bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge and barriers to implementing dementia risk reduction among older people and health professionals in community daycare centers
Authors: Aravena Jose M , Torres Waldo , Gallardo Javiera , Sobarzo Fernanda , Saavedra Gillian , Briceño Rocio , Miranda Camilo , Levy Becca R
Published: January 2025

Background

Assessing knowledge of dementia prevention from both the individual (patients) and the structural level (health professionals) in the same settings is vital to implementing dementia risk reduction programs. However, most studies have only focused on one level. Thus, this was the aim of our study.

Method

A qualitative study was conducted with two populations: patients aged 60 and older with no dementia and health professionals, attending and working at community daycare centers for older adults in Chile, respectively. People from 10 different daycare centers were invited to participate in two separate focus groups per center (patients: 5‐15 participants; health professionals: 3‐7 participants). Focus groups included the topics of cognitive changes of aging and dementia, dementia risk factors, and barriers to brain health. Thematic analysis following grounded theory and inductive analysis was performed to generate main themes.

Result

In 19 focus groups, 115 patients and 51 health professionals participated. In the main results, older adults frequently mentioned memory problems as a ‘normal part of aging’ and Alzheimer’s disease as ‘the severe stage of dementia.’ Health professionals recognize signs and symptoms of dementia. Both groups agreed that uncertainty about memory loss and Alzheimer’s disease can generate anxiety and isolation in older people. Patients showed more agreement on dementia risk factors than health professionals and were able to mention risk factors not mentioned by health professionals (e.g., TBI, air quality, neighborhood factors). Patients from high‐income municipalities were more prone to attribute Alzheimer’s disease to genetic factors than patients from other municipalities, but health professionals showed no differences. Interestingly, patients used popular figures in media with a diagnosis of dementia (e.g., Ronald Reagan) as examples of why ‘Alzheimer’s disease can’t be prevented.’ Structural barriers to brain health were similar between groups (negative experiences with healthcare and ageism). Patients referred to intergenerational contact and health professionals increasing awareness among patients' families as opportunities for brain health.

Conclusion

Health professionals highlighted the need for updates and homogenization regarding dementia risk reduction. Patients’ knowledge may be influenced by social determinants and portraits of aging and brain health. Addressing structural factors could benefit dementia prevention in both groups.
Improper modification and cleavage leads to irregular aggregation of TDP‐43 in Neurons
Authors: Xavier Joyal , Singh Meenakshi , Tamhankar Sampada P , Amin Raj
Published: January 2025

Background

TAR‐DNA‐binding protein 43 (TDP43), is a pathologic marker in neurodegenerative diseases including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. The aggregation of TDP‐43, a crucial RNA‐binding protein, is a consequence of post‐translational modifications (PTMs) that disrupt its normal function. PTMs such as phosphorylation and ubiquitination contribute to the aberrant accumulation of TDP‐43 aggregates, leading to neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). This pathological process disrupts RNA metabolism and cellular homeostasis. The current study focuses on better understanding the mechanisms associated with TDP‐43 PTMs and aggregation. Findings from these studies are essential for developing targeted therapeutic strategies to mitigate neurodegenerative diseases associated with TDP‐43 pathology.

Method

Overexpressing TDP‐43 in Ht22 hippocampal cells was accomplished by Lentiviral technology. TDP‐43 GFP over‐expressing stable cell lines were exposed to either an acidic environment (pH 6) or a neutral environment (pH 7.4) or sodium arsenate. Mitochondria, nuclei, and cytosolic fractions were isolated, and proteins were resolved by Western analysis to measure levels of TDP43. Asparaginyl endopeptidase (AEP) inhibitor (Compound 11), was used to determine its effect on aggregation of TDP43. The Aggregation assay kit was used to measure the levels of TDP‐43 aggregation. Physiological assays were used to measure the consequence of TD43 aggregation in the mitochondria (Seahorse, mitochondrial respiration) and nuclei (transcriptome analysis).

Result

We have observed the localization of AEP in the mitochondria under normal physiological pH conditions as well as total and cleaved TDP43. However, under acidic conditions and following sodium arsenate exposure, we observed an increase in pTDP43 levels as well as full‐length TDP43 in the mitochondria and nucleus when compared to normal media. Alternatively, we observed a decrease in pTDP43 in the mitochondria and nucleus following compound 11 treatment in the acidic media or sodium arsenate.

