 1.3% to 8.6% and 1.9% to 9.9%, respectively, over 107 to 2005 pg/mL. The repeatability and within‐laboratory precision of the total tau assay ranged from 1.2% to 10.8% and 1.6% to 12.5%, respectively, over 108 to 3300 pg/mL. The functional sensitivities of the Aβ42 and total tau assays were estimated to be < 200 pg/mL and < 80 pg/mL, respectively. Using ROC analysis, a ratio of Aβ42 and total tau results was able to differentiate AD from non‐AD subjects with 90% sensitivity and 95% specificity (AUC 0.95).

Conclusion

When finalized, the fully automated Aβ42 and total tau assays will have performance characteristics suitable for routine use in a clinical laboratory. The performance of the assays in combination with automation will make testing for these important biomarkers more reliable and routine.
Repeated intravenous infusion of autologous adipose‐derived stem cells improves cognitive function
Authors: Shigematsu Kazuo , Ishii Kazunari , Tahara Kenichi , Komori Naoyuki , Yamagishi Hisakazu
Published: December 2021

Background

Stem cell therapy has emerged as a promising treatment for neurodegenerative diseases caused by the accumulation of abnormal proteins. We have administered repeated infusions of autologous adipose‐derived stem cells (ADSCs) to 39 patients with amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), Parkinson's disease (PD), multisystem atrophy (MSA) (including spinocerebellar degeneration (SCD)), and Alzheimer's disease. A total of 182 infusions have been administered, and not a single side effect has been observed. In this study, we evaluated cognitive function in 9 patients with cognitive impairment after administration.

Method

This treatment was conducted after registration with the Japanese Ministry of Health, Labour and Welfare, with the consent of the patient, approval of the Ethics Committee, and approval of the Specific Review Board for Regenerative Medicine. Stem cells were harvested from the patient's own abdominal subcutaneous adipose tissue and cultured in serum‐free medium. 5.0x10^7 to 1.2x10^8 stem cells were administered intravenously 5 or 6 times at approximately a‐month intervals. The evaluation was performed by neurologist's examinations, caregiver's interview and Montreal cognitive assessment (MoCA). Amyloid PET scans were performed before and after the treatment in three patients with Alzheimer's disease.

Result

MoCA scores averaged 10.3 points before administration and 19.6 points after 5 infusions of ADSC, and there were no cases of deterioration among the 9 patients evaluated. Not only did the overall score improve, but the clock drawing visibly improved. Improvement was also observed in medical examinations and caregiver interviews. Amyloid PET scan in one case showed a decrease in brain amyloid deposition. Three patients had associated parkinsonism but showed significant improvement when assessed by Unified Prkinson's Disease Rating Scale (UPDRS). We confirmed that the administered stem cells were CD10 (neprilysin, an amyloid‐degrading enzyme) positive.

Conclusion

Improvement in cognitive function was observed after 5 doses of ADSCs infusion. No side effects were observed, confirming that this treatment is repeatable and safe. The mechanism may be amyloid removal by neprilysin, but since parkinsonism is also improved, multiple factors are considered, including neuronal regeneration and repair, improvement of blood flow, anti‐inflammatory effects, and removal of multiple abnormal proteins and deposits, such as alpha‐synuclein in Parkinson's disease.
Irregular sleep wake rhythm disorder (ISWRD) signs and symptoms reported directly from patients with dementia and caregivers
Authors: Pokrzywinski Robin , Abel Cristina , Lenderking William R , Yardley Jane , Cheng Jocelyn , Moline Margaret
Published: December 2021

Background

Sleep‐wake disturbances appear early in the course of Alzheimer’s disease (AD) and other dementias and are not uncommonly associated with disruption in circadian rhythms, such as Irregular Sleep‐Wake Rhythm Disorder (ISWRD; ICD‐10 code G47‐23). ISWRD is also associated with behavioural and functional symptoms. The objective of this study (E2006‐A001‐111; NCT04300569) was to identify signs and symptoms of ISWRD important to patients and caregivers of patients with dementia and ISWRD. The data informed a novel questionnaire, filling a measurement gap as no questionnaires specific to ISWRD in the AD population are available.

