bluuebunny/crossref_metadata_2025 huggingface dataset:
High diagnostic performance of plasma and cerebrospinal fluid beta‐synuclein in the differential diagnosis of sporadic Creutzfeldt‐Jakob disease
Authors: Rumeileh Samir Abu , Halbgebauer Steffen , Bentivenga Giuseppe , Barba Lorenzo , Baiardi Simone , Mastrangelo Andrea , Oeckl Patrick , Steinacker Petra , Mammana Angela , Capellari Sabina , Otto Markus , Parchi Piero
Published: December 2023

Background

Beta‐synuclein (beta‐syn) is an emerging biofluid marker for synaptic damage in several neurological diseases. In particular, patients with prion disease showed significantly higher cerebrospinal fluid (CSF) and blood beta‐syn levels compared to controls and subjects with other neurodegenerative disorders. However, to date, no study explored the biomarker distribution and prognostic value across the heterogeneous spectrum of sporadic Creutzfeldt‐Jakob disease (sCJD) as well as its diagnostic performance in the real‐life setting of patients with rapidly progressive dementia (RPD).

Method

Using in house established immunoassays we measured CSF and/or plasma beta‐syn concentrations in 150 patients with sCJD, belonging to the most prevalent molecular subtypes [MM(V)1, VV2 and MV2K], and in 106 subjects with non‐prion RPD. In the same cohort, we assessed CSF levels of total tau (t‐tau) and protein 14‐3‐3. We compared the diagnostic performance of CSF/plasma beta‐syn with that of classic CSF markers and we tested the possible associations of CSF/plasma beta‐syn with survival in patients with sCJD.

Result

sCJD patients showed higher CSF and plasma beta‐syn levels compared to non‐prion RPD subjects (p<0.001 for both) (Figure 1A, B). Different CSF and blood profiles of beta‐syn were observed for the most prevalent sCJD molecular subtypes (Figure 1C, D). Concerning the diagnostic value, CSF beta‐syn outperformed 14‐3‐3 (AUC 0.95 vs. 0.89, p = 0.028) but not t‐tau (AUC 0.92, p = 0.212). Further, the discriminative accuracy of plasma beta‐syn (AUC 0.91) was not inferior to that of classic CSF markers (t‐tau, p = 0.765 and 14‐3‐3, p = 0.447) and CSF beta‐syn (p = 0.135). In the whole sCJD cohort, CSF and plasma beta‐syn were significantly associated with survival at univariate analyses but not after accounting for codon 129 genotype or molecular subtype.

Conclusion

CSF beta‐syn performed similar or better compared to t‐tau and 14‐3‐3, respectively, thus, the marker might represent an alternative first‐level test in patients with suspected sCJD. Most interestingly, the high diagnostic value of beta‐syn in plasma, which was comparable to that of classic CSF surrogate markers, suggests that beta‐syn might be used as highly accurate blood surrogate marker in sCJD for patient screening and monitoring.
Involving people with dementia in dementia research: principles, challenges and practical examples
Authors: Gove Dianne , Diaz Ana , Roberts Chris
Published: December 2023

Background

Alzheimer Europe is keen to promote the involvement of people with dementia in research, not only as participants but also in the context of Public Involvement (PI), by generating ideas for research, advising researchers, being involved in consultations and being directly involved in research activities.

Method

To achieve this, in 2012, Alzheimer Europe set up the European Working Group of People with Dementia (EWGPWD). The group is currently composed of 15 men and women living with different types of dementia and from different European countries. Members of the EWGPWD provide advice and feedback to all activities of the organisation and are involved in several European projects in the context of PI.

Result

Alzheimer Europe has published a number of peer‐reviewed articles and reports on the topic of PI in dementia research carried out by members of the EWGPWD. Some of these articles were co‐authored by members of the EWGPWD.

Conclusion

During the session, we will provide an overview of (i) the context in which the EWGPWD was set up a decade ago, (ii) our approach to PI and how it has evolved overtime to adapt to new situations (e.g. in the context of the COVID pandemic), (iii) the main lessons we have learnt and what works well to ensure a meaningful contribution of members and promote respect and wellbeing, and (iv) some of the challenges we are still working on (e.g. diversity and understanding impact). We will also present some practical examples of the PI activities which we have organised in different European projects and the impact that this had for the project. The session will be jointly facilitated by a member of Alzheimer Europe and a person with dementia (i.e. a member of the EWGPWD).
Developing a Patient and Public Voice/Involvement (PPV/I) program at the Global Brain Health Institute (GBHI) with global impact
Authors: Mariano Luciano Inácio
Published: December 2023

Background

GBHI, a brain health leadership program for international fellows from across disciplines, undertook a 24‐month project to develop a PPV/I program aiming to: (1) provide a PPV/I perspective on GBHI activities; (2) introduce fellows to the principles and practice of PPV/I; (3) develop a ‘global PPV/I toolkit’; and (4) develop a PPV/I Special Interest Group to inform Senior Fellows around the world about PPV/I to support their local work in brain health.

Method

Phase 1: Recruiting an international panel of people with lived experience of dementia to inform GBHI’s work, called ‘‘Dementia Community Research Advisory Panel’ (DC‐RAP). Phase 2: Educating: We designed and implemented a dementia‐specific PPV/I training curriculum for GBHI fellows & a PPV/I awareness raising program for GBHI faculty & staff; Phase 3: Creating & disseminating: We developed a global resource document (‘toolkit’) to support the introduction of brain health professionals from different disciplines working around the world to PPV/I practice, fostering a global PPV/I dementia network; Phase 4: Evaluation: We tracked learning outcomes of the project at staff/faculty and Fellow level through Kirkpatrick model and overall project success through Kotter’s 7‐step organizational change model.

