bluuebunny/crossref_metadata_2025 huggingface dataset:
Cataracts are associated with smaller gray matter brain volume among participants in the UK Biobank
Authors: Ferguson Erin L , Buto Peter , Thoma Mary , Wang Jingxuan , Glymour M. Maria , Hoffmann Thomas J. , Choquet Hélène , Andrews Shea J , Yaffe Kristine , Casaletto Kaitlin B. , Brenowitz Willa D
Published: December 2023

Background

Visual impairments, including reduced visual acuity and cataracts, are emerging as novel and modifiable risk factors for Alzheimer disease (AD) and related dementias (ADRD). However, it is unclear whether vision impairments or cataracts are associated with structural integrity of brain regions linked to ADRD or other brain regions. We investigate associations between visual acuity, cataracts, genetic risk for cataract, and brain volumes.

Method

We analyzed 33,923 UK Biobank participants aged 55‐82 without dementia at enrollment who underwent brain MRI. Subsets had usable genetic data (n = 29,963) and visual acuity exams (n = 7,837). Participants self‐reported history of cataracts. The following imaging volumes were generated from FreeSurfer segmentations: hippocampal volume, total brain volume, and total gray matter volume. We additionally included an AD signature region defined as the cortical thickness averaged across six relevant brain regions. We calculated a genetic risk score (GRS) for cataract using 43 previously‐reported genetic variants. Linear regressions estimated the associations between brain volumes and visual acuity or self‐reported cataract, separately with adjustment for demographic and clinical confounders, intracranial volume, and imaging center. Linear regressions for brain volume using cataract GRS adjusted for ancestry principal components, sex, age, intracranial volume, and imaging center.

Result

The sample was an average of 66.0 years (SD = 6.26) at imaging, with a cataract prevalence of 2.5% (n = 863). History of cataract was associated with significantly smaller total gray matter volume (β = ‐2483 mm3, 95% CI: ‐4225 to ‐741). Increased genetic risk for cataract was significantly associated with smaller total gray matter (β = ‐485 mm3, 95% CI: ‐732 to ‐138) and total brain volume (β = ‐707 mm3, 95% CI: ‐1192 to ‐221). Neither cataract nor cataract GRS was associated with hippocampal volume or the AD signature region. Poor visual acuity (worse than 20/40 vision) was not significantly associated with any brain volumes.

Conclusion

History of and genetic risk for cataract is associated with smaller total gray matter volume, but not hippocampal volume. Our results suggest that cataract may increase risk of neurodegeneration independent of typical AD, but more investigation is needed.
Association between Trust of Researchers and Interest in Participation in Alzheimer’s Disease Biomarker Research
Authors: Wang Sophia , Epperson Francine , Eliacin Johanne , Polsinelli Angelina J , Raelly‐Muze Laureen , Asper Joseph , Van Heiden Sarah , Saykin Andrew J.
Published: December 2023

Background

The study examined whether trust in researchers affects interest in AD (Alzheimer’s disease) biomarker research participation, specifically AD blood biomarkers and MRI and PET neuroimaging, and whether this was independent of other factors commonly associated with hesitancy to participate in research, including race and knowledge of AD.

Methods

258 community‐dwelling Black and 141 non‐Hispanic White adults (age ≥ 55) who had never participated in AD research completed a survey about their perceptions of AD biomarker research. The survey asked participants to select one of three responses, “Yes,” “Unsure,” and “No” to 6 trust statements, with yes being the highest level of trust. Questions specifically assessed whether survey participants trusted researchers to keep information confidential, be honest, component, not cause harm, treat them equally, and share results with them and their community. Those who answered yes to all 6 questions were categorized as having very high trust, and those who answered no or unsure to any of the 6 questions were categorized as having lower trust. Ordinal logistic regression models were used for the analysis of outcome variables with three possible responses (i.e. interest in participation in an AD biomarker study and individual procedures, motivators for research participation). We adjusted for age, education, sex, race, and knowledge about AD.

Result

Participants with very high trust in researchers were less hesitant about doing AD biomarker research (OR 0.32 (95% CI (0.20‐0.52), P < 0.001). Participants with concerns about confidentiality, study risks, and being treated equally had greater hesitancy about doing AD biomarker research (P’s < 0.05). Concerns about researchers’ competency were associated specifically with lower interest in doing neuroimaging procedures (P’s < 0.05). Very high trust in researchers was associated with greater interest in return of results, particularly brain scans (OR 1.92 (95% CI 1.06‐3.48), P = 0.032).

Conclusion

Even after other factors known to affect AD research participation, trust remains a highly significant factor affecting the interest in AD research participation in blood biomarker neuroimaging procedures. Recruitment strategies for AD biomarker research may need to address participants’ trust concerns, specifically confidentiality, study risks, and equity.
The cultural adaptation process of the Savvy Caregiver program with the Native Hawaiian community
Authors: Jackson Alexandra , Dillard Adrienne , Kekauoha Puni , Balaz Poki'i , Dutro Natlie , Lee Kia'i , O'Sullivan Kelly , Okamoto Scott , Lewis Jordan P. , Hepburn Kenneth , Weaver Raven
Published: December 2023

Background

Family caregivers are at increased risk for experiencing multiple negative health outcomes, yet unpaid caregivers provide the majority of care for people living with Alzheimer’s disease and related dementias (ADRD).1‐3 Among Native Hawaiians (NHs), family or ʻohana caregiving is an important and common responsibility.4,5 As NHs face substantial health disparities, including a high burden of chronic disease across the lifespan, family caregivers are an important population to prioritize to promote health.6‐8 While effective evidence‐based interventions have been developed to promote caregiver mastery and wellbeing,9‐11 there are no programs specifically tailored to NH culture, language, and values.

