bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Associations of Social Support and Gait Speed Decline
Authors: Pollak Chava , Emmeline Ayers , Verghese Joe , Blumen Helena M
Published: December 2023

Background

Social support predicts functional and cognitive decline and is associated with brain regions that are important for both cognitive, and motor functions. Gait speed declines years before dementia onset, but the associations between social support and gait speed decline in aging is not well understood. This study examined longitudinal associations between social support and gait speed in older adults without dementia.

Method

Social support and gait data from 592 older adults without dementia (Mdn age 75 years, IQR 71,80, 55.3% female, 79.1% Caucasian) enrolled in the Central Control of Mobility in Aging (CCMA) study was examined. Overall support, emotional support, tangible support, affectional support, and positive social interactions, from the Medical Outcomes Study Social Support Survey at baseline were the predictors of interest. Annual change in simple (walking at normal pace) and complex (walking while reciting alternate letters of the alphabet) gait speed (cm/s) were the primary outcomes. Linear mixed effects models were used to examine the associations between change in single and complex gait speed and baseline social support, adjusting for gender, race, depression, overall cognition, comorbidities, and marital status.

Result

The mean annual change in gait speed was 1.9 cm/s during the simple walking condition and 1.07 cm/s during the complex walking condition. Tangible support was the only social support measure that predicted decline in simple and complex gait speed over a median follow up of 3 years. The annual decline in gait speed was 0.52 cm/s (p = 0.008, CI ‐0.91, ‐0.13) and 0.51 cm/s (p = 0.02, CI ‐0.95, ‐0.07) greater among those with low tangible support than among those with high tangible support during simple and complex walking conditions, respectively.

Conclusion

Tangible support is a potentially modifiable risk factor for gait speed decline Further study is needed to examine the mechanisms behind the observed associations and potentials for intervention.

This research was supported by NIH/National Center for Advancing Translational Science (NCATS) Einstein‐Montefiore CTSA Grant Number KL2 TR002558
Progressive alterations in lipid distribution and composition in a murine Alzheimer’s disease model visualized by label‐free Raman microscopy
Authors: Haessler Annika , Jung Nathalie , Windbergs Maike
Published: December 2023

Background

Alzheimer’s disease (AD) is accompanied by severe alterations in the brain lipid profile, affecting both the type and the distribution of lipids in the tissue. Moreover, literature also suggests a close association of Aβ plaques and lipids, exacerbating amyloidogenesis and plaque deposition. Thus, a spatially resolved approach is eminently important to understand the chemical nature of the progressive relationship between Aβ plaques and surrounding lipids. In the here presented study, Raman microscopy, a label‐free, chemically selective technique, was used in combination with state‐of‐the‐art statistics to analyze Aβ plaques and the surrounding tissue in a murine Alzheimer’s disease model. By encompassing differently aged diseased and healthy mice, this study aimed to generate knowledge on the alterations of Aβ plaque surrounding lipids during disease progression, whilst advancing the application of Raman microscopy within a neurodegenerative context.

Method

Regions of interest in brain sections of APP/PS1 (Amyloid‐Precursor‐Protein / Presenilin‐1) mice aged 50 days, 5 months, and 10 months, as well as healthy non‐transgenic mice were imaged using a confocal Raman microscope (WITec GmbH, Ulm, Germany). The hyperspectral Raman data sets were processed using Project 4 software (WITec GmbH, Ulm, Germany), in‐house written Matlab scripts (The Mathworks, Inc., Natick, USA) and the Matlab‐integrated RamanLight App.

Result

Using multivariate analysis, Raman signatures of the Aβ plaques, cell nuclei, mitochondria, and lipids were identified in the tissue, characterized, and compared to each other (Figure 1). Subsequently, the lipid signal was semi‐quantitatively analyzed. The results of this analysis indicate an increasing, massive abundance of lipids in the direct vicinity of the Aβ plaques with disease progression, and the biochemical Raman spectra also reveal the growing presence of long‐chained lipids around the Aβ plaque. Overall, a distinct shift of the lipid spectra and abundance, starting with disease manifestation, is observed in the proximity of the plaques.

Conclusion

The presented study shows progressive alterations in the distribution and type of lipids surrounding Aβ plaques in an AD model, spatially resolving lipid alterations and providing valuable additional biochemical insight to more established imaging methods such as fluorescence microscopy.
Access to support groups for people with Alzheimer’s Disease since the COVID‐19 pandemic in the Province of Quebec : an action research approach
Authors: Lapierre Nolwenn , Huet‐Fiola Caroline , Gaied Nouha Ben , Labrie Dylane , Côté Claudie , Vincent‐Blouin Emilie , Lamontagne Marie‐Eve , Pageau Felix , Best Krista , Poulin Valérie , Tawbi Nadia , Routier Francois
Published: December 2023

Background

People with Alzheimer’s Disease (PWAD) face reduced social participation and community engagement. Community organizations have developed resources to address these challenges. During the COVID‐19 pandemic, many of them closed, and developed online resources to avoid further increasing the social isolation of PWAD (Armitage and Nellums, 2020). However, there is no consensus regarding their effects and questions remain about the way to implement them (Fields et al., 2020; Xie et al., 2020). Therefore, this study aims to: 1) describe the online support groups implemented by community organizations (e.g., Alzheimer Society) to support PWAD during the COVID‐19 pandemic; 2) Explore the ethical aspects, the safety and respect of privacy of these online groups; 3) Evaluate the engagement of PWAD in relation to these groups and their impact on social participation; 4) Develop methods to expand these resources and make them sustainable.