Conclusion

We observed an increase in pTDP43 in cells exposed to an acidic environment. We believe this leads to aggregation levels and helps explain the consequences of cleaved TDP43 on cellular energy regulation and cell viability. Consequently, compound 11 reduces the levels of TDP43 aggregation patterns in the mitochondria and nuclei.
Development of a multi‐faceted intervention for hearing/vision support for residents with dementia in long term care'
Authors: Leroi Iracema
Published: January 2025

Context

The development of new effective and sustainable dementia care interventions requires active engagement of all service users in research studies. This ensures that interventions are tailored to meet individual needs and preferences. Here, we describe modelling and development of a multi‐faceted sensory health support intervention for residents with dementia in long‐term care, co‐designed with dementia care users and their supporters. There is a high rate of unrecognised hearing and vision loss in people with dementia, particularly in long term care (LTC) settings, which can hasten cognitive and functional decline, contribute to neuropsychiatric challenges, and increase the impact on health resource utilization.

Methods

We undertook a multistage process with key user stakeholders, interdisciplinary health experts, LTC professionals, and Patient and Public Involvement (PPI) representatives, following the UK’s Medical Research Council’s framework for the development of complex interventions.

In the first stage, we crafted an outline of the intervention by extending a previously evaluated home‐based sensory support intervention and incorporating evidence from a systematic survey of hearing rehabilitation interventions. The ‘Sensory‐Cognitive Model of Place’ served as the theoretical framework.

In the second stage, qualitative feedback from professional and PPI stakeholders, along with insights into existing care sensory health training approaches, were integrated to form a multi‐component sensory support intervention ready for field testing.

The third stage involved pilot‐feasibility trialing in a single LTC facility, with subsequent design modifications based on feedback.

The resulting Sensory Support Intervention for Residents with Dementia in Care (SSI‐RC) comprises four tiered components addressing (1) resident, (2) staff, (3) environmental, and (4) organizational levels. These include personalized sensory health status checks, staff awareness training, sensory environment audits, and organizational pathway assessments.

Conclusion

With the guidance of service users, we successfully developed and field tested the SSI‐RC, highlighting its potential for implementation in a cluster‐randomized pilot trial in LTC facilities. The collaborative approach with dementia care users and supporters ensures the intervention’s relevance and effectiveness in enhancing sensory‐cognitive health for residents with dementia. The research contributes to the broader goal of tailoring dementia care interventions to individual needs and preferences.
Boost Your Brain Health: Methods and Baseline Characteristics for a Randomized, Controlled Trial of an Online Study to Reduce Dementia Risk Factors
Authors: Turo Patricia , Benjamin Cynthia , Brodaty Henry , Sudore Rebecca L , Chesney Margaret A , Chao Linda L , Barnes Deborah E
Published: January 2025

Background

Nearly 1 in 3 older adults are living with mild cognitive impairment (MCI) or subjective cognitive decline (SCD), which places them at increased risk of developing Alzheimer’s disease or related dementias (ADRD). Behavioral interventions can improve cognitive function and reduce dementia risk factors, but most are in‐person and time‐intensive. We are conducting a randomized, controlled trial to assess the impact of 12‐ and 24‐week online interventions on cognitive function and dementia risk.

Method

Study participants are English‐speaking adults aged 55 years or older living in the U.S. who self‐report MCI or SCD, have 2 or more modifiable ADRD risk factors, and have an electronic device with video camera to participate in online classes. Participants are randomized to Brain Health Academy (asynchronous expert videos, 30 hours over 12 weeks), Brain Health Together (synchronous group Brain Health Education and Moving Together classes + individual brain health coaching, 30 hours over 12 weeks), or Brain Health Together Plus (Brain Health Together plus an additional 12 weeks of group classes and individual brain health coaching, 45 hours over 24 weeks). We used descriptive statistics to summarize self‐reported demographics and motivators and barriers to participation.

