bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences of people with Alzheimer’s disease, relatives, and dementia trainers on the usability of a tablet‐based dementia training
Authors: Schüssler Sandra , Zuschnegg Julia , Paletta Lucas , Russegger Silvia , Fellner Maria , Ploder Karin , Strobl Bernhard , Sekulic Maja , Koini Marisa , Hofmarcher‐Holzhacker Maria , Roller‐Wirnsberger Regina
Published: December 2022

Background

Non‐pharmacological interventions for people with dementia, like tablet‐based cognitive trainings, are increasingly popular to counteract the disease progression. Usability research on such trainings in the field of dementia is essential to raise acceptance and increase training intensity, as regular practice may contribute to their effectiveness. The aim was to explore the experiences of people with Alzheimer’s disease (PwAD), relatives, and dementia trainers regarding the usability of a tablet‐based dementia training.

Method

This qualitative study is part of an ongoing randomized controlled trial (project multimodAAL) which investigates the effects of an individually performed tablet‐based dementia training program (i.e., physical and cognitive exercises) in PwAD living at home. Individual interviews were conducted with people with mild AD (n = 5), relatives (n = 5) and dementia trainers (n = 5) who had been performing the training for at least 6 months. A qualitative content analysis was conducted.

Result

Participants were predominantly women (73.3%), with an average age of 73.4±11.4 years for PwAD, 66.2±10.7 years for relatives, and 43.1±10.4 years for trainers. Participants confirmed a good feasibility of the video‐provided physical exercises (e.g., coordination, strength), but some PwAD reported feeling unchallenged. Relatives and trainers wished for exercises to be more motivating (e.g., direct motivational address by the gymnast in the video, colorful sportswear). Regarding cognitive exercises, participants appreciated the varied and alternating types of exercises (e.g., puzzle, quiz) within the training sessions. Trainers and relatives recognized that PwAD particularly enjoyed exercises related to topics of their past/biography (e.g., hobbies, previous occupation) and to religious/seasonal traditions (e.g., Easter). Relatives and trainers highlighted that most PwAD needed support during the physical and cognitive exercises in terms of (technical) guidance, motivation/feedback/praise, as well as hints/tips/thought‐provoking impulses to perform their training successfully and to avoid frustration and cancellation of the training. Some suggested to extend the program regarding written and verbal support (e.g., hint button, voice assistant). Furthermore, participants emphasized a good sensitivity of the tablet‐PCs’ touch screen.

Conclusion

Results show that the presented tablet‐based dementia training is received well by participants, but there is still potential for (technical) enhancements regarding support through the exercises and motivational strategies
The Effects of Stressful Life Events on Alzheimer’s Disease Biomarkers, Neuroinflammation and Brain Integrity in Later Life: A Life Course Perspective
Authors: Palpatzis Eleni , Akinci Muge , Operto Grégory , Garcia Marina , Blennow Kaj , Zetterberg Henrik , Suridjan Ivonne , Kollmorgen Gwendlyn , Wild Norbert , Gispert Juan Domingo , Suárez‐Calvet Marc , Sánchez‐Benavides Gonzalo , Grau‐Rivera Oriol , Peña‐Gomez Cleofé , Arenaza‐Urquijo Eider M
Published: December 2022

Background

Stress is associated with adverse health outcomes, but the pathways through which stressful life events affect brain health, and the age periods most vulnerable to these effects, are unknown. We investigated these questions in relation to Alzheimer’s disease (AD) pathophysiology and brain integrity in cognitively unimpaired participants at risk for AD.

Method

In this cross‐sectional cohort study, 1168 participants completed the 18‐item Elder’s Life Stress Inventory measuring the occurrence (and age at occurrence) of stressful life events. Of these, 393 participants had data available on AD biomarkers (cerebrospinal fluid [CSF] phosphorylated‐tau and amyloid‐beta1−42/amyloid‐beta1−40 ratio measured with Elecsys® assays and NeuroToolKit panel of robust prototype assays [Roche Diagnostics International Ltd, Rotkreuz, Switzerland], respectively) and neuroinflammation markers (CSF interleukin 6 [IL‐6], soluble TREM‐2 and glial fibrillary acidic protein measured with NeuroToolKit). In total, 830 had structural magnetic resonance imaging data available for amygdala and hippocampal volume, and grey matter volume/thickness for areas of the prefrontal cortex. The association of stressful events with AD biomarkers, neuroinflammation and brain integrity (adjusting for total intracranial volume) was examined using multiple regression analyses adjusting for sex, age and education. Associations of stressful events during early life (ages 0−25), early adulthood (26−40), middle adulthood (41−55) and late adulthood (≥56) were also examined. Analyses were stratified by sex and Apolipoprotein ε4 (APOE ε4)‐status.

Result

Participants’ age ranged between 47−76 and 62.5% were women. A higher number of stressful events during life‐course was associated with an increase in IL‐6 levels among APOE ε4‐carriers; with a decreased amyloid‐beta ratio among APOE ε4‐noncarriers; and with a reduction in caudal anterior cingulate cortex volume among women. A higher number of events during early adulthood was associated with higher phosphorylated‐tau levels and prefrontal brain integrity, and during middle adulthood was associated with decreased prefrontal brain integrity (Table 1. & 2.).