Methods

This four‐stage iterative research‐action study is conducted in partnership with the Federation of Quebec Alzheimer Societies (Creswell, 2009; Rauch et al., 2014). Stage 1: involves a qualitative study to identify important factors for the development of online support groups. Stage 2: will consist of co‐creation workshops with our partners to identify areas of improvement for the different support groups offered across the province of Quebec. Following the implementation of these enhanced online support groups. Step 3: will be a sequential mixed‐methods study to evaluate the process of implementing these resources and its effects on the social isolation of PWAD. Step 4: In order to identify ways to expand these resources to other communities, co‐creation workshops will be conducted.

Expected results

Facilitators and barriers to implement online support groups that respect the safety and privacy of PWAD will be identified. The effects of these online support groups on the social isolation and the engagement of PWAD will be measured to identify best practices for online services.

Conclusion

The knowledge developed will enable community organizations to expand and refine online resources dedicated to PWAD in the community. Finally, the main social implication of this project is to provide access to safe, ethical and best practices for online support groups for PWAD.
A composite measure of atrophy using volumetric T1‐weighted and T2‐FLAIR imaging using the Boundary Shift Integral
Authors: Prosser Lloyd , Malone Ian B , Sudre Carole H , Barkhof Frederik , Fox Nick C , Cash David M , Barnes Jo , Carrasco Ferran Prados
Published: December 2023

Background

Whole‐brain volume loss using T1‐weighted imaging is an established measurement of neurodegeneration. The Boundary Shift Integral (BSI) produces reliable metrics of longitudinal volume loss, used in research studies and clinical trials. With the increased acquisition of volumetric T2‐FLAIR imaging in studies, there is opportunity to produce atrophy metrics using a composite atrophy measure (T1‐weighted and T2‐FLAIR) that is more precise than either modality alone.

Method

Data from Alzheimer’s Disease Neuroimaging Initiative (ADNI3) were used. Volumetric T1 and T2‐FLAIR weighted imaging were obtained (n = 269), for baseline and follow‐up; Table 1. T1‐weighted images were bias corrected and underwent Geodesic Information Flow (GIF), producing probabilistic brain masks. Masks were resampled to T2‐FLAIR space. The BSI was performed on serial T1‐weighted (gBSI), and T2‐FLAIR (fBSI) separately. We tested differences by diagnosis (control (CN), mild cognitive impairment (MCI) and Alzheimer’s disease (AD)) between indirect volume change, gBSI, fBSI, and composite BSI, using linear regression and effect size. We further compared metric differences within diagnosis, using pairwise correlation, paired samples t‐test, and Pitman’s test of variance.

Result

Demographic information is reported in Table 1. fBSI showed good Pearson’s correlation (r) with both gBSI (CN 0.7, p < 0.001; MCI 0.8, p < 0.001; AD 0.9, p < 0.001), and indirect change (CN 0.6, p < 0.001; MCI 0.6, < 0.001; AD 0.7, < 0.001). The composite BSI further showed good correlation with indirect change (CN 0.8, p < 0.001; MCI 0.8, p < 0.001; AD 0.8, 0.004). Mean values by diagnosis are shown in figure 1, along with paired samples t and variance tests. Pairwise comparisons reported in table 2, highlight good diagnostic group separation in all BSI metrics, with overall strong effect sizes for fBSI, composite BSI, and gBSI respectively.

Conclusion

Calculating atrophy using T2‐weighted imaging is possible using fBSI. This can be used in a composite atrophy measure using fBSI and gBSI. Both fBSI and composite BSI perform well with group separation, and with good correlations with classical atrophy metrics. Future work will explore the influence of White Matter Hyperintensities on BSI.
Therapeutic Evaluation of Thermal Heat Shock Response in Mouse Model of Alzheimer’s disease
Authors: Sharma Lalit , Sharma Rishabh
Published: December 2023

Background

The accumulation of toxic amyloid‐ß protein in brain is a hallmark of Alzheimer’s disease. The accumulation of such toxicants is prevented by a cellular protein quality control system. Molecular chaperons, which further prevent proteins from misfolding and aggregating, are produced by this system, which is mostly activated in response to acute thermal stress. This study aims to determine the therapeutic effect of frequent thermal shock on the development of Alzheimer’s disease

Method

The induction of Alzheimer’s disease was caused by the intracerebroventricular (ICV) injection of the Aß (1‐42) peptide into the ventricular system of the mouse brain. The animals were divided into four groups: normal control (NC), disease control (DC), sham control (SC), water immersion/no heat group (NH), and hot water immersion/high heat group (HH). The ICV‐Aß injection was given to the DC, NH, and HH groups to induce dementia and AD‐like symptoms. The animals in the HH treatment group were given heat shock in the form of hot water immersion for a period of 4 weeks, where each session lasted for 20 minutes. The animals in the NH group were also exposed to water immersion for 20 minutes daily for a period of 4 weeks, but the water temperature was maintained at room temperature. After the completion of the treatment period, the behavioural and biochemical parameters of the animals were assessed for learning and memory defects. The enzyme‐linked immunosorbent assay (ELISA) was carried out for the Aß estimation.

