bluuebunny/crossref_metadata_2025 huggingface dataset:
Erosion of The Supratentorial White Matter Reference for Increased Power in Longitudinal Amyloid PET
Authors: McGinnity Colm J , Peraza Luis R , Parker Richard G , Wolz Robin
Published: January 2025

Background

Use of the supratentorial white matter (sWM) as a reference region for amyloid PET, alone or in a composite, can facilitate the detection of subtle changes in amyloid load (Wong et al., 2010; Landau et al., 2015). Investigators often erode the sWM labels to reduce the influence of signal “spill‐in” from grey matter, but the optimal extent of erosion is unclear, and evaluations for 18F tracers other than [18F]florbetapir are scarce (Bullich et al., 2017). We aimed to determine the optimal extent of erosion of the supratentorial white matter by the ability to differentiate between participants who experience divergent disease trajectories.

Method

We used longitudinal PET and T1w‐MR images acquired from participants who did not have Alzheimer’s disease at baseline (sources: ADNI https://adni.loni.usc.edu/, AMYPAD https://amypad.eu/). The participants were classified as “Decline” or “Stable” according to change in cognitive measures, and alternatively in cerebrospinal fluid amyloid‐β42 (CSF‐Aβ42; where available). We used IXICO’s MultiLEAP pipeline to automatically segment the T1w‐MRI into 143 regions with high accuracy (Figure 1). Standardised uptake value ratios (SUVRs) were calculated for the global cortical region using the whole cerebellum (WC) reference region, and using pons‐eroded sWM‐WC composites after erosion by 0 – 5 (1 mm3) voxels (Figure 2). We compared effect sizes (ΔSUVR/year – Decline versus Stable) across all reference regions.

Result

In preliminary analyses using [18F]florbetaben data (scan interval 3±1 years), the WC reference region yielded Cohen’s d of 0.19 for 112 participants classified via cognitive measures, and 0.59 for 35 who could be classified via CSF‐Aβ42. The sWM‐containing composites yielded d values that were 1.8 – 2.1 and 1.08 – 1.17 times higher, respectively, depending on extent of erosion (Figure 3). For both classifications, erosion by two voxels yielded the maximal d (0.40 and 0.69) – equivalent to mean increases in SUVR of 0.8%/1.3% and 0.3%/‐0.3% per year for Decline and Stable, respectively.

Conclusion

Eroded sWM‐containing reference regions appear to offer greater sensitivity to longitudinal change than the WC. Validation of this finding in a larger population and for additional radiotracers is ongoing. We will examine the influence of scanner model on the optimal extent of erosion.
Abdominal Fat Depots are Related to Lower Cognitive Functioning and Brain Volumes in Middle‐aged Males at High Alzheimer’s Risk
Authors: Golan Sapir , Boccara Ethel , Ravona‐Springer Ramit , Inbar Yael , Zelicha Hila , Livny Abigail , Bendlin Barbara B. , Lesman‐Segev Orit H. , Yore Iscka , Heymann Anthony , Sano Mary , Mardor Yael , Azuri Joseph , Beeri Michal S
Published: January 2025

Background

High body mass index (BMI), which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. We examined associations of abdominal fat depots with cognition and brain volumes and whether sex modifies this association.

Method

204 healthy middle‐aged Alzheimer’s‐dementia (AD) offspring (mean age = 59.44, 60% females) underwent abdominal magnetic resonance imaging to quantify hepatic, pancreatic, visceral (VAT), and subcutaneous adipose tissue (SAT), assessment of cognition and brain volumes.

Result

In the whole sample higher hepatic fat % was associated with lower total grey matter volume (β = ‐0.17, p<0.01). Primarily in males, higher pancreatic fat % was associated with lower global cognition (Males: β = ‐0.27, p = 0.03; Females: β = 0.01, p = 0.93) executive function (Males: β = ‐0.27, p = 0.03; Females: β = 0.02, p = 0.87), episodic memory (Males: β = ‐0.28, p = 0.03; Females: β = 0.07, p = 0.48) and inferior frontal gyrus volume (Males: β = ‐0.28, p = 0.02; Females: β = 0.10, p = 0.33). VAT and SAT were inversely associated with middle frontal and superior frontal gyrus volumes in males and females.

Conclusion

In middle‐aged males at high AD‐risk, but not in females, higher pancreatic fat, was associated with lower cognition and brain volumes. These findings suggest a potential sex‐specific link between distinct abdominal fat with brain health. By AAIC 2024 300 participants will be scanned, additional brain pathlogies will be assesed (amyloid, tau, etc.) and secreted factors will be evaluated (GLP‐1, Amylin, PAI‐1, leptin, etc). These data may lead to the development of fat depot‐specific interventions, which are expected to prevent or delay brain atrophy and possibly cognitive decline.
Black Family Caregiving Experiences Among Relatives of Persons with Dementia
Authors: Robinson‐Lane Sheria G , Johnson Florence U , Tuyisenge Marie Jean , Jackson Jada A , Qurashi Tasneem , Tripathi Priya
Published: January 2025

Background

Despite an increasing prevalence of Alzheimer’s disease and related dementias among Black older adults, large disparities remain in early diagnosis, treatment, and support service referral. Further, services intended to support family caregivers are typically designed around older adult spousal caregivers with little consideration to the wide diversity of families affected by dementia. This qualitative descriptive study examined the caregiving experiences of Black relatives of persons with dementia with the aim of informing the development of more culturally responsive support programming.