Method

This cross‐sectional, qualitative, non‐interventional, telephone study interviewed patients and their caregivers. Caregivers were interviewed apart from the patient; patients were interviewed with caregivers present. All participants were from the US; data were collected in English and Spanish. Interview transcripts were analysed using ATLAS.ti software.

Result

15 patient/caregiver dyads and 5 caregiver‐only subjects were interviewed. For the patient group (n=20; 5 not interviewed), mean age was 79.0 (8.3)y and 75% were male. For the caregiver group (n=20), mean age was 67.5 (14.5)y and 20% were male. Both caregivers and patients noted fragmented nighttime and daytime sleep‐wake patterns, but also reported functional consequences of ISWRD. Nighttime examples included waking, wandering, and refusing to go back to sleep. Daytime examples included falling asleep at inappropriate places; appearing sleepy; losing concentration due to sleepiness; sleepiness interfering with personal care and leisure activities; needing to postpone, change, or avoid activities due to sleepiness; adverse emotional impacts, and sundowning. Few differences in terms, or their meaning, were identified between language of data collection. Based on the differing quality of patient and caregiver reports, the potential for patient anosognosia, and the ability of caregivers to observe signs and behaviours, the data suggested a caregiver‐completed observer‐reported outcome (ObsRO) measure is most appropriate for ISWRD evaluation.

Conclusion

Concepts reported by patients and caregivers uncovered ISWRD observations and functional consequences appropriate for a novel ObsRO measure that can be used in future studies of ISWRD. Support: Eisai Inc.
Reproductive factors and the risk of incident dementia: Results from the UK Biobank
Authors: Gong Jessica , Harris Katie , Peters Sanne , Woodward Mark
Published: December 2021

Background

Age‐standardised prevalence and deaths for dementia have been reported to be higher in women compared with men. The role of female‐specific endocrine and reproductive events in modulating dementia risk needs to be further clarified to explain some of these sex disparities.

Method

The UK Biobank recruited over 500,000 middle‐aged women and men. After 11.3 years, 3,701 (45% women) incident dementia occurred. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors and hormone use with dementia in women; number of children in both sexes.

Result

Adjusted HRs (95% CI) for dementia were 1.20 (1.08, 1.35) for menarche at <12, 1.24 (1.10, 1.39) at ≥15, compared to 13 years; 1.29 (1.12, 1.49) for menopause at <47 compared to 50 years; 1.13 (1.01, 1.27) for hysterectomy; 0.80 (0.72, 0.90) for use of oral contraceptive pills, and 1.56 (1.40, 1.73) for hormone replacement therapy. The number of children and dementia risk were similarly associated for women and men.

Conclusion

Hormonal transition and reproductive experiences were associated with women’s dementia risk, although the biological factors associated with childbearing are unlikely to account for the risk variation in women.
Association between ambient temperature and dementia‐related hospital admissions in England
Authors: Gong Jessica , Part Cherie , Hajat Shakoor
Published: December 2021

Background

The impacts of a changing climate on dementia burdens have not been widely explored, despite the increasing pressures associated with dementia on the public health and social care systems. This study explores the association between ambient temperature and the dementia‐related emergency hospital admission, using the national hospital inpatient dataset for England. We also examine important modifiers of the heat‐risk, including separate results for each Government region of the country.

Methods

Daily counts of emergency admissions with a primary diagnosis of dementia (ICD codes F00‐F03) and daily ambient temperature data from Met Office land surface stations were obtained for the period 2000‐2009 in England. Poisson regression was used to detect short‐term associations between daily mean temperature and daily counts of dementia admissions, adjusting for overdispersion and day‐of‐week effects, and including spline functions to model any underlying trends and seasonal patterns in the series. Distributed lag non‐linear models employing cross‐basis functions were used to characterise the exposure‐response relationship, at both national and regional levels at different lags of temperature; a 7‐day lag structure was used to explore potential delayed effects of temperature on the week leading up to admission. The modifying effects of age‐group, urban/rural residence, and quintiles of area‐level deprivation were also examined.