Results

Phase 1: DC‐RAP formed and solidified within GBHI to inform GBHI activities, provide feedback on research proposals and lay summary writing. Phase 2: We delivered a PPV/I training program for the 2020 and 2021 Fellow cohorts, which is now fully integrated into curriculum. Phase 3: The GBHI ‘Global Public Involvement in Dementia Guidelines’ were launched by a team of Senior Fellows from 10 countries, who have formed a PPV/I Special Interest Group for PPV/I practice beyond the anglosphere. Phase 4: A Kirkpatrick evaluation revealed changes in PPV/I knowledge, attitude and practices for Fellows and staff/faculty. Multiple strategic wins have enabled us to embed a culture of PPV/I at GBHI, evident in mapping against Kotter’s 7‐step organizational change model.

Conclusion

Embedding dementia relevant PPV/I in GBHI provides the potential to disseminate PPV/I principles within GBHI and globally, fostering meaningful public engagement in dementia research and projects to advance dementia understanding worldwide.
Public Involvement: the EURO‐FINGERS approach
Authors: Diaz Ana , Mangialasche Francesca , Hendriksen Heleen M.A. , Rosenberg Anna , Birck Cindy , Montague Nick
Published: December 2023

Background

The JPND‐funded project EURO‐FINGERS (2019‐2023) is part of the World‐Wide FINGERS network of multidomain trials for dementia risk reduction and prevention. It aims to develop relevant and standardised tools and methods for future trials or multidomain interventions to reduce dementia risk.

Method

Since its beginning, EURO‐FINGERS has involved people from the general public in the project by means of an Advisory Board (AB). The AB is composed of 14 people from seven different European countries, who 1) have participated in prevention trials, 2) have a diagnosis/label of Subjective Cognitive Decline, Mild Cognitive Impairment, or dementia, and/or 3) take care of someone with dementia.

Result

The AB has worked closely with the researchers in the consortium and provided input to the different tools and methods developed in the project. Due to the COVID pandemic, all this work has been online.

Conclusion

In the session, we will describe the main principles, challenges and approach used to set up the AB and meaningfully involve people with an interest in/ affected by dementia in the project. Next, we will present some of the work developed with the AB, specifically on the important topic of communication in this complex field. This will include reflections on the terminology to discuss the topic of risk reduction and dementia prevention in different contexts, as well as the more specific topic of dementia risk communication in the context of the memory clinic. The latter is an example of one of the tools which the consortium is developing. To close the session, the project coordinator and a member of the AB will address the topic of impact and value of this type of work for researchers and for members of the public.
Restoring Memory Function in a Diabetic Mice Model
Authors: Olayinka Juliet Nnenda , Akawa Oluwole Abidemi , OBISESAN ABIOLA , Awogbindin Ifeoluwa Oluleke , Green Grace Igbogi
Published: December 2023

Background

Diabetes mellitus affects memory function in Alzheimer’s disease (Baglietto‐Vargas et al., 2016). Quercetin (Qt) and vitamin (Vit E) possesses anti‐inflammatory, memory enhancing and anti‐diabetic activities (Bui and Nguyen, 2017). This study explored the effects of administering both quercetin and vitamin E against cognitive deficits and neuroinflamation in high‐fat‐diet (HFD) and streptozotocin (HS)‐induced diabetic mice

Method

Ninety male mice (n = 15) were divided into six groups and fed with HFD except the normal group for 28 days. Diabetes was induced by STZ (50 mg/kg intraperitoneally) on day 22. Weight and blood glucose levels were taken weekly. On day 15, mice in the pretreatment groups (PQt 12.5 + Vit E 200 mg/kg and PQt 25 + Vit E) commenced treatment while on day 29, mice in the posttreatment groups (PtQt 12.5 + Vit E and PtQt 25 + Vit E) commenced treatment till day 42. Memory function (Y‐maze and NORT) was performed. The hippocampus of the animal brains were harvested for biochemical assays using ELISA (acetylcholinesterase enzyme (AChE), insulin, interleukin‐ 4 (IL‐4), interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNF‐α). Immunohistochemistry was used in detecting the expression of IBA‐1.

Result

Quercetin and vitamin E significantly decreased the weight, glucose, insulin, and AChE levels in the HS‐induced mice. Memory function was restored by this combination. IL‐6 was decreased in PQt 25 + V and PtQt 25 +V; TNF‐α was decreased in PQt 25 + V and PtQt 12.5 +V while IL‐4 levels were increased in PQt 25 + V and PtQt 25 +V compared to the HS group. IBA‐1 was scarcely expressed in the PQt 12.5 mg/kg and PtQt (12.5 and 25 mg/kg) group compared to the HSgroup.

Conclusion

Administering quercetin and vitamin E restored memory function through decreasing the activity of pro‐inflammatory mediators, increasing the activity of anti‐inflammatory mediators and decreasing microglial activation in HS‐induced mice.