Method

We aimed to culturally adapt the Savvy Caregiver program with the NH community, while maintaining fidelity to the original program. We invited community members with expertise in NH culture, caregiving, and ʻōlelo Hawaiʻi (Hawaiian language) to participate in monthly meetings and work alongside the research team in adapting the Savvy Caregiver program. The goals, scope of work, and expectations for the research team and CAB were established from the outset. The Community Action Board (CAB) intentionally chose to be an “action” board as they serve as cultural experts that suggest, review, and approve all changes to the curriculum and will support the dissemination of the program.

Result

The CAB suggested modifications ranging from surface (e.g., images, terms) to deep structural adaptation (e.g., “talk story,” storytelling, cultural values, norms, and Hawaiian ways of knowing). The research team reviewed and incorporated the CAB members’ expertise. All deep structural changes were reviewed to maintain program fidelity resulting in an adapted intervention that will be pilot tested in the community.

Conclusion

While this is an ongoing and iterative process, we anticipate our approach and inclusion of a CAB has led to the effective adaptation of the Savvy Caregiver program. We also anticipate these partnerships will support the institutionalization and scaling up of the program to reach the NH community. Next steps will assess whether fidelity and the core components of the original intervention were maintained after cultural adaptation.
Agmatine prevents the memory impairment and the dysfunction of hippocampal GSK‐3β and ERK signaling induced by Aluminum nanoparticle in mice
Authors: Izadi Sadegh , Rezaei Amin , Esmaili Zahra , SoukhakLari Roksana , Moosavi Maryam
Published: December 2023

Background

The growing usage of Aluminum nanoparticles (Al‐NP) and its exposure may influence body function. Considering the proposed relationship between Al and the pathogenesis of Alzheimer’s disease (AD) and the concern about the effect of this nanoparticle on brain health and cognitive function, the use of neuroprotective agents might be helpful. According to the reported neuroprotective effects of agmatine, in the present study the possible protective effect of agmatine was assessed in mice model of Al‐NP induced memory impairment. was investigated in the present study. In addition, due to the roles of hippocampal Glycogen synthase kinase 3 beta (GSK‐3β) and ERK signaling in memory and its disorders, these pathways were also investigated.

Method

Al‐NP (10 mg/kg/p.o.) with/without agmatine (5 or 10 mg/kg/i.p.) was administered to adult male NMRI mice for 5 days. Novel object recognition (NOR) test session was used to assess cognitive function. Following the behavioral assessments, the hippocampi were used to determine the phosphorylated and total levels of GSK‐3β and ERK as well as GAPDH using western blot analysis.

Result

The results showed that Al‐NP impaired NOR memory in mice while agmatine 10 mg/kg prevented the memory deficit induced by Al‐NP. Furthermore, Al‐NP activated GSK‐3β as well as ERK signals within the hippocampus while agmatine prevented the effects of Al‐NP on GSK‐3β and ERK signals within the hippocampus.

Conclusion

Besides supporting the neuroprotective effects of agmatine, these findings suggest the possibility of the connection of hippocampal GSK‐3β and ERK signaling in the neuroprotective effect of this polyamine against Al‐NP.
Interoperability of the MIITRA atlas with complementary atlases: development of a comprehensive array of gray matter labels
Authors: Niaz Mohammad Rakeen , Ridwan Abdur Raquib , Wu Yingjuan , Zhang Shengwei , Bennett David A. A , Arfanakis Konstantinos
Published: December 2023

Background

In order to enhance the functionality of the MIITRA atlas and its interoperability with complementary atlases, a comprehensive set of gyral‐based, cytoarchitecture‐based, and functional connectivity‐based gray matter labels were constructed in MIITRA space.

Method

T1w images from the 400 older‐adults included in the construction of MIITRA atlas were nonlinearly registered using ANTs SyN to the MNI152 6thgen,MNI Colin, and the ICBM2009c templates, and volumetric labels from Harvard‐Oxford,Julich,AAL3,Buckner,CoBrALab,Hammersmith and Princeton Visual atlases were warped to the space of each participant. The ANTs‐derived transformations used to build the MIITRA T1w template were used to map the corresponding gray matter labels from raw space to exact physical locations in the final MIITRA space following a multi‐atlas correction scheme to correct for residual misregistration. T1w images from a separate group of 100 older‐adults for evaluation were nonlinearly normalized to the MIITRA template and the inverse transformation was applied to the gray matter labels to transform them to each individual’s space. The T1w image of each individual was nonlinearly registered to every other individual and the labels from the 99 other older‐adults were transformed to each individual. Pair‐wise Jaccard index for each label was calculated in every individual’s native space. The same procedure was followed for the labels obtained directly from the respective source templates.