Conclusion

Stress may affect later‐life brain health through multiple pathways, including neuroinflammation, amyloid‐beta and brain integrity, depending on APOE ε4‐carrier status and sex. Stressful events during early adulthood may promote phosphorylated‐tau in later‐life, while events during early/middle adulthood may have differential effects on brain integrity, suggesting potential windows for stress‐prevention strategies.
Usmarapride Oxalate (SUVN‐D4010): A Serotonin‐4 Receptor Partial Agonist for the Treatment of Cognitive Disorders
Authors: Abraham Renny , Subramanian Ramkumar , Rasheed Mohammed Abdul , Ravella Srinivasa Rao , Malleshwari Durga , Thentu Jagadeesh Babu , Nirogi Ramakrishna
Published: December 2022

Background

Alzheimer’s disease is a growing unmet medical need which involves a gradual decline in cognitive function. The therapeutic options for the treatment of cognitive disorders of this type are few with limited efficacy.

Method

Usmarapride was characterized for its in‐vitro properties using binding and functional assays. Its pharmacokinetic properties were evaluated both in rats and dogs. The procognitive efficacy of usmarapride was evaluated in combination with the current standard of care used for AD type dementia. As AD is associated with comorbid depression, usmarapride was evaluated for its antidepressant like activity as well.

Result

From in‐vitro functional studies, usmarapride was characterized as a partial agonist at 5‐hydroxytryptamine 4 (5‐HT4) receptors. It has excellent oral bio‐availability in rats and dogs. Usmarapride potentiated the procognitive effects of donepezil in behavioral animal models. Usmarapride also enhanced donepezil evoked acetylcholine levels in electroencephalogram (EEG) assay. Usmarapride was also found to have antidepressant like activity in an animal model of depression.

Conclusion

Usmarapride showed excellent oral efficacy in combination with donepezil in tested animal models of cognition. Additionally, usmarapride distinguish itself from currently used standard of care for the treatment of AD as it exhibits potent antidepressant like properties as well.
Heart rate variability: a novel biomarker for agitation propensity in Alzheimer’s disease?
Authors: Liu Kathy Y , Whitsel Eric A , Heiss Gerardo , Palta Priya , Reeves Suzanne J , Lin Feng Vankee , Roiser Jonathan P , Howard Robert J
Published: December 2022

Background

Agitation, a common symptom in Alzheimer’s disease (AD), may be related to impaired emotion regulation capacity with involvement of autonomic networks. Heart rate variability (HRV), an index of integrity of neural networks involved in autonomic function and emotion regulation, could be a potential marker of agitation propensity. We investigated the cross‐sectional and longitudinal association between HRV and agitation prevalence in AD using the Atherosclerosis Risk in Communities (ARIC) Study cohort that followed up participants from 1987–2013.

Method

Participants at ARIC visit 5 who were clinically diagnosed with dementia (or MCI that subsequently progressed to dementia) primarily or wholly attributed to AD were included. Agitation at visit 5 was defined based on the Neuropsychiatric Inventory agitation/aggression subscale alone, or a composite score comprising agitation/aggression, irritability, disinhibition, and aberrant motor behavior subscales. HRV measures at visits 1–5 were the root mean square of successive differences in R‐R intervals (RMSSD) and standard deviation of normal‐to‐normal R‐R intervals (SDNN) obtained from resting, supine, standard twelve‐lead electrocardiograms. The associations between agitation and visit 5 HRV or visit 1–5 change in HRV (defined as individual slope coefficients from mixed effects models) were assessed using simple regression models.

Results

Among 456 participants who had dementia during the study, N = 302 received a primary diagnosis of AD, of whom N = 120 were classified with pure AD (see Flowchart). In the pure AD subgroup, a 0.1 log‐unit higher RMSSD (odds ratio = 1.14 [1.03‐1.29]) and positive RMSSD change over the preceding two decades (odds ratio = 2.23 [1.24‐4.38]) were associated with agitation point prevalence after accounting for heart rate (change), age, sex, cognitive status, study site and race. A 0.1 log‐unit change in HRV approximated the observed difference in HRV with each decade of age. The associations persisted after accounting for use of medications with autonomic effects.

Conclusion

The finding that higher HRV was associated with agitation point prevalence in N = 120 participants clinically diagnosed with dementia solely due to AD supports the potential use of HRV as a biomarker of agitation propensity, and autonomic dysfunction as a target of treatment. Future studies are needed to explore this relationship alongside measures of emotion regulation and locus coeruleus‐noradrenergic system integrity.
Cortisol, cognition, and Alzheimer’s disease biomarkers among memory clinic patients
Authors: Holleman Jasper , Adagunodo Sofia , Kåreholt Ingemar , Hagman Göran , Aspö Malin , Udeh‐Momoh Chinedu T. , Solomon Alina , Kivipelto Miia , Sindi Shireen
Published: December 2022

Background

Chronic stress has been studied as a potential lifestyle risk factor for Alzheimer's disease (AD). Prolonged stress can lead to alterations in diurnal patterns of cortisol. This study aims to investigate the relationship between diurnal cortisol patterns, cognition, and AD biomarkers in memory clinic patients.