REFERENCES:

Baglietto‐Vargas D, Shi J, Yaeger DM, Ager R, LaFerla FM. Diabetes and Alzheimer’s disease crosstalk. Neuroscience & Biobehavioral Reviews. 2016 May 1;64:272‐87.

Bui, T. T., & Nguyen, T. H. (2017). Natural product for the treatment of Alzheimer’s disease. Journal of Basic and Clinical Physiology and Pharmacology, 28(5), 413‐423.
Wearable‐based measures of proximity and movement are associated with activities of daily living in people with dementia and perceived burden in family caregivers
Authors: Chen Kuan‐Hua , Chen Yuxuan , Levan Darius Tran , Paul Deepak , Newton Scott , Yee Claire , Merrilees Jennifer , Scheffer Julian , Chen Samson , Levenson Robert W
Published: December 2023

Background

As the disease progresses, people with dementia (PWDs) gradually lose their ability to conduct activities of daily living (ADLs) independently and increasingly rely on family caregivers (CGs) for assistance and support. This can lead to CGs experiencing increased burden. These dyadic processes may be manifested by (a) CGs’ increased physical proximity to PWDs (reflecting greater needs for CGs to monitor PWD’s needs and safety, and (b) CGs’ increased movement (reflecting greater needs to assist PWDs with ADLs and taking on additional household responsibilities). Working with an industry partner, we developed a wearable watch that measured: (a) physical proximity between PWDs and CGs; and (b) movement of CGs and PWDs in their homes. In the current study, we examined how these wearable‐based measures correlated with standard measures of PWD’s ADLs and CG’s burden.

Method

PWDs and CGs each wore a low‐energy Bluetooth watch that provided long‐battery‐life (up to four months). The watches broadcasted information about proximity to three Bluetooth receivers placed in different rooms (which helped us determine the proximity between the PWDs and CGs) and used a three‐axis accelerometer to determine movement on a second‐by‐second basis. In a nationwide US sample, 27 PWDs diagnosed with dementia or mild cognitive impairment and their co‐residing familial CGs wore these watches over a six‐month period. CGs also completed online questionnaires assessing PWDs’ ADLs (Lawton Instrumental Activities of Daily Living) and their own perceived burden from caregiving (Zarit Burden Interview) at the beginning and the end of the study.

Result

Over the six‐month period, greater increases in PWD‐CG proximity were associated with greater increases in CG’s burden (r = 0.57, p = .009). In addition, greater increases in CGs’ (but not PWDs’) movement were associated with greater decreases in PWD’s ADLs (r = ‐0.55, p = .005).

Conclusion

These wearable devices show promise of providing scalable remote measures that are associated with ADLs in PWDs and burden in CGs. Findings also underscore the dyadic nature of dementia caregiving, with assessments of CGs useful for understanding changes in ADLs in PWDs, and assessments of PWDs useful for understanding changes in burden in CGs.
Unobtrusive In‐Home Digital Monitoring of Frontotemporal Dementia: Feasibility and Adherence
Authors: Wise Amy B. , Paolillo Emily W. , Beattie Zachary T , Wu Chao‐Yi , Rodrigues Nathaniel , Gothard Sarah , Heuer Hilary W. , Forsberg Leah K. , Chavez Diana , Holiday Kelsey , Mendez Mario F. , Boeve Brad F. , Boxer Adam L , Kaye Jeffrey A , Rosen Howard J. , Staffaroni Adam M.
Published: December 2023

Background

Frontotemporal Dementia (FTD) patients are geographically dispersed and often have behavioral and/or motor deficits that limit access to in‐person clinical trials and research. To address these participation barriers, we investigated the feasibility of installing in‐home sensor technologies to remotely assess everyday functioning in FTD.

Method

We aimed to recruit 20 FTD participants with a variety of clinical syndromes, including behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), corticobasal syndrome (CBS), and progressive supranuclear palsy (PSP). We also aimed to enroll a study partner for each participant that lived in the same home to serve as a control. The Collaborative Aging Research Using Technology (CART) platform was installed in participants’ homes to collect continuous data for up to two years, using motion sensors, physiological monitoring devices (e.g., scales, sleep sensors), electronic pillboxes, and wearable actigraphs. Computer use and driving patterns were also tracked. Technology was installed either via a study coordinator visit or remotely through video and written instructions, based on schedule and logistics. Participants were asked to complete a weekly Qualtrics survey about time away from home, visitors, and health changes.

Result

Of the 159 UCSF participants available for recruitment through ALLFTD and other FTD projects, 28% (N = 45) met inclusion criteria. Of those 45, ten were ineligible due to advanced disease severity or relocation to an assisted living facility. A third (36%, N = 17) declined due to overwhelmed study partners (N = 3), declined any subproject participation (N = 7), sensitivity to participant’s diagnosis (N = 2), or lack of response (N = 5). Two additional participants were recruited through UCLA’s ALLFTD cohort. The platform has been installed in 19 homes (bvFTD: n = 10; PPA: n = 5; CBS/PSP: n = 4). Two homes discontinued due to death or relocation to assisted living facility. Mean data collection is 360 days (max = 527). Of 103 reported technological issues, 92% were resolved without additional home visits, either by phone or email. Participants completed 65% of weekly health questionnaires.