Result

Behavioural assessments in the Y‐maze and morris water maze showed that the animals given daily heat exposure for a period of 4 weeks resisted the detrimental memory effects of the ICV‐Aß injection and had better memory than the water immersion group with no heat treatment given. Increased levels of lipid peroxidation and decreased levels of glutathione were significantly (p<0.05) antagonised by hot water immersion treatment. ELISA showed the lower level of Aß in hot water immersion/high heat group animals when compared to the disease control animals.

Conclusion

The study concluded that frequent heat exposure from hot baths and saunas may reduce the risk of developing dementia and Alzheimer’s‐like symptoms in old age.
Prediction of Mild Cognitive Impairment Using a Hybrid Audio‐Visual Approach: An I_CONECT Study
Authors: Poor Farida Far , Alsuhaibani Muath , Fard Ali Pourramezan , Mahoor Mohammad , Dodge Hiroko H
Published: December 2023

Background

Cognitive decline can affect speech, language, head pose, eye gaze, and facial expressions in older adults. Artificial Intelligence (AI) can assist in automated prediction and monitoring of the progress of cognitive decline. Our previous work shows that utilizing unimodal linguistic features or facial features separately can lead to the prediction of cognitive impairment. We hypothesize that utilizing multimodal features from both audio and video can lead to a more accurate AI algorithm in differentiating those with mild cognitive impairment (MCI) from those with normal cognition (NC).

Method

We utilize deep learning methods (DL), specifically Transformers to extract both linguistic and facial features to predict whether an older subject is MCI or NC. Data is collected through Internet‐Based Conversational Engagement Clinical Trial (I‐CONECT) (NCT02871921) aiming to determine the effects of social interactions (video chats) on cognitive functions. Videos and respective transcribed audios of three themes; Summertime (30 participants), Halloween (32 participants), and Self‐care (30 participants) are selected based on “Good” video qualities. Dataset is balanced (half are diagnosed with MCI).

Facial features are extracted from video frames through a convolutional Autoencoder, and then a Bidirectional Encoder Representations from Transformers (BERT) model captures temporal facial information. Linguistic features are generated by the DistilBERT language model being deployed on the transcribed audio. We used a 10‐fold cross‐validation approach to train and test the models separately. For each modality, the probability scores given by the transformers are fused using a majority voting method.

Result

Accuracy, F1 score, precision, recall and area under the curve (AUC) are the evaluation metrics in this study. Score‐level fusion outperforms previous non‐hybrid methods of MCI prediction. Audio‐visual fusion leads to promising results for Summertime, Halloween and Self‐care with accuracy of 84.8%, 85%, and 84.5% and AUC of 86%, 86.1%, and 85.7%,respectively, which are marked improvements from the previous findings (48% accuracy using linguistic features alone and 67.8% using facial features alone).

Conclusion

The results of our study show that the proposed multimodal approach improves the accuracy of the AI/ML model in distinguishing MCI from NC. That is, audio‐visual fusion could outperform other single methods.
Quantifying caregiver sleep disturbances using a dyadic model of dementia
Authors: Quigg Mark S , Youngkin Anna E , Manning Carol A
Published: December 2023

Background

Sleep disturbances including insomnia, poor sleep quality, and sleep fragmentation appear to play a role in the development and progression of Alzheimer’s disease (AD) in older adults, but may also affect the health of caregivers. The purpose of this pilot study was to objectively quantify daily rest: activity patterns and polysomnography of the sleep of people with dementia (PWD) and their caregivers (CGS).

Method

Participants: Six dyads with PWD and their primary CGS. Actigraphy: Wrist actigraphy recorded for 14 days divided into fixed rest (2200‐0600) and activity (0600‐2200) periods. Polysomnography: recorded and scored for 1 night for each dyad member separately. Variables: sleep onset latency (SOL), total sleep time (TST).

Result

Average activity measures showed no differences within dyads for average daytime or nighttime activity, indicating the activity levels of CGS are highly reflective of the activity of their PWD partners. Despite similar activity levels, CGS displayed sleep deficits compared to their partners, with significantly increased SOL (p = 0.004). Additionally, with the exclusion of one outlier, all CGS received less TST than their demented partners. These deficits were present even when sleeping separately from their partners.