Result

Of 397 individuals who have completed screening, 40% were ineligible, 25% declined, and 35% enrolled and have been randomized to date. Enrolled participants have a mean (SD) age of 70 (8) years and 3 (1) modifiable risk factors; 75% are female, 24% are non‐White or Hispanic, and 23 states from across the US are represented. The greatest motivators to study participation are wanting to keep one’s brain as healthy as possible (89%) and being worried about changes to memory or thinking (81%). Time commitment was perceived as the greatest barrier (30%). Most participants indicated they were already making changes to improve brain health.

Conclusion

Many older adults with MCI/SCD and modifiable risk factors for ADRD are interested in participating in online brain health programs and are highly motivated to make lifestyle changes to keep their brains healthy. We anticipate that enrollment will be completed by May 2024.
Activation of the glutamate transport in astrocytes via GLT‐1 reshapes the glutamatergic brain network
Authors: Martins Gabriel Colissi , Limberger Christian , Peixoto Guilherme G. Schu , Aliaga Antonio , Aliaga Arturo Aliaga , Rosa‐Neto Pedro , Zimmer Eduardo R.
Published: January 2025

Background

Glutamate is the main excitatory neurotransmitter in the brain, acting through ionotropic and metabotropic receptors, such as the neuronal metabotropic glutamate receptor 5 (mGluR5). The radiotracer [11C]ABP688 binds allosterically to the mGluR5, providing a valuable tool to understand glutamatergic function. We have previously shown that neuronal [11C]ABP688 binding is influenced by astrocyte activation. Specifically, the activation of glutamate transport in astrocytes via glutamate‐transporter‐1 (GLT‐1) results in an elevated [11C]ABP688 binding within the ventral anterior thalamus, but no changes in other regions. However, whether changes at the network level occur remains elusive. We evaluated Glutamatergic Brain Networks (GBNs) before and after activating astrocytes.

Method

Micro‐PET acquisitions were performed in adult Sprague‐Dawley rats (n = 5) at baseline and after a pharmacological challenge to activate astrocytes. Before the scan, rats received either saline (vehicle) or ceftriaxone (CEF, 200mg/kg), an antibiotic that induces GLT‐1 activation. Then, [11C]ABP688 was administered i.v., followed by a 60‐minute dynamic scan. The nondisplaceable binding potential (BPND) was estimated using the simplified reference tissue model, with the cerebellum as a reference region. [11C]ABP688 BPND was extracted for 12 volumes of interest. GBNs based on [11C]ABP688 regional BPND were assembled with a multiple sampling scheme in MATLAB (p‐value < 0.05).

Result

Astrocyte activation induced GBN hyperconnectivity after astrocyte activation, with the strength of association between the cerebral hemispheres, such as in the frontal and parietal cortices (Figure 1, A‐B). After GLT‐1 activation, the connections were diffused, including regions that were not part of the network at baseline, such as the cerebellum. Graph measures show a significant increase in global efficiency, average degree, density, and average clustering coefficient (Figure 1, C‐G). These measures indicate an increase in connections and network cohesiveness. The reduction in assortativity can be related to the new regions on the GBN after the challenge.

Conclusion

Our results show that GBNs assessed with [11C]ABP688 are sensitive to astrocyte activation. Alterations in glutamate levels, as observed in dysfunctions like glutamatergic excitotoxicity present in AD, could disrupt the cohesion of the glutamatergic network, leading to brain dysfunction.
Modifier Effects of APOE E2 and E4 Alleles on the age at onset of Alzheimer Disease in Puerto Rican G206A Mutation Carriers: A Family‐Based Study
Authors: Kannappan Balaji , Cheng Rong , Nguyen Tu , Jimenez‐Velazquez Ivonne Z. , Piriz Angel , Maldonado Aleyda , Vardarajan Badri N. , Reyes‐Dumeyer Dolly , Lantigua Rafael A. , Jin Zhezhen , Mayeux Richard , Lee Joseph H.
Published: January 2025

Background

APOE E4 (APOE4 henceforth) is recognized as a major genetic risk factor for late‐onset Alzheimer's disease (AD), with its impact varying across ethnic subgroups. We investigate the risk of APOE4 and the protective effect of APOE E2 (APOE2 henceforth) in individuals carrying the high‐risk G206A mutation in the PSEN1 gene (G206A henceforth), known to cause early‐onset AD. Despite the G206A mutation's strong association with AD, there is noticeable variability in age at onset among carriers. We aim to elucidate the modifying effects of APOE2 and APOE4 alleles on age at onset for AD among G206A carriers and non‐carriers, accounting for known confounders and their genetic background differences.