Method

Participants diagnosed with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or AD dementia were recruited from Karolinska University Hospital memory clinic in Sweden (n=155). Baseline cognition was measured using five cognitive domains (memory, working memory, processing speed, perceptual reasoning, overall cognition), operationalized as average z‐scores. Diurnal cortisol patterns were assessed using five salivary cortisol measures: awakening levels, cortisol awakening response, bedtime levels, the ratio of awakening to bedtime cortisol levels (AM/PM ratio), and total daily output. AD biomarkers Aβ42, total tau (T‐Tau), and phosphorylated tau (P‐Tau) were measured from cerebrospinal fluid. Cognition was measured at follow‐up (average 32 months) in a subsample of participants (n=57).

Result

Awakening cortisol levels were significantly higher in AD dementia compared with SCI. Greater cortisol awakening response was associated with better memory performance (OR= 1.57, 95% CI: [1.10 – 2.23]), while a greater AM/PM ratio (OR= 2.21, 95% CI: [1.15 – 4.25]) and lower bedtime cortisol levels (OR= .64, 95% CI: [.40 – 1.01]) were associated with better overall cognition. Cortisol measures were not associated with cognitive decline during follow‐up or with AD biomarkers in the full sample. However, in stratified analyses, higher awakening cortisol levels were associated with lower CSF Aβ42 in amyloid‐positive participants (b= ‐60.13; 95% CI [‐102.73 ‐ ‐17.52]), while higher bedtime cortisol levels (b= .09; 95% CI [.02 ‐ .17]) and a lower AM/PM ratio (b= ‐.12; 95% CI [‐.23 ‐ ‐.02]) were associated with higher CSF T‐Tau in amyloid‐negative participants.

Conclusion

This study shows that diurnal cortisol patterns are associated with cognitive performance in memory clinic patients. In people without amyloid pathology, cortisol may affect cognition through neurodegeneration‐related mechanisms, leading to the observed correlation with T‐Tau. Meanwhile, in amyloid‐positive participants, the greater pathology level may affect cortisol patterns. Further research should investigate the complex relationship between cortisol, cognition, and brain pathology.
The impact of Alzheimer’s Disease on care partners
Authors: Hahn‐Pedersen Julie Hviid , Larsen Tove Holm
Published: December 2022

Background

The burden of informal caregiving of people with Alzheimer’s Disease (AD) is often overlooked. We wanted to provide an overview of the burden of AD for care partners and to explore how the burden increases with disease progression through a systematic literature review.

Method

A protocol was developed before searches in PubMed, Embase, PsycINFO, and Cochrane Library were run October 2021 via the Silvi.ai‐platform. Eligible studies were published in English and provided data from 2010 or later. Two reviewers screened titles and abstracts independently. A single reviewer conducted full‐text analysis and data extraction, and a PRISMA overview was generated. Studies were quality ranked in accordance with Oxford quality grading scale.

Result

911 hits were identified of which 61 studies were relevant for data extraction. Most care partners were women. The majority of studies reported moderate‐to‐severe levels of impact on care partners life (using the Zarit Burden Interview (ZBI) and the Maslach burnout inventory) and on care partners’ overall quality of life (using the WHO Quality of Life questionnaire);1,2 care partners exhibited higher levels of stress, depression, and anxiety compared to control groups.3,4,5,6 Females had significantly higher score on care partner burden than males (measured by the Caregiver Burden Inventory (CBI)).7 The higher the number, frequency and severity of symptoms affecting patients, the more intense care partner distress as measured by the Neuropsychiatric Inventory Distress Scale.8 The care partners of people with severe dementia due to AD reported the greatest care partner burden measured by the short version of the ZBI and the CBI.9,10 There was a clear correlation between hours of care giving and score of the ‘Activities of Daily Living’ questionnaire. The higher the score, the more hours of care giving.11,12,13,14

Conclusion

Being a care partner to a person with AD is often associated with emotional stress, depression, anxiety, low overall QoL as well as impact on physical health. Female care partners are disproportionally affected compared to males. The more severe the AD, the larger the burden. More research within the field is required to illuminate the true health consequences for care partners of people with AD.
VRCT: Randomized Controlled Trial Evaluating the Impact of Virtual Reality Therapy on BPSD and QoL of Acute Care In‐Patients With Dementia
Authors: Appel Lora , Appel Eva , Kisonas Erika , Lewis Samantha , Rosenberg Jarred , Appel Julian , Smith Christopher
Published: December 2022

Background

Virtual Reality (VR) is increasingly considered a valuable therapy tool for managing behavioural and psychological symptoms (BPSDs) and quality of life (QoL) in dementia (Parsons, 2013). However, rigorous studies are still needed to evaluate its impact in acute care settings (Appel, 2021). This study evaluated the impact of VR‐therapy on managing BPSDs, falls, and length of stay (LoS) and QoL for inpatients with dementia admitted to an acute care hospital.

Method

An open longitudinal interventional randomized controlled trial was conducted between April 2019 and March 2020 (ClinicalTrials.gov, ID:NCT03941119). A total of 69 participants (age ≥65, diagnosis of dementia, did not meet exclusion criteria) (Figure 1) who were randomly assigned either followed standard of care (Control Arm, n = 35 or received VR‐therapy every 1‐3 days (Intervention Arm, n = 34) (Figure 2). VR‐therapy entailed watching 360‐degree‐VR‐films on a HMD for up to 20 minutes (Figures 3 and 4). Instances of daily BPSDs documented in EMR nursing notes were categorized based on the Neuropsychiatric Inventory (NPI). QoL measures included the Quality of Life in Late‐Stage Dementia scale (QUALID) and semi‐structured interviews conducted at scheduled visits. Structured observations (including the standardized “ObsRVR” tool) and interviews were used to measure treatment feasibility (Figure 5).

