bluuebunny/crossref_metadata_2025 huggingface dataset:
Dementia needs assessment in Latine communities: strengths, challenges and policy opportunities in Wisconsin, USA
Authors: Pinzon Maria C Mora , de Cordova Susie C Fernandez
Published: December 2023

Background

Latinx populations are 1.5 times more likely to develop ADRD than non‐Latinx whites. Despite their heightened risk, they are more likely to be undiagnosed, under‐diagnosed and misdiagnosed. This is exacerbated by the lack of culturally appropriate information addressing ADRD to combat culturally specific stigma and misconceptions, as well as a dearth of culturally suitable resources. Infrastructure development that engages the community and community organizations can assist in overcoming these challenges by addressing community needs, capitalizing on existing resources, fostering sustainability, and promoting health equity.

Method

Using a modified version of the instruments included in the ACT on Alzheimer’s® Dementia Friendly Communities Toolkit, we evaluated the ADRD related needs and other social needs (e.g. transportation) that Latine communities experience in Madison, Wisconsin (USA). The instrument was distributed via email to community organizations and individuals serving Latine individuals in the area. Additionally, a community advisory group contributed to the identification of existing assets/priorities and strategic planning.

Result

The strengths identified for the community were: a sense of community that leads to individuals caring for one another and wanting to provide for one another’s needs, and the availability of a variety of community organizations and individuals who play a role in serving people living with dementia and their care partners. The absence of bilingual/bicultural resources to serve individuals was cited as the most significant challenge, followed by the lack of information regarding dementia, and the paucity of care options for those who are not eligible for Medicare or Social Security benefits. Table 1 reflects the most important services needed in the community. Reimbursement/Service fees (e.g., organizations use Medicare/Medicaid funding and do not have additional revenue sources to serve individuals without insurance), educational requirements for employees without a comparable requirement on language proficiency, and limited funding for multi‐language services were identified as pertinent policies.

Conclusion

Community members viewed dementia education and awareness of care services as crucial. Collaboration with current organizations to provide additional resources that enable them to implement culturally and linguistically appropriate processes for all is key to ensure the sustainability of future endeavors.
Exploring Culturally‐safe Dementia Care Policy in First Nation Community of the James and Hudson Bay Region in Northern Ontario, Canada
Authors: Shrestha Hom Lal , Shrestha Lucy
Published: December 2023

Background

Culturally‐safe dementia care (CSDC) is new dynamic concept that empowers clinical and traditional health care practitioners to provide culturally respectful care for older adults with dementia. The World Health Organization’s (WHO) recognized diverse Indigenous local community partners, members and leaders as critical community stakeholders for dementia care and prevention worldwide in 2018. However, there is a critical lack of policy framework and evidence‐based research on CSDC globally. As dementia spreads as a global epidemic, the dementia prevalence among First Nations people over the age of 60 is expected to quadruple by 2031, compared to a 2.3‐fold increase among non‐First Nations people in Canada. The Mamow Ahyamowen Partners (2019) study found a higher dementia mortality rate of 7% in the James and Hudson Bay region of Northern Ontario between 1992 and 2014, compared to 23% in Ontario overall.

Method

A qualitative research design is employed in conjunction with a community‐based participatory rural dementia action research approach to conduct four participatory Focus‐Group Discussions with physicians, nurses, caregivers, and community partners with 24 to 32 participants to explore the knowledge, experience, barriers and challenges to develop knowledge of CSDC policy. Thematic analysis and the Total Quality Framework will be used for quality rigour, and a two‐eyed seeing framework and explanatory dementia models will be applied in the perspectives and worldviews of the physician‐patient‐community to honour cultural care, diet, language, ethical and spiritual pathways.

Result

This research will lay foundation for policymakers to develop knowledge of CSDC policy, care plan and guidelines. This will guide the development of educational interventions and curricula and community support systems that are aimed at building and sustaining the capacity of healthcare professionals and community partners to begin integrated biomedical and Indigenous traditional dementia care practices.

Conclusion

This research endeavours to equip physicians, nurses, allied health care workers, community partners (Elders, knowledge‐holders and traditional healers) and the community support systems to initiate CSDC on a global scale to implement the WHO Global Action Plan on the Public Health Response to Dementia (2017‐2025). Inclusion of Indigenous community partners as community stakeholder are underpinning to bridge the dementia equity gap.
Rat Model of Aerodigestive Dysfunction in Alzheimer’s Disease
Authors: Rowe Linda M , Russell John A , Connor Nadine P
Published: December 2023

Background

Oral nutrition and aspiration pneumonia are significant factors impacting survival in patients with Alzheimer’s disease and related dementias (ADRD). Patients with ADRD demonstrate impairments to critical aerodigestive functions, including: prolonged oral phase durations, impaired masticatory performance, and prolonged swallow apnea durations. However, the pathophysiology underlying these functional changes is poorly understood. Establishing a translational model of swallowing dysfunction in ADRD will be critical for identifying underlying mechanisms of aerodigestive dysfunction and optimizing clinical treatments.