Result

The overlap was higher for the AAL3 labels obtained from MIITRA with an average pair‐wise Jaccard index of 0.59 and standard deviation of 0.08, compared to 0.55±0.1 for the AAL3(Fig1A) labels obtained from the MNI Colin template. The pair‐wise Jaccard index for the Julich(Fig1C) and CoBrALab labels(Fig2A) was 0.54±0.13 and 0.75±0.17 from MIITRA and, 0.53±0.14 and 0.74±0.17 from ICBM2009c. For the Harvard‐Oxford(Fig2B), Buckner(Fig2C), Hammersmith(Fig1B) and Princeton Visual(Fig2D), the pairwise Jaccard was 0.68±0.14, 0.61±0.07, 0.71±0.10 and 0.35±0.06 respectively from MIITRA and 0.66±0.11, 0.61±0.08, 0.67±0.11 and 0.32±0.08 respectively from MNI152 template. Heat maps representing the Jaccard‐index for each template are shown in Fig3.

Conclusion

Gray matter labels from MIITRA showed higher pair‐wise overlap suggesting that labels from MIITRA space allows more consistent segmentation of the gray matter of the older‐adult brain compared to the labels obtained from templates constructed using younger or middle‐aged data.
Community NGO intervention for Alzheimer’s patients rehabilitation
Authors: Pal S , Roy T , Guha B
Published: December 2023

Background

Alzheimer’s patients Rehabilitation services aren’t well‐developed concept in resource‐Poor nations due to poor economics & lack of expertise. With limited resources we wanted to explore these rehabilitation services in rural villages.

Rural/tribal areas of India lung Alzheimer’s patients [Ca] patients lack rehabilitation support available only in city hospitals. Our 12‐year CBO is training youth volunteers & traditional faith halers in marginalized communities to provide rehabilitation.

Method

Around 1340 cases of Alzheimer’s will be in rural/tribal of India by 2025, but hospitals lack dedicated Rehabilitation program. patients returning to villages after onco‐therapy in cities urgently need Rehabilitation support to suit their economic, social, cultural background. Since August 2018 Our NGO clinic started free advise on Rehabilitation. [n = 91]. With 6 trained nurses, two physicians, we screened patients. Average age 62 years, M:F ratio 75:25. Our support services devised as‐per need of Patients in consultation with family & stretched over 21 months included conselling, physiotherapy, occupational therapy, rehabilitation. Responses assessed with Quality of life scale by Flanagan Quality of Life Scale (QOLS) & psychological evaluation by Likert psychometric scale. This presentation demonstrates project in developmental stages & basic operational facts. Initially started as practically oriented guidance center & later developed in well‐organized set‐up offering free rehabilitation services in villages. It comprises NGO staff and traditional faith healers.

Result

Our program highlights variability of psychological & Socio‐medical aspects in rehabilitation. Patents needed medical interventions in 18%, psychological approaches in 84% while remaining 16% needed combination of both.

Conclusion

This is pilot project running on community donation. We plan to document, evaluate this in large sample size, but resource restriction didn’t permit. To overcome this, we plan networking of European NGO’s, advocacy experts at AAIC‐2023 Venue for better study design, technical support & collaborative efforts. I do not claim “I transformed whole community of patients but we had certainly taken initiative by this cost‐effective approach”.
Electrical field strength from anodal prefrontal tDCS determines degree of white matter integrity changes in amnestic MCI patients
Authors: Kang Dong Woo
Published: December 2023

Background

An electrical field (EF) strength induced by tDCS affects a therapeutic effect. Additionally, sequential tDCS has improved white matter integrity in cognitively impaired patients. However, researchers have not evaluated the impact of EF strength on white matter integrity in the prodromal stage of dementia. This study aimed to elucidate the effect of EF strength from prefrontal anodal tDCS on white matter integrity change and the modulating role of relevant genetic and pathologic factors in this effect in amnestic mild cognitive impairment (MCI) patients.

Method

In 55 amnestic MCI patients, we delivered anodal‐tDCS (2 mA/day, five times/week, for two weeks) over the left dorsolateral prefrontal cortex (DLPFC), calculated the EF strength for the left inferior frontal gyrus and DLPFC through the stimulation navigation program analysis. Additionally, we assessed the white matter integrity by diffusion tensor imaging before and after two weeks of stimulation; finally, we evaluated the modulating factors: amyloid‐beta (Aβ) deposition, APOE ε4‐allele status, and BDNF polymorphism.

Result

As the EF intensity in the left inferior frontal gyrus increased, the range of changes in white matter integrity significantly increased in left anterior thalamic radiation, corticospinal tract, inferior fronto‐occipital fasciculus, and inferior longitudinal fasciculus. Additionally, we found that greater change in white matter integrity was observed with higher regional EF strength in the APOE ε4 non‐carriers and BDNF MET non‐carrier, which could be attributed to an interaction between these modulating factors and EF intensity in the left anterior thalamic radiation and right uncinate fasciculus.

Conclusion

These findings provide evidence for the precision‐medicine‐based application of tDCS in the prodromal stage of dementia, inducing the optimized therapeutic effect.
Managing Alzheimer’s patients in rural areas of developing country
Authors: Pal S , Guha B , Roy T
Published: December 2023

Background

National‐health‐registry based data demonstrates Psychosocial support & treatment‐availability are major issues for Alzheimer’s ‐sufferers in resource‐poor‐nations. Hence our Non‐Government‐Organisation analysed & made this public health‐policy paper recommendation’s.

NGO’s are close to rural/tribal‐communities. Cost of running NGO is economical than medical‐institution. Medical treatment cost is prohibitive and inaccessible for majority patients in Asia. Government‐Health‐Departments need to workout strategy to increase access to care.