Method

This study examined the modifying effects of APOE2 and APOE4 on the risk of AD onset between non‐carriers and carriers of the G206A mutation using multivariable Cox proportional hazards models, examining 505 individuals from 87 Puerto Rican families. We further examined whether APOE2 or APOE4 behave differently in the 2 ethnic subgroups: the Hispanic Whites (H‐White) vs. Hispanic Non‐Whites (H‐Non‐Whites).

Result

As expected, the G206A consistently showed a significant increase in AD risk (HR=10.61, p=9.60E‐30). When APOE4 was examined together with the G206A, it weakly increased the risk (HR=1.72, p=1.81E‐3), while APOE2 showed a weak protective effect but was not significant (HR=0.83, p=0.53). We then examined the APOE effects in ethnic subgroups. Given the small sample size in the H‐Non‐Whites, we compared the mean age at AD onset rather than computing HR. For H‐Whites carrying both G206A‐APOE2, the average age at onset was 60.3 years. Among H‐Non‐Whites, there was only one G206A‐APOE2 carrier, and this person remained unaffected until 87.5 years. Although based on a single case, this significant delay in AD onset signals a potentially critical area for future research in understanding the mechanisms behind the APOE2 protective effect.

Conclusion

The APOE2 allele shows protective effects on AD onset in G206A carriers, specifically in H‐Non‐Whites. A single case of late‐onset in a H‐Non‐White G206A‐APOE2 carrier highlights the need for in‐depth research into APOE2's role across ethnicities. G206A notably heightens the risk of early AD onset, with APOE4 contributing moderately.
Levels of plasma ADAM10, education, and cognitive performance of healthy older adults and persons living with Alzheimer’s disease from a middle‐income country
Authors: Cominetti Marcia Regina , Pedroso Renata Valle , Victoriano Pedro Henrique Moreira , de Sousa Danilo Barroso , Palma Leticia Fernanda , Grigoli Marina Mantellatto , Popolin Cecilia Patricia , da Silva Vanessa Alexandre , de Oliveira Sabrina Dorta , Manzine Patricia Regina , Pelegrini Lucas Nogueira de Carvalho
Published: January 2025

Background

Blood‐based biomarkers are gaining attention lately, and recent evidence supports the potential role of ADAM10 as an Alzheimer’s disease (AD) biomarker. However, most available information on these biomarkers comes from high‐income countries, where the population is usually highly educated. The influence of years of education (YoE) and older age on cognitive performance is well described in the literature, and they are risk factors for dementia. Therefore, in this study, we aim (1) to analyze whether education mediates the relationship between age and cognitive performance even among those with few YoE and (2) to compare plasma levels of ADAM10 in healthy controls (HC) and persons living with AD (PLwAD).

Methods

In this cross‐sectional and analytical study, participants (n=81) were low‐educated older adults from a middle‐income country (Brazil) and were assigned into two groups: HC (n=37) and PLwAD (n=44). The Mini‐mental State Examination (MMSE) evaluated cognitive performance. SDS‐Page and Western‐Blotting were used to obtain plasma levels of ADAM10.

Results

Participants’ mean age and YoE were 75.5 (7.9) and 4.9 (3.5) respectively. PLwAD patients were older (t=‐4.67; p<0.0012), had fewer YoE (t=3.53; p=0.002), performed worse in MMSE (t= 1.72; p<0.001), and had higher levels of ADAM10 in plasma (t=‐2.24; p=0.31). The mediation analysis suggested a total effect of age on MMSE score of ‐0.366 (p<0.001; 95%CI [‐0.53 to ‐0.20]), a direct effect of age (controlling for YoE) on MMSE score of ‐0.302 (p<0.001; 95%CI [‐0.47 to ‐0.13]) and an indirect effect of age on MMSE score, via YoE, of ‐0.0803 (95%BCaCI [‐0.18 to ‐0.01]). Finally, the logistic regression analysis suggested that higher levels of plasma ADAM10 increase the probability of being diagnosed with AD (Exp(B) = 2.099; 95% C.I. for Exp(B) [1019 to 4.321]).