Methods

Adult male TgF344‐AD rats (n = 6) and wild type rats (WT; n = 6) underwent videofluoroscopy (60 fps) to assess swallowing kinematics at 12 months of age. Jaw movement, bolus position, and diaphragm movement (proxy for respiration) were analyzed off‐line. All rats underwent a hypoglossal nerve electrical stimulation protocol, with the protruded tongue attached via small suture to a force transducer. All rats were stimulated maximally at a range of frequencies from 1 Hz – 140 Hz.

Results

The AD group had significantly slower mastication rates (p = .037) and prolonged swallow apnea durations (p = .017) compared to WT. The AD group produced significantly lower forces at 60 Hz (p<.001) and 80 Hz (p<.001), indicating a higher frequency of nerve stimulation was required to elicit a given force of isometric tongue muscle contraction.

Conclusion

The TgF344‐AD rat demonstrates functional mastication and swallowing decline consistent with clinical findings in patients with ADRD, with concomitant alterations in tongue muscle contractile properties and can serve as a valuable tool for interrogating biological and physiological mechanisms of aerodigestive dysfunction.
Factors influencing choice and ability to age in place: A qualitative study with patients, caregivers, and clinicians
Authors: Auriemma Catherine L , Silvestri Jasmine , Butt Maayra , McMillan Julia , Turner Dania , Klaiman Tamar , Harkins Kristin , Karlawish Jason , Halpern Scott D
Published: December 2023

Background

“Aging in place” (AIP), the ability to remain in one’s home with age, has broad appeal to policy makers and professionals providing services to adults with serious illness. AIP is viewed as both an intervention for people with dementia (PWD) and as a desirable outcome. However, it’s not clear that AIP is always associated with sustained quality of life, and in some circumstances, may hinder it. As clinical and policy efforts increase to promote AIP for PWD, it is imperative to understand how AIP aligns with patient and family values and what factors influence choice and ability to remain in one’s home.

Method

In this qualitative study, we explored stakeholders’ perspectives on what makes a “good day” for a PWD and their family caregivers and decision making around AIP. We conducted semi‐structured interviews among PWD or cognitive impairment, family caregivers of PWD or cognitive impairment, and clinicians who care for PWD. Participants were purposively sampled to enroll individuals with a range of dementia severity, professional expertise, and demographic characteristics. All interviews were audio‐recorded and transcribed. De‐identified transcripts were reviewed by the research team independently and during weekly consensus meetings to identify relevant themes. Sample size was determined by reaching thematic saturation within each stakeholder sub‐group.

Result

We conducted 70 interviews among 13 patients, 33 caregivers, and 24 clinicians (Table 1). Caregiver burden, caregiver guilt, patient independence, patient safety, perceptions of care facilities, and financial consideration were all themes that influence whether a person can and will AIP (Table 2). Among patient‐caregiver dyads who wished to prioritize AIP, a change in the patient’s living situation was only pursued if and when a “breaking point” was reached by the caregiver. Themes were organized in a conceptual model as patient, caregiver, or systems factors (Figure).

Conclusion

Numerous factors influence the ability and choice of PWD and their family caregivers to AIP and likely impact the quality of life of patient and family caregivers as dementia progresses. Any program seeking to enhance AIP must take these factors into account. Furthermore, measuring success of AIP will need outcome measures that better capture these dimensions.
Sleep alterations in two different rodent models of Alzheimer’s disease
Authors: Hector Audrey , Dufort‐Gervais Julien , Caiado Maria J Da Costa , Provost Chloé , Fernandes Karl JL , Mongrain Valérie , Brouillette Jonathan
Published: December 2023

Background

In Alzheimer’s disease (AD), sleep alterations are among the first clinical symptoms observed. It is also well‐established that sleep loss affects hippocampal function. Moreover, sleep disturbances enhance the risk of developing AD, but the underlying mechanisms remain unclear. There is mounting literature indicating that soluble low‐molecular‐weight amyloid‐beta oligomers (Aβo) are particularly neurotoxic,1 and their specific contribution to sleep disturbances should be defined. Recently, dysregulation of lipid metabolism was reported in AD and 3xTg‐AD mice,2 but its relation to sleep also need to be assessed. Therefore, our work has two objectives: 1) define the effect of Aβo on different sleep variables and 2) verify whether stearoyl‐coenzyme A desaturase (SCD), an enzyme involved in controlling fatty acid unsaturation, contributes to sleep disturbances in 3xTg‐AD mice.

Method

Chronic hippocampal injections of soluble Aβo were done in wild‐type male rats, and electroencephalographic (EEG) measurements were performed to define wake/sleep alterations. Additionally, female 3xTg‐AD mice received a 28 day‐treatment with an SCD inhibitor, and EEG recordings were performed either 14 or 28 days post‐treatment

Result

Results show that the time spent in wakefulness, slow‐wave sleep (SWS) and paradoxical sleep was preserved in Aβo‐injected rats. However, for their frontal cortex, EEG spectral activity during wakefulness was increased by Aβo for slow‐wave activity (SWA; 0.5‐5 Hz) and low‐beta activity (16‐20 Hz), whereas it was decreased during SWS for theta (5‐9 Hz) and alpha activity (9‐12 Hz). Moreover, the theta activity/SWA ratio was decreased during wake and SWS. Concerning 3xTg‐AD mice, they spend more time in SWS during their active period compared to littermates. The number of individual bouts of wake and SWS was increased in 3xTg mice. Ongoing analyses will assess the impact of SCD on sleep variables in 3xTg mice.