Result

VR‐therapy had a statistically significant effect (p = .014) in reducing aggressivity (i.e., physical aggression and loud vociferation). A sentiment analysis of patient responses to the semi‐structured interviews on QoL revealed a statistically significant impact of VR therapy (p = .013). No statistically significant impact of VR therapy was found for other BPSDs (e.g., apathy), falls, or LoS or QoL as measured by the QUALID. VR‐therapy was overall an acceptable and enjoyable experience for participants and no adverse events occurred as a result of VR‐therapy.

Conclusion

Immersive VR‐therapy appears to have an effect on aggressive behaviours and QoL in acute care patients with dementia. Although the RCT was stopped before reaching the intended sample size due to COVID‐19 restrictions, trends in the results are promising. We suggest conducting future trials with larger samples and, in some cases, more sensitive data collection instruments.
Feasibility of implementing a standard cognitive assessment in Italian academic and non‐academic memory clinics
Authors: Grazia Alice , Cappa Stefano F , Marra Camillo , Agosta Federica , Caffarra Paolo , Galimberti Daniela , Bruni Amalia Cecilia , Ferrarese Carlo , Teipel Stefan , Boccardi Marina
Published: December 2022

Background

A previous survey conducted among the European Alzheimer´s Disease Consortium (EADC) of academic memory clinics showed mild propensity (65%) towards implementing the clinician’s Uniform Dataset (cUDS), a standard cognitive assessment consistent with the US Uniform Dataset‐3rd, to diagnose mild cognitive impairment (MCI). Currently, in Italy translation and adaptations of the cUDS is in progress. Here, we evaluate the cUDS implementation feasibility in Italian academic and non‐academic settings.

Method

The 382 clinicians affiliated to the Italian Society of Neurology on Dementia (SINDem) were invited to complete the EADC online survey translated into Italian, investigating centers current practices, acceptability and feasibility of cUDS implementation. We used a mixed‐methods design to perform descriptive statistics, logistic regressions and qualitative analysis of clinicians' comments to investigate hurdles, facilitators and mechanisms impacting implementation.

Result

Sixty‐two clinicians participated from 14 of the 20 Italian regions. Response rates were unevenly distributed: 56% from Northern, 16% Central and 27% Southern regions (χ2(1) = 39, p = .0005). Centers were equally distributed among academic (48%) and non‐academic (52%) institutions(χ2(1) = 30, p = .899), had a variable yearly patient flow (M = 454;SD = 686) and mainly offered neurological (90%) and psychological (87%) services. 88% reported to use formal definitions for the diagnosis of MCI. 10% of academic and 30% of non‐academic clinicians reported full reimbursement of assessment. Fifty‐nine responders (95%) expressed willingness to implement cUDS. The most frequent facilitators were the availability of neuropsychologists(26%) and of tests' material(23%). 42% of non‐academic clinicians envisioned no specific barrier; 12% envisioned lack of neuropsychologists training, 12% cultural issues and 12% unavailability of local norms. 24% of academic clinicians identified time‐economic factors as barriers.

Conclusion

Our data showed very high acceptability for cUDS. Lower need of cross‐compatibility with previous standard might explain the higher acceptability in SINDem compared to EADC. Indeed, EADC clinicians are more reluctant due to the lack of compatibility and digital tools supporting harmonization with local datasets. Similar to EADC, SINDem academic clinicians reported the need for tests' material, but neuropsychologists’ training‐availability and finances were considered more important in Italy. Despite the small sample size, these results inform the design of future implementation in SINDem memory clinics.
Molecular and cellular responses to amyloid beta revealed from single cell analysis of surgical brain biopsies
Authors: Kamath Tushar , Gazestani Vahid , Dolan Michael John , Nadaf Naeem , Vanderburg Charles , Leinonen Ville , Macosko Evan
Published: December 2022

Background

The accumulation of amyloid beta is a diagnostic hallmark of Alzheimer’s disease. However, the cell types that are most sensitive to its accumulation, and the transcriptional pathways that are induced by amyloid beta in specific cell types, remain incompletely understood.

Method

We performed single nucleus RNAseq analysis (n = 1.1 million profiles) on frontal cortical biopsies (n = 58) from individuals undergoing shunt placement for idiopathic normal pressure hydrocephalus (iNPH). Of these 58 biopsies, 21 were positive of amyloid beta, and 8 were positive for both amyloid beta and hyperphosphorylated tau. We clustered the profiles into 92 distinct clusters, and performed an integrative analysis with 30 published human and mouse datasets. We tested for proportional loss or gain of specific populations in the presence of amyloid or amyloid + tau, and identified differentially expressed genes in each population.

Results

Activated microglial and astrocytic populations were proportionally over‐represented in the pathology‐containing biopsies. Compared with postmortem datasets, the biopsy‐derived profiles showed dramatically lower activation of immediate‐early gene signatures, suggesting stronger fidelity of measured transcriptional programs to the in vivo human cell states. Comparative analysis of microglial populations with published datasets of other diseases revealed transcriptional pathways specifically induced by amyloid accumulation. Specific subsets of layer 1 interneurons were under‐represented both in amyloid‐positive biopsies, and in published datasets generated from early (Braak stage < 4) postmortem tissue.