Result

There was some suggestion of seasonality in dementia admissions, with numbers peaking in the summer and winter months each year. After seasonal adjustment, there was an increase in the risk of dementia‐related hospital admission associated with high temperature, with adverse effects becoming apparent once daily mean temperatures rose above 15.0°C. At the national level, we estimated an approximately 10% increase in the risk of dementia admission for every 5°C increase in temperature above 15.0°C. When disaggregated by regions, the risk was highest in London. Separate results by age‐group, deprivation and urban/rural residence will be presented.

Conclusion

The findings are likely to have important public health implications for priority settings, such as for hospital emergency department planning during hot seasons. The dangers of heat‐induced symptoms among dementia sufferers can be anticipated by caregivers whenever hot weather is forecast.
Telehealth outreach programming in the Pacific island of Guam: Providing access to dementia care support services during the COVID‐19 pandemic
Authors: Twaddle Iain K. B. , Hattori‐Uchima Margaret Perez , Orallo Rhoda Gaba , Gutierrez Nikolas Jude
Published: December 2021

Background

The COVID‐19 pandemic has led to heightened levels of isolation and loneliness for millions of individuals and families worldwide, resulting in adverse health and mental health outcomes. Persons with dementia and their family caregivers are particularly vulnerable due to the deleterious impact of social isolation on both dementia symptoms and caregiver burden. One of the greatest challenges for dementia patients has been accessing dementia care services during COVID‐19 lockdowns. In the Pacific island of Guam, the pandemic quickly led to the closure of senior centers, adult day care centers, family caregiver support programs, and other social services for older adults and their families in March 2020. As a result, persons with dementia suddenly found themselves isolated at home and dependent upon family members to provide round‐the‐clock care. This presentation will describe the development of an innovative telehealth outreach program that was launched in Guam in the summer of 2020, three months after the first COVID‐19 case had appeared on the island. The program was designed to provide improved access to social support and specialized community services for persons with dementia and their family caregivers. There are four components: (1) virtual family caregiver support groups where participants can share the stresses and challenges of caring for a loved one with dementia with others who are going through similar experiences; (2) virtual presentation and consultation sessions led by dementia care specialists from the community providing easy access to dementia care information and services; (3) 24/7 family caregiver support networks through mobile messaging apps to mitigate social isolation and ensure the availability of support in times of crisis; and (4) telehealth family counseling for persons with dementia and their family members employing narrative approaches that embrace the oral storytelling traditions of Pacific island cultures. The community response has been strong with approximately 50‐60 family caregivers and persons with dementia participating in the program monthly. Project outcomes suggest that telehealth outreach services represent an effective and sustainable approach to connecting persons living with dementia and their family caregivers to community resources during times of isolation.
Plasma biomarkers for the AT(N) classification and for the detection of Alzheimer’s disease
Authors: Alcolea Daniel , Delaby Constance , Muñoz Laia , Torres Soraya , Estellés Teresa , Zhu Nuole , Barroeta Isabel , Carmona‐Iragui Maria , Illán‐Gala Ignacio , Santos‐Santos Miguel A. , Altuna Miren , Sala Isabel , Sánchez‐Saudinós Mª Belen , Videla Laura , Valldeneu Sílvia , Subirana Andrea , Pegueroles Jordi , Hirtz Christophe , Vialaret Jérôme , Lehmann Sylvain , Karikari Thomas K. , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik , Belbin Olivia , Blesa Rafael , Clarimón Jordi , Fortea Juan , Lleó Alberto
Published: December 2021

Background

Plasma markers are now available for all categories in the AT(N) classification. However, their agreement with CSF markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis and follow‐up of patients with Alzheimer’s disease (AD) through an easy and minimally invasive approach. We aimed to assess the agreement between plasma and CSF markers for the AT(N) classification.