In resource‐poor‐setting unaffordable cost leads to poor‐therapeutic‐compliance & therefore high mortality. We developed training program to evolve sound /sustainable Alzheimer’s‐care for rural communities

Methods

No national‐program for financial help to Alzheimer’s patients exists in india. Treatment programs designed towards rural/tribal population needed. Since four years we offer guidance for drug‐therapy‐funding. This project is unique, as we are training NGO health workers to assist patients community in improving access to care. Depending on support given by donors, we provide financial‐assistance for treatment. We improved access to governmental hospitals. Initially we started with two towns & intend to offer our services to 23 villages by 2025.

Results

We did face hiccups in mobilising volunteers/resources. Our strategy has minimum maintenance‐cost & high‐acceptability. Forums like AAIC‐2023 conference must support NGO‐activists to form workgroups with AAIC conference‐participants to further develop this concept on larger scale.

Conclusion

Economical‐factors/access to therapy changes out‐come of treatment. With little training, few resources our community NGO in rural/tribal India formed well knit volunteers‐group who are giving free part‐time dedicated service. psychosocial‐support improves QOL reducing difficulties faces by resource‐poor‐southern countries. We urge participants to share views/expertise on this burning‐issue at AAIC‐2023‐venue to come out with sustainable policy paper for Asian nations.
“His reality certainly isn’t the reality that we know”: Care partner responses to differing realities among assisted living residents with dementia
Authors: Kemp Candace Lynn , Morgan Jennifer Craft , Perkins Molly , Burgess Elisabeth O , Hill Andrea M , Pullon Emerald , Bender Alexis Anne
Published: December 2023

Background

In the United States and elsewhere, assisted living (AL) has become a primary provider of residential long‐term care for persons living with dementia. Residents typically are supported by care convoys, or networks, comprised of their family and friends, AL staff, as well as external care providers, all of whom exert influence on residents’ daily lives. As with other persons living with dementia, AL residents sometimes experience confusion over time, place, and scenario. Care partner responses to these differing realities are consequential to residents’ care experiences, quality of life, and ability to engage with others and in activities they find meaningful. Here, we examine, in‐depth, care partner responses to residents' confusion, the complex factors influencing their reactions, and the resulting outcomes.

Method

We present analysis of qualitative data gathered from the study, “Meaningful Engagement and Quality of Life among Assisted Living Residents with Dementia,” involving six diverse AL communities, each studied for a one‐year period. Researchers conducted 2,109 hours of participant observation captured in detailed fieldnotes. We also followed 59 residents with dementia and 167 of their care partners, conducting interviews to learn how best to promote meaningful engagement. Specifically, we analyzed all data relevant to residents’ “differing realities” and “care partner responses.”

Result

Care partners varied in their responses to residents’ differing realities. Some, including many AL staff, routinely attempted to redirect residents by changing the subject and/or physically redirecting (e.g., if a widowed resident was searching for her husband). Certain care partners joined residents by attempting to understand their realities and “going along with them.” A small minority of care partners, mostly family members, ignored or attempted to correct or truth tell. Factors affecting care partner responses included: the nature of resident confusion and associated expressions and a care partner’s role, dementia knowledge and care resources, beliefs, and experiences. Truth‐telling or correcting frequently, though not always, led to frustration, anxiety, and socially withdrawing whereas responses that acknowledged the person’s reality frequently had better resident outcomes.

Conclusion

Findings have implications for training, practices, and policies aimed at enhancing care interactions and quality of life among persons living with dementia.
Spot, treat and stop delirium: Acceptability and feasibility of a novel ‘Delirium Wheel App’ to identify and manage delirium in a care home setting in the United Kingdom
Authors: Negi Rashi
Published: December 2023

Background

Delirium is common in elderly, frail residents in care home settings, who may already be suffering from dementia. The prevalence of delirium in nursing homes can be up to 60%. Care home staff are potentially in a unique position to identify the subtle changes that can precede a full‐blown episode of delirium. Towards this aim, as a part of frailty initiative West Midlands, a delirium app, called ‘Delirium Wheel’ (https://rb.gy/ns80hw) was developed.

Method

In order to explore the feasibility of the Delirium Wheel (DW) app to support care home staff to care for patients experiencing delirium, a feasibility study was carried out between October 2022 to May 2023 in 6 care homes in Staffordshire. The care homes were given delirium app training and a survey was carried out to assess their baseline knowledge and skills in the identification and management of delirium. A further survey was carried out 12 weeks following the implementation of the app, with qualitative interviews carried out with a sample of the care home staff.

Result

The study is currently at Stage 1 of the data collection phase and the initial surveys have been collected evaluating baseline knowledge and practice within the care homes. Staff members have now been interviewed as part of Stage 2 of the study process, with the qualitative data currently being transcribed. The full results are expected to be reported by the end of April 2023.

Conclusion

This study is the first research which formally tests this unique app as a digital tool to support healthcare professionals in the identification and management of a very common condition such as delirium. This empowers care home staff to have confidence in their own skills and have an app to support if there is any clinical uncertainty. As a result of this intervention, the probability of patient’s being able to be managed within the care home setting increases, leading to better patient related outcomes.
Transcriptional risk score in Alzheimer’s disease: from pathology to cognition
Authors: Pyun Jung‐Min , Park Young Ho , Wang Jiebiao , Bennett David A. A , Bice Paula , Kim Jun Pyo , Kim SangYun , Han Moon‐Ku , Saykin Andrew J. , Nho Kwangsik
Published: December 2023

Background

Transcriptional risk scores (TRS), a summation of polarized expression levels of functional genes, have been proposed for disease risk assessment using transcriptome profiles. Our previously developed blood‐based TRS showed associations with diagnosis and neuroimaging biomarkers for Alzheimer’s disease (AD). Here, we developed brain‐based TRS models and calculated TRS using brain tissue‐based transcriptome profiles.

