bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing risk taking and decision making associated with late‐life onset mild psychotics symptoms in cognitively normal older adults
Authors: Ismail Zahinoor , Aarsland Dag , Ballard Clive G , Corbett Anne , Creese Byron 
Published: December 2023

AbstractBackgroundLate‐life onset psychosis assessed in the Mild Behavioral Impairment framework (MBI‐psychosis) is a risk factor for dementia and known to be associated with impaired reasoning and memory in people without dementia. There is evidence that psychotic symptoms across diagnostic boundaries share some common genetic and neuropsychological correlates. In this study we aimed to determine whether MBI‐psychosis is associated cognitive deficits typically associated with other psychoses. To do this, we examined the relationship between MBI‐psychosis and scores on a specialised decision making and risk‐taking test, the Cambridge Gambling Task (CGT), performance on which is impaired in people with earlier life psychotic syndromes.Method476 participants were drawn from the online PROTECT registry on the basis of the Mild Behavioural Impairment Checklist (MBI‐C) ratings indicating psychosis and invited to complete the Cambridge Gambling Task. The association between performance on six CGT outcome measures, assessing elements of risk taking and decision making, and MBI‐psychosis was tested using linear regression (controlling for age, sex and education level).ResultOverall, there was little evidence of a substantial impact of MBI‐psychosis on CGT scores. Our study was powered to detect medium effect sizes. We found modest evidence of higher risk taking associated with more severe MBI‐psychosis scores (β = ‐0.1, SE = 0.05, p = 0.04) but this did not survive multiple testing correction.ConclusionThis is the first time a specialist decision making and risk‐taking test has been conducted in MBI‐psychosis. Although MBI‐psychosis is associated with a range of cognitive impairments in later‐life and dementia risk it appears that any shared neuropsychological basis with other psychoses is limited (though we cannot rule out a small non‐clinically significant effect size). This has possible implications for the diagnostic classification of later‐life onset mild psychotic symptoms.
Identification of pathogenic SORL1 genetic variants in Alzheimer’s disease patients
Authors: Holstege Henne 
Published: December 2023

AbstractBackgroundAn estimated ∼2‐3% of early‐onset Alzheimer’s disease (AD) patients carry a predicted rare damaging variant in the SORL1 gene, which encodes the SORLA receptor protein. While protein‐truncating variants (loss‐of‐function, LOF) occur almost exclusively in AD patients, the large majority of damaging variants are missense variants. However, the effect of individual missense variants on AD risk varies widely, warranting a variant pathogenicity screen.MethodsWe prioritized genetic variants in SORL1 by investigating to what extent they lead to familial disease when they occur in protein homologs. We used a sample of 18,959 non‐related AD cases from the ADES/ADSP studies to investigate the age‐at‐onset in carriers of a prioritized SORL1 variant relative to WT SORL1 in context of APOE genotype. Second, since functional SORLA is cleaved at the neuronal membrane into soluble SORLA (sSORLA) we used Western Blot and proteomics to test whether SORL1 variants affected the level of sSORLA in CSF.ResultsCompared to SORL1 wild type AD patients, carriers of prioritized SORL1 variants had an expedited age at onset similar to carriers of LoF variants: of those homozygous for APOE‐ε4 who carried a prioritized SORL1 variant, 80% had AD by age 61 (95%CI 60‐NA, n = 6) compared to 73 for WT‐SORL1 carriers (95%CI 72‐73, n = 1091). Of those heterozygous for APOE‐ε4 who carried a prioritized SORL1 variant, 80% had AD by age 71 (95%CI 68‐76, n = 62) compared to age 78 WT‐SORL1 carriers (95%CI 78‐78, n = 4816). Of those negative for the APOE‐ε4 allele with a SORL1 variant, 80% had AD by 83 years (95%CI 78‐90, n = 54) compared to 85 years for WT‐SORL1 carriers (95%CI 85‐85, n = 5773). These effects were absent for non‐prioritized missense variants. Second, using WB we found that sSORLA levels in carriers of pathogenic missense variants were reduced to ∼50% relative to carriers of benign SORL1 variants, while levels of truncating SORL1 variants were reduced to ∼65%.DiscussionPrioritizing SORL1 missense variants according to variant‐effects in protein homologs leads to variants that expedite the age‐at‐onset independent of APOE background. Carriers of pathogenic missense or truncating variants have low CSF‐sSORLA levels, which may serve as a biomarker for impaired SORL1.
Researcher turned care partner: Perspectives on lived experience of navigating ADRD
Authors: Gelmon Sherril B 
Published: December 2023