Conclusion

The results support the presence of sleep alterations (indicative of poor sleep quality) in AD models, and suggest that sleep phenotypes could serve as a non‐invasive marker of early AD.

1. Brouillette J, et al. J Neurosci 2012;32:7852‐7861.

2. Hamilton LK, et al. Nat Commun 2022;13:2061.
Primary Care Detection of Cognitive Impairment Leveraging Health & Consumer Technologies in Underserved Communities: The MyCog Strategy
Authors: Bonham Morgan , Yoshino‐Benavente Julia , Curtis Laura M , Hosseinian Zahra , Bass Michael , Diaz Maria , Batio Stephanie , Kwasny Mary , Lovett Rebecca , Russell Andrea , Kim Minjee , Shono Yusuke , Linder Jeffrey , Nowinski Cindy J. , Gershon Richard C. , Wolf Michael S
Published: December 2023

Background

Early identification of cognitive impairment (CI), including Alzheimer’s disease and related dementias (ADRD), is a top public health priority. Yet in primary care settings that manage the health of most community‐dwelling older adults, less than half of patients with any CI are detected and/or diagnosed. Among community health centers that serve marginalized patients, rates of detection may be far lower. To address this, we sought to test a primary care‐based strategy (‘MyCog’) to improve CI detection as part of an NIH‐sponsored consortium (DetectCID).

Method

The MyCog strategy includes a brief iPad‐based, self‐administered, electronic health record (EHR)‐linked cognitive assessment that leverages two well validated measures from the NIH Toolbox Cognition Battery and has easily interpretable results with ‘turnkey’ recommendations to enhance clinical decision making. Clinician and practice administrator feedback was sought via cognitive interviews and focus groups to ensure the assessment could properly function in typical workflows. Based on this feedback a self‐administered tool was built, with a simple interpretable result (yes or no, cognitive impairment detected). It was then validated in one academic geriatrics practice among 111 older adults.

Result

The refined self‐administered tool was further validated in a geriatric clinical population, with interviewer and self‐administered MyCog versions strongly correlated (Spearman r = 0.75) and similar average response time per trial (0.914 sec. vs. 0.958 sec.). Use of the two tests demonstrated acceptable AUC values separately for detecting CI (0.84 and 0.79, respectively). But combined, these measures provide incremental diagnostic utility (AUC = 0.95).

Conclusion

We will launch the MyCog Trial at 24 practices from a national network of primary care centers for older adults on Medicare that will be randomized to MyCog or usual care. Clinics receiving MyCog will utilize a protocol to implement the intervention during Medicare Annual Wellness Visits and whenever a cognitive concern is expressed. Findings from the DetectCID consortium and MyCog Trial will directly inform future standards in primary care settings, especially those that serve health disparate patient populations.
Elevated Amyloid‐β and Tau Levels in the Brain are Associated with a Reduced Abundance of Neuroprotective Gut Bacteria
Authors: Ngouongo Yannick Joel Wadop , Muhammad Jazmyn A , Kautz Tiffany F , Satizabal Claudia L. , Himali Jayandra Jung , Seshadri Sudha , Fongang Bernard
Published: December 2023

Background

Recent research suggests that differences in the gut microbiome composition may contribute to the pathogenesis of neurological disorders, including Alzheimer’s disease (AD). Animal studies have shown that fecal microbiota transplantation reduces amyloid plaques in mouse AD models. However, whether the buildup of Aβ and tau deposits in the brain are associated with shifts in the human gut microbiota composition is understudied.

Method

We used stool specimens and neuropathological measures from 140 middle‐aged individuals (Table 1: mean age 56, 54% Female) from the Framingham Heart Study (FHS) to assess the link between the gut microbiome composition and Aβ Positron Emission Tomography (Aβ‐PET) in a global composite brain measure, and tau‐PET deposits in the rhinal cortex and the inferior temporal cortex. We quantified gut microbiome composition using 16S rRNA sequencing. We performed multivariable association and differential abundance analyses, adjusting for age, sex, body mass index, and other confounders.

Result

Multivariable association results (Figure 1) indicated significant associations (adjusted p‐value < 0.001) between both Aβ‐PET and tau‐PET levels with abundance of genera Butyricicoccus and Ruminococcus. Moreover, differential abundance analysis (Figure 2) showed that these bacteria have lower than expected abundance in individuals with elevated Aβ‐PET and tau‐PET measures (Aβ‐PET, Ruminococcus: OR = 0.89, [0.88, 0.91]; Butyricicoccus: OR = 0.77, [0.72, 0.81]); (tau‐PET in the rhinal cortex: Ruminococcus: OR = 0.82, [0.8, 0.83]; Butyricicoccus: OR = 0.91 [0.88, 0.94]); (tau‐PET in the inferotemporal cortex:, Ruminococcus: OR = 0.79 [0.78, 0.81]; Butyricicoccus: OR = 0.83 [0.81, 0.86]). Conversely, we observed an increased abundance of genera Cytophaga (tau‐PET in the rhinal cortex, OR = 1.78, [1.15, 2.75]) and Alistipes (tau‐PET in the rhinal cortex, OR = 1.19, [1.17, 1.22]) in individuals with high Aβ‐PET and tau‐PET levels. Finally, functional analysis showed that Butyricicoccus and Ruminococcus are butyrate‐producing bacteria harboring neuroprotective effects.

