bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitigating risks of online engagement; considering the contexts and mechanisms of cybercrime among older adults
Authors: Burton Alexandra , Tripathi Kartikeya , Cooper Claudia
Published: December 2023

Background

This talk will explore how benefits of remote interventions can be realised for older people with cognitive impairments alongside risk mitigation, drawing on a realist review of how and in what circumstances older people become victims of cybercrime. We aimed to identify factors leading to older adults' victimisation, and review theory and evidence for interventions to reduce victimisation risks.

Method

We conducted a realist review synthesising published literature and gathering stakeholder experiences via an online workshop to understand how, why and in what circumstances older adults are at risk of financial cybercrime victimisation. We used the evidence to develop a programme theory and Context, Mechanism, Outcome Configurations (CMOCs) to explain the mechanisms by which older adults become victims of financial cybercrime in different contexts, and to inform the development of interventions to produce desired outcomes of reducing and preventing cybercrime.

Result

We analysed 52 primary and secondary data sources and consulted with 21 stakeholders from across health, social, legal, and financial sectors. Our programme theory comprised 16 CMOCs describing how social isolation, cognitive decline, physical and mental health problems; wealth status, limited cyber security skills or awareness, societal attitudes and content of scams led to increased risk of victimisation. Only evidence for interventions to enhance cyber security awareness and skills of potential older victims was identified. Targeting offender motivation, redesign of security software to increase usability by older people and training programmes for professionals and family members are rational, yet untested interventions. A shift in societal attitudes, conveying positive messages, of older people’s rights to be safely active online, is needed too.

Conclusion

Protection from cybercrime is instrumental to supporting ageing in a digital world. Incorporating cyber security awareness into future interventions that promote social connectedness, cognition and healthy lifestyles, alongside legal structural protections, and measures to improve societal attitudes towards financial cybercrime victimisation will help older adults navigate online spaces safely. Training programmes targeting older adults, or their supporters should be deliverable by a range of professionals for greatest reach; and be co‐designed with end users to ensure that if they are useful, they are acceptable and used.
Clinical effectiveness of the NIDUS randomised control trial of a tailored, goal‐focused intervention for increasing goal attainment in people living with dementia and their family carers
Authors: Budgett Jessica , Barber Julie , Hunter Rachael M , Rapaport Penny , Lord Kathryn , Livingston Gill , Manthorpe Jill , Hoe Juanita , Rockwood Kenneth , Howard Robert J , Butler Laurie , Orgeta Vasiliki , Walters Kate , Cooper Claudia
Published: December 2023

Background

Most people living with dementia want to remain living in their own homes and are supported to do so by family carers. We have co‐produced, with family carers of people with dementia and health and social care professionals, a psychosocial intervention (NIDUS‐family). NIDUS‐family is the first fully manualised intervention that is tailored to personal goals of people living with dementia and their families and is delivered by facilitators without clinical training. The intervention utilizes components of behavioural management, carer support, psychoeducation, communication and coping skills training, enablement, and environmental adaptations, with modules selected to address dyads’ selected goals.

Method

A randomised, two‐arm, single‐blind, multi‐site clinical trial involving 302 people living with dementia‐family carer dyads. Dyads were randomised 2:1 to receive the NIDUS‐family intervention with usual care (n = 204) or usual care alone (n = 98). The intervention group received over 1 year, 6‐8 video call or telephone sessions (or face to face if COVID‐19 restrictions allowed) in the initial 6 months, followed by telephone follow‐ups every 1‐2 months to support implementation, with a trained facilitator. We will evaluate the effect of NIDUS‐family and usual care on attainment on goals set by family carers towards the care recipient living as well as possible at home, as measured by Goal Attainment Scaling (GAS), compared to usual care alone at 12‐month follow‐up. Secondary outcomes measures include functioning, neuropsychiatric symptoms of care recipients, time remaining living at home and care costs, and family carer mood, quality of life and reported abusive behaviours.

Result

The trial recruited to target, with good adherence to the intervention (85% fully adherent) and trial retention to date (87% at 6‐month follow‐up). The trial’s 12 month follow up data will be completed in early May 2023 and results will be analysed and ready to share by July 2023.

Conclusion

Our intervention, which we adapted to include remote delivery prior to commencement due to the COVID‐19 pandemic, aims to address barriers to living as well and as independently as possible. If effective, NIDUS‐family is potentially scalable to benefit many people living with dementia and their family carers.
Transcranial pulse stimulation (TPS) as a method for treating the central nervous system of patients with Alzheimer’s disease
Authors: Ziegenbein Marc , Rößner‐Ruff Vanessa , Clark Daniel
Published: December 2023

Background

Dementia ‐ one of the most common diseases in old age ‐ is often only diagnosed at a late stage. Therefore patients with dementia have often a 1.4 to 3.6 times greater risk of treatment as an inpatient. Consequently it is highly relevant within the caring system to identify and treat the onset of dementia at the earliest possible opportunity.