Method

We integrated AD genome‐wide association study summary and expression quantitative trait locus data to prioritize target genes using Mendelian randomization and then calculated individual TRS by summing the polarized z‐scores over the target genes. We used brain transcriptome data from the Religious Orders Study and Rush Memory and Aging Project cohort (ROSMAP; N = 634) as a discovery set and the Mount Sinai Brain Bank cohort (MSBB; N = 244) as a replication set. We performed association analysis of TRS with AD diagnosis, amyloidopathy, tauopathy, and cross‐sectional and longitudinal cognitive function. We compared AD classification performance of TRS with polygenic risk scores (PRS) using a machine learning approach (Fig. 1).

Result

Higher TRS values were significantly associated with AD compared to cognitively normal controls (Table 1). Higher TRS values were also related with amyloidopathy, tauopathy, poor cognitive performance, and faster cognitive decline. The AD classification performance of PRS was increased with the inclusion of TRS up to 12% with the area under the curve value of 0.842 (Fig. 2). These findings were replicated in the replication dataset.

Conclusion

Our results showed that brain‐based TRS is associated with AD pathology and clinical course. Furthermore, TRS improves the AD classification performance of PRS. Along with static PRS, dynamic TRS based on transcriptional expression levels at a given time could be a potential disease‐stage specific AD biomarker.
Changes of brain metabolites in early Alzheimer’s disease: A high‐field magnetic resonance spectroscopy study on medication treatment effect
Authors: Zhang Ningnannan , Zhang Zhang , Song Xiaowei
Published: December 2023

Background

AD involves deficits in essential brain chemicals. A functional neurocompensatory response in brain regions critical for executive control has been reported for early AD. It is unclear whether such an effect can be detected in brain metabolites and affected by medication treatments. In this study, we used single‐voxel proton magnetic resonance spectroscopy (SV‐1H‐MRS, short as MRS here) to quantify neurochemical changes non‐invasively. Our objectives are to 1) examine differences in key neurometabolites between brain regions either compromised or preserved in early AD and 2) test the potential effect of medication treatment on metabolite levels in the brain regions.

Method

Sixteen participants with early AD (76.8±8.0 yrs, 56.2% female) and 20 normal controls (73.6 ± 6.3 yrs, 60% female) had two MRS sessions six months apart. AD patients took cholinesterase inhibitors as part of standard care following the baseline scan. MRS acquisition used 4T MRI with LASER sequence from two voxels (5.12cm3), respectively placed in the posterior cingulate gyri (PCG) and the left dorsolateral prefrontal cortex (DLPFC). Spectra data were fitted using fitMAN and analyzed using ANOVA for main effect and interactions (voxel placement, subject group, scan time).

Result

The level of many metabolites was greater in the DLPFC than in the PCG voxels (Fs>4.01, ps<0.050), regardless of the subject group. Participants with early AD had lower levels of NAA and Gln (absolute value and ratio to Cr) and higher Cr/NAA than controls across the brain regions (Fs>4.09, ps<0.047). Post‐treatment, a change in Ala/Cr, Gly/Cr, Gly/NAA, and Lac/NAA (Fs>4.04, ps<0.048). There was an increase in Syl only in the DLPFC voxel (Fs>6.71, ps<0.029), whereas there was a decrease in Gly/NAA in the PCG voxel (F = 11.47, p = 0.005). In contrast, in controls, NAAG in the PCG voxel decreased between baseline and follow‐up (Fs>5.08, ps<0.027).

Conclusion

The data showed a lower level of several metabolites essential for maintaining neuronal function and connectivity in early AD than normal aging, especially in brain regions that are compromised early in the disease process. The study suggested a positive impact of clinical management of early AD on enabling neurocompensation for at least six months.
Ante‐mortem cognitive trajectories of older adults with cerebrovascular disease across Aβ and tau biomarker profiles determined at autopsy in the National Alzheimer’s Coordinating Center database
Authors: Rosenich Emily , Lim Yen Ying
Published: December 2023

Background

Alzheimer’s disease (AD) is characterised biologically by beta‐amyloid (Aβ) plaques and tau tangles, but autopsy studies reveal that most older adults also present with cerebrovascular disease (CVD) markers. Effects of biological AD on cognition in the context of concurrent CVD remain unclear. In older adults with CVD pathology, this study sought to determine ante‐mortem cognitive trajectories associated with Aβ/tau positivity or negativity (+/−) at autopsy.

Method

Participants aged 65‐95 classified as cognitively unimpaired at baseline from the National Alzheimer’s Coordinating Center database, with ≥1 follow‐up between 2005‐2015, and available autopsy/APOE data were included (N = 924). Autopsy indicated that all participants had at least one of six CVD pathology markers. Participants were classified into four groups (A−T−, A+T−, A−T+, A+T+) based on semiquantitative Consortium to Establish a Registry for Alzheimer’s Disease neuritic plaque staging and Braak staging. Linear mixed models including group × time interactions assessed rate of change in Preclinical Alzheimer’s Cognitive Composite scores, episodic memory, and executive function. Interactions between age, sex, APOE ε4 × time and the interval between death/the final study visit were included as covariates.