Conclusions

The use of fresh cortical biopsies enabled a faithful measurement and analysis of glial states induced by the accumulation of amyloid beta. Specific subsets of layer 1 interneurons are particularly sensitive to depletion by amyloid beta accumulation in frontal cortex.
Differential rates of internalisation and effects on reactivity of postmortem human tau in human astrocytes
Authors: Reid Matthew J , Noble Wendy , Perez‐Nievas Beatriz G.
Published: December 2022

Background

Highly phosphorylated tau aggregates emerge in affected areas of human tauopathy brain as disease progresses as a result of prion‐like spread and/or replication of seeds. Evidence suggests that astrocytes may influence tau spread. However, the efficiency of uptake of disease‐associated tau species is not well defined, nor are the effects of tau uptake on astrocyte reactivity and function. We are investigating tau uptake in human astrocytes, and how resulting changes in their reactivity and functions affect their support for human neurons in vitro.

Method

Human iPSC‐derived astrocytes were established, and their gene and protein expression profiles characterised. Aggregated tau was isolated from human postmortem Alzheimer’s disease (AD) brain. AD brain tau and corresponding extracts from control (CTRL) human brain were spiked into iPSC‐astrocyte cultures and the efficiency of tau uptake was measured, in parallel with assessment of reactivity markers. Mechanisms of tau uptake and its intracellular processing were investigated. Astrocyte conditioned media was collected and applied to iPSC derived cortical neurons to determine the impact of tau‐induced astrocyte changes on measures of neuron health.

Result

iPSC‐derived astrocytes express mature astrocyte markers. Aggregated tau from AD brain was readily internalised by these cells. Morphological, gene expression and protein expression changes were detected, suggesting that exposure to AD‐brain tau is sufficient to induce reactive response in these astrocytes. Variations in the rate and extent of uptake, and in markers of reactivity, were observed that reflect heterogeneity between different AD cases. Preliminary data indicates that cells may degrade internalised tau aggregates via lysosomal pathways and that tau‐induced astrocyte reactivity negatively impacts neuron health.

Conclusion

Our data shows that human astrocytes readily internalise AD brain‐derived tau aggregates, inducing changes in astrocyte reactivity and function, related to characteristics of the tau, that are detrimental to neurons. This supports an emerging body of evidence that astrocytic tau may influence neurodegeneration in AD.
Patient’s reaction to smartwatch based interventions in a controlled environment: preliminary results from the SAMi intervention study
Authors: Goerss Doreen , Köhler Stefanie , Rong Eleonora , Bieber Gerald , Teipel Stefan
Published: December 2022

Background

Assistive technologies show promising features to support people with cognitive impairment in daily life, e.g. mobile sensors for falls detection or getting lost. On the other hand, smartwatches bear potential to not only monitor but also interact with the user. While sensor based monitoring in dementia care is already part of many projects, direct interaction of people with cognitive impairment with smartwatches is little investigated.

Method

Based on qualitative studies, we designed interventions for a usual consumer smartwatch. We conceptualized two different tasks: A) drinking water and B) circling bells on a worksheet. Moreover, we implemented two different modes of intervention‐intensity affecting vibration patterns, alarm sounds, text sizes, display times or appearance of images and animations. We observed patients’ reactions to interventions A and B remotely via cameras. In case of failure, interventions were repeated up to three times. Here we present data of the interim analysis after completion of n=20 patients that were equally assigned either to mode 1 (regular interventions) or mode 2 (intensive interventions). In addition to observations, participants feedback was obtained with questionnaires. Patients were diagnosed with MCI (n=7) or dementia (n=13) in the local memory clinic.

Result

We found it feasible to study patient‐smartwatch‐interactions with a mixed methods approach. The majority of participants (n=18) were able to successfully complete at least one of two tasks, see Fig. 1. Circling bells (B) was completed only by 11 participants, while drinking water (A) was solved by 16 participants. The regular interventions were successful in 24%, the intensive interventions in 65%. Repetitions did not lead to an improvement of outcome in 13 cases, but in two cases. Reasons for insufficient task completion varied, e.g. patients showed unexpected reactions such as circling the picture on the smartwatch or doing arm circles. One patient fell asleep and did not react at all.

Conclusion

Remote observation of patients’ reaction to smartwatch based interventions is technically challenging but offers intriguing insights into human‐computer interaction. User‐centered design for patients with MCI or dementia differs from the approach for usual smartwatch users and needs to respect special needs and requirements.
Does adherence to the Mediterranean diet have differential effects on brain health for those living within and outside of the Mediterranean region?
Authors: Gregory Sarah , Ritchie Craig W. , Shannon Oliver , Stevenson Emma , Blennow Kaj , Muniz‐Terrera Graciela
Published: December 2022

Background

The Mediterranean diet (MedDiet) is a primarily plant‐based eating pattern. High adherence to a MedDiet has been associated with a 10‐40% lower incidence of dementia. There is limited evidence exploring associations between the MedDiet and Alzheimer’s disease (AD) pathology.