Conclusions

Although there were some recruitment and retention challenges, these findings generally provide preliminary support for the feasibility and sustainability of conducting comprehensive in‐home passive data research in FTD.
Technology co‐design and feasibility of a smartwatch‐based interventions to support ADL in people with dementia
Authors: Goerss Doreen , Köhler Stefanie , Teipel Stefan
Published: December 2023

Background

The number of smartwatch users worldwide continuously increased within the last 5 years. Still, older adults and patients with dementia miss to profit from opportunities of wearable assistive technologies. Factors that influence technology adoption were reviewed extensively in theory, based on theoretical models and scales, but empirical evidence is scarce.

Method

We hypothesized that interventions from smartwatches can trigger certain behaviors in PwD or persons with MCI to address specific domains which are affected in neurodegenerative diseases. Based on semi‐structured interviews with caregivers, medical experts and persons with dementia (n = 10, respectively) we identified four domains with need for assistance. After prototype testing, we implemented two tasks presented by the smartwatch, covering the domains “nursing” and “activity”. The watch prompted the user to A) drink some water and B) circle bells on a worksheet. Participants were randomly assigned to group 1 (regular, n = 20) or group 2 (intensive, n = 20). The modes varied in intervention‐intensity with two different levels of vibration intensity, loudness and additional animations. If patients did not react as intended, interventions were repeated up to three times, irrespective of the group. Observations took place in a university hospital. Patients’ reactions were remotely observed via cameras. Participants’ feedback was obtained with questionnaires after the observation.

Result

Participants of group 1 and 2 did not differ with respect to mean age, cognition (MMST) or sex. Interventions in intensive mode were more often successful (n = 30/40) than regular interventions (n = 18/40). “Non‐responder” (patients that completed no task) were only found in group 1 (n = 6). Task A was completed more often (n = 32/40) than task B (n = 16/40). Surprisingly, repetitions improved the outcome only in 4 cases, but failed in 32 cases. The vast majority of participants reported sufficient visibility and audibility of smartwatch content (n = 35/40). Obtaining users’ feedback was challenging via usability questionnaires, which contained negatively and positively worded items on a 5‐step Likert scale.

Conclusion

Smartwatches can be customized to interact positively with older adults with cognitive impairment and influence behavior of PwD or MCI at least on short‐term. Further empirical studies are necessary to enhance design and functional range of devices.
The effect of computerized cognitive training and exercise on white matter integrity: a secondary analysis of a randomized controlled trial
Authors: Lien Ryu , Dao Elizabeth , Brinke Lisanne F Ten , Silva Nárlon Cássio Boa Sorte , Liu‐Ambrose Teresa
Published: December 2023

Background

As a consequence of aging, the structure of the brain can be negatively impacted, and consequently, cognitive function. Although aerobic exercise and computerized cognitive training (CCT) are promising lifestyle interventions to prevent or delay cognitive decline, the underlying mechanisms of the effect of CCT, with or without exercise, on cognitive function remain poorly understood. Diffusion tensor imaging (DTI) is a neuroimaging technique for detecting changes in white matter (WM) tissue. Common DTI metrics such as fractional anisotropy (FA) can be summarized as a measure of overall WM integrity. The aim of this analysis was to explore the effect of CCT, with or without exercise, on WM integrity in healthy older adults.

Methods

This sub‐analysis included 65 community‐dwelling older adults aged 65‐85 years. Participants were enrolled in an 8‐week proof‐of‐concept randomized controlled trial and were assigned to either: 1) Group‐based CTT (Fit Brains; FBT; n = 19) 3x/week for 1hr plus 3x/week home‐based training; 2) Group‐based CCT preceded by exercise (ExFBT; n = 22) 3x/week for 1hr plus 3x/week home‐based training or; 3) Group‐based balanced‐and‐toned (BAT; n = 24) classes 3x/week for 1hr (control). DTI scans were acquired at baseline and at trial completion. Analysis of covariance (ANCOVA) evaluated treatment effects on FA at trial completion controlling for baseline age, MoCA, BMI, and FA. We conducted planned contrasts of FBT vs. BAT and ExFBT vs. BAT. In addition, we included an exploratory comparison between ExFBT vs. FBT.

Results

We found significant group differences in fornix and superior longitudinal fasciculus (SLF) FA at trial completion. Planned contrasts revealed significantly greater fornix FA in BAT vs. FBT (mean difference = 0.015, 95%CI = 0.002‐0.029). Also, fornix FA was significantly greater in ExFBT vs. FBT (mean difference = 0.017, 95%CI = 0.003‐0.031). In addition, SLF FA was significantly greater in ExFBT vs. FBT (mean difference = 0.008, 95%CI = 0.001‐0.014) at trial completion.

Conclusion

These findings suggest CCT alone may be detrimental to WM integrity, potentially due to its sedentary nature.
Relationship between telomere shortening and early subjective depressive symptoms and cognitive complaints in older adults
Authors: Koh Seong‐Ho , Han Myung‐Hoon , Lee Eun‐Hye , Yoo Hyun‐Jung , Park Hyun‐Hee , Choi Seong Hye
Published: December 2023

Background

Telomere length (TL) has been reported to be associated with depression and cognitive impairment in elderly. Early detection of depression and cognitive impairment is important to delay disease progression. Therefore, we aimed to identify whether TL is associated with early subjective depressive symptoms and cognitive complaints among healthy elderly subjects.

Method

This study was a multicenter, outcome assessor‐blinded, 24‐week, randomized controlled trial (RCT). Measurement of questionnaire and physical activity scores and blood sample analyses were performed at baseline and after six months of follow‐up in all study participants. Linear regression analyses were performed to identify whether early subjective depressive symptoms, cognitive complaints, and several blood biomarkers are associated with TL.