Part of a new treatment center, a psychiatric clinic in the Hanover area (Wahrendorff) has concentrated on treating patients with a mild or moderate form of Alzheimer’s disease as early as possible on an outpatient basis. The method of transcranial pulse stimulation (TPS®) with the Neurolith® system is used. Acoustic pulses generated outside the body are introduced specifically into the brain regions requiring treatment. The aim being the release of growth factors and an improvement in cerebral blood flow, as a means of maintaining and promoting cognitive performance for as long as possible. The poster contribution shows reports from clinicians, patients and relatives, using TPS®. The development of cognitive performance in the course of treatment is also considered.

Method

The data collection for the quantitative study design will take place at the clinic in the period from 06/2021 to 10/2022 (N = 61). Cognitive performance is recorded using the Montreal Cognitive Assessment (MoCA test) and the experience reports via interview.

Result

Results of repeated measurement and analysis of the variance in terms of cognitive performance (MoCA test, baseline and follow‐up measures) showed cognitive improvements.

Conclusion

Transcranial pulse stimulation is a new and promising approach in the treatment of Azheimer’s disease.
Cobalt exposure triggers impairments in cognitive and anxiety‐like behaviors, brain oxidative stress and inflammation, and hippocampo‐amygdala histomorphological alterations: Protective role of aqueous Prosopis africana seed extract
Authors: Oria Rademene Sunday
Published: December 2023

Background

Cobalt toxicity has become a health concern in recent years, due to overexposure resulting in neurological impairments like dementia. With a growing interest in the therapeutic roles of herbs, in toxicity research, it’s worth looking into the curative effects of aqueous Prosopis africana seed extract, a plant rich in flavonoids on cobalt‐induced dementia‐like and anxiogenic behaviour.

Method

We treated rats with Cobalt (CoCl2) or CoCl2 in combination with aqueous Prosopis africana seed extract (PAE) orally for 14 days. Control rats received distilled water for the same period. Following treatments, behavioral experiments for cognition and anxiety, analysis for oxidative stress, inflammation, histological and immunohistochemical analysis were performed.

Result

Results revealed that CoCl2 reduced the exploration time, recognition index in the novel object recognition test, percentage spontaneous alternation in the Y‐maze tests, and reduced open arm entry and duration in elevated plus‐maze. However, treatment with PAE improved these parameters to levels comparable with those of the control group. Furthermore, PAE therapy reduced CoCl2‐induced surge in hydrogen peroxide, malondialdehyde, TNF‐α and IL‐1β levels in brain homogenate, while also increasing superoxide dismutase and reduced reduced‐glutathione activities. CoCl2 exposure resulted in obvious features of neurodegeneration like nuclear disintegration, nuclear shrinkage, and cytoplasmic vacuolations of the cells of the hippocampus and amygdala, with an increased expression of GFAP. The hippocampal and amygdala histology improved after PAE administration, while exacerbated GFAP expressions were attenuated.

Conclusion

These findings imply that PAE may be anxiolytic and can help reduce cognitive impairments and hippocampal damage caused by CoCl2 neurotoxicity, via mechanisms that involve attenuation of oxidative stress and neuroinflammation.
Association of the cognitive reserve with the age of onset of mild cognitive impairment and dementia in patients with or Alzheimer’s disease. Antioquia, Colombia.
Authors: Orrego Natalia Trujillo , Medina Marisol , Sanchez Juan Pablo , Londono Natalia , Parra‐Rodriguez Mario A , Aguirre‐Acevedo Daniel C. , Lopera Francisco
Published: December 2023

Background

The cognitive reserve (CR) has been associated with the extension/compensation of the mental functioning of individuals affected by a neurodegenerative disease in the early stages of the disease. Most of the analyses evaluating CR are in high‐income countries, while there is a lack of capturing the variability related to low‐middle‐income environments such as Colombia. Objective: to analyze the relationship between CR and the age of onset of MCI and/or dementia by Alzheimer’s disease (AD) in patients from Antioquia‐Colombia.

Method

A retrospective cohort study of 194 individuals. Clinical and socioeconomic characteristics were described using absolute and relative frequencies, followed by a mixed principal component analysis to represent the CR. A Varimax rotation was used for its interpretation, generating Z scores for the CR and the resulting dimensions. CR was categorized according to the median as high or low. This categorization aims to assess differences in the onset time of MCI and dementia by AD for the survival analysis and Cox regression with multiple imputation models (m = 30). We also examined all data to estimate the raw effect and adjusted for age, sex, and area.

Results

from 194 patients, 151 informed the age of onset of MCI, and 165 were later diagnosed with dementia by AD. There were differences between 5 and 9 years in the median age of onset of MCI and dementia by AD, with a later onset for patients with high CR. The CR hazard ratios (HR) were 1.05 and 0.97 for MCI and dementia, respectively. The ratio for the total score tended to be null after adjustment with confounding variables. However, its dimensions remained significant. Specifically, the HRs for an academic position, growing environment, and family status increased the speed of onset of the outcomes for MCI: 1.43, 1.06, and 1,72 and dementia: 1.40, 1.12, and 1.68.