Method

Our study explored cross‐sectional associations between MedDiet and AD outcomes in the European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study (EPAD LCS), comparing effects between those living within and outside of the Mediterranean region. After deriving MEDAS scores, to quantify adherence to the MedDiet, we used linear regression analyses to test for associations between the MedDiet and hippocampal volume, white matter lesion volume (WMLV) cerebrospinal fluid Abeta 1‐42 and phosphorylated tau and cognition. Participants were categorised by Mediterranean or non‐Mediterranean region according to European Union classification.

Result

We included 1625 participants from the EPAD LCS baseline dataset, mean age 65.48 (±7.40) years, majority female (55.9%), majority with family history (66.3%) and minority APOEε4 carriers (39.0%). Mediterranean participants had higher MEDAS scores compared to non‐Mediterranean participants (7.44 (±1.60) vs 7.20 (±1.74), p = 0.007). Higher adherence to the MedDiet was associated with lower log WMLV in fully adjusted models (b: ‐0.06, standard error (SE): 0.02, p<0.001), indicating better brain health. Geographical region analysis found this effect only in Mediterranean participants (fully adjusted: b: ‐0.10, SE: 0.03, p<0.001). Exploratory analysis further showed this effect was only apparent in male, and not female, participants. For non‐Mediterranean participants, higher adherence to the MedDiet was associated with lower Four Mountains Test scores (fully adjusted: b: ‐0.25, SE: 0.08, p = 0.003), indicating poorer brain health. Analyses are corrected using the Benjamini‐Hochberg False Discovery Rate estimation.

Conclusion

Our findings suggest that adherence to the MedDiet is associated with better brain health in those living within, but not outside of, the Mediterranean region. One explanation may be a difference in the duration of exposure to this diet (i.e., life‐long versus later life adoption in Mediterranean vs. non‐Mediterranean regions). This study highlights the need to further explore who the MedDiet is particularly effective for with regard to brain health outcomes, to better inform public health campaigns and patient level interventions.
The Dynamic Impacts of Dementia on Preventive Care Utilization
Authors: Lin Zhuoer , Chen Xi
Published: December 2022

Background

Dementia can greatly affect individuals’ decision‐making and wellbeing; and impose substantial burdens on individuals, families, and society. Identifying earlier signals of dementia risk may offer people more time to prepare for the future, helping to delay the onset or slow the progression of dementia. However, lack of evidence documenting the impacts of dementia and its early signs on health care utilization largely limits our understanding of early presentation of the disorder. To fill the gap, this study investigates the short‐term and long‐term impacts of dementia on preventive care decisions, discovering early signs of the disorder and facilitating disease early diagnosis.

Method

Data were obtained from Health and Retirement Study, a nationally representative longitudinal study of Americans 50 or older. Individuals’ dementia status were assessed in 1995‐2018. 3,488 persons with incidence of dementia were identified and 22,619 consecutive person‐waves before and after the incidence of dementia were included. To quantify the short‐term effects of dementia, for each individual with an incidence of dementia, we examined the changes in preventive care utilization around the first occurrence of dementia relative to his/her own behaviors when he/she is non‐demented. To examine the long‐term effects of dementia, we further compared the dynamic changes of behavioral outcomes between individuals who developed dementia and those who never developed the disorder, covering up to 18 years before and 6 years after the incidence of dementia.

Result

Incidental dementia was associated with significant reductions in preventive care utilization, including cholesterol test, flu shot, mammogram, and prostate test, relative to individuals’ own behaviors before the disorder. Moreover, the impact tended to increase over time, with significant larger effects in waves after the onset of dementia compared to incidental changes. Our long‐term dynamic estimation further corroborated the findings. In particular, consistent and growing declines were observed in preventive care utilization 4‐6 years before the incidence of dementia. The effects of dementia were strong and robust across types of preventive care, population groups, and model specifications.

Conclusion

Our findings highlight the salient impact of dementia risk on preventive care utilization, which may increase individuals’ vulnerability to health shocks, exacerbating the deterioration of cognitive function.
Impact of a smart‐clothes home nursing program in Taiwan during heightened COVID‐19 restrictions
Authors: Shyu Yea‐Ing L , Huang Huei‐Ling , Sung Ya‐Li , Lin Chung‐Chih
Published: December 2022

Background

The COVID‐19 pandemic has required restrictions of daily activities, which has been found to impact the lives of persons with dementia and their family caregivers, who have multiple care demands. The lack of relevant studies in Taiwan emphasized the need to explore the experiences of family caregivers of older persons with dementia faced with the intensified restrictions to control COVID‐19, and the impact of the availability of a smart‐clothes home nursing program.

Method

This qualitative study used semi‐structured interviews with family caregivers of older persons with dementia. Participants were recruited from dementia clinics of a medical center in northern Taiwan from a subset sample of a larger study on smart clothes assisted home nursing care. A total of 12 family caregivers who participated in the original study were interviewed during the follow‐up period; seven were caregivers of a person with dementia wearing a smart vest, which transmitted information to a home care nurse. Interviews were conducted by telephone because the conditions of the pandemic prevented face‐to‐face interviews. Recorded interviews were transcribed and analyzed using content analysis.