Result

Altogether, 137 relatively healthy elderly individuals (60‐79 years old) were enrolled in this prospective RCT. We observed an approximate decrease of 0.06 and 0.11−0.14 kbps of TL per one point increase in the geriatric depression scale and cognitive complaint interview scores, respectively, at baseline and after six months of follow‐up. We also found an approximate decrease of 0.08−0.09 kbps of TL per one point increase in interleukin (IL)‐6 levels at baseline and after six months of follow‐up.

Conclusion

Our study showed that both early subjective depressive symptoms and cognitive complaints were associated with a relatively shorter TL in relatively healthy elderly individuals. In addition, based on our findings, we believe that IL‐6 plays an important role in the relationship between shortening TL and early subjective depressive symptoms and cognitive complaints.
Perceived Usefulness and Perceived Ease of Decision to Use Non‐Face‐To‐Face Service Among Family Caregiver of People with Dementia
Authors: Park Myonghwa , Lee Dong Young , Kim Seon Hwa , Lee Jin Hee
Published: December 2023

Introduction

The prevalence of dementia is increasing worldwide. It will further increase by more than 50 million by 2050. Over 50% of persons with dementia are receiving care by family caregivers such as spouse or children in Korea even after introducing the long‐term care insurance system in Korea. The outbreak of COVID‐19 resulted in shifting to non‐face‐to‐face services to persons with dementia and family caregivers especially in provision of education and support. Non‐face‐to‐face services allows older persons with dementia and caregivers to participate beyond limitation of time and place during COVID‐19 pandemic.

Purpose

This study tested perceived usefulness and perceived ease of non‐face‐to face service using The Technology Acceptance Model (TAM). The TAM can explain variables such as perceived usefulness and perceived ease of technology use. Perceptions of using non‐face‐to‐face services influences the intention of use of the service. Thus, this study aims to investigate the awareness and demands for non‐face‐to‐face services among family caregivers of persons with dementia.

Method

A cross‐sectional study was conducted from 2021 to 2022 at 25 dementia centers, South Korea. Family caregivers who were 18 years/ older who had no difficulty in reading, understanding and writing had participated. An online and offline survey was used to collect data on preferred method of information access, use of smart devices, non‐face to face services and support needed for family caregivers and persons with dementia, perceive usefulness, perceived ease, and intention of non‐face‐to‐face service use.

Results and Discussion

A total of 284 caregivers responded. Seventy percent of respondents preferred online group education and self‐help groups as the best methods of getting information about dementia. Among respondents, 75% of them had smartphones. Most of them need support such as training on how to use non‐face‐to‐face services (41.2%), 24‐hour available information center (44.4%) and discount on internet usage fee (29.9%) to facilitate their use of non‐face to face service. Perceived usefulness (p <.01) and perceived ease of use (p <.01) influences the intention of use of non‐face‐to‐face services among family caregivers.
NeuralCIM® in Neurodegenerative Disorders: a hope to travel the path of Alzheimer’s.
Authors: Pérez Leslie , Pérez Saily Sosa , Obaya Teresita Rodriguez , Amable Nelky Urrutia , Silva Carmen Valenzuela , González Carmen Elena Viada , Monzón Kalet León
Published: December 2023

Background

NeuroEPO (NeuralCIM®) is a variant of EPO, which contains low sialic acid. NeuralCIM® is devoid of hematopoietic effects and produces clinical benefits in subjects with mild‐to‐moderate Alzheimer’s clinical syndrome. NeuralCIM® has received accelerated approval as a treatment for mild‐moderate AD, from the Cuban Regulatory Authority (CECMED).

Method

NeuralCIM® 0.5 mg was evaluated in patients who, after completing the clinical trial, continued to be treated with the drug, whether they had been included in the NeuralCIM® or placebo arm during trial. They were compared with subjects who did not request to continue treatment or who never received it, because they were included in the placebo group during the clinical study.

Result

After the clinical trial, the patients who continue to be treated with NeuralCIM® for two years from their inclusion in the clinical study, stabilized the disease. On the other hand, the subjects who did not continue the treatment with the drug, present a cognitive impairment characteristic of the progression of the disease. No serious adverse events related with NeuralCIM® were reported.

Conclusion

NeuralCIM® treatment, stabilized the progression of AD clinical syndrome, during two years of treatment.
Patient‐related factors and mortality associated with nasogastric tube feeding in advanced dementia
Authors: Cheng ‐ Heng Li , Cheong Chin Yee , Tay Poh Peng , Yap Philip Lin Kiat , Malhotra Chetna
Published: December 2023

Background

Previous studies have not shown survival benefit for long‐term enteral feeding. However, these studies were mostly done in residents of nursing homes, where quality of care may vary. Patients cared for in their own home may have more consistent quality of care. The aim of this study is to explore if NGT feeding prolongs life in community‐dwelling PWSDs and if not, what are other factors that may influence survival in PWSDs. Additionally, we wanted to explore patient‐related factors associated with NGT feeding to better understand the patient profile of PWSDs on NGT

Method

Community‐dwelling PWSDs with a FAST 6c score or higher, were evaluated and followed‐up for a median duration of 25 months as part of the PISCES study, a prospective longitudinal cohort study.