Result

A+T+ adults demonstrated significantly faster cognitive decline on all outcomes in the ∼10 years preceding death compared to A−T−, A+T−, and A−T+ adults (Table 1, Figure 1, d = 0.15 – 0.39). At final visit prior to death, a greater proportion of A+T+ adults (36%) received a dementia diagnosis compared to A−T+ (14%) or A+T− (15%) (p <.001). When analyses were restricted to exclude dementia diagnoses, significantly faster decline on all outcomes (p’s <.001, d = 0.06 – 0.36) was similarly observed in A+T+ adults compared to A−T−, A+T− and A−T+ adults (Figure 2). Cognitive trajectories were equivalent between A−T− and A+T− for all outcomes (p’s >.55).

Conclusion

ln older adults with CVD pathology, A+T+ at autopsy was associated with greater cognitive decline over 10 years preceding death compared to A+T−, A−T+, and A−T− older adults. Faster cognitive decline in this group in the context of low final visit dementia diagnoses may suggest that post‐mortem A+T+ is associated with a steep trajectory of cognitive decline ante‐mortem, but that dementia progression is not inevitable.
Poor self‐rated health is associated with faster cognitive decline and greater small vessel disease in older adults with type 2 diabetes
Authors: Ramsingh Nadia , Lin Hung‐Mo , Ouyang Yuxia , Ravona‐Springer Ramit , Livny Abigail , Soleimani Laili , Bendlin Barbara B , Ben‐Meir Mery , Heymann Anthony , Sano Mary , Azuri Joseph , Beeri Michal S
Published: December 2023

Background

Self‐rated health (SRH) is a predictor for poor health outcomes and cognition. Older adults with type 2 diabetes (T2D) have multi‐morbidity and greater cognitive impairment. In this study we investigated the association of SRH with cognitive decline and brain pathology in older adults with T2D.

Method

Participants (n = 1,149) were from the Israel Diabetes and Cognitive Decline study, SRH was an age referential question categorized to low (n = 210), moderate (n = 410) or high (n = 529). Cognition was measured by four cognitive domains: episodic memory, executive functions, language, and attention/working memory. Global cognition was the average of the cognitive domains. Statistical models adjusted for sociodemographic, cardiovascular, and clinical variables. In a randomly selected subsample (n = 230) that had MRI, we examined relationships between baseline SRH and brain characteristics (white matter hyperintensities (WMHs), hippocampal, and total gray matter volumes).

Result

The association of low SRH with decline in executive functions accelerated over time, when compared to high SRH (est = ‐0.0036; p = <0.001). This pattern was also observed for the association of low versus high SRH with global cognition (est = ‐0.0023; p = 0.010). Low SRH at baseline was associated with higher volumes of WMHs (est = 9.8420; p<0.0008). SRH was not associated with other cognitive domains, or with hippocampal and total gray matter

Conclusion

Low SRH is associated with cognitive decline in T2D older adults and may serve for risk assessment and enrichment. WMHs may represent an underlying mechanism.
Circadian rhythms in older adults are associated with sleep quality, cognitive function, and ß‐amyloid burden: an accelerometry analysis of the Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial ‐ LEARNit
Authors: Eckhardt Joanna L , Isenberg A. Lisette , Stradford Joy , Aslanyan Vahan , Fenton Laura E. , Monreal Teresa , Pa Judy
Published: December 2023

Background

Several studies demonstrate circadian rhythm disturbances in patients with Alzheimer’s disease. However, less is known about circadian rhythms in older adults with early mild cognitive impairment. Wrist‐worn accelerometers provide continuous, objective, high resolution quantification of 24‐hour rest activity rhythms. This study examines the relationship between circadian rhythms and sleep, cognition, and ß‐amyloid (Aß) burden.

Method

This study examines baseline data from the “Lifestyle Enriching Activities for Research in Neuroscience Intervention Trial” (LEARNit). Sixty‐six older adults ages 55‐80 experiencing early cognitive changes wore a GENEActiv accelerometer for approximately 30 consecutive days. Accelerometer data was analyzed using the R package GGIR (version 2.8‐1), and circadian rhythm measures were extracted using the GGIR secondary package ActCR (version 0.3.0). Circadian rhythm variables include intradaily variability (fragmentation), interdaily stability (rhythm synchronization to light‐dark cycle), acrotime (peak activity time), and Midline Estimated Statistics of Rhythm or MESOR (mean activity level). Up‐MESOR and Down‐MESOR represent the timing of activity increasing above or decreasing below MESOR, respectively—lower values of each indicate a phase advance (shift towards morning), whereas higher values indicate a phase delay (shift towards evening). Sleep was assessed as mean sleep efficiency and Wake After Sleep Onset, or WASO (accumulated wakefulness after sleep onset). Cognitive tests include the Montreal Cognitive Assessment (MoCA) for global cognition and attention/processing speed (Digit Symbol Task). Aß burden was measured by positron emission tomography standard uptake value ratio for fifty‐six participants. Age‐adjusted linear regression models were used to test associations between circadian rhythms and sleep, cognition, and Aß.