Conclusion

The main findings of this pilot dyadic study reveal that the daily rest:activity patterns of CGS reflect that of their partners. Importantly, despite similar day‐ and nighttime activity, CGS had worse overall sleep than their demented partners, with lowered TST and significantly increased SOL. These findings occurred even when dyads were sleeping separately, indicating that sleep disruptions in CGS cannot be exclusively attributed to nighttime activity of the PWD. Our dyadic model currently is being applied to studies with larger sample sizes in order to determine the impacts of caregiving on sleep.
Bilingualism in the Clinical Diagnosis of Mild Cognitive Impairment and Dementia
Authors: Rosselli Monica , Velez‐Uribe Idaly , Coombes Stephen A. , Barker Warren W , Duara Ranjan , Smith Glenn E. , Curiel Rosie E , Loewenstein David A. , Marsiske Michael
Published: December 2023

Background

Neuropsychological assessments determine the presence of cognitive impairment in Alzheimer’s Disease and Related Dementias (ADRD). These tests are susceptible to the influence of cultural and linguistic variables. Bilingualism is a potential contributor to cognitive reserve in elderly individuals. Positive effects of bilingualism have been observed in executive function tasks, while negative effects have been reported on verbal fluency tests. Maintaining two active languages may modify cognitive and brain reserve among bilinguals, but evidence is inconsistent and contradictory. We investigated the relationship between bilingualism and neuropsychological test performance in aging participants from the 1Florida ADRC using a longitudinal design.

Methods

We studied 238 Latino older adults (age 71.79 ± 8.01 years old, 65% female). 158 Latino participants were Spanish‐English bilinguals; 80 were Spanish monolinguals. Bilingualism was assessed by a proficiency questionnaire. Six cognitive composites were developed (Figure 1). We investigated cognitive test change scores between language group, visit (2 visits: M = 14.61 months; SD = 3.52), and diagnosis (normal, MCI, dementia) using 2×2×3 repeated measures ANCOVAs (age and level of education). Cognitive scores were correlated with frontal and temporal brain volumes in bilinguals and monolinguals separately.

Results

Main effects of the diagnostic group and visit were significant for all composites (ps < .001), with the dementia group showing the lowest scores. No significant main effect of Bilingualism was observed for any of the composites. An interaction between visit and bilingualism was seen for the Trail Making Test B‐ A. Three‐way interactions were found between diagnostic groups, visit, and bilingualism for the Verbal composite and the Logical Memory delay subtest (part of the Memory composite). A more significant decline in the monolingual groups was observed, more so in the dementia group. Significant correlations were found between most composites in both language groups, being more related to the temporal than frontal lobe areas, using MRI volumetric measures.

Conclusion

Bilingualism seems to interact with cognitive decline in aging. It is essential to consider the individual’s level of bilingualism to obtain an accurate assessment of cognitive impairment. The interaction of bilingualism with other sociodemographic and cognitive variables will be discussed.
How much would England’s National Health Service have to invest to bring its capacity to deliver an Alzheimer’s treatment to G7 average capacity levels?
Authors: Mattke Soeren , Shi Zehao , Hanson Mark , Mitchell Susan , Lynch Chris , Kalonji Kirstie MacLean , Lanman Lydia
Published: December 2023

Background

The arrival of disease‐modifying treatments for Alzheimer’s disease (AD) creates a substantial challenge for health systems because of the large patient pool and a complex diagnostic pathway, and in particular, for those countries that already have comparatively low capacity to provide timely, accurate AD diagnostic services. We estimate how much NHS England would have to invest over 10 years to bring its memory assessment services infrastructure up to the average capacity of the other G7 countries and project the resulting changes in wait times for a disease‐modifying Alzheimer’s treatment.

Method

Desk research and expert interviews for capacity and cost data. Markov model to estimate the effect of investment on wait times because of limited capacity for specialist visits and confirmatory biomarker testing.

Result

England has the lowest number of MRI and PET scanners and the second lowest number of AD specialists of the G7 countries (Table 1). Closing this gap would require an estimated investment of ∼GBP 5.5 billion over 10 years, of which 9% would go toward acquisition of 126 PET and 1,196 MRI scanners including building modification, maintenance and IT equipment cost, and 91% to support operative costs (salaries, CSF assays, tracers, and facility use). On an annual basis, this number amounts to GBP 99 per capita and 3.1% of the overall NHS budget. Wait times in the diagnostic process to determine treatment eligibility would go from an average 58 months to 10 months by year 10 of the investment (Figures 1 and 2)

Conclusion

As a result of a long‐standing underinvestment in health system infrastructure, wait times to receive an AD treatment would be substantial in England. Targeted investments aimed at increasing the NHS’ capacity to the average of the remaining G7 countries would decrease those wait times significantly. While the required investment is sizeable, the cost of inaction is equally so, since the disease would progress to more severe and costly stages while patients are held up on wait lists.
Lifestyle activities contribute to cognitive reserve in mid‐life, independently of education, in cognitively healthy middle‐aged individuals at risk for late‐life Alzheimer’s disease
Authors: Deng Feng , El‐Sherbiny Sandra , Heneghan Amy , Dounavi Maria‐Eleni , Ritchie Karen , Muniz‐Terrera Graciela , Malhotra Paresh A , Ritchie Craig W , Lawlor Brian , Naci Lorina
Published: December 2023

Background

It is now acknowledged that Alzheimer’s Disease (AD) processes are present decades before the onset of clinical symptoms, but it remains unknown whether lifestyle factors can protect against these early AD processes in mid‐life. Intellectually, physically, and socially stimulating lifestyle activities are associated with maintenance of late‐life cognitive abilities (Chan et al., 2018), and lower cognitive impairment in AD (Livingston et al., 2020). We asked whether such activities contribute to cognitive reserve (CR) from mid‐life, in cognitively healthy individuals who are at risk for late‐life AD.