Conclusion

Our results suggested that education mediates the effect of age on cognitive performance, even among those with fewer YoE. Also, higher levels of ADAM10 in plasma are associated with AD diagnosis. These findings hold significance as they offer a distinctive perspective from a middle‐income country with diverse demographics, potentially shaping future research and informing healthcare strategies in analogous settings.
Experiences recruiting from neighborhoods based on area deprivation index (ADI)
Authors: Russ Eunji , Kind Amy J.H. , Gillen Daniel L , Witbracht Megan G. , Ritchie Marina , Duran Edwin , Grant‐Freeman Zion T , Medina Melany , Grill Joshua D
Published: January 2025

Background

Few interventions have demonstrated efficacy for increasing diversity in Alzheimer’s disease (AD) clinical research and fewer still have targeted disadvantaged neighborhoods specifically. As part of a larger study to test recruitment strategies into the UC Irvine Consent‐to‐Contact Registry (C2C), we qualitatively assessed experiences of conducting community‐based outreach throughout disadvantaged neighborhoods in Orange County, California.

Method

We are conducting an interrupted time series design to test recruitment interventions, stratified by Area Deprivation Index (ADI), a validated measure of neighborhood disadvantage. The experiment tests Facebook advertisements, mailed postcards, and in‐person outreach. We report the experiences of in‐person outreach in diverse neighborhoods in the first year of outreach for a two‐year study. We used the ADI to characterize the location of 223 Orange County community‐based organizations, including, 36 churches, 42 senior centers, 47 libraries, and 98 other venues. Outreach events at community‐based organizations or other venues were targeted across ADI quintiles during the first week of every study period. Our diverse team of research staff, faculty, community Speaker’s Bureau members, and undergraduate volunteers were trained to conduct outreach in the community to provide education on brain health and information about research opportunities via resource tables and educational presentations.

Result

Since February 2023, we have conducted 30 events (14 presentations and 16 tables). Seven events were provided in a non‐English language (i.e., Spanish, Korean, Mandarin, and Vietnamese). We reached 205 people from tabling and 359 from presentations. Among 564 individuals reached, n = 33 provided information to register for the registry on site and n = 18 registered for a specific research study. Twenty‐two individuals reported difficulty in registering for the registry due to the absence of an email address, unfamiliarity with QR codes, or the need for family assistance to complete online forms (64% of these were from the two highest ADI quintiles). Site‐specific barriers included lack of media equipment, promotional support from site, and space for outreach.

Conclusion

Identifying barriers to effective community‐based outreach in diverse neighborhoods will be important to developing strategies in improving brain health communication and research on recruitment of underrepresented communities.
Impact of a Timely Diagnosis of Early Alzheimer’s Disease on Functional Outcomes
Authors: Briesacher Becky A , Zhang Ning A , Juday Timothy R , Frech Feride H , Batrla Richard
Published: January 2025

Background

The National Plan to Address Alzheimer’s Disease (AD) prioritizes timely diagnosis of mild cognitive impairment (MCI) as one of its key goals. Studies describing the downstream consequences of not having a timely diagnosis in this vulnerable population are limited. The study objective will evaluate the relationship between a timely MCI diagnosis and decline in functional outcomes compared to a missed diagnosis.

Method

This observational study utilizes 2008‐2020 data from the Health and Retirement Study (HRS), a longitudinal panel study that surveys a representative sample of 20,000 people age >50 years in the US every 2 years. Our study is research in progress; final data will extend through 2022. Cognition was assessed by a validated tool, Telephone Interview for Cognitive Status (TICS). A timely diagnosis of MCI is defined as a self or proxy report of a healthcare provider diagnosis in the HRS within 2 years of an MCI‐qualifying score on the TICS. Survival analyses will be used to assess longitudinal change every two years between diagnosed and missed diagnosis groups.

Result

Preliminary analyses identified a study population of 4712 patients with an MCI‐qualifying score; 303 (6.4%) reported a timely MCI diagnosis. Ongoing analyses will shed light on the impact of a timely MCI diagnosis on functional outcomes.