Result

Participant characteristics are summarized in Table 1 and results are summarized in Figure 1. Intradaily variability (b = ‐0.095, p = 0.03) and interdaily stability (b = 0.34, p = 0.01) were both associated with mean sleep efficiency. Intradaily variability (b = 1.41, p<0.001) and interdaily stability (b = ‐4.45, p<0.001) were associated with WASO. Up‐MESOR was associated with MoCA total score (b = ‐0.41, p = 0.03). Up‐MESOR (b = ‐2.12, p = 0.006), Down‐MESOR (b = ‐1.99, p = 0.02), and acrotime (b = ‐4.20, p<0.001) were associated with Digit Symbol score. Down‐MESOR was significantly associated with Aß (b = ‐0.029, p = 0.02).

Conclusion

Circadian rhythm robustness is positively associated with better sleep quality. Participants with dynamic circadian rhythm phases demonstrated poorer cognition and higher Aß burden.
Differential Heart Rate Variability Profiles During Sleep in Older Adults with Remitted Early‐onset versus Late‐onset Depression
Authors: Kong Shawn Dexiao , Espinosa Nicole , McKinnon Andrew C , Gordon Christopher J , Wassing Rick , Hoyos Camilla M , Mowszowski Loren , Hickie Ian B , Naismith Sharon L
Published: December 2023

Background

Sleep is a physiological state involving a dynamic autonomic profile that is ideal for detecting subtle changes in autonomic nervous system functioning. The current study sought to determine if heart rate variability (HRV) during different periods of sleep is impaired in older adults with early‐onset (EOD), late‐onset (LOD), and no history of lifetime depression (NOD).

Method

A total of 188 older adults aged 50‐90 years were recruited from the Healthy Brain Ageing clinic at the Brain and Mind Centre, University of Sydney. This samples comprised 49 participants with EOD, 37 with LOD, and 102 with NOD. Each participant underwent medical, psychiatric and neuropsychological assessments, as well as overnight polysomnography.

Result

Findings show that for HRV during wake‐after‐sleep‐onset (WASO), only older adults with remitted EOD have significantly lower SDNN and Shannon Entropy, two HRV indices of interest, in comparison to the NOD group, suggesting that those with EOD have diminished overall autonomic function and cardiac complexity respectively. By contrast, older adults with remitted LOD have significantly lower parasympathetic activities during deeper sleep stages (i.e. N2 and N3), as evidenced by a reduction in high‐frequency HRV relative to the EOD group. Overall, our findings suggest that the EOD and LOD phenotypes have differential heart rate profiles during sleep.

Conclusion

A history of depression, in particular whether this history is early‐ or late‐ onset, is associated with the integrity of autonomic functioning during both wakefulness and sleep in older adults. HRV may have potential as a biomarker of depression and could complement other biomarkers to enhance diagnostic accuracy and prognostic monitoring. As older adults with early‐life depression seem to experience more pronounced autonomic dysfunction, this further emphasizes the need for early and effective interventions, as well as proactive preventative strategies for those with remitted major depressive disorder.
Detection of Behaviors of Risk exhibited by People with Dementia with Privacy Protecting Videos
Authors: Mishra Pratik K. , Iaboni Andrea , Ye Bing , Newman Kristine , Mihailidis Alex , Khan Shehroz
Published: December 2023

Behavioural symptoms of dementia present a significant risk within long‐term care homes, resulting in difficulties supporting residents and monitoring their safety due to limited staffing resources. Existing video surveillance infrastructure can be used to monitor and automatically detect clinically important behaviours that can put the residents at risk. An anomaly detection approach can be used to detect behaviours of risk from videos due to their infrequent and diverse nature. However, most existing video anomaly detection approaches focus on appearance‐based features, which can put the privacy of a person at risk and is also susceptible to pixel‐based noise. In this study, we explored different privacy‐protecting approaches and present a conditional average neighbour score method to detect behaviours of risks in videos from a dementia care unit. The conditional average neighbour score method considers that behaviours of risk in people with dementia are sometimes momentary, but often they persist over time. In this study, we used semantic segmentation masks approach to protect participants’ privacy by obscuring them in the video. The privacy‐protecting inputs were used to train a customized spatio‐temporal convolutional autoencoder and identify behaviours of risk as anomalies. The video was collected on a dementia care unit and composed of approximately 21 hours of training data (normal activities) and 9 hours of test data (normal activities and behaviours of risk events). In comparison to RGB input (0.822), we obtained an equivalent area under the receiver operating characteristic curve (AUC ROC) performance of 0.823 for the segmentation mask‐based privacy‐protecting approach. Further, using the conditional average neighbour score method, we improved the AUCROC performance to 0.83 for the segmentation mask‐based privacy‐protecting approach. The results signify that it is possible to use surveillance videos from a dementia care unit to detect behaviours of risk as anomalies, and that privacy protecting methods work as well as methods using the raw videos. This research paves the way to improve the quality of life of residents and reduce injuries in residential care homes, while respecting their privacy.
Use of Expanded Non‐genetically Modified Natural Killer Cells (SNK01) with Enhanced Cytotoxicity in Patients with Advanced Alzheimer’s Disease – Interim Report of a Phase I trial
Authors: Gil Clemente Humberto Zúñiga , Gallo Blanca Isaura Acosta , Díaz Rufino Menchaca , Amescua Cesar Alejandro , Hui Lucia , Lee Hank , Mata Juan , Chang Paul , Song Paul Y
Published: December 2023

Background

Misfolded protein deposits are known to illicit a cascade of autoreactive neuroinflammation and damage in Alzheimer’s disease (AD). It is clear that removing these proteins by themselves will not fully address this complex process. Natural Killer (NK) cells are an essential part of the innate immune system that have been shown pre‐clinically to slow progression of amyloid deposition as well as identify and eliminate autoreactive T‐cells and damaged neurons. SNK01 is a first‐in‐kind, autologous non‐genetically modified NK cell product with significant increased cytotoxicity and over 90% activating receptor expression that can be consistently produced from any donor. We hypothesize that SNK01 could be consistently produced from any advanced AD patient and that it would be safe and potentially beneficial.