AbstractThis presentation will illustrate the lived experience of a health services researcher who was a care partner for her husband with ADRD. This couple engaged for 11 years with an academic Alzheimer’s center for clinical management and participation in several clinical trials. This care partner was motivated to care out of love and concern, learning by doing and taking on unfamiliar responsibilities. Few people understood the personal time commitment and challenges, and the hours of vigilance to ensure her husband was safe, healthy, and living at home with dignity. She was challenged to maintain her scholarly career.The needs of care partners are often unmet. Caring for a family member can lead to psychological and physical distress. Personal experience highlighted the need for information about ADRD progression, financial and legal advice, routine and respite care, and psychological support. Support programs did not address the advanced stages of disease. COVID‐19 reduced supports and increased isolation. This care partner learned to effectively support and care while navigating the Alzheimer’s disease delivery and research systems, and identifying relevant resources to support the family dyad. Since the husband’s death, the researcher has refocused her research agenda to study strategies, policies and mechanisms to enable care partners, clinicians and researchers to coproduce care systems that better support care partners.This researcher’s experience highlights the need to recognize and value the essential role the care partner plays in supporting the person with ADRD. Care partner resources are frequently determined and designed by expert health and social service providers. Person‐centered health initiatives are enhanced through coproduction where patients, partners, and clinicians develop, deliver, assess and improve the relationships and actions that contribute to the health of the person with ADRD.Coproducing care and support for a person with ADRD requires actively engaging the care partner to represent their personal dyad, and inviting them to articulate the resources, services and supports they need to navigate their journey as a care partner that will complement clinical care. This presentation will frame the context for the three presentations that follow, illustrating approaches to effectively coproducing ADRD care.
Lipopolysaccharide aggravates depressive‐like behavior via increasing microglial inflammation, decreasing microglial ramification, and altering tryptophan level in obese rats
Authors: Chunchai Titikorn , Chinchapo Thirathada , Pintana Hiranya , Arunsak Busarin , Janjek Sornram , Kerdphoo Sasiwan , Nawara Wichwara , Thonusin Chanisa , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2023

AbstractBackgroundLong‐term high‐fat diet consumption has been shown to induce endotoxemia, microglial dysmorphology, and depressive‐like behavior (1, 2). Previous studies demonstrated that the kynurenine pathway of tryptophan metabolism plays an important role on mediating the depressive‐like behavior in response to inflammation (3, 4). However, the effects of lipopolysaccharide as endotoxin on the alterations of microglial profiles/morphologies, changes in brain metabolites, as well as depressive‐like behavior in obese condition have never been investigated.MethodSixteen male Wistar rats were randomly divided into two groups to fed with either normal diet (ND, n = 8) or the high‐fat diet (HFD, n = 8) for 12 weeks. At week 12, animals in each dietary group were subsequently divided into two subgroups (n = 4 per subgroup) to receive either a single dose of vehicle (1 ml of 0.9% normal saline solution, intraperitoneal (i.p) injection, or lipopolysaccharide (LPS, 0.5 mg/kg, i.p. injection). After the injections for 12‐16 hours, all animals were measured depressive‐like behaviors and blood was collected. Then, animals were sacrificed, and brains were obtained for further molecular investigation.ResultWe found that LPS‐treated HFD‐fed rats, not LPS‐treated ND‐fed rats and vehicle‐treated HFD‐fed rats, increased microglial IL‐1β mRNA level (p<0.05, Figure 1). In addition, LPS‐treated ND‐fed rats and vehicle‐treated HFD‐fed rats significantly decreased microglial ramification as indicated by decreasing branch points, whereas LPS‐treated HFD‐fed rats showed the lowest microglial branch points (p<0.05, Figure 1). The level of brain tryptophan and depressive‐like behavior increased in both LPS‐treated ND‐fed rats and vehicle‐treated HFD‐fed rats, when compared with those of vehicle‐treated ND‐fed rats (p<0.05, Figure 1). Interestingly, LPS‐treated HFD‐fed rats showed the highest brain tryptophan level and freezing duration during Force Swimming Test (FST) (p<0.05, Figure 1).ConclusionThese findings indicate that LPS aggravates depressive‐like behavior in obese condition by increased microglial hyperactivation, and possibly be related to its regulation of kynurenine metabolism.
What do public high school teachers in Nigeria know about dementia?
Authors: Olaniyi Olajumoke , Ogunyemi Adedoyin O , Olusanya Adedunni W 
Published: December 2023