Conclusion

the onset times of the MCI and dementia were five years later in subjects with higher CR. Thus, a high academic position, a protective growth environment, and a family status that favors social relationships were associated with the reduction in clinical symptoms of AD since the early stages.
Central‐acting vs. Peripheral‐acting Angiotensin Converting Enzyme‐inhibitors and the risk of Alzheimer’s disease: A cohort study
Authors: Adesuyan Matthew , Brauer Ruth , Jani Yogini
Published: December 2023

Background

Cerebral Angiotensin converting enzyme (ACE) has been shown to cleave amyloid‐beta (Aβ) and its expression may have a protective effect on the risk of Alzheimer’s disease (AD). However, there are conflicting reports of the association between ACE‐inhibitors (ACEi) and AD. ACE‐i drugs differ in their ability to cross the blood brain barrier and inhibit cerebral ACE activity. No previous study has investigated the effect of ACE‐i on the risk of AD based on their different pharmacological properties.

Method

A population based cohort study was performed using real‐world data from the IQVIA Medical Research Database (IMRD‐UK). Adults aged ≥40 years initiating ACEi therapy were followed from 2000‐2021. Based on previous studies of tissue‐specific ACE‐activity and radio‐labelled imaging after administration of ACEi, we classified ACEi as either central (CA) or non‐central (NC) acting. New users of CA‐ACEi were compared with new users of NC‐ACEi. Diagnostic read codes linked to clinical diagnoses were used to measure the primary outcome of incident AD. Potential confounders including, laboratory results, socioeconomic status, comorbidities, co‐prescriptions, smoking, alcohol and body mass index were adjusted for using multivariable Cox proportional hazard regression to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CI).

Result

The cohort included 808,180 new ACEi initiators, with 7,356 newly diagnosed with AD during a median follow up of 8 (IQR 4‐12) years. The crude incidence rate (IR) for users of CA‐ACEi was 18.6 per 10,000 PYAR (95% CI 18.2‐19.1) and 21.6 per 10,000 PYAR (95% CI 19.3‐24.2) in NC‐ACEi initiators. The adjusted HR for the associated risk of AD in CA‐ACEi compared to NC‐ACEi was 0.83 (95% CI, 0.74‐0.94; p = 0.002). Primary results were robust to sensitivity analysis that required the outcome of AD to include both a clinical diagnosis and prescription for symptomatic treatment of AD; HR 0.80 (95% CI 0.69‐0.92; p = 0.002).

Conclusion

Conversely, CA‐ACEi with penetrative blood‐brain‐barrier properties were associated with a lower risk of AD compared to NC‐ACEi. This may be due to improved cerebral blood flow and the prevention of angiotensin II‐mediated inhibition of acetylcholine. Our results question the significant contribution of ACE mediated Aβ degradation.
The Relationship between dementias and zip codes in the US: The African American community and higher rate of Alzheimer’s disease
Authors: Shah Yogesh
Published: December 2023

Background

Not many people will connect the dementia rate with the person’s ZIP Code, but unfortunately, our ZIP Code significantly influences our overall health, including dementia. Many Black Americans experience a higher rate of Alzheimer’s and vascular dementia compared to whites, and the disproportionate impact is devastating, especially for black women. The risk of developing Alzheimer’s is two to three times higher for Black Americans—who are diagnosed at later stages—than for the general population.

Method

Through literature search, small group discussion with African American community members and faith‐based community leaders, education about relationship between dementia and zip codes was addressed.

Results

Faith‐based communities can play a significant role in improving chronic conditions, awareness, and early detection, especially in the African American patient population.

Conclusion

As the U.S. population ages and communities of color become a higher proportion of the older population, a higher percentage of those with Alzheimer’s disease will be people of color. It is not entirely clear why Black Americans are at a higher risk. Still, current research suggests that the increase may be related to three factors: Higher rate of Chronic conditions ‐ the connection between vascular conditions and dementia; Delayed diagnosis ‐ Black participants in Alzheimer’s disease research studies were 35% less likely to be diagnosed than white participants and Social Determinants of Health (SDOH) ‐ there is a link between SDOH and dementia. Unfortunately, in the USA, our zip code is more important than our genetic code.
Tolerability and Likeability of a Cognitive Training Program in an Outpatient Memory Care Clinic
Authors: Ashish Dev , Anderson Allan A
Published: December 2023

Background

Patients with mild cognitive impairment (MCI) or early stages of dementia often search for treatments to improve their cognitive and daily functioning or help with managing their deficits. Research suggests that multi‐component non‐pharmacological interventions provided to patients with caregivers have similar benefits as pharmacological treatments but without any side effects. Previously, we presented about developing a multi‐component and multi‐domain cognitive training program for patients and care partners. Here, we present the information about the tolerability, likability, and efficacy of the cognitive intervention.

Method

The cognitive training consists of approximately 20 sessions provided to dyads of patients with MCI or early stages of dementia and their care partners. The cognitive training program includes three main components:

• Psychoeducation, training, and problem‐solving for healthy brain behaviors.

• Psychoeducation, training, and problem‐solving for compensatory strategies.

• Psychoeducation and cognitive training addressing attention, processing speed, executive functioning, and memory domains.

A total of 14 patients started the treatment (male = 9; female = 5) that ranged 62 to 85 years of age. Diagnoses included MCI due to TBI (n = 1), Alzheimer’s (n = 1), Vascular (n = 1), or unclear (n = 5) etiologies; or dementia due to Alzheimer’s (n = 2), Parkinson’s (n = 1), Mixed (n = 3) etiologies. At the end of the training, patients completed a brief survey about their experiences.