Method

In this Phase 1 dose escalation study (NCT04678453), SNK01 was administered intravenously (IV) every three weeks for a total of 4 treatments using a 3+3 design in pts with advanced disease confirmed by complete evaluation including PET scan. The starting dose was 1×109 SNK01 cells and the highest dose was 4×109SNK01 cells. Primary endpoint was safety and secondary endpoints included changes in MMSE, immune cytokines, and CSF protein levels.

Result

As of January 1, 2023, 9 pts out of a proposed 12 with advanced PET scan confirmed Alzheimer’s disease have been enrolled. Median age is 79 (range 56 – 84) and five were female. Median MMSE baseline score was 14 (range 2 – 23). NK cells were successfully activated and expanded from every patient. No treatment related adverse events were observed. Two patients showed improvement in their MMSE at six‐months compared to their pre‐treatment baseline, three patients showed no deterioration in their MMSE at six‐months, two patients progressed but at a much slower rate than they previously had, and two patients did not return for their six‐month follow‐up.

Conclusion

SNK01 with high cytotoxicity and activating receptor expression can be consistently produced from patients with advanced AD. SNK01 was very safe and appears to have some clinical activity in advanced AD. This data warrants further investigation in a larger Phase II trial with a longer treatment dosing duration.
Perceptions of Shared decision making in cognitive impairment of LTC recipients
Authors: Doan Thao , Jung Jihye , Kim Jinju , Park Myonghwa
Published: December 2023

Background

Shared decision‐making (SDM) plays a dominant model in healthcare systems in bringing numerous benefits to healthcare settings, healthcare providers, and patients. Promoting SDM in long‐term care (LTC) is also crucial since the LTC recipients were vulnerable to cognitive impairments and received healthcare services from diverse health professionals. This study aimed to assess the perceptions of LTC recipients toward SDM in situations of cognitive impairment.

Method

A survey and one‐to‐one interview were provided to LTC recipients which explored the role of patients and family members in the decision‐making process related to their health care in the condition of cognitive impairments.

Result

Thirty‐eight LTC recipients participated in the SDM survey. The participants had a mean age of 77.9 (years) and were diagnosed as eligible LTC recipients for 9.01 (years). In general, most participants expected their healthcare providers to share knowledge about their diseases, and information for medical treatments. The participants described their health symptoms to their healthcare providers in as much detail as possible when they arrived at the hospital since they understood their important role in engaging decisions related to their health. In particular, 65.8% preferred to have been informed about their health conditions, and diseases. 42.1% believed that they, family member(s), and their doctor(s) should be involved together in deciding the best option(s) for their treatment. 52.6% thought that they should be played as the most important person in deciding their treatments for their own health even in those with cognitive impairments.

Conclusion

This study revealed the potential of implementing the SDM model in the LTC system, especially under the condition of cognitive impairments. The LTC recipients desire to be involved in the decision‐making process related to their health even if they are in cognitive impairments. Implementing the SDM model in the LTC system potentially results in promising person‐centred care, especially for enhancing the self‐control of the recipients with cognitive impairment and their families.
Elderly Role Performance Occupational Therapy
Authors: Choi Junsu , Jung Minye
Published: December 2023

Background

Dementia is a disease that is often seen in the elderly, and the elderly are less involved in their roles due to aging. Decrease in participation in various roles can cause physical and cognitive problems. Therefore, through systematic review of previous studies, we try to confirm the cognitive improvement and various positive effects of the elderly who participated in various roles.

The purpose of this study was to identify the effects, role type, and dependent variables, and outcomes in studies on the role performance occupational therapy for the elderly.

Method

The databases were collected using RISS, RISS, Pubmed, CINAHL, EMBASE, SCOPUS, Web of Science. The studies were selected according to the PRISMA flow chart. Finally, seventeen studies were selected for analysis. The selected seventeen studies was evaluated using the qualitative level model of the evidence‐based study and CASP randomized controlled trial checklist, CASP case control checklist, and CASP qualitative checklist.

Result

There were 6 randomized controlled studies corresponding to level I, and 6 studies satisfied all items of the CASP checklist. Occupational therapy intervention was the most common with 13 studies on the role of self‐caregiver. The roles of hobbyist and organizational member were 9 studies, respectively, and the roles of friend was 7 studies in order. Mental health was the most common evaluation tool for the dependent side to derive the outcome of intervention with 8.Physical health and quality of life evaluation were found to be six each..

Conclusion

Through this study, we learned about various roles and occupational therapy interventions that the elderly can play, and we learned evaluation tools that can measure the effectiveness of role performance. In addition, through the evaluation tool, the physical and cognitive effects of role participation, and social participation were known. Role‐oriented occupational therapy intervention should be induced to participate in various roles for the prevention of dementia and cognitive improvement of the elderly.