Result

215 PWSDs were evaluated, 9.8% (n = 21) had NGT at baseline. Compared to those without NGT, PWSDs on NGT were more likely to have had a stroke (66.7% vs 29.9%, p = 0.001), recent pneumonia (28.6% vs 7.2%,p = 0.001), recent oral antibiotics (57.1% vs 26.8%,p = 0.004) and higher Bedford Alzheimer Nursing‐Severity Scale scores(BANS‐S)(22.4 vs 18.2,P = 0.00). Although PWSDs with NGT had lower physical and verbal behavioural problems(P<0.05), there was increased use of restraints (71.4% vs 44.3%,p = 0.018), pressure sores(28.6% vs 10.8%,p = 0.02) and they had poorer Quality of life(QoL) in late‐stage dementia(QUALID) scores (27.8 vs 22.6,p = 0.006), and no difference in malnourishment rate (19% vs 20%, p = 0.865). PWSDs with NGT had no survival benefit (HR 1.42, 95%CI 0.689‐2.91) despite adjustment for significant comorbidities and dementia severity, however BANS‐S and malnourishment predicted mortality

Conclusion

While NGT use in PWSDs does not predict mortality, poorer BANS‐S scores and malnourishment were associated with higher mortality and this may be because they imply more advanced dementia. PWSDs on NGT had more advanced dementia and comorbidities. Increased use of restraints despite lower behavioural problems could have been pre‐emptive to prevent removal of NGT, while the lower QoL scores might be attributed to more advanced dementia and use of NGT with restraints. These findings can help clinicians and families make informed decisions on tube feeding.
The lived experience of people with memory difficulty or dementia from diverse ethnic backgrounds living in South Africa
Authors: van Wyk Adele
Published: December 2023

Background

The perception of dementia is culturally constructed and could differ significantly between Western and non‐Western cultures (Botsford & Harrison Dening, 2015). The term ‘dementia’ is unfamiliar to many people in non‐Western settings, who believe that memory loss is a normal part of ageing for which nothing can be done (Johnston et al., 2020, Mwendwa et al., 2021). Perceptions may determine if dementia symptoms or diagnosis would result in social support, or stigma and discrimination (Gallagher‐Thompson et al., 2012), which may affect the quality of life of the person with memory difficulty or dementia (PWD), either positively or negatively. The majority of health professionals place marked emphasis on early diagnosis, but the medicalization of dementia may create problems in some groups, rather than alleviate pressure (Summerfield, 2008).

Understanding how dementia is constructed and dealt with in diverse settings can inform the development of accessible support and services.

Method

Up to four repeated interviews were conducted with 18 PWDs and 30 care partners from Coloured, Black African, and White backgrounds. Following verbatim transcriptions and thematic analyses of 103 qualitative interviews, the themes of relationships and social connection emerged as central to participants’ experiences.

Result

Relationship quality and social connection emerged as important themes for both PWD and their care partners. Although there were cultural differences in approaches to care, participants’ ethnic background or socio‐economic status did not drive help seeking behaviour in this sample.

Conclusion

PWD and their care partners would benefit from services that focus on supporting the care relationship, promote social connection and raise awareness of dementia in the community.
#WhatsYourPlan – expediting progress towards targets of the WHO Global Action Plan on Dementia
Authors: Arthurton Lewis , Lynch Chris
Published: December 2023

Background

In 2017, all 194 Member States of the World Health Organization (WHO) unanimously adopted the Global Action Plan on the public health response to dementia 2017‐2025, the primary aim being for countries to implement National Dementia Plans (NDP). However, as outlined in Alzheimer’s Disease International’s (ADI) recent From Plan to Impact report, WHO Member States have been far too slow to act ‐ falling far short of the 146 countries target. In response, ADI launched the #WhatsYourPlan campaign, in collaboration with ADI Members, with the single‐minded aim of galvanising governments to act on their 2017 commitment.

Method

Strategizing and working with ADI Members, official communications were sent to relevant ministries to enquire as to the status of the NDP, and to request a formal meeting. For Ministries where a response was not obtained, subsequent letters were sent to elicit a response. ADI has also, in some instances, sought advice and utilised WHO regional and national offices, and other multilateral bodies and stakeholders, to help follow up with Ministries of Health for those that have been willing to engage.

Result

To date, 52 ADI members and thus 52 countries have joined the campaign. In total from the onset of the campaign, over 205 official communications have been shared with Member States, resulting in a total of 29 high‐level meetings. In total 20 Member States have committed to developing an NDP, just over a third of all participating ADI Members and over half of the number of plans already in existence in WHO Member States.

Conclusion

Only with robust NDPs can governments prepare their health and care systems to meet the complex needs of those affected by dementia. As ADI moves forwards into the second year of the campaign, the mission and scope remain, however with added urgency as the 2025 deadline gets nearer. The campaign will expand accordingly through awareness raising campaigns, media and social media engagement, and regional ADI/WHO meetings, whilst solidifying the successes of the previous year. Ultimately, with the intention of educating the public on why NDPs are so important, and to empower them to ask their own governments: #WhatsYourPlan?
Longitudinal Retinal Findings in Individuals with Mild Cognitive Impairment over a Two Year Period
Authors: Hemesath Angela , Kundu Anita , Allen Ariana , Joseph Suzanna , Ma Justin , Robbins Cason B , Grewal Dilraj S , Fekrat Sharon
Published: December 2023

Background

Changes in the retina, an embryologically brain‐derived structure, are exemplar of measurable pre‐clinical findings in neurodegenerative disease. However, limited data exists on the utility of retinal imaging in mild cognitive impairment (MCI). Changes in the retina over time may act as a quantitative measure of disease progression.