Conclusion

We showed that elevated measures of Aβ‐PET and tau‐PET in the rhinal and the inferior temporal cortex are associated with a reduced abundance of butyrate‐producing Butyricicoccus and Ruminococcus in the gut of middle‐aged individuals from the FHS. As these bacteria harbor neuroprotective effects, further studies are needed to elucidate underlying mechanisms and assess their therapeutic potential.
Adapting iSupport program around the world: a cross‐cultural study
Authors: Fiordelli Maddalena , Messina Anna , Magelli Arianna , Amati Rebecca , Albanese Emiliano
Published: December 2023

Background

iSupport is an online evidence‐based intervention developed by the World Health Organization (WHO) to provide training and support to informal caregivers of people with dementia. WHO provides general guidelines to support countries adapting the intervention to local contexts and needs. iSupport is being adapted by a variety of teams in over 30 countries composing an international network. Cultural adaptation of evidence‐based interventions has the potential to increase their effectiveness, usability, and scalability (Theobald et al., 2018). This cross‐cultural investigation aims to collect and synthesize methodologies used for the cultural adaptation of iSupport worldwide.

Method

We designed and conducted this qualitative study under the auspices and in collaboration with the WHO’s brain health unit who led communication with iSupport network members. Between August‐September 2022, we carried out online semi‐structured interviews with local study coordinators and implementers. We explored definitions of cultural adaptation, methods used, stakeholders’ and caregivers’ involvement, and measures used to ensure and monitor external validity. Interviews lasted on average one hour, and we conducted thematic analysis of verbatim transcripts.

Result

We interviewed 25 participants from 11 countries, including Wales, Australia, and Spain where we conducted multiple interviews as they run multiple adaptation processes. We found that the length of the process was variable, caregivers’ associations were always involved, and the implementers were mainly research and/or governmental institutions. The adaptation process included focus groups as data collection method and a constant exchange with WHO. Active listening and flexibility were essential to the adaptation process, while team multidisciplinary was a plus. Common challenges included difficulties in recruiting caregivers, limited time and economic resources for the project, and cultural diversity within the same country. Lessons learnt included the importance of involving caregivers and actively listening to them, multiple stakeholders’ involvement, the complexity and richness of multifaceted national cultures, the importance to adapt different program formats, and the need to further harmonize adaptation and monitoring procedures.

Conclusion

Our results provide support to the promotion of knowledge exchange among and beyond the iSupport international network, which facilitates the harmonization of iSupport implementation procedures and informs best design and implementation practices.
Usability and acceptability of ‘iSupport for dementia’: insights from multiple culturally adapted versions
Authors: Ulate Mauricio Molinari , Teles Soraia , Bahillo Alfonso , Gratão Aline Cristina Martins , Ottaviani Ana Carolina , Ferreira Ana , Ferreira Camila Rafael , Paúl Constança , Monteiro Diana Quirino , Barham Elizabeth Joan , Orlandi Fabiana de Souza , van der Roest Henriëtte G. , Guzmán José Miguel Toribio , de Cruz Keila Cristianne Trindade , Correa Larissa , Platon Luis , Maciel Luiza Barros , Martin Manuel Angel Franco , Zazzeta Marisa Silvana , Ribeiro Oscar , Pavarini Sofia Cristina Iost , Oliveira Déborah
Published: December 2023

Background

e‐Health interventions have shown to be effective in supporting informal caregivers of people living with dementia (PLwD) and have been explored as a solution to overcome the accessibility issues of conventional face‐to‐face interventions. However, uptake and retention in such interventions might be hindered by a lack of user‐centred design and poor usability. Understanding the usability and acceptability of e‐health interventions may help save costs and improve user experience and engagement. The methods and results from three usability and acceptability studies of three culturally adapted versions of WHO’s iSupport for dementia (Brazil, Portugal and Spain) are presented

Method

Three mixed‐methods studies have been conducted in Brazil, Portugal, and Spain. Participants were caregivers of PLwD (combined n = 79) and health/social support professionals (n = 12). The usability and acceptability assessment protocols included pre and post‐usability testing surveys, task performance on iSupport’s interface, validated scales (System Usability Scale and Computer System Usability Questionnaire), structured and semi‐structured interviews, and focus groups. Thematic analysis was used to analyze text data.

Result

Participants’ perceptions of iSupport’s usability were excellent for both the Brazilian and the European‐Portuguese versions (86.5 and 89.5 points in the SUS, respectively). When measured, success rates were high for tasks performed in the interface, suggesting easiness of use. In its different country‐specific versions, iSupport’s interfaces were described as user‐friendly, and its contents as useful and responsive to caregivers’ needs. Several suggestions associated with the program’s layout, functional requirements, and content were identified as necessary to improve the usability and acceptability of iSupport.