AbstractBackgroundThe number of dementia cases is projected to triple in the next 20‐25 years with majority of the increase in developing countries including Nigeria. Teachers can act as excellent educators by playing a key role of delivering important health education messages to students that target early adoption of healthy behaviours and reduce stigma. However, there is no assessment of school teachers’ understanding of dementia in Nigeria.MethodThis was a cross‐sectional study of 300 high school teachers, aged 18 years or older, and working in public schools in Lagos, Nigeria. A 14‐item questionnaire with yes/no or don’t know responses was used to assess their knowledge about dementia from June to November 2022. The data obtained were analysed using IBM Statistical Package for Social Sciences (SPSS) Version 25.ResultThe mean age of respondents was 42.9 ± 9.9 years and 59.3% of them were females. The majority (81.0%) had heard about dementia and 32.0% knew someone with dementia. The mean score for knowledge about dementia was 7.4 ± 0.2 points out of 14 points. More than half of the respondents (56.0%) reported that dementia is a normal part of ageing, 29.7% considered dementia to be a mental illness, and a half (50.0%) of the participants did not know if dementia could be cured. The level of dementia knowledge was not significantly associated with age or with education level.ConclusionOur results suggest that the teachers had a fair knowledge of dementia. There is a need to better educate school teachers and improve their knowledge about dementia. Emphasis on the risk factors, prevention, and symptoms of dementia should be included in the educational content.
Systematic Review on the Social Participation Assessment Tool for Older Adults
Authors: Lee Hamin , Kim Mi Kyeong , Park Hae Yean , Yun Sohyeon , An Hyun Seo , Kim Inhye 
Published: December 2023

AbstractBackgroundDue to the extension of the life expectancy of the elderly population, the importance of living healthy rather than simply leading a life in old age is emphasized. It is difficult to maintain social participation for older adults because most of them experience the termination of work or childcare which have been their major life roles. Considering that social participation is a factor that has a multifaceted effect on the health of older adults, it is necessary to understand and promote older adults’ social participation. This systematic review aims to analyze the literature using social participation assessment tools for older adults and presented the frequency of use, assessment items, and methods of each assessment.MethodUsing databases from Pubmed, Medline, CINAHL, and Web of Science, a total of 2,423 studies were collected. 18 studies were selected according to the selection and exclusion criteria.Result9 studies (50%) were published in the last five years. In the case of research design, 12 studies (66.6%) were designed as cross‐sectional survey studies, which were found to be the most common. There were a total of 11 assessment tools for older adults’ social participation among 18 studies. The most widely used assessment tool was Assessment of Life Habits (LIFE‐H), which was used in a total of 7 studies (38.9%). It was found that the components were different for each tool. Most of the assessment tools were in the form of self‐reporting questionnaires. Frequency of the participation was the most common method. Others asked the degree of difficulty and a number or status of participating activities.ConclusionIn this study, a total of 18 pieces of literature were reviewed to analyze the assessment tool that measured the social participation of older adults of 65 and above. A total of 11 assessment tools were derived, and LIFE‐H was the most frequently used. Through this study, it is expected that clinicians or researchers can help when judging and selecting social participation assessment tools, and that appropriate tool selection can lead to a better understanding of the social participation of older adults.
Integrated Primary Care Model Prevents Hospitalizations for People Living with Dementia
Authors: Clevenger Carolyn K , Medders Laura J , Khakharia Anjali , Moore Miranda 
Published: December 2023