Results

Five out of 14 patients completed the training. Four patients with MCI who completed the treatment demonstrated improvements in cognition, quality of life, improved mastery of daily activities, reduced complaints of cognitive dysfunction, and reduced caregiver burden. Only one patient with dementia completed the treatment and remained stable. All patients who completed the treatment found it helped in their daily functioning and patients rated the treatment 4 out of 4, where 4 stands for “very likely” they would recommend this training to someone who is experiencing cognitive difficulties.

Four patients with MCI with significant psychological symptoms did not complete the program and five patients with dementia needed more support with caregiving and resources.

Conclusion

Multi‐component and multi‐domain cognitive training program with patients and care partners is best tolerated by patients with MCI. Further research will establish statistical and clinical significance.
Increased monocyte activity identified in Alzheimer’s disease by in depth single‐cell genomic and proteomic analysis
Authors: Xu Stacy , Schulz Michael , Schmidt Ronny , Richter Mario , Klein Marco , Hufnagel Katrin , Schroeder Christoph , Scolnick Jonathan
Published: December 2023

Background

Alzheimer’s disease (AD) patients show sustained levels of inflammation in the brain and the peripheral immune system. It is not known how various peripheral blood mononuclear cells (PBMCs) differ in AD patients and whether those differences can act as biomarkers of AD. Here we performed a multi‐omic profiling of PBMCs from AD patients and compared the composition of their cell type and cell state as well as their gene and protein expression to normal controls.

Method

Single‐cell proteogenomics analysis was performed on PBMCs from 20 AD patients and 15 controls using Singleron Biotechnologies’ ESCAPE platform. Seven of the AD and four control samples were additionally analyzed for bulk protein expression using Sciomics’ scioDiscover platform.

Result

Bulk proteomics identified 100 proteins with a significant differential abundance between AD patients and controls. Data point to a higher platelet activation and degranulation, as well as changes in the EGFR / MAPK3 and VEGF signaling in AD. As an individual marker CD163 was identified at a higher abundance in AD PBMCs pointing to an increase in monocyte / macrophage activity.

From the single‐cell analysis we found that AD patients had significantly more CD14+ monocytes. We further found that the CD14+ monocytes could be split into seven clusters based on their gene expression with only two clusters having a significantly higher number of cells in AD patients. One of the overrepresented clusters showed high expression of Alarmin genes, suggesting an increased inflammatory environment, while the other cluster showed a higher level of HLA expression suggesting a state primed for activation.

Conclusion

We found significant changes in both gene and protein expression in PBCMs from AD patients that indicate an increased inflammatory state . While there was a good overlap of findings between gene and protein expression, some of the changes are only seen at the protein level, while others are only observed at the level of gene expression. The combination of the two measurement techniques provides us with additional insights into inflammatory nature of the peripheral immune system in AD patients and provide hints at the mechanisms different cells use to generate those inflammatory signals.
Novel Nutrition‐Related Genetic‐Clinical‐Radiological Nomogram to Predict Behavioral and Psychological Symptoms in Patients with Alzheimer’s Disease
Authors: Jiang Jiwei , Li Wenyi , Xu Jun
Published: December 2023

Background

Behavioral and psychological symptoms of dementia (BPSD) are important and heterogeneous disturbances in Alzheimer’s disease (AD), affecting patient quality of life and increasing caregiver burden. Few effective treatments are available due to the complex reasons. This study aimed to develop a reliable genetic‐clinical‐radiological model for predicting the risk of the BPSD in patients with AD and further to explore the underlying mechanism of BPSD.

Method

We conducted a nested case‐control study, including 110 AD patients with BPSD, and 55 matched AD patients without BPSD from the Chinese Imaging, Biomarkers and Lifestyle (CIBL) Cohort. The participant data collected in this study comprised demographic data, medical history, the APOE e4 allele carrier status and the variants of SNP sites of the CLU, SORL1, ABCA7, MTHFR, COMT, and the CETP. The comprehensive assessment, including MMSE, ADL, MNA, CBI, and PSQI were compared between the two groups. The regional brain volumes of all patients were performed with structural 3DT1‐weighted imaging. Multivariate logistic regression analyses were used to identify the independent genetic, clinical and radiological influencing factors associated with BPSD. We developed a novel nomogram for predicting the risk of BPSD in the patients with AD, and the predictive ability was evaluated by receiver operating characteristic (ROC) curves and concordance index.

Result

A multivariate conditional logistic regression model demonstrated that CETPrs1800775*A variants, the lower scores of MNA scales, the higher scores of CBI scales, and the obvious atrophy of brainstem were significantly independently associated with BPSD in patients with AD. A novel nomogram was established to predict the risk of BPSD in patients with AD based on the findings of multivariate conditional logistic regression (Figure 1). The internal validation of AUC‐ROC value of this predictive model was 0.925 with a high sensitivity (89.1%) and specificity (83.6%) (Figure 2).