Conclusion

The Brazilian and European‐Portuguese versions of iSupport were considered acceptable and usable by family caregivers of PLwD. Lessons learned, challenges identified, and methods used to assess the usability and acceptability of iSupport may be replicated and/or used to inform the development of other country‐specific versions within iSupport’s network, potentially lowering the development costs and improving the appropriateness of those versions. Usability and acceptability studies of iSupport are key to discovering design problems and usage patterns of the program, and are therefore valuable for planning feasibility studies and effectiveness trials.
iSupport for South Asian carers in the UK
Authors: Kurana Suman , Fisher Emily , Azadi Afra , Begum Aziza , Ahuja Banika , Proctor Danielle , Windle Gill , Flynn Greg , Singh Gurmel , Mukaty Nuvera , Masterson‐Algar Patricia , Mahmood Saleyha , Spector Aimee E , Stott Joshua
Published: December 2023

Background

There is a pressing need for interventions tailored to diverse clinical and demographic populations of dementia caregivers. The South Asian community represents the largest minority ethnic group in England and Wales. However, this community is underserved in research with many online interventions not addressing the specific care needs of South Asian carers in the UK. In this community, awareness about dementia is reported to be lower in comparison to the general population. Additionally, high levels of stigma and pressures to keep care within the family can limit help‐seeking. The World Health Organization’s ‘iSupport’ is an online intervention that can be tailored to meet the needs of diverse populations.

Method

‘iSupport’ will be adapted for caregivers of UK‐based South Asian people with dementia (with translations into Bengali, Punjabi and Urdu). Stakeholder consultation and co‐design involving caregivers, healthcare professionals, researchers and charity representatives will employ a range of methods including focus groups, think‐aloud and semi‐structured interviews to support the cultural adaptation of iSupport in all three languages.

Result

Adaptations for the UK South Asian population include: tailoring translations and cultural nuances that reflect the South Asian diaspora; the use of audio and videos to increase access to carers with a range of literacy levels; and addressing misconceptions about defining oneself as a caregiver. Next steps include testing the feasibility and acceptability of the adapted Bengali iSupport intervention.

Conclusion

These tailored interventions will better support the knowledge and skills of South Asian caregivers. The e‐health approach enables broad reach and offers support to those unable to access interventions due to cultural and language barriers, resulting in informed communities and improved wellbeing outcomes for carers and people with dementia.
Empowering Carepartners Navigating Younger‐Onset Dementia
Authors: Cose Diana Shulla , Dean William
Published: December 2023

Lorenzo’s House, an international nonprofit empowers families living with younger‐onset dementia through our holistic model.

Younger‐onset dementia does not just impact the person diagnosed, it impacts a whole family. Younger families are too often undiagnosed, under‐resourced and misunderstood in the dementia community. With this diagnosis comes a dramatic shift in a family’s dynamic and they are alienated from popular dementia resources geared towards people who are diagnosed later in life. Younger‐onset strikes people in their 30s, 40s, 50s and early 60s. There is an urgency for support as there has been a 200% increase between 2013‐2017 in this age range, according to a 2020 report by BlueCross BlueShield. This gap in appropriate services and alarming uptick leaves families on an isolated path, searching for resources, support, and basic understanding.

Younger carepartners are in a uniquely important and difficult position as they are responsible for being the primary carepartner to their loved one, breadwinner for the household, and for parenting independently ‐ all while navigating the complexities of the diagnosis. There is a need for personal connection and resource exchange. The best guidance often comes from people walking a similar path.

At Lorenzo’s House we ensure carepartner paths cross. Our Healing Spaces and Carepartner Connections offer this innovation of personalized connection and resource exchange. Our Healing Spaces unite a community of carepartners from across the globe. These are spaces of bravery, understanding and respite exclusively designed for younger families navigating dementia. Through our gender based Bright Brunch and Light Lounge sessions, carepartners listen deeply, exchange resources and build community. Carepartner Connections is a proven model designed to create one‐on‐one carer matches that support social emotional wellness and exchanges relevant resources. By building a digital and in‐person international network of carepartners, we cure isolation by uniting common journeys.
Interhemispheric EEG Coincidence during REM sleep correlates with mild cognitive impairment
Authors: Milman Noah , Reynolds Christina L , Dude Jason , Boyd Jill , Zangrilli Maggie , Recoder Natasha , Ju Yo‐El , Lim Miranda
Published: December 2023

Background

There exists a bidirectional relationship between sleep disruption and neuropathology in Alzheimer’s disease (AD). Interhemispheric EEG coincidence during sleep polysomnography (PSG) may reflect coordination of brain networks. While several EEG features of non‐REM (NREM) sleep, such as slow wave activity, are associated with proteins and measures related to AD pathogenesis, less is known about EEG features of rapid eye‐movement (REM) sleep in AD. We assessed EEG features across hemispheres during REM, NREM, and wake states, comparing participants with mild cognitive impairment to cognitively‐normal participants.