Methods

Three focus groups of family caregivers (n1 = 6, n2 = 6, n3 = 5) who self‐identified as Black/ African American and reported providing supportive care for a relative over the age of 55 with dementia or evidence of cognitive impairment were convened to answer the primary research question, “what characterizes the experience of Black adults providing supportive care to a relative with dementia?” Virtual focus groups took place via Zoom and transcripts were analyzed thematically by a team of 5 trained coders following the rigorous and accelerated data reduction technique (RADaR).

Results

Participants, primarily non‐spousal caregivers, identified seven barriers and three facilitators of family caregiving. Barriers included 1) financial challenges, 2) familial expectations and lack of support, 3) managing difficult emotions, 4) managing challenging behaviors of care recipients, 5) dealing with gaps in medical care/ supportive services, 6) preventing or managing institutionalization, and 7) making lifestyle adjustments that support family care. Family caregiving facilitators included 1) faith and/ or faith communities, 2) having a healthcare background, and 3) support from local agencies and community programs.

Conclusion

Though caregiver experiences align with resilience frameworks, systemic changes are necessary that engage wholistic care delivery models inclusive of multidisciplinary teams that center family as the unit of care. With appropriate multidisciplinary team engagement, families may be more readily connected to social and financial resources that support ongoing community living and quality of life.
Alzheimer disease clinical progression by intellectual disability levels in Down syndrome
Authors: Vaqué‐Alcázar Lídia , Videla Laura , Carmona María , Benejam Bessy , Barroeta Isabel , Hoyo Laura Del , Hernandez Aida Sanjuan , Rodríguez‐Baz Íñigo , Arriola‐Infante José Enrique , Arranz Javier , Maure‐Blesa Lucía , Morcillo‐Nieto Alejandra O. , Bejanin Alexandre , Lleo Alberto , Bartrés‐Faz David , Fortea Juan , Fernandez Susana
Published: January 2025

Background

The extended life expectancy in individuals with Down Syndrome (DS) has led to the emergence of age‐related diseases, with Alzheimer’s disease (AD) being particularly noteworthy due to its nearly full penetrance. The level of intellectual disability (ID), regarded as a proxy for cognitive reserve (CR), explains heterogeneity in cognitive and functional abilities. Despite this, there is a notable lack of exploration into the characterization of resilience factors and their potential influence on the progression along the AD continuum in this population. The main goal was to study whether premorbid ID levels (i.e., Mild, Moderate, Severe) could influence the AD clinical onset (prodromal [pDS] or dementia [dDS] diagnosis) and cognitive trajectories among asymptomatic DS (aDS).

Method

We analyzed longitudinal data (> 6 months follow‐up) from a single‐center cohort study involving DS adults (aged >18 years) recruited at the Alzheimer‐Down Unit from the Catalan Down Syndrome Foundation and Hospital of Sant Pau. Clinical progression was evaluated using Kaplan‐Meier curves, ANOVA was conducted to test differences in the age of onset across ID groups, and cognitive trajectories (assessed with Cambridge Cognitive Examination for Older Adults with Down Syndrome [CAMCOG‐DS]) were analyzed using linear mixed‐effects models to explore age‐related effects by ID.

Result

A total of 778 adults with DS (mean [SD] age, 43.32 [11.07] years; 361 women [46.4%]; aDS = 527, pDS = 86, dDS = 165) were included. Kaplan‐Meier curves showed that aDS with ID‐Severe progressed faster (p = .0016; Figure 1A), whereas no differences were found in the prodromal stage (p = 0.270; Figure 1B). While no significant differences were identified regarding the age of onset for pDS (Figure 1C), the ID‐Severe slightly showed a later age of dDS diagnosis than ID‐Mild (p = .044; Figure 1D). CAMCOG‐DS scores were higher for ID‐Mild than those with ID‐Moderate (mean [SE] difference, −19.24 [1.68]); p<.001). Nevertheless, there were no group differences among trajectories (Figure 2A), neither when estimated by different age ranges (Figure 2B).

Conclusion

Despite the lack of evidence, there is an increasing interest in understanding how CR proxies contribute to cognitive resilience in DS. Further analyses including AD‐related biomarkers are essential to uncover the neurobiological mechanisms involved, which could significantly contribute to targeted primary prevention strategies.
Total Healthcare Costs across the Alzheimer’s Disease Continuum in the United States (US)
Authors: Monfared Amir Abbas Tahami , Hummel Noemi , Naslazi Emi , Khachatryan Artak , Zhang Raymond , Gao Ran , Zhang Quanwu
Published: January 2025

Background

This study describes the total healthcare costs integrating direct, indirect, and intangible or emotional cost components across the severity stages of Alzheimer’s disease (AD) in US.