Method

Middle‐aged individuals (aged 40‐59 years, mean = 52 years) from the PREVENT Dementia study (www.preventdementia.co.uk) were assessed at baseline (N = 210, 62/148 male/female) and two‐year follow‐up (N = 188, 55/133 male/female), with cognitive ability (multidomain battery) and brain health (total grey matter volume, functional brain network segregation) measures. Mid‐life activities were measured using the Lifetime of Experiences Questionnaire, which comprises occupational as well as intellectually, physically, and socially stimulating leisure activities. Dementia risk was assessed with the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score.

Result

Multivariable linear regression showed that intellectual, physical, and social activities undertaken in mid‐life made a unique contribution to episodic and relational memory in mid‐life, independent of occupation and CAIDE at baseline (β (se) = 0.04 (0.02), p = 0.02, Figure 1a) and follow‐up (β (se) = 0.07 (0.02), p = 0.002, Figure 1b). Furthermore, these activities moderated the relationship between cognitive ability and brain health at follow‐up (β (se) = 3.47 (1.40), p = 0.01), with verbal and visuospatial functions, and short‐term (conjunctive) memory of people with higher activity levels less dependent on their brain functional integrity (Figure 2), consistent with the concept of CR (Brayne et al., 2010). Such a moderation by these mid‐life activities was more prominent in individuals with higher CAIDE scores (β (se) = 4.28 (1.83), p = 0.02, Figure 3).

Conclusion

These findings suggest that modifiable lifestyle activities contribute uniquely to CR and may offset cognitive decrements due to AD risk in mid‐life. They support the targeting of modifiable lifestyle activities for the prevention of Alzheimer’s disease.
Pathways linking educational attainment to cognitive functioning among older Brazilians
Authors: Farina Mateo
Published: December 2023

Background

Cognitive impairment in Brazil is a growing population health concern. Studies suggest that Brazil may have one of the highest age‐standardized prevalence of Alzheimer’s disease and related dementias (ADRD) in the world. However, improving education attainment among older adults may lead to a decline in cognitive impairment across the population in the coming years. The purpose of this study is to examine the pathways that link educational attainment to cognitive functioning in Brazil, a highly unequal, resource rich society.

Method

I use the 2016 Brazilian Longitudinal Study of Aging, a nationally representative study of Brazilian older adults 50+, to predicting cognitive functioning at first interview. I use structural equation modeling to predict direct and indirect effects of education via childhood socioeconomic characteristics, adulthood socioeconomic conditions, health behaviors and health conditions on overall cognitive functioning as well as specific domains of cognition (memory vs. non‐memory).

Result

Findings provide evidence of both indirect and direct pathways from education to cognitive functioning. The indirect pathways were mainly found through adulthood SES achievement (although health conditions had their own association with cognitive functioning). Additionally, indirect effects were limited among adults with 8+ years of education, suggesting that prior to 8 years of education the impact of education on cognitive functioning may be through cognitive development that is carried forward into older adulthood.

Conclusion

This study shows the importance of early childhood education and the potential benefits for later life cognitive functioning, which has broad implications for cognitive health in rapidly aging countries with more recent early childhood educational expansion.
Challenges in identification of HIV‐Associated Neurocognitive Disorders, a focus on low and middle income countries
Authors: Paddick Stella‐Maria
Published: December 2023

Background

HIV‐associated neurocognitive disorders (HAND) are highly prevalent amongst people living with HIV (PLWH), especially in Sub‐Saharan Africa (SSA) where the majority of PLWH live. Current HAND identification measures lack accuracy in older PLWH on treatment, with substantial heterogeneity observed in SSA prevalence meta‐analyses There is a need to better understand the current cognitive phenotype of this newly emergent population, to develop appropriate screening tools. We report two linked studies.

Study 1 compared diagnostic accuracy of the International HIV dementia scale (IHDS), and Identification and Interventions for Dementia in Elderly Africans (IDEA) screen, for identification of HAND in older PLWH in Tanzania

Study 2 aimed to identify cognitive domains significantly associated with symptomatic HAND (s‐HAND) in older PLWH in Tanzania, with potential utility in future screening measures.

Method

A systematic sample of 253 PLWH aged ≥ 50 attending a Government clinic underwent comprehensive HAND evaluation by consensus American Academy of Neurology (AAN) criteria including locally‐normed low‐literacy clinical neuropsychological assessment. A diagnostic accuracy study of the IHDS and IDEA screen versus AAN criteria was completed with strict blinding. Participants were offered identical annual reassessment at Y1 Y2 and Y3 and the relationship of cognitive domains with s‐HAND in a logistic mixed effects model

Result

HAND was highly prevalent (47%) at baseline, increasing to 57.9% at year 3.