Conclusion

Final analyses will clarify results and provide an indication of the impact of a timely MCI diagnosis on functional outcomes.
Associations between peripheral blood DNA methylation and FDG‐PET signal in AD individuals
Authors: Perquim Lavinia , de Bastiani Marco Antônio , Machado Luiza Santos , Borelli Wyllians Vendramini , Povala Guilherme , Schlickmann Thomas Hugentobler , Pascoal Tharick A. , Rosa‐Neto Pedro , Cristino Alexandre Santos , Zimmer Eduardo R.
Published: January 2025

Background

Epigenetics plays a crucial role in regulating genetic transcription and responding to environmental and lifestyle changes without altering the DNA sequence. Their dysregulation is associated with AD, presenting potential as blood biomarkers. However, no study has evaluated whether peripheral blood (PB) epigenetic biomarkers are associated with brain metabolism, indexed by FDG‐PET, a classic Imaging AD biomarker. Thus, we explore the associations between PB DNA methylation and FDG‐PET signal in the brain of cognitively unimpaired (CU) and AD individuals.

Method

We evaluated CU=43 and AD=122 individuals from the ADNI cohort who underwent FDG‐PET imaging and PB DNA methylation analysis. Methylation data were analyzed using the minfi R package. Correlation analysis was performed with the statistically significant differentially methylated regions (DMRs) (p<0.005) and the regional FDG‐PET standardized uptake value ratio (SUVRs) values extracted with the DKT atlas. Voxel‐wise associations between FDG‐PET and DMRs were tested using linear regressions accounting for group, gender, age, and APOE4 status. The analysis was corrected for multiple comparisons using cluster‐wise RFT (p<0.05).

Result

We identified 478 DMRs (Figure 1), multiple of them significantly associated with regional FDG‐PET SUVRs (Figure 2). The voxel‐based analysis demonstrated that DMR cg02041677, located in the ATE1 gene, was negatively associated with FDG‐PET signal in the left hippocampus, right orbitofrontal gyrus, and right medial temporal gyrus (tmax=‐4.28, ‐4.04, ‐3.58, respectively; p‐value<0.001). The cg11128212, in the intron, nearby two lncRNA (ENSG00000289046, ENSG00000274591), was positively associated with brain metabolism in the left hippocampus, left temporal pole, and left middle temporal gyrus (tmax=4.08, 3.98, 3.80, respectively; p‐value<0.001) while the cg11901271, located in intron, nearby of a LncRNA (ENSG00000287358), showed positive correlations with FDG‐PET in the Left hippocampus (tmax=5.35, respectively; p‐value<0.001) (Figure 3).

Conclusion

Here, we show that PB DMRs exhibited a significant pattern of association with brain glucose metabolism in vulnerable AD regions. LncRNAs are important transcriptional regulators, the methylation could impact gene expression in AD and present potential as blood biomarkers.
Hyperbaric Oxygen therapy for older adults with T2D and Mild Cognitive Impairment ‐ A baseline characteristics
Authors: Benari Ori , Ravona‐Springer Ramit , Sano Mary , Bendlin Barbara B. , Livny Abigail , Almog Ganit , Leroith Derek , Beeri Michal S
Published: January 2025

Background

Hyperbaric oxygen therapy (HBOT) is a treatment in which oxygen‐enriched air (up to 100%) is administered to patients in a chamber at a pressure above one atmosphere absolute and is approved for the treatment of T2D ischemic wounds. Type 2 diabetes (T2D) is a risk factor for dementia. Ischemia due to vascular pathology is hypothesized to be an underlying mechanism for this association. Evidence small clinical trials suggests that HBOT improves hypoxic/ischemic brain injuries, consequently inducing brain angiogenesis, leading to cognitive improvement.

Method

We have conducted a double blind, placebo controlled, clinical trial on brain and cognitive outcomes in elderly with T2D and mild cognitive impairment (MCI) to compare the effects of HBOT vs. sham. This analysis reports the baseline characteristics of those recruited.