Method

This was a longitudinal study consisting of MCI patients and cognitively normal controls over the age of 50. Exclusion criteria included diabetes, uncontrolled hypertension, glaucoma, and retinal pathology. Zeiss Cirrus HD‐5000 AngioPlex optical coherence tomography (OCT) and OCT angiography (OCTA) and Mini Mental State Exam were performed at study entry and year 2.

Result

Eighty‐seven eyes of 42 MCI patients and 83 eyes of 42 controls were analyzed. Controls were matched by age (range 58‐84 years) and sex (51% male, 49% female). Average MMSE at baseline was 26.3 in MCI and 29.3 in controls (p < 0.01). There were no significant differences in rate of change (ROC) of OCT/OCTA data between controls and MCI patients at baseline. The ROC of MMSE at year 2 was ‐0.33 in controls vs ‐1.78 in MCI (p = 0.12). The ROC of OCTA perfusion density (PD) was significantly different (p < 0.04) in year 2, with an ROC of 0%/year in controls and ‐0.1%/year in MCI for both 3×3 ETDRS circle and ring as well as 6×6 ETDRS circle, inner ring, and outer ring. Changes in vessel density (VD) at year 2 were significant (p <0.04) in 3×3 ETDRS circle and ring as well as the 6×6 ETDRS circle, inner ring, and outer ring.

Conclusion

At baseline, there was no significant difference in OCT and OCTA metrics between MCI patients and controls, which is consistent with previous work. However, after 2 years of follow‐up, there is a significantly greater velocity of decline in OCTA PD and VD in MCI patients compared to controls prior to a significant change in MMSE scores. Longitudinal assessment of these retinal microvascular differences in MCI may be a strong marker of progressive disease preceding measurable cognitive changes.
Comparison between DSQIID total/sub‐item scores and plasma p‐tau elevation in adults with Down syndrome
Authors: Kasai Takashi , Takeuchi Chisen , Shinomoto Makiko , Tatebe Harutsugu , Kitani‐Morii Fukiko , Ohmichi Takuma , Fujino Yuzo , Tokuda Takahiko
Published: December 2023

Background

People with Down syndrome (DS) are at a high risk of developing Alzheimer’s disease (AD) with aging. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) is an appropriate screening tool for detecting dementia in DS. However, it remains unclear whether this questionnaire genuinely reflects the neuropsychiatric signs of DS‐AD with biomarker‐based diagnoses.

Method

To validate the usefulness of DSQIID for detecting DS‐AD, we conducted this cross‐sectional observational study comparing plasma tau phosphorylated at the threonine 181 residue (p‐tau) level of a representative AD biomarker to the total score and each sub‐item score of the DSQIID. Plasma p‐tau levels and apolipoprotein E (ApoE) types were determined in 56 individuals with DS. Among these patients, 43 completed the DSQIID. Thirty‐three controls were enrolled to set the reference value for plasma p‐tau levels.

Results

The plasma p‐tau level in the DS group was age‐dependently elevated and reached an abnormal cut‐off over the age of 40 years. Age‐related elevation of p‐tau level was steeper in DS individuals with the ApoE4 allele than in those without ApoE4, validating the usefulness of plasma p‐tau as a surrogate indicator of AD‐DS development. In contrast, although DSQIID total and some sub‐item scores were positively correlated with plasma p‐tau level, all these significant correlations disappeared after age adjustment. Moreover, two sub‐items, “Talks to self” and “Generally appears more forgetful,” were significantly negatively correlated with plasma p‐tau level after age‐adjustment.

Conclusion

These results suggest that there is room for improvement in DSQIID for detecting DS‐AD.
Hippocampal Volume and Circadian Rhythm Characteristics
Authors: Moon Chooza , Hoth Karin F , Magnotta Vincent A , Perkhounkova Yelena , Hopkins Lauren , Zhang Meina , Lee Jihye , Hein Maria , Burgess Helen J
Published: December 2023

Background

Hippocampal atrophy is one of the prominent neurodegenerative features of Alzheimer’s disease and related dementias. Alterations in circadian rhythms and 24‐hour rest activity rhythms can exacerbate cognitive aging and neurodegeneration. The aim of this study was to examine how 24‐hour rest activity rhythms and circadian rhythms are associated with hippocampal volume.

Method

We studied 61 older adults’ data (mean age±SD = 70.0±7.2). T1‐weighted anatomical images from 3T MRI data were collected and processed using the BRAINSTools toolbox. Hippocampal volume was divided by intracranial volume (ICV). Dim light melatonin onset (DLMO) was used to assess circadian timing. Area under the curve (AUC) was calculated based on melatonin levels 6 hours prior to the bedtime. 10‐day actigraphy data assessed 24‐hour rest activity rhythms. Multiple linear regression was used to develop a model for hippocampal volume, controlling for age and sex. Additional covariates (i.e., depressive symptoms, hypertension, coronary artery disease, handedness, and ICV) and moderating effects of age and sex were examined.