Method

Utilizing Health and Retirement Study (HRS) data (1994‐2018), a bi‐annual US national survey of older adults, we assessed out‐of‐pocket and indirect costs, including unpaid caregiving services, missed workdays, and early retirement. HRS, analyzed with sampling weights, provided a representative US national sample. Mild cognitive impairment (MCI) and AD severity were ascertained using the modified telephone interview of cognitive status (TICS‐M). Besides data from HRS, 100 pairs of patients and their caregivers were referred by physicians and surveyed for quality of life (QoL). Patient and caregiver responses to QoL were converted to utility values. The MCI‐ or AD‐specific health utility value was subtracted from the age‐standardized health utility value from the general US population to derive the estimate of utility reduction due to AD. Intangible costs were calculated using the willingness to pay threshold of $150,000 for one quality‐adjusted life year gained. Direct costs were derived from current literature, comprising patient and caregiver healthcare costs, patient social care costs and nursing home costs. Costs were adjusted to the 2023 US price index.

Result

HRS patient sample (N = 18,786) with MCI (n = 17,885) and AD (n = 901) were aged 67.8±10.7 and 80.9±9.3 years, 55.7% and 63.3% female, and 28.3% and 0.9% employed, respectively. A total of 100 patient‐caregiver pairs with MCI (n = 27) and AD (n = 73) were surveyed, with 21% and 47% of patients > 75 years, 59% and 48% female, and 7.4% and 4.1% employed, respectively. Figure 1 shows mean annual costs per patient across AD severity levels, with direct costs from literature, indirect costs estimated from HRS and intangible costs estimated from the patient‐caregiver survey. Total annual healthcare costs increased from $69,380 for MCI to $150,488 for severe AD.

Conclusion

This study provides a comprehensive view of escalating healthcare costs with worsening AD severity, emphasizing the need for targeted interventions to address the multifaceted economic impact on patients, caregivers, and society.
Remote associations between beta‐amyloid and tau are mediated by between‐network connectivity
Authors: Hojjati Seyed Hani , Butler Tracy A , de Leon Mony J. , Gupta Ajay H , Nayak Siddharth , Luchsinger Jose A. , Chiang Gloria , Razlighi Qolamreza R
Published: January 2025

Background

The accumulation of tau tangles and beta‐amyloid (Aβ) are hallmarks of Alzheimer's disease (AD). Despite the hypothesis that Aβ may trigger tau spread across remote brain regions, the specific pathological processes remain unclear.

Methods

Our study utilized 18F‐Florbetaben Aβ positron emission tomography (PET), 18F‐MK6240 tau PET, and resting‐state functional magnetic resonance imaging (rs‐fMRI). We included 361 healthy control (HC) subjects from the Northern Manhattan Study of Metabolism and Mind (NOMEM) [mean age 64.96 ± 3.17 years, 230 females]. Among them, 46 subjects underwent follow‐up scans at 2 to 3 year intervals. Additionally, 120 HC subjects from the Brain Health Imaging Institute (BHII) studies were included (mean age 68.71 ± 6.16 years, 54 females). Cross‐sectional elderly subjects were categorized into four groups based on normal (n) and abnormal (a) levels of Aβ and tau, as compared to young normative subjects (age < 40): nAβ/nTau, aAβ/nTau, nAβ/aTau, and aAβ/aTau. Assortativity, a graph theory metric, was computed on the average functional connectivity maps for each group. We also compared the connectivity between the limbic network and other functional networks among these groups of subjects. Finally, using longitudinal subjects, we explored the role of between‐network connectivity of the limbic network in mediating the association between cortical Aβ in six functional networks and annual tau elevation in the limbic network.

Results

Figure 1 illustrates that among the four groups in both datasets, aAβ/nTau subjects displayed the highest assortativity values (0.767 for NOMEM and 0.627 for BHII). In both datasets, aAβ/nTau showed significant increases (t‐value > 4.49, p‐value < 0.0001) in between‐network connectivity of the limbic network (Figure 2) compared with the other three groups. 14 Aβ‐positive subjects achieved highly significant results (p‐value < 0.013) for indirect relationships in all six functional networks (Figure 3).

Conclusion

Our study highlights the early accumulation of Aβ and its role in increasing between‐network connectivity. We also demonstrated that between‐network connectivity mediates the remote relationships between Aβ and tau pathologies in the preclinical stages of AD.
Holistic dementia care continuum from the point of diagnosis to the end of life: Progress and challenges in translating national dementia policies into daily practice in Japan
Authors: Nakanishi Miharu , Ogawa Asao , Nishida Atsushi
Published: January 2025

Background

The WHO’s Global Dementia Action Plan comprises seven action areas, including dementia diagnosis, treatment, care, and support. Palliative care is called for as a core component of the care continuum from the diagnosis to the end of life. Japan has pursued a holistic care approach in dementia policies. However, from our review, we found that palliative care components are not fully represented. We aim to present how Japanese policies have been translated into practice and highlight challenges that remain to be addressed.

Method

We performed empirical research derived from real‐world data to examine the potential gaps between policies and daily practice in Japan. We focused on four topics: advance care planning, neuropsychiatric symptoms, physical restraint in acute care, and end‐of‐life care.

Result

Engagement of advance care planning was typically triggered by a clinical dementia diagnosis, and the doctor providing the diagnosis was not often involved in the conversation with the patient. We developed a psychosocial intervention program (DEMBASE®) to reduce neuropsychiatric symptoms in collaboration with a Swedish BPSD‐registry team, for which effectiveness was verified. Physical restraint of inpatients was prevalent even in units with a dementia care benefit. The onset of the COVID‐19 pandemic triggered the shift to hospital deaths, which were uniquely observed in deaths from dementia.