Conclusion

The novel predictive genetic‐clinical‐radiological model and nomogram based on the CETPrs1800775*A variants, MNA scores, CBI scores and brainstem volume can be useful for predicting the risk degree of BPSD in the patients with AD. This finding suggests nutrition‐related gene and brain region could risk BPSD through regulating the nutritional status for further exploring the underlying mechanism of BPSD.
Effects of mindfulness‐based intervention on neuropsychiatric symptoms and psychological well‐being in older adults with subjective cognitive decline and mild cognitive impairment: A meta‐analysis of randomised controlled trials
Authors: Rose Lin SY , Su Jingjing , Abu‐Odah Hammoda , Bayuo Jonathan
Published: December 2023

Background

Neuropsychiatric symptoms (NPS) are highly prevalent and could progress cognitive decline towards dementia among the population with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Although emerging studies showed that mindfulness‐based intervention improved psychological well‐being among clinical and community population, its effectiveness for people at the pre‐dementia stages remain largely unknown. This meta‐analysis was conducted to examine the effect of mindfulness‐based intervention on NPS and psychological well‐being among this preclinical cohort.

Method

Eligible studies published from inception to August 2022 were retrieved from MEDLINE, EMBASE, JBI‐EPB, Web of Science, PubMed and Cochrane. Literature search and data extraction were conducted by two independent researchers. Methodological quality of the included studies was assessed by the Cochrane Risk‐of‐Bias Assessment Tool. Meta‐regression was conducted to examine the effects of intervention design and sample characteristics on study heterogeneity.

Result

Eighteen randomized controlled trials (n = 974) published between 2013 and 2022 were identified. Mindfulness‐based intervention had significant immediate post‐intervention effects on improving anxiety (SMD = ‐0.39, 95%CI‐0.76,‐0.03, stress (SMD = ‐0.58;95%CI‐0.91,‐0.25), and quality of life (SMD = 0.50, 95%CI0.04,0.95), no significant effect was detected for depression, apathy, mindfulness, and stress‐related biomarkers. No statistically signifciant follow‐up effects were detected for depression and anxiety. Meta‐regression suggested that the studies applied on SCD was associated with larger effect size in depression, while Kundalini Yoga and Kirtan Kriya mindfulness meditation was associated with greater improvement in anxiety.

Conclusion

This review demonstrated the beneficial effects of mindfulness‐based intervention on anxiety, stress, and quality of life in the population with SCD and MCI. Future studies may incorporate informal mindfulness practice to facilitate its translation into everyday living. More rigorously designed and large‐scale randomized controlled trials evaluated by both self‐report and physiological parameters are warranted.
A multimodal digital biomarker of functional deficits in early‐stage Alzheimer’s disease: results of the RADAR‐AD study
Authors: Vairavan Srinivasan , Lentzen Manuel , Muurling Marijn , de Boer Casper , Atreya Alankar , Curcic Jelena , Hinds Chris , Conde Pauline , Grammatikopoulou Margarita , Scebba Gaetano , Lazarou Ioulietta , Nikolopoulos Spiros , Brem Anna‐Katharine , Coello Neva , Visser Pieter Jelle , Fröhlich Holger , Narayan Vaibhav A , Wittenberg Gayle , Aarsland Dag
Published: December 2023

Background

Remote monitoring technologies (RMTs), such as smartphone apps, smartwatches, and in‐home sensors, are rapidly changing the way functional and cognitive performance is measured in Alzheimer’s disease (AD) patients. Here, we present results from the European RADAR‐AD study on the use of multimodal data streams for the identification of functional deficits across all syndromic stages of AD.

Method

Four study groups (Healthy controls (HC), preclinical AD (pre. AD), prodromal AD (pro. AD), and mild AD) were included in this cross‐sectional study. The RMT features (gait measures from Timed up and Go (TUG), Dual Task Effect (DTE) using physilog, acoustic features from Speech task in Mezurio, neurocognitive function using Altoida, managing finances with Banking app) with in‐clinic neuropsychological (NP) tests, activities of daily living with Amsterdam IADL and demographics (age, gender, education years) were analyzed for different combinations of the multimodal digital biomarker of disease stage in AD across different pairwise comparisons. The analysis includes data from 175 participants (HC = 67, Pre.AD = 26, Pro.AD = 50, Mild AD = 32) collected for 8 weeks. An extreme gradient boosting (XGBoost) machine learning model was trained to obtain a multimodal biomarker of AD disease stage with repeated cross‐validation (5‐fold with 4 repeats) (Figure 1). This investigation is part of the ongoing RADAR‐AD study.

Result

The multimodal combination of RMTs achieved a mean AUC of > 0.60 in all pairwise comparisons with a mean AUC > 0.65 for HC vs (Pre.AD, Pro.AD and Mild) (Figures 2 and 3). The addition of NP tests increases the performance considerably across all pairwise comparisons except HC vs Pre.AD.

Conclusion

Our results highlight the advantage of combining RMTs to identify functional deficits in the early stage of AD. In particular, in prodromal and mild AD patients, a combined signal shows much more strength compared to individual tests.