Result

Acrophase was positively associated with hippocampal volume (b = 0.12, p = .016). Interaction between mesor and age (b = ‐1.22, p = .006) indicated that positive effect of mesor (b = 8.58, p = .007) on hippocampal volume decreased with age. Advanced DLMO time (b = 0.16, p = .005) and greater AUC/10 (b = 0.05, p = .046) were associated with increased hippocampal volume. Amplitude and Pseudo‐F‐Statistics were not associated with hippocampal volume.

Conclusion

The findings indicate delayed peak activity time (acrophase), delayed circadian timing (DLMO), and greater mesor and melatonin (AUC) were associated with increased hippocampal volume. The effect of mesor decreased with age. Future studies using larger sample sizes and prospective designs are needed to better understand the relationships.
Sex Differences on Tau, Astrocytic and Neurodegeneration Plasma Biomarkers
Authors: Labonte Jacob , Pettway Erika C , Sugarman Michael , Zetterberg Henrik , Blennow Kaj , Ashton Nicholas J. , Karikari Thomas K , Tripodis Yorghos , Martin Brett M , Palmisano Joseph N , Stern Robert A , Killiany Ronald J , Aparicio Hugo J , Goldstein Lee E , Qiu Wendy , Mez Jesse B. , Banks Sarah J , Alosco Michael L
Published: December 2023

Background

Sex differences have consistently been identified on autopsy, neuroimaging, and cerebrospinal fluid outcomes related to Alzheimer’s disease (AD). Mechanisms for these associations are unclear. Blood‐based biomarkers are practical alternatives for the investigation of mechanisms of AD, in addition to accurate disease detection and monitoring. The objective of this study was to examine sex differences across a panel of blood‐based plasma biomarkers in participants with and without cognitive impairment due to AD.

Methods

The sample included 567 participants (248 males, 319 females) from the Boston University AD Research Center (BUADRC). Participants completed a battery of neuropsychological tests. Cognitive diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. All participants had at least one blood draw between 2008 and 2018 at the BUADRC. Plasma samples were analyzed using Simoa for phosphorylated tau (p‐tau181), total tau (t‐tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). Linear regression models tested associations between sex and each plasma biomarker, controlling for age, racial identity, education, and APOE ε4 carrier status. Analyses were repeated stratified by APOE ε4 carrier and CDR status.

Results

Table 1 shows sample characteristics (mean age = 74.41, 13.3% Black/African American). As shown in Table 2, the multivariable linear regressions showed significant sex effects for plasma GFAP, such that females had higher plasma GFAP levels than males (p<.001). Among APOE ε4 carriers (n = 223) and participants with a CDR≥1 (n = 111), the associations with GFAP remained and the magnitude of associations were stronger compared to APOE ε4 non‐carriers and those with a CDR<1. Figure 1 shows plots of the association between sex and each plasma biomarker. There were no other sex effects across the other plasma biomarkers in the entire sample or when stratified by APOE ε4 carrier or CDR status.

Conclusions

Females had higher plasma GFAP levels than males regardless of APOE ε4 status and cognitive status. Reactive astrocyte processes associated with neurodegenerative diseases can be measured by plasma GFAP. Biological differences in these processes may explain observed associations between sex and risk for AD. The study highlights the dynamic utility of plasma biomarkers for the study of AD and longitudinal analyses of this cohort are planned.
What are the most prevalent combinations of modifiable dementia risk factors that can be targeted in multidomain lifestyle intervention in Canada?
Authors: Son Surim , Speechley Mark R. , Montero‐Odasso Manuel
Published: December 2023

Background

Not all risk factors have the same weight in dementia development, and the combinations of common risk factors differs across individuals and populations. The goal of this study is to estimate the potential population impact of modifiable risk factors for dementia in Canada, and to identify the combinations of the modifiable risk factors that could prevent many dementia cases in Canadian adults.

Method

This is a secondary analysis of data from the Canadian Longitudinal Study on Aging Comprehensive Cohort (n = 30,009). The prevalence and population attributable fraction (PAF) of 12 modifiable lifestyle risk factors established in the Lancet Commission Report 2020 were calculated using baseline data. The prevalence of every possible dyad, triad, and tetrad combination of the risk factors was estimated. All analyses were stratified by 2 sex strata (male, female) and 4 age strata (45‐54, 55‐64, 65‐74, 75+).

Result

The combined PAF of the 12 lifestyle risk factors was 49% in the Canadian population. The single risk factors that contributed the most were physical inactivity (11.3%), hearing loss (6.9%), and obesity (6.9%) in Canada, whereas social isolation (0.4%), alcohol (1.1%), and smoking (1.4%) had substantially smaller effects (Table 1). The most prevalent risk factor dyad was physical inactivity and sleep disturbance (34%). Obesity, physical inactivity, and sleep disturbance was the most prevalent risk factor triad (14%). The tetrad of hearing loss, obesity, physical inactivity, and sleep disturbance had the highest prevalence (4.9%). The prevalent risk factor combinations were similar in the two younger age groups and both sexes, but not in the two older age groups (Table 2).

Conclusion

Nearly 50% of dementia cases in Canada can be prevented by modifying 12 lifestyle risk factors. The most prevalent combinations of risk factors differ before and after the age of 65, but not by sex. The most prevalent risk factor combinations consist of physical inactivity, sleep disturbance and obesity in the two younger age groups, and hearing loss, sleep disturbance and obesity in the two older age groups. These findings may help strategically target tailoring multidomain dementia intervention programs to have the greatest impact in the Canadian population.