AbstractBackgroundPeople living with dementia (PLWD) have high rates of total and ambulatory care sensitive hospital admissions and emergency department utilization. Ambulatory care sensitive hospital admissions are those that could be avoided by robust outpatient care. The Integrated Memory Care (IMC) is a comprehensive dementia care model where patients and their family caregivers access dementia‐sensitive geriatric primary care.MethodsWe conducted a retrospective observational study of adult patients of IMC, Cognitive Neurology (CN), and Primary Care (PC) clinics aged 65 and older with a diagnosis of dementia in 2019‐2021. We matched patients by age, gender and race and measured the risk of hospitalization using logistic regressions controlling for clinic. Additionally, we conducted a regression adjusted for state of illness (proxied by activities of daily living (ADL)) for the IMC and CN clinics.ResultsOverall 509 patients seen in IMC were matched with 490 CN patients and 509 PC patients. Most patients were female and white and aged 70‐85. IMC patients had higher overall ADL scores than CN indicating more functional dependence. CN [PN] had 10% [2 times] higher odds (Odds Ratio (OR): 1.107; 95% Confidence Interval (CI): 0.87‐1.41; OR: 2.037; 95% CI: 1.440‐2.882), when compared to IMC patients in unadjusted models. After adjusting for ADL scores, CN patients had 66% higher odds (OR: 1.662; 95% CI: 1.260‐2.193) of having a hospital admission during the study period.ConclusionsDementia‐sensitive primary care reduces the rate of total and ambulatory‐sensitive hospitalizations reducing healthcare costs and causing less disruption to care.
Increased levels of Osteopontin are associated with dementia in the presence of cerebral small vessel disease
Authors: Gardener Hannah , Ghare Smita S. , Ariko Taylor , Gutierrez Jose , Wright Clinton B. , Goldberg Ronald B , Cooper Gregory , Shields Christopher B , Barve Shirish , Rundek Tatjana 
Published: December 2023

AbstractBackgroundOsteopontin is a proinflammatory cytokine associated with systemic vascular, inflammatory, and autoimmune diseases. It has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that plasma osteopontin is a deleterious neuroinflammatory marker increased in people with dementia and cerebral small vessel disease (CSVD).MethodWe conducted a pilot study in participants in the longitudinal multi‐ethnic Northern Manhattan Study (NOMAS). Three groups were selected based on their dementia status and evidence of subclinical CSVD, and chosen to be similar in age, sex, and education attainment: No Dementia/No CSVD (n = 19), Dementia/No CSVD (n = 22), and Dementia+CSVD (n = 21). Dementia (any type) was diagnosed by consensus adjudication following a series of comprehensive neuropsychological assessments and a review of medical history. CSVD was indicated by silent brain infarcts, perivascular spaces, cerebral microbleeds, and white matter hyperintensity volumes on MRI. Osteopontin was measured by quantitative solid‐phase ELISA. Multinomial logistic regression was used to examine the difference in osteopontin levels across groups, adjusting for key determinants of CSVD and neurodegeneration in NOMAS, including age, race/ethnicity, BMI, and brain volume.ResultOsteopontin levels were substantially elevated in the Dementia+ CSVD group (mean = 70.69±39.00 ng/ml) and only slightly increased in the Dementia/No CSVD group (mean = 45.46±19.11) compared to the No dementia/No CSVD group (mean = 36.43±15.72). Osteopontin was associated with dementia+CSVD (Odds Ratio (OR) per ng/ml = 1.06, 95%CI 1.02‐1.11) in unadjusted analysis, and this remained consistent and significant after adjusting for covariates, including brain volume. Osteopontin was strongly correlated with WMHV (Pearson r = 0.46, p = 0.0001), but not with other components of CSVD.ConclusionIn this pilot study, we observed a significant relationship between increased levels of osteopontin and dementia. This link is predominately driven by vascular contributions to dementia through the presence of CSVD, specifically through the burden of white matter lesions on MRI. Brain volume, a marker of neurodegeneration, does not seem to influence this relationship. Our study provides further evidence to suggest that underlying white matter disease and CSVD are likely targets of deleterious osteopontin expression in dementia.
The associations of diet quality trajectories with cognitive frailty in community‐dwelling older adults
Authors: Lee Ting‐I , Chen Ling‐Wei , Chiou Jeng‐Min , Chen Ta‐Fu , Chen Jen‐Hau , Chen Yen‐Ching 
Published: December 2023