Result

Interview data showed family caregivers’ felt the care recipient’s health was compromised and functional conditions intensified as Covid‐19‐related pandemic restrictions increased. Specific concerns included a lack social interactions, decreased daily activity levels, loss of interest and lack of motivation for activities, increased mood and behavioral problems, a decline in physical function and an increase in health problems. Family caregivers were also impacted by these restrictions, with significant increases in severity of caregiver role strain, including feeling trapped, a lack of in‐home support, profound powerlessness, and worries about the person with dementia contracting the coronavirus. The smart‐clothes assisted home nursing care program offered supplementary support to family caregivers by providing on‐time interactions, helping them manage health problems, enhancing predictability of the care recipient’s behaviors, and providing caregivers with emotional support.

Conclusion

The findings of this study support alternative care such as implementation of technology‐assisted home health services to meet caregiver needs to facilitate family caregiving of persons with dementia during the necessary restrictions in activities during the COVID‐19 pandemic.
Exploring Traditional Healing and Medicine in Dementia Care for Indigenous Populations in North America, Australia, and New Zealand: A Policy Advocacy and Practice
Authors: Shrestha Hom Lal , McArthur Michael , Rowe Robyn L , Wabie Joey‐Lynn , Maar Marion , Walker Jennifer D
Published: December 2022

Background

Access to culturally‐safe dementia assessment, diagnosis, and care in Indigenous populations worldwide is an emerging challenge. In 2018, the World Health Organization recognized traditional healers as stakeholders in dementia care and prevention globally. Traditional healers contribute to dementia assessment, diagnosis, and care in unique ways, and play a catalytic role in the process of culturally‐safe dementia care planning and assessment with health care providers at the community level. The purpose of this scoping review was to understand the roles and experiences of traditional healers, to evaluate strategies for integration between Indigenous traditional healing and western dementia care approaches, and to examine the policy barriers and research gaps in North America, Australia, and New Zealand.

Method

The scoping review methodology used was the Joanna Briggs Institute (JBI) approach that included six steps: protocol development based on participants, content and context framework, development of a search strategy, selection of relevant studies, charting of relevant data, synthesis, and reporting of results, and conducting stakeholder consultation.

Result

Searched English literature in select bibliographic databases, including CINAHL, EMBASE, Medline and PsycINFO. The initial search identified 516 papers published between 2000 and 2020 that met the search criteria. After 164 duplicates were removed, we screened 352 titles and abstracts, excluding the 209 that did not meet the inclusion criteria. The second stage review of 143 full‐text studies resulted in the further exclusion of 141 studies. Only two studies from Canada met all inclusion criteria for this study and explored the potential integration of traditional healing in dementia care and the roles, perceptions, and experiences of traditional healers.

Conclusion

This study emphasizes the inclusion of traditional healers, knowledge‐holders, and Grandmother groups that can contribute to building an evidence‐based dementia care decision‐making process for Indigenous people with dementia. Integration of Indigenous traditional healing and medicine in dementia care is a path to culturally‐safe dementia care and assessment. diagnosis. The study has policy implications for health care provider education and advocacy needs to engage with traditional healers in dementia care. It recommends two community‐based models to establish culturally‐safe dementia care between traditional healers and healthcare providers in a seamless collaboration.
A 2‐year Choral Singing intervention with community‐dwelling older adults at risk of cognitive decline to improve bio‐psychological outcomes: An open‐label Randomized Controlled Trial
Authors: Ng Ted K.S. , Mahendran Rathi , Kua Ee‐Heok , Feng Lei
Published: December 2022

Background

Few randomized controlled trials (RCTs) have investigated the effects of choral singing (CS) on community‐dwelling older adults at‐risk of cognitive decline. Specifically, scarce literature exists on the effects of CS on affective symptoms and other bio‐psychological risk factors of cognitive decline, including low‐grade inflammation and perceived stress. Extant interventional studies on CS lack robust RCT design incorporating an active control arm controlling for active components which are not intervention‐specific. Addressing these gaps in knowledge, we initiated the CS‐RCT and hypothesized that a 2‐year CS intervention with older adults at risk of cognitive decline will improve affective, i.e., depressive and anxiety, symptoms, high‐sensitivity c‐reactive protein (hs‐CRP) levels, and perceived stress.

Method

Conducting a parallel‐arm and open‐label RCT, we recruited 93 community‐dwelling older adults at‐risk of cognitive decline, i.e., self‐reported cognitive complaints, cognitive impairment based on neuropsychological test scores or had multiple medical risk factors of dementia. They were randomized into either the treatment arm, CS, or the active control arm, the health education program (HEP) matched with non‐intervention‐specific components. Both the CS and HEP arms involved weekly 1‐hour group sessions held continuously for two years in parallel. In this paper, we examined the a priori registered (ClinicalTrials.gov Identifier: NCT02919748) secondary outcomes of the RCT at baseline, 1‐year, and 2‐year time‐points. The outcomes were depressive and anxiety symptoms, hs‐CRP levels, and perceived stress, using the Geriatric Depression Scale‐15 (GDS‐15), Geriatric Anxiety Inventory‐20 (GAI‐20), commercial plasma hs‐CRP ELISA kit, and the perceived stress scale (PSS), correspondingly. Linear‐mixed models were used to examine the effect of CS on all measures using intention‐to‐treat. Benjamini‐Hochberg procedure was used to correct for multiple testing.

Result

Compared to the HEP arm, CS participants experienced no significantly modified scores on GDS‐15, GAI‐20, plasma hs‐CRP levels, and PSS throughout the 2‐year intervention time‐points.