Method

We measured Aβ, pTau181 and neurofilament light (NfL) in plasma samples of the SPIN cohort (Barcelona, Spain). Plasma Aβ‐peptides were quantified by Aβ immuno‐purification followed by mass spectrometry analysis. Plasma levels of pTau181 and NfL were measured using the ultrasensitive Single Molecule Array (Simoa, Quanterix). We assessed the correlation between plasma and CSF markers and calculated areas under the ROC curve (AUC) for individual plasma biomarkers to detect positivity/negativity in their respective category. We also calculated the accuracy of plasma biomarkers for the detection of the A+T+ profile.

Result

We included a total of 150 participants from the SPIN cohort, comprising patients with AD (n=27), Lewy body dementia (n=52), frontotemporal lobar degeneration‐related syndromes (n=25) and 46 cognitively normal participants.

As shown in Figure 1, we found moderate correlation between plasma Aβ composite and CSF Aβ1‐42/Aβ1‐40 (Rho=‐0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001). The plasma Aβ composite, pTau181 and NfL yielded AUC of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective categories. These accuracies were similar when other CSF cutoffs were applied (Figure 2). The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A‐T‐ participants (Figure 3).

Conclusion

Plasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. This signature could be applied in clinical routine as an early step for the diagnosis of AD or to detect AD copathology, optimizing the selection of potential candidates for disease modifying therapies.
The challenges of the family caregivers in caring of late onset schizophrenia and very late onset schizophrenia‐like psychosis: Caregiver risk of burden and neurodegenerative disease
Authors: Prabawati Chlara Yunita
Published: December 2021

Background

The challenges of taking care family member with Late Onset Schizophrenia (LOS) and Very Late Onset Schizophrenia Like Psychosis (VLOSLP) were enormous, include physiological and phycological factors. Family caregiver who taking care patients with schizophrenia experience emotional, physical, and financial challenges and lead of the caring process include decision of the patient’s institutionalizations. This study to investigate the burden experienced by family caregiver taking care to their family member with Late Onset Schizophrenia (LOS) and Very Late Onset Schizophrenia Like Psychosis (VLOSLP). Moreover, the impact of their challenges of the caring were maintain the FCG emotional wellbeing and how they cope of family caregivers’ strategies for the challenges.

Method

This study was cross ‐sectional, descriptive and correlational study. a total of 172 of Dyad FCG were recruited. the research instrument included the Revised Memory Behavior Checklist (RMBC), The Zarid Burden Interview (ZBI), and the Brief Psychiatric Rating Scale (BPRS). Descriptive study, Independent sample t‐test correlation and one‐way ANOVA were use to examined.

Result

The results indicated of more than 76% FCG were burdened and 29% exhibited Dementia. There was positive correlation of FCG Burden with patients Onset (Beta =1.27, p =<.01), FCG sex, Income (Beta =1.31, p =<.01), and level education (Beta =1.28, p =<.01). There was statistically positive correlation of FCG high burden with the level cognitive of FCG (Beta =1.32, p =<.01).

Conclusion

The findings improve our understanding about burden and emotional wellbeing in taking care of major schizophrenic with Late Onset Schizophrenia (LOS) and Very Late Onset Schizophrenia Like Psychosis (VLOSLP) especially for women might need a management for their cope with their own feelings. The findings of the study might benefit for health professional to plan the strategies focusing on help challenges of the family caregivers especially for women. the lesson learner from the FCG of LOS might be used to improve the caregiving strategies on patients with VLOSLP.
Remote cognitive assessment of older adults in rural areas by telemedicine and automatic speech and video analysis
Authors: König Alexandra , Zeghari Radia , Guerchouche Rachid , Bremond Francois , Bultingaire Vincent , Robert Philippe , Linz Nicklas
Published: December 2021

Background

Early detection of cognitive impairments is crucial for successful implementation of preventive strategies. However, in rural isolated areas or so‐called ‘medical deserts’, access to diagnosis and care is very limited. With the current pandemic crisis, now even more than ever, remote solutions such as telemedicine platforms represent great potential and can help to overcome this barrier. Moreover, current advances made in voice and image analysis can help overcoming the barrier of the physical distance by providing additional information of a patients’ emotional and cognitive state. Therefore, the aim of this study is to evaluate the feasibility and reliability of a videoconference system for remote cognitive testing empowered by automatic speech and video analysis.