This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (grant No 806999). www.imi.europa.eu. This communication reflects the views of the RADAR‐AD consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.
Motor‐cognitive dual tasking in the clinical setting: a sensitive measure of functional impairment in early Alzheimer’s disease
Authors: Brem Anna‐Katharine , Scebba Gaetano , Curcic Jelena , Muurling Marijn , de Boer Casper , Coello Neva , Atreya Alankar , Conde Pauline , Fröhlich Holger , Grammatikopoulou Margarita , Hinds Chris , Lazarou Ioulietta , Lentzen Manuel , Narayan Vaibhav A , Kozak Rouba , Nikolopoulos Spiros , Vairavan Srinivasan , Visser Pieter Jelle , Wittenberg Gayle , Aarsland Dag ,   RADAR‐AD Consortium
Published: December 2023

Background

Gait is a complex everyday activity that depends upon supraspinal activity and a host of cognitive functions such as attention and executive functions. As cognition declines in neurodegenerative diseases, the interaction and competition for neuronal resources during motor‐cognitive dual‐tasking (e.g., walking while talking) might be a sensitive measure of subtle functional impairments in early Alzheimer’s disease (AD). Here, we aim to identify gait deficits due to neuronal competition across the AD spectrum.

Method

This investigation is part of the ongoing Remote Assessment of Disease and Relapse – Alzheimer’s Disease (RADAR‐AD) study. We attached three inertial measurement units (accelerometer and gyroscope) to both feet and one hip to assess dual task effects (DTE) assessing gait performance with/without concurrent serial subtraction‐by‐1 task in four groups: 1) amyloid negative healthy controls (HC, N = 59); and 2) amyloid positive preclinical AD (PreAD, N = 30); 3) prodromal AD (ProAD, N = 51); and 4) mild‐to‐moderate AD dementia (MildAD, N = 44) (Table 1). We furthermore investigated associations of DTE with observer‐reported cognition.

Result

Group comparisons showed that dual‐tasking induced lower cadence and increased stance, which were significantly different between HC and ProAD. Several DTE measures of variability differed significantly between PreAD and MildAD, with variability in the path length separating best between PreAD and ProAD (Table 2, Figure 1). DTE measures were associated with observer‐rated divided attention only in the MildAD group.

Conclusion

Neuronal competition as assessed with motor‐cognitive dual‐tasking, specifically the DTE variability, might reflect functional deficits already in early AD, and could be a valuable additional measure to detect early impairments not captured by cognitive or motor tests alone. Future studies should implement an adaptive cognitive load to improve sensitivity/specificity in early AD stages and investigate the use of sensor technologies in predicting and monitoring changes in gait and fall prevention in later stages of the disease.

This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (grant No 806999). www.imi.europa.eu. This communication reflects the views of the RADAR‐AD consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.
First insights exploring Activities of Daily Living performance captured through activity sensors in a Smart Home Environment as an indicator of cognitive decline: A cross‐sectional Analysis
Authors: Alepopoulos Vasilis , Grammatikopoulou Margarita , Lazarou Ioulietta , Mpaltadoros Lampros , Nikolopoulos Spiros , Oikonomou Vangelis P , Stavropoulos Thanos G , Tsolaki Magdalini , Kompatsiaris Ioannis
Published: December 2023

Background

Smart homes offer a unique potential not only for supporting various users’ needs but also for monitoring their activities. Herein the findings of the RADAR‐AD Smart Home study are presented. Using data from activity sensors installed in a smart home environment simulating real‐life conditions, we aim to detect deficits while performing Activities of Daily Living (ADLs) in three known groups of people in different stages of cognitive decline related to Alzheimer’s Disease (AD).

Method

In a fully equipped Smart Home (https://smarthome.iti.gr/), Fibaro smart plugs (to monitor power consumption), motion‐, door‐, flood‐sensors and panic buttons were installed. During their 24 hour visit, participants [13 Healthy Control (HC), 14 Preclinical AD (PreAD), 13 Prodromal AD (ProAD)] (Table 1) followed a protocol listing a number of ADLs (e.g., meal/beverage preparation) (Table 1). Data collection, feature extraction (i.e., activity duration, number of repetitions) and visualization of ADLs were performed through the CARL data collection and analysis platform for assisted living (https://carl.iti.gr/). (Figure 1). Two‐Way ANOVA and Mann‐Whitney were used to test the statistical significance between the groups.

Result

Comparing Activity Duration for different ADLs and groups (Figure 2), HC executed the ADLs in less time compared to PreAD and ProAD, while PreAD showed no difference in the majority of the tasks compared to ProAD. Three activities were completed by 50% of the HC, 36% of the PreAD and only 17% of the ProAD. Two‐way ANOVA revealed a statistically significant interaction between the effects of cognitive decline and Activity Duration F(3,106) = 3.504, p = 0.034. Mann‐Whitney analysis for the complex task “Meal Preparation” showed decreased duration for HC compared to PreAD (U = 33.00, p = 0.042) and ProAD (U = 17.00, p = 0.052).

Conclusion

The RADAR‐AD Smart Home study provides a proof‐of‐concept for the use of home‐based sensors for investigating ADLs in patients with cognitive decline.

This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (grant No 806999). www.imi.europa.eu. This communication reflects the views of the RADAR‐AD consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.
Involving patients, participants and the public in designing research analysis: a case study
Authors: Gregory Sarah , Robertson Martin , Ross David , Penman Eileen
Published: December 2023

Background

The importance of patient and public involvement (PPI) throughout the research cycle is becoming increasingly recognised. Despite this, PPI contributors remain absent from the data analysis stage in many quantitative studies. Here we report on the experience of incorporating PPI in the statistical analysis planning stage of a project investigating associations between cortisol and brain health in the EPAD Scotland cohort. The aim of the initial planning meeting was to explore public and patient understanding of cortisol and brain health and identify important research questions to these contributors.