Conclusion

Japanese dementia policies promote “aging in place,” which is now a mainstream strategy globally. However, dementia care remains suboptimal. Baseline palliative care should be integrated into dementia diagnoses, treatment, care, and support.
Advancing Early Detection of Alzheimer’s Disease in the Primary Care Setting in the United States
Authors: Mielke Michelle M. , Kurzman H. Ricky , Hu Yan Helen , Cho Min , Liss Jonathan , Burns Jeffrey M , Obisesan Thomas O , Hornbecker Michael , Pallay Arnold , Smith Steven R. , Honig Lawrence S. , Parker Monica W , Bell Joanne , Hampel Harald
Published: January 2025

Background

Recent advances in diagnostics have made it possible to identify early signs of the pathophysiological changes underlying Alzheimer’s Disease (AD) via blood tests. However, the use of blood‐based biomarkers (BBBMs) for the early detection of AD may be limited in primary care settings despite its potential for wide access and early detection of AD (PMID: 37295421). Therefore, there is a need to understand the barriers and facilitators of BBBM testing for AD in primary care.

Method

We employed a combination of qualitative research, advisory board, and quantitative survey to engage with clinical/scientific advisors and community‐based physicians in primary care. In‐depth interviews with primary care physicians (PCPs) (n = 23) were conducted to understand the current awareness and clinical practice of AD identification in the primary care setting, followed by an advisory board to establish hypotheses about the barriers and opportunities of BBBM testing in the primary care setting. We subsequently conducted a quantitative survey with US PCPs (n = 600) to understand their attitudes and beliefs on screening and diagnosing AD in their practice, including opinions and willingness to use BBBM as part of the evaluation of individuals with mild cognitive impairment (MCI) or mild dementia.

Results

Preliminary findings revealed that the majority of PCPs believe that MCI/mild AD is underdiagnosed and BBBM will likely facilitate better and faster diagnosis. Identified obstacles encompass inadequate financial coverage for BBBM testing, limited awareness among PCPs regarding the tests’ availability and value, limited awareness about monoclonal antibody (mAb) treatment for early‐stage AD, and lack of understanding of where and how to incorporate BBBM testing into primary care. Suggested solutions included education to equip PCPs with necessary knowledge on BBBM testing, clear guidelines on incorporating BBBMs simultaneously with clinical and cognitive assessments, and adequate financial coverage for both BBBMs and mAb treatments. Final survey results will be presented at the AAIC.

Conclusion

The findings suggest that PCPs recognize the substantial value of BBBMs in detecting early AD, and that there is an urgent need for a concerted effort to improve awareness and address the barriers to adopting BBBMs in primary care.
Low Food Security is Related with More Memory Complaints in a Clinic‐Based Sample of Latino Adults
Authors: Saenz Joseph , Tanner Laura
Published: January 2025

Background

Low food security has been linked with both diminished objective cognitive outcomes and lower subjective assessments of cognition in studies across the globe. Subjective memory complaints may be an important indicator of memory problems experienced in one’s daily life. However, few studies have explored links between low food security and subjective memory in Latinos, despite the higher prevalence of food insecurity in the Latino population. The aim of this study is to investigate potential links between low food security and subjective memory complaints in a sample of Latinos.

Method

We used the Sangre Por Salud (SPS) data, a sample of Latino adults from a federally qualified community health center in Phoenix, Arizona who enrolled between 2013 and 2018. Individuals age 45+ (n = 1,041) are included in our analytic sample. Food security was assessed using the Household Food Security scale and memory complaints were measured using the Frequency of Forgetting scale. Potential links between low food security and subjective memory complaints were tested using linear regression controlling for demographic factors (age, gender, education, nativity), self‐rated health, and perceived social support.

Result

Preliminary results indicated that 75% of the sample were highly/marginally food secure, 18% had low food security, and 7% had very low food security. Food security was more common in the US born and among those with higher social support. In multivariate analyses, compared to the highly/marginally food secure, low food security related with 0.26 standard deviations higher memory complaint (p<0.01) whereas very low food security related with 0.28 standard deviations higher memory complaint (p<0.05).

Conclusion

Findings suggest an association between experiences of low food security and higher subjective memory complaints in Latinos. Subjective memory complaints are related with future cognitive impairment and dementia. Future studies should evaluate the potential cognitive benefits of interventions targeting food insecurity.
Identification of Chemical Tool Compounds to Investigate the Role of Lyn Kinase in TREM2‐Mediated Microglia Activation and Phagocytosis
Authors: Weerawarna Pathum M , Robo Michael T , Chu Shaoyou , Mason Emily R , Davis Chris , Angus Steven P , Richardson Timothy I.
Published: January 2025

Background

Lyn kinase, a member of the Src family of tyrosine kinases, predominantly phosphorylates ITIM and ITAM motifs linked to immune receptors and adaptor proteins, and is emerging as a target for Alzheimer’s disease (AD). The role of Lyn in TREM2‐mediated microglial activation and phagocytosis, a critical pathway for clearing Aβ plaques, remains unclear and potent, selective, and brain penetrant Lyn inhibitors are unavailable. In this study, we report the characterization of Lyn kinase inhibitors from the literature as well as the establishment of an advanced virtual screening platform at the IUSM‐Purdue‐TREAT‐AD center to identify new type II Lyn inhibitors suitable as molecular probes.