Method

EEG was collected during an attended overnight polysomnogram from the Biomarkers of Alzheimer’s Disease in Sleep and EEG (BASE) cohort (n = 87, average age 70.7 ± 4.6 years), 19 of whom had Clinical Dementia Rating (CDR) of 0.5, considered Mild Cognitive Impairment (MCI) and the rest healthy controls (HC). A custom low frequency (0.5 – 8Hz) EEG oscillatory peak detector was implemented in MATLAB across six EEG leads (F3, F4, C3, C4, O1, and O2). Interhemispheric EEG coincidence between lead pairs was calculated as the number of mini‐epochs with oscillatory peaks in both leads divided by the number of mini‐epochs with a peak in either or both leads.

Result

Neither sleep macro‐architecture (total time in any stage of sleep, wake after sleep onset, number of awakenings and sleep efficiency) nor spectral power density in delta or theta frequency bands differed between HC and MCI groups. Interhemispheric EEG coincidence was reduced during REM sleep in F3‐F4 (Frontal), C3‐C4 (Central) and O1‐O2 (Occipital) lead pairs in the MCI group compared to HC, all regions p<0.0001. REM F3‐F4 coincidence was negatively correlated with nighttime awakenings (r ‐0.4, p<0.0001). Performance on the Word‐Pair Task, which measures memory, was correlated with REM F3‐F4, C3‐C4, and O1‐O2 coincidence (r0.29 p0.009; r0.27 p0.01; r0.25 p0.03, respectively).

Conclusion

A novel neurophysiological marker of interhemispheric EEG coincidence, specific to lower frequency spectra during REM sleep, differentiates MCI from HC and correlates to memory performance. Interhemispheric EEG coincidence may reflect coordination of brain networks during REM and may be sensitive to changes in cognitive status that would otherwise go undetected by traditional analyses of sleep macro‐architecture.
Developing the 4R model for care delivery, coordination, and patient and their care partners self‐management for suspected or diagnosed Alzheimer’s disease and related dementias
Authors: Weldon Christine B , Zwerling Jessica , Martin Joanna , Wolf Michael S , Rapkin Bruce , Nair Kavita V , Phillips Kathryn A , Epperly Mikele , Yagnik Supriya Kumar , Trosman Julia R
Published: December 2023

The incidence of Alzheimer’s disease and related dementias (ADRD) is on the rise, but diagnoses are frequently delayed, and treatment options are limited. Nevertheless, systematic care protocols and plans of action for patients and their care partners (partners) are widely thought to enhance patient outcomes, facilitate patients/partners' sense of control and optimize patients’ quality of life. However, in ADRD, these approaches are lacking or limited in their ability to facilitate care or enable patient/partner self‐management. We explored whether the 4R model, previously tested in oncology, could address these gaps in ADRD (4R = Right Information/Care/Patient/Time).

The 4R model is a novel approach and set of clinician‐ and patient‐facing tools for care planning and delivery, which addresses challenges to appropriate timing and sequencing of complex care and patient self‐management. 4R demonstrated significant improvement in patient self‐management and timing/sequence of care delivery in cancer (Trosman, JCOOP 2021). Under 4R, patients/partners and care teams use a novel plan of action called Care Sequence® that systematically guides them through care.

Herein, we developed the scope of comprehensive ADRD care based on guidelines, literature and expert input (Figure‐1); compared relevant aspects of ADRD and advanced cancer to understand whether and how previous 4R work may apply (Table‐1); and conducted interviewed experts in ADRD to identify relevant gaps and implications to a potential use of the 4R model in ADRD (Table‐2).

Our findings indicate that adapted to ADRD, the 4R model has the potential to improve the timeliness of diagnosis, care initiation and subsequent care, as well as care coordination and patient/partner self‐management. The 4R model may give providers a concrete template‐based care plan for communicating with other specialties and with patients/partners. A concrete plan of action may remove the barrier of providers’ hesitancy to engage in screening and diagnosis of ADRD with their patients. 4R may also help patients/partners to seek help with potential cognitive issues through a concrete plan of action, restoring the sense of control and improving their ability to self‐manage aspects of the care process. Our next step is a U.S.‐based project to design and evaluate the 4R model ADRD, starting with Alzheimer’s.
Examining sex differences in Alzheimer Disease neuropathology in Down Syndrome
Authors: Head Elizabeth
Published: December 2023

Background

People with Down syndrome (DS) have a higher risk of developing Alzheimer disease (AD), due to an extra copy of the amyloid precursor protein (APP) gene on chromosome 21. Overexpression of APP is associated with increased production of amyloid beta (Aβ) in DS, and contributes to early onset of AD. Some studies suggest women with DS are at a higher risk for AD, while others find the opposite. Sex differences may be mediated by estrogen, which is critically involved in neuronal survival and modulation. We hypothesized that lower levels of ERα protein would correlate with increasing AD pathology in DS.

Method

We examined 35 brains (frontal and occipital cortices) of people with DS and DS with AD. Serial sections were immunostained for phosphorylated tau (pTau ‐AT8) and Aβ (6E10) along with ERα and quantified using QuPath. Spearman rank correlations using log transformed % load data were calculated, Kruskal‐Wallis was used to compare men and women.