Methods

PPI contributors responded to adverts circulated in three established PPI groups in the United Kingdom (UK), signing up to attend an online meeting. PPI contributors were sent a meeting pack prior to the meeting, including brief pre‐reading and refreshment to enjoy during the meeting. The online meeting began with a brief presentation giving an overview of the topic, with interactive polls and open discussions incorporated into the session plan. All PPI contributors were sent a voucher to recognise their time commitment.

Results

Nine PPI contributors joined the meeting, and generally reported a good awareness of the association between cortisol and psychological stress, with less confidence of the association with physical health (Figure 1). Picking from a list of possible analysis options, PPI contributors were most interested in exploring associations between cortisol and depression, sleep and personality, in the context of brain health research (Figure 2). PPI contributors gave insights from their personal experience of neurodegenerative disease and posed further questions for research.

Conclusion

PPI contributors were valuable stakeholders in the statistical analysis planning process, identifying a number of research topics that would be valuable to explore. Future work will continue to involve PPI contributors to explore questions around cortisol and depression, sleep and personality, as well as associations with occupational and lifetime exposure to stress which were highlighted as topics of interest in the open discussion.
Development of an innovative computerized assessment of instrumental activities of daily living
Authors: Reppermund Simone , Numbers Katya T. , Lin Pinghsiu , Delbaere Kim , Wesson Jacqueline , Clemson Lindy , Ginige Jeewani Anupama , Trollor Julian N , Draper Brian , Brodaty Henry
Published: December 2023

Background

Functional impairment is a diagnostic criterion for dementia and distinguishes mild cognitive impairment (MCI) from dementia. Self‐ or informant reports are most commonly used but can be biased and may not reflect actual functional ability. Alternatives include performance‐based assessments, such as the Sydney Test of Activities of daily living in Memory disorders (STAM). The aim of this study is to develop, and validate, a new computerised diagnostic tool (C‐STAM) to assess functional ability that can be administered remotely to increase accessibility. The C‐STAM will realistically simulate everyday activities to assess functional performance.

Method

The C‐STAM is being developed by a multidisciplinary team of psychologists, old age psychiatrists, occupational therapists, and computer scientists. A Delphi study with 31 international experts was conducted to select and refine suitable tasks. An additional step is consultation with consumers (i.e., older people with and without cognitive impairment) and caregivers who have an active role in shaping the C‐STAM. A pilot study with 30 people aged 60+ with normal cognition, MCI, and dementia plus their informants will assess feasibility and user‐experience. After adjustments based on the pilot study, we will conduct a validation study with 180 participants and their informants.

Result

The Delphi study resulted in nine C‐STAM tasks, addressing the domains of communication, shopping, dressing, community mobility, handling finances, managing medications, and memory. Feasibility and acceptability of these tasks will be confirmed through pilot testing and the validation study. We will develop an automated scoring and interpretation guide, age‐ and sex‐specific norms, and clinical cut‐offs to differentiate the three diagnostic groups. Automated data exporting and reporting will be useful for clinical referrals and in research and will facilitate interpretation and communication of results across different clinical settings.

Conclusion

The C‐STAM will facilitate early diagnosis of dementia and MCI and will enable a better understanding of disease progression by monitoring functional ability in a time‐ and resource‐efficient way. Results will be used to inform service development to better meet the needs of people with dementia for access to appropriate assessments of functional performance. The C‐STAM will be freely available for use by clinicians and in research.
Brain gray matter volume mediated the relationship between plasma p‐tau and cognition of early Alzheimer’s disease
Authors: Wan Ke , Yin Wenwen , Tang Yating , Zhu Wenhao , Wang Zhiqiang , Zhou Xia , Zhang Wei , Zhang Cun , Yu Xianfeng , Li Chenchen , Zhao Wenming , Zhu Xiaoqun , Sun Zhongwu
Published: December 2023

Background

Cognitive deterioration and atrophy of the brain gray matter volume (GMV) are the main symptoms of Alzheimer’s disease (AD). Accumulated pieces of evidence have shown that plasma concentrations of phosphorylated‐tau (p‐tau) performed better in early diagnosing, differentiating, and monitoring the progression of AD. However, the relationship between plasma p‐tau concentrations, the GMV of brain regions, and cognitive function remains poorly understood. Previous studies indicate that brain GMV may mediate the relationship between biomarkers and cognitive function, and in this study, we aimed to investigate whether GMV plays a mediating role in the association between plasma p‐tau concentrations and cognition.

Method

99 participants in total, including 47 patients with a diagnosis of early AD and 52 cognitively unimpaired (CU) individuals, were enrolled in this study. All participants completed laboratory tests, magnetic resonance imaging scans, and neuropsychological assessments. Plasma p‐tau217 and p‐tau181 concentrations were measured using an enzyme‐linked immunosorbent assay kit. Voxel‐based morphometry was performed to assess brain GMV. Partial correlations and mediation analyses were performed in the AD group.