Method

We first performed a thorough literature survey and found 14 reported Lyn kinase inhibitors. We then validated their Lyn inhibitor activities and Lyn selectivities using the HotSpot kinase assay. We tested these compounds for microglia activation in a high‐content imaging assay using HMC3 (human) and BV2 (mouse) microglia‐like cell lines. We also performed kinome profiling in these cells to evaluate cellular target engagement and selectivity. Finally, we screened a million‐compounds using a computational pipeline that combined molecular docking, shape‐based screening, and MD simulations to identify novel and potent type II Lyn kinase inhibitors.

Result

Our findings revealed that Type I inhibitors, particularly Saracatinib and Bosutinib, potently inhibit Lyn within the picomolar (pM) range. On the other hand, Type II inhibitors, such as Masitinib and Imatinib, displayed pronounced >20‐fold selectivity for Lyn over Hck with low nM Lyn inhibitor activities. Saracatinib and Bosutinib significantly induced phagocytosis in HMC3 cells, whereas Type II inhibitors demonstrated moderate activity in both HMC3 and BV2 cells. Our virtual screening platform identified a new type II Lyn inhibitor with picomolar activity and good Lyn/Hck selectivity.

Conclusion

We have successfully evaluated previously reported inhibitors and introduced a novel type II Lyn kinase inhibitor with picomolar (pM) activities suitable for use as chemical probes to investigate the role of Lyn in TREM2‐mediated microglial activation.
LATE‐LIFE EDUCATION IMPROVES ADULT EXECUTIVE FUNCTION: THE PROAME TRIAL
Authors: Friedlaender Clarisse Vasconcelos , de Faria Rocha João Victor , dos Santos Tomaz Kelle Luisa , Ruppert Emma Patrice , Lourandes Aida , Zacarias Ana Paula , de Castro Magalhães Assenção Joanna , Rincon Luciana Paula , Ribeiro Norton Gray Ferreira , Rosen Howard J. , Grinberg Lea T. , Maciel Francisca Izabel Pereira , Caramelli Paulo , de Paula França Resende Elisa
Published: January 2025

Background

Education is a recognized modifiable dementia risk factor. To boost cognitive reserve and reduce dementia risk in Brazil’s vulnerable populations, we conceived a literacy program (PROAME trial) targeting low‐educated adults, aiming to explore how executive function and individual differences influence program effectiveness.

Method

We screened 130 adults, with 108 meeting enrollment criteria. They were allocated in control (CG, n = 51) and intervention (IG, n = 57) groups, according to residence area. Subjects underwent a comprehensive neuropsychological assessment at baseline and after six months, covering global cognition, executive function, memory, and language.

Result

We excluded 28 participants for incomplete post‐intervention assessments. 77 completed all procedures, with 62 (CG = 26; IG = 36) finishing all executive function tasks. Mean age = 59.16 years (±9.22), mean education = 2.21 years (±2.20), with 62.3% mixed‐race, 29.5% Black, and 75.8% female. Mini‐Mental State Examination mean score = 22.08 (±2.74). We created an executive function composite score (EFCS) including phonemic verbal fluency, reverse digit span, and rapid naming. Comparing EFCS pre‐ and post‐ intervention using a linear regression, participants (in both groups) with higher baseline EFCS showed less post‐intervention improvement (ANCOVA; F = 6.233; p<0.001). IG displayed significant EFCS enhancement compared to CG (p = 0.003). Considering possible adult illiteracy causes, participants who reported learning difficulties exhibited the lowest EFCS at baseline, compared to rural residence, lack of family support, and childhood labor groups.

Conclusion

The literacy program positively impacted executive function. IG exhibited significant EFCS improvement after six months, demonstrating late formal education acquisition as an effective cognition‐enhancing strategy. Notably, those with lower initial executive function levels experienced greater improvements, suggesting enhanced benefits for those initially lacking executive skills. However, the learning difficulties group derived lesser benefits from the intervention, highlighting the importance of considering individual differences. Childhood learning difficulties may hint at undiagnosed developmental disorders, influencing cognitive reserve development early on. Recognizing the pivotal role of executive function in enhancing cognitive reserve, promoting this domain through literacy‐focused interventions can be a valuable tool in preventing cognitive decline and dementia.
LatAm‐FINGERS: Navigating Diversity in the Engagement of a Subcontinental Trial for Dementia Prevention
Authors: Calandri Ismael Luis , Crivelli Lucia , Caramelli Paulo , Lopera Francisco , Nitrini Ricardo , Sosa Ana Luisa , Vellila Lina Marcela , Salinas‐Contreras Rosa Maria , Suemoto Claudia Kimie , Yassuda Monica Sanches , Sevlever Gustavo , Acosta Daisy M , Charamelo Ana , Cusicanqui María Isabel , Custodio Nilton , Delgado Carolina , Duque Lissette , Velazquez Ivonne Z. Jimenez , Leon‐Salas Jorge M , Snyder Heather M , Carrillo Maria C. , Kivipelto Miia , Allegri Ricardo ,   LatAm‐FINGERS Consortium
Published: January 2025

Background

LatAm‐FINGERS is the first non‐pharmacological multicenter randomized clinical trial aimed at preventing cognitive impairment in Latin America. It encompasses twelve countries that collectively represent 45% of the territory in the Americas. Its objective is to reach populations that, despite sharing commonalities such as language, are culturally and economically diverse. Above all, these populations have different perspectives on goals related to healthy aging, access to healthcare, and participation in clinical trials. The challenge is twofold: on one hand, achieving commitment across all centers to ensure recruitment and adherence; on the other hand, utilizing these strategies to instill awareness in society about the scourge of dementia and the possibility of its prevention.