Method

60 participants (aged 55 and older) with and without cognitive impairment are recruited. A complete neuropsychological assessment including a short clinical interview are administered in two conditions, once by telemedicine and once by face‐to‐face. The administration procedure is randomized. Acceptability and user experience are assessed among participants and clinicians in qualitative and quantitative manner. Speech and video features will be extracted and analyzed to obtain additional information on mood and engagement levels.

Result

Similar results were obtained on the several cognitive test measures when comparing the remote to the face‐to‐face administration method. Word recall (r=0,928) and picture naming task (r=0,939) showed the strongest correlation. Acceptability of the tool was relatively high with preference even in the remote method for more convenience.

Conclusion

Results support the feasibility and reliability of remote cognitive testing through administration via a telemedicine tool. These systems can be used for remote disease monitoring, enabling patients to be assessed in their own homes and improve utilization of expert assessors allowing them to conduct neurocognitive testing remotely.
Evaluation of visit‐to‐visit blood pressure variability on global cognitive impairment and cognitive decline in an ethnically diverse cohort: The multi‐ethnic study of atherosclerosis
Authors: Daniel George , Hughes Tim M , Bertoni Alain , Chen Haiying , Hayden Kathleen M
Published: December 2021

Background

Hypertension and diabetes are key modifiable risk factors for Alzheimer’s disease and related dementias. Research has typically focused on blood pressure (BP) levels, despite evidence that high BP variability (BPV) over time may predict poorer cardiovascular, neuropathological, and neurocognitive outcomes. We assessed associations between BPV and global cognition in a cohort of participants from the Multi‐Ethnic Study of Atherosclerosis (MESA), including 4 ethnoracial groups: White, African‐American, Chinese, and Hispanic.

Methods

Longitudinal BP data across 6 MESA examinations were used in multivariable linear and logistic regression analyses to determine the association BPV and cognitive function, decline, and incident impairment. Two measures of long‐term BPV (Average Real Variability [ARV] and Variability Independent of the Mean [VIM]) and group‐based latent BP trajectories were estimated over an average of 9.4 years. The Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS), were administered at MESA Exams 5 and 6, an average of 6.3 years apart. This enabled the assessment of cognitive function, decline, and cognitive impairment, defined as performance in the lowest 10% of groups stratified by age, education, and race.

Results

Participants (N=1314) had a mean baseline age of 57 years, and were 50% female and 48% White. Increased systolic and diastolic BPV were associated with poorer performance across all measures and with increased global cognitive decline in unadjusted models. Higher systolic (β = ‐0.06, P=0.05) and diastolic (β = ‐0.08, P=0.005) ARV was predictive of increased CASI decline after adjustment for demographic and clinical characteristics, including mean BP. Significant interactions and subsequent stratified analyses indicated that the strongest relationships between BPV and global cognition were in participants older than age 65, White or Black, APOE ε4 non‐carriers, males, and non‐antihypertensive medication users. Higher and more variable latent systolic and diastolic BP trajectories predicted reduced performance on the CASI, DS, or DSC tests before and after adjustment for clinical and demographic characteristics.

Conclusion

Results suggest high BPV is a risk factor for global cognitive dysfunction and decline, independent of mean BP levels, in this middle‐aged, healthy, and multi‐ethnic population. Relationships may differ across demographic, genetic, and clinical characteristics.
The Yonsei Lifestyle Profile for adults and the older adults: Development and test‐retest reliability
Authors: Park Ji‐Hyuk , Park Kang‐Hyun , Han Dae‐Sung
Published: December 2021

Background

Lifestyle is one of the vital determinants for health and quality of life for the older adults. This study aimed to assess the psychometric properties of the Yonsei Lifestyle Profile (YLP) in community‐dwelling adults and older adults,