Result

Concentrations of both plasma p‐tau217 and p‐tau181 were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p‐tau217 concentrations, GMV, and Mini‐Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p‐tau217 concentrations and MMSE scores. We did not find a significant correlation between plasma p‐tau181 concentrations and MMSE scores.

Conclusion

The findings indicate that p‐tau217 was a promising biomarker for central processes affecting brain GMV and cognitive function. It may provide potential targets for future intervention and treatment of tau‐targeting therapies at the early stage of AD.
Role of Hearing‐Health‐Care Professionals in supporting Patients with Dementia Risk.
Authors: Jayakody Dona
Published: December 2023

Background

For those aged over 65, hearing loss is another major chronic illness. Our findings have revealed that untreated hearing loss is associated with an increased risk of frailty (Tian et al 2021), emotional loneliness (Jayakody et al 2022), and depression (Jayakody et al., 2018). Further, we found an association between hearing loss and cognitive impairment and dementia in non‐tonal language, (Jayakody et al 2018; Ford et al 2018) and tonal language speakers (Fu et al; 2021, 2022, Nicholas et al., 2021).

Method

In this presentation we will discuss the following: knowledge, attitudes and current practices of hearing health care professionals in treating older adults with comorbid hearing loss and cognitive impairment, hearing biomarkers to identify those at risk of dementia and hearing rehabilitation of older adults at risk of cognitive impairment.

Results

The outcomes of Knowledge, Attitudes and Practice surveys conducted in Australia, China, India, Sri Lanka, Turkey and USA identified gaps in the knowledge and practices of hearing healthcare professionals in cognitive impairment and hearing loss.

Our findings also suggest that those with subjective memory complaints, mild cognitive impairment and dementia perform significantly worse than healthy controls in both subjective central auditory processing tasks and objective electrophysiological assessments (Jayakody et al., 2020, Tarawneh et al., 2022).

Finally, our results revealed rehabilitation using cochlear implants and hearing aids reduce the rate of cognitive decline in older adults (Jayakody et al., 2017, 2020)

Conclusions

Hearing healthcare professionals play an essential role in supporting older adults at risk of Dementia. A better understanding of the consequences of untreated hearing loss, providing training to reduce the gaps in their knowledge and practices in treating older adults at risk of comorbid hearing loss and dementia and providing training to use suitable assessment tools to identify cognitive impairment in clinical settings early would be helpful.
GRIN2B genotypes and APOE haplotypes affect the age at onset of Alzheimer’s dementia as well as variations in dementia staging according to the use of Memantine
Authors: de Oliveira Fabricio Ferreira , de Almeida Thais Emanuele , de Almeida Sandro Soares , Smith Marilia Arruda Cardoso , Bertolucci Paulo Henrique Ferreira
Published: December 2023

Background

Memantine antagonizes the N‐methyl‐D‐aspartate (NMDA) type of glutamate receptor leading to possible behavioral improvement and a synergistic effect with cholinesterase inhibitors on slower functional and cognitive decline in Alzheimer’s dementia (AD). Some receptor genes can contribute to variable excitotoxicity and pharmacological response. NR2B is a common subunit of functional NMDA receptors, whereas the GRIN2B gene is mapped to 12p12, and rs3764028 has been associated with variable GRIN2B transcription and human susceptibility to AD. We sought to evaluate associations of promoter GRIN2B genotypes and APOE haplotypes with the age at onset of AD and cognitive and functional response to Memantine.

Methods

In this prospective pharmacogenetic study, participants with late‐onset AD according to National Institute on Aging – Alzheimer’s Association criteria were screened with the Clinical Dementia Rating Sum‐of‐Boxes, the Index of Independence in Activities of Daily Living, Lawton’s Scale for Instrumental Activities of Daily Living, the Mini‐Mental State Examination, the Severe Mini‐Mental State Examination, and a 15‐item Clock Drawing Test, and followed for one year. Genotyping was undertaken with TaqMan® Real‐Time Polymerase Chain Reactions for rs429358 and rs7412 (APOE haplotypes), and with Polymerase Chain Reactions for rs3764028 (GRIN2B). Associations of APOE haplotypes and rs3764028 genotypes with the age at dementia onset were assessed and, after stratification according to APOE‐ε4 carrier status, the presence of each genotype of rs3764028 was linked with use of Memantine or not for test score variations, significance at p<0.05.

Results

Among 190 consecutive outpatients, 141 used Memantine (74.2%); mean age at dementia onset was 73.23±6.4 years‐old, with 128 women (67.4%) and 62 men (32.6%), 101 APOE4+ carriers (53.2%) and 89 APOE4‐ carriers (46.8%). APOE‐ε4/ε4 carriers had earlier AD onset by almost five years (p = 0.004), whereas the A allele of rs3764028 had a cumulative effect on later onset of AD (p<0.0001). Memantine protected APOE4‐ carriers of the CC genotype of rs3764028 regarding Clinical Dementia Rating Sum‐of‐Boxes variations (p = 0.018), but not regarding other test score variations.

Conclusions

Genotypes of rs3764028 and APOE haplotypes are associated with the age at onset of AD, as well as with variations in dementia staging according to the use of Memantine. (Supported by FAPESP grant #2015/10109‐5)