AbstractBackgroundDiet quality is an essential modifiable factor that has been associated with cognitive performance and physical function. However, few studies investigated the association of diet quality trajectories with “cognitive frailty.” This study aimed to identify specific diet quality trajectories and explore their relationship with cognitive frailty in Taiwanese community‐dwelling older adults.MethodThis 11‐year cohort study (2011‐2022) recruited 520 non‐demented older adults at baseline (2011‐2013). The global and domain‐specific cognition was assessed by the Taiwanese version of the Montreal Cognitive Assessment and a battery of neuropsychological tests. Physical frailty was assessed by a modified version of the criteria of Fried et al. The presence of both physical frailty and MCI was defined as cognitive frailty. Diet quality was assessed by the modified Alternative Healthy Eating Index, which includes seven components obtained from a semi‐quantitative food frequency questionnaire. Growth mixture modeling was used to identify diet quality trajectories over 11 years. The generalized linear mixed model was used to explore the association of energy‐adjusted diet quality trajectories with cognitive frailty over time adjusting for important covariates.ResultThis study identified four diet quality trajectories: 1) worsening, 2) low‐moderate‐low, 3) moderate‐low‐moderate, and 4) still low. Compared to trajectory 4, trajectory 3 had lower odds of worsening frailty [adjusted odds ratio (aOR) = 0.48; 95% confidence interval (CI): 0.27, 0.85], worsening cognitive‐frailty (aOR = 0.52; 95% CI: 0.30, 0.92), and impaired logical memory‐frailty (aOR = 0.42‐0.53). In addition, trajectory 1 had lower odds of worsening impaired logical memory‐physical frailty (aOR = 0.53; 95% CI: 0.32, 0.86) compared with trajectory 4. No association was found for trajectory 2.ConclusionWe found that the moderate‐low‐moderate diet quality trajectory lowers the odds of worsening frailty and cognitive frailty. Further studies on different ethnic groups will help researchers to clarify the temporal relationship between diet quality and cognitive frailty.
Real‐time quaking‐induced conversion assay using a small‐scale substrate production workflow for the diagnosis of Creutzfeldt‐Jakob disease
Authors: Chongsuksantikul Adipa , Thanapornsangsuth Poosanu , Saraya Abhinbhen Wasontiwong , Hiransuthikul Akarin , Hemachudha Thiravat 
Published: December 2023

AbstractBackgroundThe lack of a dedicated surveillance program for prion disease, particularly in low‐ and middle‐income countries (LMICs), has hindered the global effort to address this public health threat. Although CSF Real‐time quaking‐induced conversion (RT‐QuIC) is considered the most reliable test for sporadic Creutzfeldt‐Jakob disease (sCJD), its availability in LMICs is limited due to its cost and technical difficulty in generating the recombinant prion protein substrate (recPrP). This study aimed to evaluate the performance of RT‐QuIC with recPrP produced in‐house through a small‐scale method – i.e. the application of reusable pre‐packed chromatography columns and subsequent dialysis.MethodCSF specimens from patients suspected of having prion disease were consecutively collected and stored between October 2015 and November 2022. Those with available CSF for RT‐QuIC analysis were included in this study. Electronic medical record data were reviewed to clinically classified participants as probable sCJD or non‐sCJD. CSF RT‐QuIC was performed using in‐house recPrP and 2nd generation (improved‐QuIC) protocol (Orrú et al., 2015). Its specificity and sensitivity for diagnosing probable sCJD were reported, along with details of other clinical data and investigations.ResultAmong 38 eligible participants, with a median (interquartile range) age of 64 (56.5‐70) years and 15 (39.5%) female, 12 had probable sCJD and the remaining 26 unequivocally suffered from non‐prion disorders. MRI and EEG were suggestive of sCJD in 100% (12/12) and 50% (6/12) of sCJD participants, respectively. PRNP gene sequencing was performed in all sCJD and 7 non‐sCJD participants, all of whom had MM genotype without mutation. RT‐QuIC was positive in 11/12 sCJD participants (sensitivity 0.92, 95% confidence interval (CI) 0.65‐0.99) and negative in all non‐sCJD participants (specificity 1.00, 95%CI 0.87‐1.00). CSF tau/p‐tau ratio showed sensitivity and specificity of 0.67‐1.0 and 0.85‐1.0, respectively.ConclusionRT‐QuIC using recPrP generated through a small‐scale workflow demonstrated great performance in detecting sCJD. Given its performance results along with its low cost, this technique could feasibly be implemented in LMICs and potentially be the first step towards establishing local prion disease surveillance programs that will strengthen the global efforts.