Methods

Our aim is to describe the recruitment strategies and their effectiveness in the design and implementation of the initial phases of the trial. The most relevant strategies included: a) decentralized design, where the 12 site principal investigators collaborated across all phases of the trial design rather than merely implementing it. They were asked to present solutions and barriers based on the idiosyncrasies of their target population and share them with the rest. b) assess cultural beliefs about clinical trials, c) disseminate information about dementia prevention strategies, d) collaborate with community partners in outreach and recruitment.

Results

The most utilized strategies included 1) assess population with cognitive complaints or concern for prevention (for centers with clinical setting) and 2) community dissemination for universities and research centers. A total of 1,877 candidates were evaluated, of which 1,232 were included. Pre‐screening strategies were implemented to reduce staff burden at most centers.

Conclusions

Our results demonstrate that, despite the diversity present in Latin America, it is possible to conduct a unified trial with successful recruitment. Carefully designed strategies that respect local culture, coupled with knowledge of local stakeholders, hold the key to success. Moreover, it highlights that a clinical trial, in addition to being a tool to test treatment effectiveness, can serve as a catalyst for awareness campaigns.
Challenges engaging patients with dementia and their care partners in hearing rehabilitation research
Authors: de Resende Luciana Macedo , Machado Mariane Gomes , Machado Thaís Helena , Ferreira Michele Gomes , Thuller Douglas , Caramelli Paulo
Published: January 2025

Background

Hearing rehabilitation has been a promising approach to improve cognitive outcomes. An ongoing study identified some barriers to engage patients in counseling sessions and using their hearing devices. Here we present the results from the first stage of a Sense‐Cog Brazil pilot study, the recruitment phase.

Method

Observational pilot study with 184 patients with dementia assisted in a Neurocognitive Outpatient Clinic from the University Hospital (Hospital das Clínicas/ Universidade Federal de Minas Gerais, Belo Horizonte, Brazil). Procedures in the two‐step recruitment phase were, first performing an audiometric screening, and second a thorough neurocognitive testing and complete audiological assessment. Inclusion criteria were as follows: bilateral sensorineural hearing loss, diagnosis of dementia, availability for patient and communicative partner to participate in hearing rehabilitation and counseling groups. Patients with dementia with Lewy bodies, aphasia or frontotemporal dementia were excluded from the pilot. Descriptive analysis was performed.

Result

From the initial 184 patients, 20 (10.9%) were not able to perform hearing screening due to difficulties with audiometric tasks or obstruction of the external ear canal. A total of 164 (89.1%) patients were able to finalize audiometric screening and 69 (42.7%) were referred to bilateral hearing aids fitting. However only 54 (32.9%) were able to perform cognitive tests. From these 54 patients included in the pilot, 10 (18.5%) refused to take part in the study. Main reasons were: caregivers not believing in hearing rehabilitation benefits, not having time to participate, and not acknowledging hearing results. Also, some difficulties in performing the hearing assessment, a test which requires an experienced audiologist, the patient’s cooperation and comprehension of the task.

Conclusion

The patients’ loss in the recruiting and selecting process was mainly due to the lack of perception of the possible benefits of hearing rehabilitation, especially from the caregivers' perspective. This is an important issue to be addressed in the continuation of the study. An additional challenge was having a trained team to assess dementia patient’s hearing. Furthermore, special care should be taken when assessing cognition with dementia patients with hearing loss.
Telerehabilitation Interventions in the management of Alzheimer’s disease: An Implication for rehabilitation care in Sub‐Saharan Africa
Authors: Akinwola Mary , Oladosu Monsurat , Oladimeji Olawale O , Okafor Joshua , Fredrick Isaac , Okoro Winnifred Omono , Adekolurejo Tobi
Published: January 2025

Background

Alzheimer’s disease is estimated to reach 139 million people by 2050, with an increase in people living with functional limitations caused by the disease (Alzheimer’s Disease International). However, telerehabilitation presents a promising solution to improve functional outcomes in patients with Alzheimer’s disease. This systematic review investigates the use of telerehabilitation therapies worldwide for the treatment of Alzheimer’s disease and cognitive impairments. This study is the first to provide telerehabilitation insights for managing Alzheimer’s disease in Sub‐Saharan African under‐developed countries.

Method

This systematic review examined telerehabilitation, Alzheimer’s, and cognitive impairment in published studies. Keywords were used to search PubMed, Embase, Cochrane Library, PEDro, Science Direct, SpringerLink, and IEEE Xplore. The search was limited to 2018 studies, not areas. For two screening steps, four reviewers extracted the studies into an Excel spreadsheet. RCT bias was examined using the CASP Randomised Controlled Trial Standard Checklist. The Consolidated Framework for Implementation study identified barriers, successes, and recommendations. Finally, two reviewers used narrative synthesis to identify data themes.