Conclusion

In contrary to previous studies using passive controls, compared to HEP as an active comparator, CS did not improve affective symptoms and two other bio‐psychological risk factors of cognitive decline in at‐risk community‐dwelling older adults. Our findings highlight the critical importance of examining real‐world‐efficacy of a nonpharmacological intervention among a community‐based sample (Stage 3).
Characterizing Disrupted Cellular Crosstalk Signaling Networks in Alzheimer’s Disease Using Single‐Nuclei Transcriptomics
Authors: Albanus Ricardo D'Oliveira , Brase Logan , You Shih‐Feng , Soriano‐Tarraga Carolina , Benitez Bruno A. , Cruchaga Carlos , Karch Celeste M. , Harari Oscar ,   The Dominantly Inherited Alzheimer Network
Published: December 2022

Background

Genetics and molecular studies have implicated multiple genes, pathways, and cell types in Alzheimer’s disease (AD) risk and progression. How these genes and pathways perturb and are modulated by brain cellular crosstalk networks have not been deeply characterized.

Method

We generated single‐nuclei transcriptomic profiles (snRNA‐seq) of parietal lobes from 67 donors from the Knight ADRC and DIAN brain banks, representing neuropathological‐free controls and AD cases from pre‐symptomatic and AD[1]. We estimated cellular crosstalk patterns among the brain cell types based on the expression of known ligand‐receptor pairs[2] and reconstructed the co‐expression network upstream and downstream of these ligand‐receptor pairs to determine how these signals are propagated across cells[3].

Result

We analyzed ∼294K high‐quality nuclei and identified six major cell populations[1]. We observed changes in cellular crosstalk patterns between controls and AD, with the largest involving microglial interactions (increased in AD, OR = 1.31, p = 8.94e‐11). Cellular interactions directly involving AD‐related genes[4] as either the receptor or the ligand were enriched for neuron‐microglia pairs (OR = 2.74, p = 4.41e‐15), and the majority (64.9%) codified for microglial cell membrane receptors, supporting the role for these cells in AD. We observed an increase in the frequency of a subset of interactions involving AD‐related genes in microglia when comparing pre‐symptomatic and AD individuals, suggesting correlation with pathological burden. These included TREM2‐semaphorin (neuron‐microglia, 4.38‐fold increase). We performed a comprehensive study of the microglial co‐expression networks up/downstream of these interactions and provided additional evidence of their association with Braak stage. The TREM2‐semaphorin neuron‐microglia interaction is predicted to directly propagate signals into a sub‐network associated with microglia activation, involving four genes from the HLA family previously implicated in AD. Furthermore, the neuronal co‐expression network had significant enrichment for AD‐related genes including CELF2 (OR = 2.10, p = 5.32e‐3), consistent with AD‐related genes in neurons propagating signals into microglia. We replicated these results in public snRNA‐seq studies and are currently validating these findings experimentally.

Conclusion

This study reveals the role of cellular crosstalk in AD biology and identifies disruptions in neuron‐microglia interactions as an important component of AD pathology. In addition, we show that cellular crosstalk networks can directly modulate genes previously associated with AD (Figure 1).

References:[1]https://doi.org/10.1101/2021.11.30.21267072; [2]PMID:32103204; [3]PMID:33853780;[4]PMID:30820047
Segregation of brain systems is associated with cognitive and eye movement performance in the general population
Authors: Coors Annabell , Zeng Weiyi , Breteler Monique M.B. , Ettinger Ulrich
Published: December 2022

Background

The human brain is a large‐scale network, which contains multiple segregated and functionally specialized systems. The organization of brain systems has been reported to change in a dedifferentiated way with increasing age. We investigated how age and sex are associated with brain system segregation during resting‐state in a large population‐based sample. Further, we analysed whether interindividual differences in the amount of brain system segregation are associated with cognitive and eye movement performance.

Method

The analyses were based on 3,256 participants (30‐95 years) of the Rhineland Study, a community‐based cohort study in Bonn, Germany. Functional connectivity (FC) was extracted from 200 ROIs within 7 systems (control, default, visual, somatomotor, dorsal attention, ventral attention and limbic) using resting‐state functional MRI acquired from 3T Siemens MAGNETOM Prisma MRI scanners. Segregation index was calculated using a previously established measurement taking the difference between mean within‐system FC and mean between‐system FC as a portion of mean within‐system FC. We assessed cognitive performance with tests for memory, processing speed, executive function and crystallized intelligence and an eye movement test battery. We used multivariable regression models to assess the relation between brain segregation index and cognitive and eye movement performance with adjustment for possible confounders.

Result

The global system segregation index decreased by 0.17 standard deviations (sd) per 10 years increase in age (95% confidence interval (CI): ‐0.19 – ‐0.14). Men had on average a 0.08 sd higher global system segregation index than women (95% CI: 0.02 – 0.15). Higher global system segregation was associated with higher performance in global cognition, processing speed, executive function, working memory and episodic verbal memory, and with lower crystallized intelligence. Additionally, higher global system segregation was associated with faster initiation of prosaccades and antisaccades.

Conclusion

Higher system segregation is beneficial for cognitive and eye movement tasks that place demands on processing speed, executive function and working memory, but crystallized intelligence is better when segregation is lower.