Method

A lifestyle profile for adults and the older adults was developed through two approaches. First, a comprehensive literature review and Delphi studies with an expert panel were conducted to develop the items of the multidimensional lifestyle profile questionnaire. Second, the instrument psychometric properties were assessed in a sample of community‐dwelling older adults in South Korea. In total, 156 older adults completed the YLP. Internal consistency was analyzed using Cronbach’s alpha (α) reliability coefficient. Test‐retest reliability, using an intraclass correlation coefficient (ICC), was assessed based on scores attained two weeks apart,

Result

Sixty items were developed based on the comprehensive literature review and Delphi studies. The total scale of the YLP was .83 which reflects high internal reliability. The alpha values of the YLP subscales ranged from .80 to .74 for all participants. Regarding the test‐retest reliability, the ICC was .97 for the total scores of the YLP, ranging from poor to good (0.50–0.99) for the YLP subscales. Thus, it was confirmed that the YLP has good test‐retest reliability statistics.

Conclusion

The YLP developed to measure the multidimensional lifestyle factors of older adults is a valid instrument to apply in community‐dwelling adults and older adults. Therefore, the YLP questionnaire can be used in clinical practice when health‐care practitioners evaluate their client’s lifestyle.
Association of a MIND diet with the risk of dementia and brain structure in a French older population
Authors: Thomas Aline , Féart Catherine , Helmer Catherine , Catheline Gwenaelle , Samieri Cécilia
Published: December 2021

Background

The MIND diet score for brain health is a 15‐item score combining neuroprotective dietary components (e.g. green leafy vegetables, nuts, berries, whole grains, fish). A higher MIND diet score was associated with slower cognitive decline and lower risk of Alzheimer’s disease; however, its relationship with brain structure has not yet been investigated. Taking advantage of a large population‐based cohort of older adults, we constructed a MIND diet score adapted to French dietary habits and we evaluated the associations of the score with the risk of dementia and Alzheimer’s disease (AD). In a secondary analysis, we investigated the cross‐sectional relationship between the MIND diet score and gray matter structure assessed by Magnetic Resonance Imaging (MRI).

Method

We included 1,412 dementia‐free participants (aged ≥65) from the Three‐City Bordeaux study. A 148‐item Food Frequency Questionnaire and a 24‐hour recall administered at home in 2001‐2002 were used to calculate a MIND diet score, adapting component thresholding to French habits and guidelines (when applicable). Incidence of dementia and its subtypes from 2001‐2002 until 2017‐2018 was adjudicated by an expert committee. A subset of 207 participants were included in an ancillary MRI study in 2010‐2011. Gray matter volume and cortical thickness within the cortical signature of AD (i.e., 9 regions with cortical thickening predictive of subsequent AD) were estimated using FreeSurfer 5.1.

Result

Over a median follow‐up of 9.7 years (maximum 16.3 years), 356 participants (25.2%) were diagnosed with dementia, including 240 participants (17.0%) with AD. In multivariable Cox models, a higher MIND diet score was associated with lower risks of dementia (Hazard Ratio [HR] = 0.89 for each 1‐point increase of score; 95% Confidence Intervals [CI] = 0.83‐0.95) and AD (HR = 0.88; 95% CI = 0.81‐0.96). In the MRI sub‐study, a higher MIND diet score was significantly associated with higher total grey matter volume (β=2.54 mm3 for 1 point of score, p=0.005) and greater thickness in the AD signature (β=0.02 mm for 1 point of score, p<0.001).

Conclusion

This large population‐based study provides further evidence and new mechanistic insights for the role of the MIND diet in the prevention of dementia and AD.
Two dual GLP‐1/GIP receptor agonists show superior protective properties compared to liraglutide in the APP/PS1 mouse model of Alzheimer’s disease
Authors: Holscher Christian
Published: December 2021

Background

Type II diabetes is a risk factor for developing AD, and we have previously tested liraglutide, an analogue of glucagon‐like peptide 1 (GLP‐1) that is on the market to treat diabetes, in patients with MCI/Alzheimer’s disease (ELAD study) and shown that it improves cognition and memory (ADASexec) and reduces shrinking of the temporal lobe and grey cortical matter (MRI scans). Novel dual GLP‐1/GIP receptor agonists have been developed by us that can enter the brain at a higher rate than drugs that had been developed to treat diabetes. Here, we tested the protective effects of the dual agonists DA4‐JC and DA5‐CH, and DA4‐JC in direct comparison with liraglutide in the APP/PS1 mouse model of AD.