At baseline, both IHDS and IDEA had limited diagnostic accuracy for HAND (AUROC 0.639–0.667 IHDS, 0.647–0.713 IDEA). On secondary analysis of longitudinal data, tests of verbal learning and memory, categorical verbal fluency, visual memory and visuoconstruction had AUROC > 0.7 for s‐HAND (0.70 ‐ 0.72; p<0.001 for all). Tests of visual memory, verbal learning and memory (delayed recall and recognition memory), psychomotor speed, language comprehension and categorical verbal fluency were independently associated with s‐HAND (p<0.01 for all). Neuropsychological impairment pattern varied by education.

Conclusion

Current HAND screening tests no longer perform well in the new population of older PLWH in Africa. Tests most associated with s‐HAND include broad cortical and subcortical domains, some not included in existing HAND screening tests and vary by educational background. This should be considered in future HAND screening measure development.
Suitability of Neuropsychological Tests for Assessments of Dementia in Africa
Authors: Bellaj Tarek
Published: December 2023

Background

Neuropsychological assessment is a centerpiece element for detecting, diagnosing, and following‐up the evolution of a dementia syndrome. It should be based on valid, reliable, standardized, and culturally suitable tests. However, the majority of the available tests were developed in western countries, and little is known about how these tests were translated and adapted in Africa in concordance with the international guidelines of psychological measurement. The aim of this review is to inspect closely the available neuropsychological tests used in Africa during the last three decades, examine their psychometric qualities, and analyze their cultural appropriateness to the local populations.

Method

We performed a systematic review on published articles dealing with the neuropsychological assessment of dementia in the 54 African countries during the latest 30 years on main scientific search databases (Web of Science, Academic Search Ultimate (Ebsco), ScienceDirect, Scopus, PubMed, APA PsycArticles, Embase, Cochran). The search keywords were: dement* and (neuropsych* or *cognit*) and (assessment or evaluation or test*) and country, without restrictions about the language of publication. Our approach is fourfold: i) papers' extraction, ii) tests identification, iii) concordance analysis, and iv) appropriateness evaluation.

Result

We identified a list of different tests used in each country and estimated the level of their concordance with the international guidelines of psychological measurement regarding the translation and adaptation procedures as well as the type of validity, reliability, and the availability of local standardized data. More than the two‐thirds of the identified tests did not respect the international guidelines of psychological measurement in developing, translating and adapting neuropsychological tests for the screening and assessment of dementia in Africa.

Conclusion

We focused on the importance to fix measurement’s issues in the neuropsychological assessment of dementia in Africa. A suggested list of recommendations was provided to improve it especially that Africa is the second most populous continent after Asia and its elderly population is showing the most rapid increase in the world.
Closing the sex/gender gap in dementia: homing in on the vasculature (biomarkers)
Authors: Elahi Fanny M , Buckley Rachel F.
Published: December 2023

As we move toward precision medicine approaches, we cannot continue to pursue a one model fits all. Sex differences in brain aging and degeneration have been reported across the spectrum of research methodologies from human epidemiological studies and drug trials to model systems of degenerative brain disease. Blood proteomic biomarkers combined with clinical data can provide useful multi‐modal disease models in humans to uncover important biological associations with relevance to human disease. Small vessel disease in aging or AD is prevalent in the aging populations and represents a common and important risk factor for cognitive impairment. Dysregulated angiogenesis is emerging as a relevant pathology in SVD‐related vascular cognitive impairment with potential for therapeutic modulation. Recent work by our group and others is suggesting that the association of plasma markers of angiogenesis with clinical outcomes is sex dimorphic. Results demonstrate several age and sex‐dependent associations between groups of markers that capture both beneficial and pathological aspects of angiogenesis in aging. Much remains to be uncovered regarding underlying mechanisms, interactions with neurodegenerative pathologies, and ideal windows for sex‐informed therapeutic interventions on angiogenesis. However, the emerging body of work on sex differences regarding angiogenesis in aging, AD and other neurodegenerative disorders, represents a critical first step toward demonstrating the relevance of sex/gender to therapeutically oriented studies of vascular pathologies in dementia‐causing diseases.
Acceptability and Requirements for Digital Interactive Television Systems in Geriatric Institutions
Authors: Naudé Bérangère , Rigaud Anne‐Sophie , Dacunha Sébastien , Pino Maribel
Published: December 2023

Background

Information and communication technologies have great potential to address the psychosocial needs of Older Adults (OAs) living in geriatric institutions. With the development of Digital Interactive Television (DiTV) systems, communication, entertainment, online purchases and other functionalities and services are accessible directly on a television screen. Thus, DiTV could be a promising and accessible solution to help meet several needs of OAs, especially in geriatric settings.

Method

A mixed‐methods research was conducted to identify barriers of DiTV use among geriatric residents with the aim of identifying accessible specifications for the system, and recommendations for its implementation. First, semi‐structured interviews were conducted within 3 French nursing homes already equipped with a DiTV (OAs: n = 18; professionals: n = 6). Interviews were then transcribed with the MAXQDA software and processed using a thematic deductive analysis inspired by a multidimensional health technology assessment model. Secondly, user tests compared the ability to use a DiTV (e.g., errors made and need of assistance) by OAs living in geriatric institutions (n = 20), and OAs living at home (n = 15). Four questionnaires (e.g., socio‐demographic and technological habits questionnaire, System usability Scale (SUS), and Technology Assessment Model (TAM)) helped identify the acceptability and usability of the DiTV.