Result

Nine published studies were from high‐income countries. In the case of telerehabilitation intervention, video conferencing was found to be the most common (66%). There were a total of 5 RCT studies and all reported improved cognitive and physical functioning outcomes similar to the control groups. The feasibility studies showed that telerehabilitation patients adhered to treatment. Internet accessibility was a key impediment for rural areas receiving home‐based therapies. Direct supervision, individualized exercise prescriptions, and group exercise treatment facilitate remote telerehabilitation.

Conclusion

The use of telerehabilitation improves cognitive and physical results in Alzheimer’s disease and cognitive impairment patients. This study only covered high‐income nations, but it offers insights for developing sub‐Saharan African countries to improve Alzheimer’s disease management via telerehabilitation. This comprehensive study can help Sub‐Saharan African healthcare practitioners establish telerehabilitation programmes for Alzheimer’s disease and cognitive impairment patients to enhance their functional results.
Does virtual reality increase the emotional well‐being benefits of online psychoeducation? Preliminary results in informal caregivers of people with Alzheimer’s disease
Authors: Festari Cristina , Solorzano Claudio Singh , Gattuso Maria , Bonomini Cristina , Rosini Sandra , Ferrari Clarissa , Zanetti Orazio , Pievani Michela , Morganti Francesca
Published: January 2025

Background

Increasing findings have proven that virtual reality (VR) is a promising approach for improving knowledge, self‐efficacy, and empathy in educational programs (Dhar, DigitHealth. 2023). The purpose of an ongoing randomised clinical trial is to enhance mental wellbeing of dementia patients' informal caregivers (iCGs) by including a VR‐based empathy training into an online psychoeducation program.

Method

60 iCGs of mild‐to‐moderate patients with Alzheimer’s disease were randomized in an online 6‐week psychoeducational program (control arm) or in the same psychoeducational program integrated with VR (experimental arm). VR consisted of 360‐degree videos and allows caregivers to experience dementia symptoms from the patient’s perspective. Before and after the intervention, iCGs completed validate scales to assess burden (ZBI), perceived stress (PSS), anxiety (STAI‐Y1&2) and perceived self‐efficacy for caregiving tasks (RSCSE). Pre‐post differences were tested with paired t‐tests.

Result

27 iCGs assigned to the control arm (mean age = 56; female: 82%; children: 63%) and 29 to experimental arm (mean age = 54; female: 79%; children: 68%) concluded the intervention. At baseline, iCGs show similar level of burden (ZBI: t(54) = ‐0.793, p = 0.431), stress (PPS: t(54) = ‐0.483, p = 0.631), anxiety (STAI‐Y1: t(54) = ‐0.197, p = 0.845; STAI‐Y2; t(54) = 0.363, p = 0.718). The VR‐based intervention decreased levels of burden (ZBI: t(28) = 2.154; p = 0.040; Cohen’s d = 0.400), stress (PPS: t(28) = 2.177, p = 0.038; Cohen’s d = 0.404), state anxiety (STAI‐Y1 = t(18) = 2.400, p = 0.23, Cohen’s d = 0.446) and increase two domains of caregiving self‐efficacy: responding to disruptive patient behaviors (RSCSE‐RDB: t(28) = ‐2.358, p = 0.026; Cohen’s d = 0.438), and controlling upsetting thoughts (RSCSE‐CUT: t(28) = ‐2.126, p = 0.042; Cohen’s d = 0.395). In the control arm, changes due to intervention did not reach statistical significance.

Conclusion

These preliminary results support the feasibility and effectiveness of psychoeducation program integrated with VR in improving perceived self‐efficacy in managing an AD patient and decreasing distress in iCGs. These results should be confirmed in larger samples.
Assessing Cognitive Risk Factors in a Young Population: Findings from a Cognitive Neurology Service of Argentina
Authors: Berrios Waleska , Perez Agustin , Basalo Maria Jose Garcia , Segui Milagros , Deppleler Solange , Basalo Maria Mercedes Garcia , Turner Flavia , Majul Mariana , León Betsabe , Melnitzky Agustina , Chinen Laura , Quintana Marcos Ojea , Golimstok Angel , Giordano Ximena , Fernandez Maria Cecilia
Published: January 2025

Background

It is common for individuals under the age of 65 to consult neurologists for cognitive complaints ranging from subjective cognitive issues to mood disorders that affect cognitive function. The challenge is rule out attention deficit hyperactivity disorders, other psychiatric causes, and cognitive impairment.

In 2020, the Lancet Commission released a report analyzing 12 modifiable risk factors (MRFs) by age group. A recent study found that 6 of these factors, among others, were associated with the risk of Young‐Onset dementia: lower formal education, alcohol use disorder, social isolation, hearing impairment, diabetes, and depression.

This study aimed to identify cognitive risk factors in a young population with cognitive complaints.

Method

Retrospective and descriptive study based on a neuropsychological evaluation database that focused on individuals aged between 40 and 60 who were assessed for cognitive complaints from July 2017 to July 2022. We collected demographic data, family history of neuropsychiatric disorders, 12 MRFs per the Lancet Commission, neuropsychological patterns, and diagnosis.