Result

No significant differences in protein levels of ERα, Aβ, or tau were observed when comparing men and women with DS. However, we found higher levels of ERα protein were associated with higher levels of Aβ in the gray matter of the occipital cortex (R = 0.7078; p = 0.0005) in all cases. This positive correlation was driven primarily by women. Females with DS showed a significant positive association with Aβ and ERα (R = 0.93; p = 0.00012) whereas men showed a weaker trend (R = 0.62; p = 0.057). In contrast, no significant associations between ERα, Aβ or pTau were observed in the frontal cortex. PTau measures in the occipital cortex in women with DS were positively associated with ERα (R = 0.61; p = 0.055), whereas men with DS showed a slight negative, though not significant association (R = ‐0.29; p = 0.41). There was no such trend in the frontal cortex.

Conclusion

These results suggest ERα, in contrast to our original hypothesis, may be increasing in response to AD pathology to preserve neuronal health in the occipital cortex. Lack of similar positive associations in the frontal cortex may be related to AD progression, with the occipital cortex being affected later in disease, giving us the opportunity to observe increased ERα.
Female TgF344‐AD hippocampal plasticity after estrogen deprivation
Authors: Rae Rosaria Josephine , Smith Lindsey , Goodman Anthoni , McMahon Lori L
Published: December 2023

Background

Alzheimer’s Disease (AD) is the seventh leading cause of death worldwide, disproportionately affecting women, with two‐thirds of individuals with AD being female. A decrease in circulating ovarian estrogen during menopause is believed to be a contributing factor to this discrepancy in disease prevalence. AD pathology is known to impact synaptic transmission in the hippocampus, resulting in memory deficits, a hallmark symptom of AD. This study investigates the effect of estrogen deprivation in the dentate gyrus (DG) and CA1 region, areas affected early on in the disease and crucial for memory. As the disease progresses, deficits are seen in the dentate gyrus prior to CA1 region supporting the anatomical spread of the pathology.

Method

Synaptic signaling was assessed in DG and CA1 hippocampal subregions of 9 month old TgF344‐AD female rats who underwent long‐term (from ages 3 to 9 months) ovarian hormone deprivation. Extracellular dendritic field potential recordings were conducted in the DG by stimulating the medial perforant path onto dentate granule cells, and in the CA1 region by stimulating Schaffer collateral axons. Input/output relationship, paired pulse ratio, and long term potentiation were assessed, analyzed, and statistically compared between TgF344‐AD rats and non‐transgenic hormone deprived littermates.

Result

It was found that AD females were able to maintain synaptic transmission as there were no significant differences found in the input/output relationship, paired pulse ratio, or long term potentiation between AD animals and their controls.

Conclusion

These results show that at this early stage in the disease, ovarian estrogen deprivation does not accelerate synaptic impairment. These results also suggest the possibility that a compensatory mechanism exists at these synapses to maintain function.
A Pragmatic Pilot Phase Preliminary Results of Daily Engagement in Meaningful Activity Professional Program for home care patients with subjective cognitive decline
Authors: Lu Yvonne YF
Published: December 2023

Background

A substantial number of home health older patients with subjective cognitive decline (SCD) require more time, structure, and guidance to complete tasks and adjust to new skills and environments, thereby presenting complex demands on home health services and caregivers. Without support, patients with SCD often lose their sense of control, have fewer personal choices, disengage from meaningful activities, and have less confidence in their ability to manage daily challenges and other chronic illness issues. Our multi‐component intervention titled, Daily Engagement in Meaningful Activities Professional (DEMA‐Pro) intervention was developed based on five preliminary studies shown to improve health outcomes and promote confidence in managing daily challenges in patients with SCD. The objectives of pragmatic pilot phase study were to 1) evaluate the feasibility and benefits of a DEMA‐Pro for patients with SCD; 2) explore nurses’ experience of DEMA‐Pro implementation.

Method

We used a one‐group, pre‐ and post‐intervention design and recruited 49 patients with SCD, aged 50+, from the four home healthcare sites to receive six weekly DEMA‐Pro telephone sessions. The Outcome and Assessment Information Set D (OASIS‐D) were collected at starting date (pre‐intervention) and discharge date (post‐intervention). Quantitative surveys and qualitative focus group methods were used to explore the DEMA‐Pro nurses (n = 3) experiences of implementation.

Result

The consent rate was 67.1%, the completed intervention rate 36.7%, and the partial completed intervention rate 25.5%. For 36 subjects with discharge data available, both IADLs and self‐care scores improved (d = 3.11 and d = 2.66, respectively). Specifically, those that completed all 6 DEMA‐Pro sessions (n = 14), partial completers (n = 12), and non‐completers (n = 10), had improved scores on IADLs (d = 4.0, 4.2, and 2.5, respectively) and Self‐Care (d = 3.7, 3.1 and 2.0, respectively). Completers had greater improvement than non‐Completers for both outcomes and greater improvement on IADLs than partial completers (all p‐values < 0.03). Nurses reported high satisfaction with their training, and high confidence that the implementation of the intervention met patient and caregiver needs.