Result

Preliminary results showed that DiTV systems can be well accepted by OAs who recognize the advantage of this system in terms of communication and entertainment. However, its use may be hindered by organizational (e.g., workload), technological (e.g., ergonomic issues), human (e.g., health issues), ethical (e.g., privacy), and safety factors (e.g., frustration due to technical problems). The second part of the study revealed that OAs living in geriatric institutions made more initiation errors and needed more assistance (help or confirmation) in comparison to OAs living at home, even though the DiTV provides some guidance on the remote‐control buttons.

Conclusion

Beyond organizational, safety, and technological issues, the presentation and training on the DiTV are essential to reassure and accompany OAs in the discovery of a new device, even one as familiar as the television.
Closing the sex/gender gap in dementia: homing in on the vasculature (in vitro/iPSCs)
Authors: Blurton‐Jones Mathew
Published: December 2023

Induced pluripotent stem cell (iPSC) models are increasingly being used to model the blood brain barrier (BBB) and to examine the contributions of genetic risk factors to neurovascular disease. While clinical and rodent studies clearly demonstrate the importance of sex in vascular‐related neurodegeneration, only a handful of published studies have thus far begun to employ iPSC modeling to examine the biology that underlies these sex‐related differences. Early reports suggested that female iPSC‐derived brain microvascular endothelial cells (BMECs) exhibit increased transendothelial electrical resistance (TEER) and thus decreased permeability than male BMEC counterparts. Conversely, male pluripotent cells were found to differentiate more readily into BMECs. However, these initial studies were often underpowered and failed to account for the considerable variability inherent between iPSC lines. More recently, consortiums have begun to generate and examine BMECs and glia from a large number of subjects with various neurodegenerative diseases. While much of this work is currently unpublished, these large‐scale datasets further support the concept that sex alters the transcriptome and function of BMECs and vascular‐associated glia. The development and use of ‘isogenic’ male and female iPSC lines derived from Klinefelter syndrome subjects is providing another powerful new approach to study sex‐dependent effects on cellular function. Both the complexity and utility of in vitro iPSC‐modeling of brain vasculature continues to improve and now includes both bioengineered vascular networks and vascularized organoids. In addition, recent progress with xenotransplantation models is providing further avenues to study the interactions between human glial, blood brain barrier function, and cerebral amyloid angiopathy. Nevertheless, there remains a pressing need to further examine and understand both the intrinsic and extrinsic effects of sex on BBB function and vascular‐related neurodegenerative disease, a topic that will be extensively discussed during this AAIC perspectives panel.
Relative Validity of the revised RUSH Food Frequency Questionnaire and MIND diet screener: Capturing the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) dietary pattern
Authors: Tangney Christy C , Agarwal Puja , Ventrelle Jennifer , Aggarwal Neelum T. , Dhana Klodian , Arfanakis Konstantinos , Barnes Lisa L.
Published: December 2023

Background

The original MIND diet score was derived from analyses of the RUSH food frequency questionnaires completed by Rush Memory and Aging Project participants. Once the tool was revised to include specific foods reflecting evidence about neuroprotection, the concurrent validity of the revised RushFFQ (rRushFFQ) was examined and further compared it with a MIND diet screener.

Methods

Using baseline data from 603 MIND diet trial participants (NCT 02817074), we calculated MIND scores using responses from 1) the rRushFFQ (142‐item questionnaire), and 2) a set of seven one‐day food records. We compared these scores with one another and with that of the MIND diet screener (14‐item questionnaire). A random sample of specimens were analyzed for plasma antioxidants (n = 442), and plasma free fatty acids (n = 433).

In a sample of 149 participants, partial correlations of scores across the three independent dietary tools were run. To examine extent of bias among the different dietary tools, Bland Altman plots with limits of agreements were constructed for MIND scores from the rRushFFQ with those from the food records and that of the diet screener.

Results

The average age of the larger sample (n = 603) was 70.3 ± 4.3 years with over half the sample being retired and married; 65% were women. Circulating concentrations of several carotenoids (lutein +zeaxanthin, lycopene as well as alpha and beta‐carotenes) were positively associated with MIND scores. Among the sample of 149 adults, (69.8 ± 4.3 years, 67.4% women), MIND scores for rRushFFQ, food records, and screener were 7.2 ± 1.6, 6.0 ± 1.6, 7.7 ± 1.8, respectively. Correlations were moderate in strength and highly significant — MIND scores from rRushFFQ with those for food records, r = 0.52; food records and MIND diet screener, r = 0.57, and for rRushFFQ with diet screener, r = 0.85. Significant moderate agreement (kappas) was observed for 8 of 14 MIND components.