Result

A total of 155 participants, comprising 69% males (mean age 71.26) and 31% females (mean age 70.23), met the eligibility criteria to commence hyperbaric oxygen therapy (HBOT) with a Total Clinical Dementia Rating (CDR) of 0.5, Mini‐Mental State Examination (MMSE) score greater than 23, and no contraindications for HBOT. The average MMSE score was 28.5 for males and 28.4 for females. Beck’s Depression Inventory (BDI) revealed a mean score of 5.1 for males and 6.1 for females. Notably, 119 participants exhibited impairment in the CDR memory domain (CDR > 0) and other associated domains.

Conclusion

Recent studies have indicated that hyperbaric oxygen therapy (HBOT) can stimulate neuroplasticity and enhance cognition in individuals recovering from strokes and traumatic brain injuries. However, the impact of HBOT on cognition in patients with Type 2 Diabetes (T2D) who are at a high risk of dementia remains to be established. The outcomes of this study, if successful, could furnish compelling evidence regarding the potential benefits of HBOT on brain function and cognition within this distinctive patient population.
“A combined potential biomarker candidate and drug target quantified using Single Molecule Array ‐ GFAP and NFL implication in the progression of Dementia.”
Authors: Anwar Masroor , Dey Sharmistha , Dey Aparajit Ballav , Lee Jinkook
Published: January 2025

Background

The lack of knowledge about the onset and progression of dementia hampers its early diagnosis and possible treatment leading to severe condition like Alzheimer’s disease. Technological advancement like new brain network modeling tools might provide insight into the disease progression but a broader view of the biochemical changes induced by dementia in an early and pre‐symptomatic stage needs to be explored. Therefore, a multicentric longitudinal study was designed to quantify proteins molecules associated with cognitive impairment.

Method

We measured the levels of four protein molecules Aβ1‐42, Aβ1‐40, GFAP, and NfL in plasma of 1619 participants comprising of 14% (Alzheimer’s Disease) AD patients, 39% (Mild cognitive impairment) MCI patients and 47% Geriatric controls (GC). The quantitative measurement was performed using flexible, robust, and ultra‐sensitive immunoassay platform SIMOA (Single Molecule Array). Statistical significance was defined as p < 0.05. All statistical analyses were performed in the Prism ver. 5.03 program (GraphPad Software Inc, La Jolla, CA, USA).

Result

The comparative analysis showed plasma protein concentrations of NFL and GFAP were significantly higher in AD and MCI patients compared to GC group (p < 0.001) whereas no significant difference was observed for Aβ1‐42 and Aβ1‐40. Interestingly gender wise analysis of NFL showed the concentration difference between GC versus AD was significantly higher in female compared to male (concentration difference Male; 23.78pg/mL Female; 3.47pg/mL). NFL and GFAP exhibited higher correlation with increasing age. Concentration of GFAP significantly increased in all the three age groups (60‐70years p<0.01, 71‐80years p<0.001, 81years and above p<0.0001) in AD patients compared to GC.

Conclusion

We showed a correlation between a profile of four plasma protein biomarkers in development and progression of dementia patients. Our findings indicate that higher plasma NFL and GFAP expression may be a biomarker for AD risk and could predict progression from prodromal to probable AD dementia.
What happens next? Repeated administration of a social and structural determinants of health questionnaire in an Alzheimer’s Disease Research Center
Authors: Stites Shana D. , Humphreys Valerie , Kuz Carolyn , Schumann Rosalie , Halberstadter Kimberly , Mechanic‐Hamilton Dawn
Published: January 2025

Background

Social and structural determinants of health (SSDoH) must be measured longitudinally in order to better understand the effects of lived experiences on the trajectories of Alzheimer’s disease and related dementias (ADRD) outcomes. We repeated administration of an SSDOH survey to examine response rates and response consistency in a sample of cognitively typical older adults.

Method

One online survey and one follow‐up survey were administered to cognitively unimpaired participants (n = 135) in the UPenn Alzheimer’s Disease Research Center clinical cohort ∼1.5 years apart. The ∼225 items covered the following categories: (1) Education, (2) Economic Status and Strain, (3) Occupation, (4) Stressors and Subjective Stress, (6) Subjective Social Support and Status, and (7) Sociodemographic data, which included age, race, language, disability, neighborhood, sex, sexual orientation, and gender identity questions. We summarize pilot data on item and instrument completion rates and changes in participant responses.