Result

A total of 307 neuropsychological evaluations were analyzed, of which 63% were females. The diagnoses were categorized as mild neurocognitive disorder (MND) in 45% of cases, deficit in 32%, normal cognitive performance in 21%, and major neurocognitive disorder in 2%. The most frequent neuropsychological pattern was non‐amnestic MND, observed in 115 (37.5%) cases. In 125 (40.7%) cases, family history was reported; in 186 (63%) cases, depressive symptoms were observed according to the Beck Depression Inventory‐II, while physical inactivity was reported in 160 (68%) of cases, hypertension in 107 (35%) of cases, obesity in 83 (27%) of cases, and 59 (21%) of cases reported living alone. Notably, physical inactivity was associated with cognitive impairment (p 0.04), indicating that patients with physical inactivity are 2.2 times more likely to experience cognitive impairment compared to non‐sedentary patients.

Conclusion

A notable number of individuals displayed a family history of cognitive impairment, as well as symptoms of depression and MRFs including hypertension and physical inactivity. Only physical inactivity was found to be a contributing factor to cognitive impairment, highlighting the significance of addressing lifestyle factors in maintaining cognitive health.
Access to primary care psychological therapy services for people living with dementia
Authors: Baou Celine El , Saunders Rob , Buckman Joshua , Richards Marcus , Bell Georgia , Fearn Caroline , Cooper Claudia , Pilling Stephen , Crutch Sebastian J , Zimmermann Nikki , Brotherhood Emilie V , John Amber , Stott Joshua
Published: January 2025

Background

Psychological therapies are recommended for people living with dementia who experience depression or anxiety. However, people living with dementia often experience specific barriers to accessing services providing such interventions, notably due to the stigma associated with dementia. This study sought to understand pathways to entering and receiving treatment after referral to primary care psychological therapy services for people living with, versus without dementia.

Method

Linked national data from England from over 4 million individuals referred to NHS Talking Therapies for anxiety and depression (NHS TTad) services were used to identify 6623 people living with dementia referred to these services between 2012 19. We compared rates of access and entry into treatment between people living with dementia and a propensity score matched cohort of people without a diagnosis of dementia, adjusting for a range of socio‐demographic (age, gender, ethnicity) and therapy factors (e.g waiting times).

Result

We found that once people living with dementia were referred to NHS TTad, they were less likely to access services (ie actually receive an assessment) [AdjOR = 0.61 (0.56; 0.67) p<.0001]. Once assessed, they were also less likely to receive treatment [AdjOR = 0.68 (0.62;0.75, p<.0001] than people with no diagnosis of dementia. Services were twice as likely to be deemed “not suitable” (based on discharge codes recorded by clinicians) for people living with dementia [AdjRRR = 1.97 (1.68; 2.30) p<.0001]. were similar between typical (e.g., memory‐led Alzheimer’s disease) dementias, and atypical dementias (e.g. frontotemporal dementia).

Conclusion

This study highlights inequalities in access to psychological therapies for people living with dementia. There is a need to make services more accessible to improve the rate of treatment initiation for people living with dementia that are referred and assessed for psychological therapies.
Healthy Aging Through the Senior Years (HATS) Study: A longitudinal cohort study of brain health and dementia among Black older adults in the United States
Authors: Sheets Kerry M. , Knopman David S. , Petersen Ronald C. , Vemuri Prashanthi , Jones Clarence , Murray Anne
Published: January 2025

Background

The higher prevalence and incidence of later life dementia among older Black Americans compared to older White Americans is incompletely understood and understudied. HATS is designed as a companion to the Mayo Clinic Study of Aging (MCSA) with a focus on identification of modifiable cardiovascular contributions to brain health among Black older adults living in urban areas in the upper Midwest.

Method

HATS is enrolling 300 U.S. Black Minnesotans from the Twin Cities area aged 55 to 90 years without advanced dementia. Enrollment started 4/2023 and is expected to be complete by the end of 2025. Recruitment is primarily community‐based, led by two community engagement partners, the Linc and the Hue‐MAN Partnership. Electronic health record‐based recruitment will begin in 2024. Data collection includes medical comorbidities, structural and social determinants of health, cardiovascular health, functional status, physical performance, specific and non‐specific blood‐based biomarkers of Alzheimer’s disease, and comprehensive assessment of cognitive and neuropsychiatric status. Brain MRIs will be obtained on a subset of participants. A core component of HATS is distribution of meaningful health information back to participants and their community, guided by input from the HATS community engagement partners. The HATS cohort will serve as an initial effort to develop age and education adjusted normative cognitive test data for urban Black older adults in the upper Midwest.

Result

As of January 22 2024, HATS has enrolled 40 participants with a mean age of 70 years (range 51‐90) and mean education of 15 years. Mean informant‐reported Everyday Cognition scale‐12 score is 1.1 (range 1‐1.7), mean Short Test of Mental Status (STMS) score is 31 (range 24‐37), and CDR sum of boxes scores range from 0‐4 consistent with enrollment of participants with normal and mildly impaired cognition.

Conclusion

HATS is a novel longitudinal cohort study that is well‐positioned to advance understanding of risk factors for dementia among Black Americans living in urban areas in the upper Midwest. Recruitment is ongoing with a focus on enrolling older adults with a wide range of cognitive function. Ongoing community engagement is a central feature of HATS.