Conclusions

The rRushFFQ was successful in capturing components of the MIND dietary pattern. Concordance of MIND scores from rRushFFQ with those from seven one‐day food records and the MIND diet screener as well as positive associations with blood nutrients and MIND food components support the use of these tools for future studies.
Formal Care Providers Experiences with Indigenous Understandings of the Stages of Dementia in Diverse Indigenous Communities in Canada and the United States
Authors: Jacklin Kristen , Blind Melissa J , Ketcher Dana , Warry Wayne , Lewis Jordan P. , Dertinger Melinda , Arredondo Brandylyn , Pederson Collette , Johnson January , Trudeau Rhonda , Pitawanakwat Karen , Strong Lois , Summers Marlene , Martin Wesley , Lambrou Nickolas H. , Zuelsdorff Megan , Gleason Carey E.
Published: December 2023

Background

This paper explores Indigenous understandings of the progression of dementia through the early/mild, middle/moderate, and late/severe stages of dementia through the experience of on‐reservation dementia care providers. There is scant but growing literature on Indigenous understandings of dementia but to our knowledge none have examined how Indigenous conceptualization of the illness stages relate to the biomedical staging categories which dominate dementia education and care models.

Method

We conducted sequential focus groups (SFGs) with the same local health care staff/formal caregivers that work with Indigenous older adults (n = 17) over 4‐5 sessions (n = 14) in four diverse Indigenous reservation communities in USA and Canada. The SFG design provided an opportunity for a progressive and deep discussion of perceptions of early, middle, and late stages of dementia among their Indigenous patients. SFGs were recorded, transcribed, thematically coded and grouped according to the Alzheimer’s Association (AA) definitions of early, middle, and late‐stage dementia.

Result

These data suggest that Indigenous experiences with the stages of dementia do not align with the AA framework. Specifically, early dementia is not widely recognized as an illness or part of the disease trajectory; rather, moderate symptoms in the AA framework are most frequently described as the beginning of dementia. Participant descriptions of symptoms in the middle and late stages were more closely aligned with Indigenous lived experience and beliefs. Significantly, a return to childhood or infancy was widely used to describe late‐stage dementia. Participant discussions revealed that they gave prominence to periods of transitions and the overall experience as opposed to a segmented/staged approach.

Conclusion

Indigenous dementia illness models may not align with biomedical approaches to disease staging, potentially leading to inappropriate and ineffective clinical conversations and dementia education efforts. For example, while infantilization of elderly individuals is usually advised against by professionals, describing a loved one as returning to an earlier stage of their life aligns with Indigenous teachings of the circle of life. Further ethnographic research is needed with Indigenous family caregivers and persons living with dementia to verify these findings and provide insight into culturally safe care.
Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients
Authors: Holleman Jasper , Daniilidou Makrina , Kåreholt Ingemar , Matton Anna , Aspö Malin , Hagman Göran , Udeh‐Momoh Chi T. , Kivipelto Miia , Solomon Alina , Sindi Shireen
Published: December 2023

Background

Neuroinflammation is considered a hallmark of the Alzheimer’s disease (AD) pathogenic process. Dysregulations in stress hormones (cortisol) may increase AD risk and are related to brain atrophy. This cross‐sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates.

Method

188 participants were recruited from the Karolinska University Hospital memory clinic (Stockholm, Sweden), and underwent magnetic resonance imaging or computed tomography. Four visual rating scales were applied to the scans: medial temporal lobe atrophy (MTA), global cortical atrophy (GCA), white matter lesions (Fazekas), and posterior atrophy (Koedam). Additionally, participants provided saliva to assess diurnal cortisol patterns, and underwent lumbar punctures for cerebrospinal fluid (CSF) sampling. Five cortisol measures were used: awakening levels, bedtime levels, cortisol awakening response (CAR), total daily output, and the ratio of awakening to bedtime levels (AM/PM ratio). Nineteen CSF neuroinflammation markers were categorized into five composite scores (mean z‐scores): proinflammatory cytokines (Interleukin (IL‐)6, IL‐8, IL‐15, IL‐12/IL‐23 p40, CC chemokine ligand (CCL)4, CXC chemokine ligand 10), other cytokines (IL‐5, IL‐16, CCL17), angiogenesis markers (Vascular endothelial growth factor (VEGF), VEGF‐D, VEGF‐receptor 1, Placental growth factor), vascular injury markers (Serum amyloid A, C‐reactive protein, Vascular cell adhesion molecule‐1, Intercellular adhesion molecule‐1), and glial activation markers (YKL‐40, CCL2). Ordinal logistic regressions were conducted to assess associations between cortisol patterns, neuroinflammation scores, and visual rating scales, and interactions between cortisol patterns and neuroinflammation composite scores in predicting visual rating scales.

Result

Higher levels of angiogenesis markers were associated with greater odds of more severe white matter lesions. Furthermore, awakening cortisol levels, bedtime levels, CAR, and total daily output independently interacted with ‘other cytokines’ scores to predict MTA, CAR and total daily output independently interacted with ‘proinflammatory cytokines’ scores to predict white matter lesions, and the AM/PM ratio interacted with angiogenesis markers to predict GCA. No associations were found between cortisol patterns and visual rating scales.

Conclusion

This study provides evidence for potential interplay between diurnal cortisol patterns and neuroinflammation. While this study does not provide information on causality, these findings suggest that neuroinflammation is involved in the pathway between chronic stress and AD.