Conclusion

The DEMA‐Pro has shown benefits and feasibility that will need further testing in a large pragmatic trial in homecare settings.
Immunomodulating mechanisms of human neural stem cell transplantation in a transgenic Alzheimer’s disease mouse model
Authors: Chen Kevin S , McGinley Lisa M , Noureldein Mohamed , Hayes John M , Rigan Diana M , Kwentus Jacquelin F , Mason Shayna N , Mendelson Faye E , Savelieff Masha G , Feldman Eva L
Published: December 2023

Background

Many pathways are implicated in pathogenesis of Alzheimer’s disease (AD). Stem cells are a promising strategy to simultaneously correct multiple pathways; however, therapeutic mechanisms of stem cells are not well described. Here, we used spatial transcriptomics to quantitate gene expression following intracranial transplantation of human neural stem cells (hNSCs) in a mouse model of AD.

Method

The 5XFAD mouse model was utilized. An hNSC cell line (HK532‐IGF1, Palisade Bio) was transplanted into fimbria fornix of the hippocampus (6 total injections, 180,000‐600,000 total cells). Spatial memory was assessed by Morris water maze. Amyloid plaques were assessed by immunofluorescence and ELISA. Hemibrains were submitted for spatial transcriptomics (Visium 10X, 10X Genomics) and significant differentially expressed genes (DEGs) were identified (p < 0.05). Pathway enrichment was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), and CellChat network analysis examined communication between cell populations.

Result

hNSC transplantation restored learning curves of 5XFAD mice in Morris water maze, mimicking wild‐type performance (Fig 1A). However, there were no changes in amyloid‐beta burden (Fig 1B‐C). Spatial transcriptomics elucidated non‐amyloid hNSC therapeutic mechanisms. In hippocampal subregions, we discovered 1061 normalized DEGs. KEGG pathway analysis revealed significant impact on protein processing (“ubiquitin mediated proteolysis”, “protein export”, and “proteosome”), “long‐term potentiation,” and “metabolic pathways” (Fig 2). Plaque induced genes were normalized upon hNSC transplantation, particularly in microglia (Fig 3A). A reduction in stage 1 and stage 2 disease associated microglia (DAM) was seen, without affecting homeostatic microglia (Fig 3B). CellChat analysis showed hNSCs interacted with stage 1 and stage 2 DAM along many pathways (Fig 3C). Pathologic signaling between hippocampus and DAM upregulated in the 5XFAD model was again normalized upon hNSC transplantation.

Conclusion

Transplantation of hNSCs rescued memory in 5XFAD mice. No change in amyloid plaque burden was noted, but spatial transcriptomics revealed many genes dysregulated in 5XFAD that were normalized with hNSC transplantation. hNSCs interacted with and normalized populations of stage 1 and stage 2 DAM. Our results suggest that hNSCs exert beneficial effects in part by modulating microglia‐mediated neuroinflammation in AD.
Longitudinal sleep instability predicts cognitive decline and is associated with increased MRI‐visible perivascular space burden
Authors: Keil Samantha A , Schindler Abigail G , Piantino Juan , Lim Miranda , Willis Sherry L , Iliff Jeffrey J
Published: December 2023

Background

Although emerging data suggest a direct link between sleep duration, aging, and cognitive performance, the impact of longitudinal sleep patterns have on Alzheimer’s disease‐associated pathology and cognitive decline remains unclear.

Method

Utilizing longitudinal data on self‐reported sleep duration collected within the Seattle Longitudinal Study, we used a Cox proportional hazard (CPH) regression to evaluate the relationship between longitudinal sleep factors on the development of cognitive decline. Additional analysis in a sub‐cohort utilized multivariate linear regression prediction analyses to evaluate the predictive value of these longitudinal sleep factors on the incidence of developing cognitive impairment over an interval of 10 years.

A cohort within the study received MRI and FLAIR neuroimaging, enabling the assessment of the impact these longitudinal sleep factors have on subcortical white matter MRI‐visible perivascular space burden (PVS). A semi‐automated segmentation algorithm accounted for PVS total burden and volume, as well as average PVS width, length, and median volume across participants, blinded by group.

Result

CPH analysis found years of education (HR 1.12, 95% CI 1.02, 1.22), APOE4 status (HR 2.18, 95% CI 1.37, 3.49), higher depression scores (HR 1.08, 95% CI 1.04, 1.13), short sleep phenotype (HR 1.78, 95% CI 1.03, 3.08) and increased sleep variability (HR 3.10, 95% CI 1.66, 5.80) were significantly associated with cognitive impairment. Further, when including these factors into our linear regression prediction analyses, age (p<0.0001), depression (p = 0.01) and sleep variability (p = 0.042) were significant predictors of cognitive impairment over a 10‐year period.

Preliminary analysis showed significant association between high sleep variability and increased whole‐brain PVS volume (p = 0.04) and length (p = 0.03), with a significant correlation between sleep variability and median PVS volume (p = 0.04). Follow‐up analysis evaluated PVS features within the wider cohort.

Conclusion

These findings suggest that variability in longitudinal self‐reported sleep duration exerts a previously unappreciated influence on downstream cognitive performance and pathological processes, potentially including glymphatic dysfunction. These findings elaborate the link between sleep instability, aging, cognitive decline and neuropathologic disease state. Future studies should evaluate these findings on an independent cohort to assess whether sleep variability of different time scales (weeks, years, decades) exerts similar effects on these outcomes.