Methods

First we tested the dual GLP‐1/GIP agonist DA4‐JC and compared it with liraglutide at equal doses of 10nmol/kg bw ip. once‐daily for 8 weeks in the APP/PS1 transgenic mouse model of AD. DA5‐CH was tested separately in the same model. Memory formation in the water maze, synaptic plasticity (LTP) in area CA1 of the hippocampus using in vivo electrophysiology techniques, amyloid plaque load, and chronic inflammation was evaluated using histological and western blot techniques.

Results

When comparing DA4‐JC with the GLP‐1 analogue liraglutide in the APP/PS1 mouse model of AD, DA4‐JC was more effective in reversing memory loss in the water maze task, was superior in enhancing synaptic plasticity (LTP) in the hippocampus, in reducing amyloid plaque load in the cortex, and in lowering pro‐inflammatory cytokine levels of TNF‐alpha and IL‐1ß in the brain compared to liraglutide. DA5‐CH also reduced memory impairments, amyloid plaque load in the brain, and normalized synaptic plasticity in the hippocampus while reducing inflammation in the brain.

Conclusion

The results show that the dual GLP‐1/GIP receptor agonists DA4‐JC and DA5‐CH are effective in treating AD and show great promise to be a superior treatment for AD than liraglutide.
Association of resting heart rate with cognitive decline and dementia in older adults: A prospective population‐based study
Authors: Imahori Yume , Vetrano Davide Liborio , Xia Xin , Grande Giulia , Ljungman Petter , Fratiglioni Laura , Qiu Chengxuan
Published: December 2021

Background

Resting heart rate (RHR) is easily assessed and predicts future risk of cardiovascular (CV) events. However, large‐scale population‐based studies investigating the relationship of RHR with dementia and cognitive decline are scarce.

Method

We analysed data from baseline dementia‐free participants of the population‐based Swedish National study on Aging and Care in Kungsholmen (n=2423, age ≥60 years, mean age 71 years, female 61%) who were regularly followed from 2001‐2004 through 2013‐2016. RHR was assessed using a 12‐lead ECG at baseline. Incident dementia was diagnosed following the DSM‐IV criteria and global cognitive function was assessed using Mini‐Mental State Examination (MMSE). We used Cox proportional hazard models and linear mixed‐effects models with random intercepts and slopes to investigate the associations of RHR with incident dementia and cognitive decline, respectively, while controlling for demographics (age, sex, and education), smoking, physical activity, CV risk factors, and existing cardiovascular diseases.

Result

During the 12‐year follow up period, 332 participants developed dementia. As a continuous variable, per 10‐bpm increase in RHR was significantly associated with 12% increased risk of dementia (multi‐adjusted hazard ratio [HR] 1.12, 95% CI 1.02, 1.23). As a categorical variable, the multi‐adjusted HR (95% CI) of dementia associated with RHR (bpm) of <60, 60‐69 (reference), 70‐79, and ≥80 were 1.00 (0.75, 1.33), 1.00 (reference), 1.19 (0.89, 1.59), and 1.47 (1.04, 2.06), respectively. The multi‐adjusted β‐coefficients (95% CI) of MMSE score associated with the four categories of RHR were 0.01 (‐0.05, 0.07), 0.00 (reference), ‐0.10 (‐0.16, ‐0.03), and ‐0.16 (‐0.24, ‐0,08), respectively. There was no statistical interaction of RHR with gender and APOE ε4 allele on dementia risk (P for interaction >0.1).

Conclusion

Higher RHR is associated with increased risk for dementia and greater cognitive decline independent of CV risk factors and related diseases in a general population of older adults.