Result

81 of 135 participants completed the follow‐up survey, which is a response rate of 60%. Most participants completed most items. The two measures with the lowest completion rates were: Calgary Charter on Health Literacy Scale (74/81) and the Perceived Stress Scale (69/81). Some participants who did not complete a given measure during the first administration did complete that measure during the second. In addition, responses on most measures, single items or multi‐item scales, varied between the administrations. Some responses appeared to change because of ambiguity in the item’s phrasing, administration process, or reflected changes over time in the constructs being assessed.

Conclusion

Overall, it was feasible to repeatedly administer a survey of SSDoH items to a group of cognitively unimpaired older adults. The response rate was reasonable but lower than expected in a group of volunteer research participants indicating that multiple modes of administration may be useful for increasing engagement. Differences in the data produced from repeated administration of measures was useful in identifying ambiguity in items and methods that aid in improving research rigor and reproducibility. The data are also useful in understanding the temporal stability or instability of SSDOH experiences among these research participants.
Associations between New Deal emergency employment of teachers and teachers per student with late‐life cognition among Health and Retirement Study Participants
Authors: Eng Chloe W. , Rehkopf David , Modrek Sepideh
Published: January 2025

Background

Higher school quality, and decreased student‐teacher ratio in particular, is associated with improvements in late‐life cognition. New deal emergency employment programs in the 1930s provided funding for hundreds of thousands of teachers in response to sweeping school budget cuts of the Great Depression. We examine the association between increased area‐level teacher employment through the Public Emergency Work (PEW) programs and late‐life cognition.

Method

Black and White Health and Retirement Study participants (age 50+ years) were linked to 1940 census records with childhood geographic information (n = 7,726). Average z‐standardized imputed memory scores across biennial survey waves (1998‐2018; mean follow‐up: 4.4 years) were estimated as a function of census county‐level PEW teachers employed per 1,000 students, adjusting for the census county‐level ratio of full‐time teachers employed per 1,000 students. Teachers per student was calculated separately for segregated vs. non‐segregated states, with race‐specific teachers per student calculated historically de jure segregated Jim Crow states. Analyses were stratified by rurality due to contextual differences in classroom structure between rural and urban students. Mixed linear regression models with random intercepts were adjusted for individual/area‐level covariates with state fixed effects.

Result

Most (76.5%) participants lived in districts with at least one PEW teacher (Figure 1). PEW teacher employment was higher in areas with more Black residents, higher unemployment, and fewer homeowners. Residence in areas with no employment of teachers through PEW was associated with a ‐0.1002 (95% CI: ‐0.1971, ‐0.0033) SD decrease in late‐life memory (Table 1). Benefits of additional PEW teachers for late‐life memory was slightly larger in areas with more existing full‐time teachers (B = 0.0006; 95% CI: 0.0001, 0.0012), and the negative association between no PEW teachers and late‐life memory was slightly attenuated in areas with more existing full‐time teachers (B = 0.0037; 95% CI: 0.0002, 0.0073; Table 2). Number of PEW teachers was not associated with late‐life memory in rural areas.

Conclusion

Childhood residence in urban areas that did not receive additional teacher employment through PEW programs was associated with lower late‐life memory; effects were stronger among areas with fewer existing full‐time teachers. Rural/urban discrepancies may reflect differential allocation and exposure to PEW programs.
High‐performance plasma proteomic biomarker candidates in early Alzheimer's disease
Authors: Xie Yuhan , Sun Hui , Liu Fang , Zheng Yaonan , Zhang Mang , Ma Xin , Yu Xin , zhang nan , huang chaolan , Wang Huali
Published: January 2025

Background

The present study aimed to establish a panel of plasma proteins that are associated with cognitive performance and amyloid‐β burden and establish their utility for distinguishing early Alzheimer’s disease (AD) from healthy controls.

Method

Plasma from fifty patients with early AD (all amyloid‐positive) and forty‐nine healthy controls (HCs) were assayed using quantitative mass spectrometry. The weighted correlation network analysis (WGCNA) was used to explore the association between plasma protein levels and cognitive performance and filter out the high‐performance plasma proteomic biomarker candidates. Further correlation analysis was used to examine these proteins’ association with amyloid‐β burden in AD brain measured with PET imaging.

Result

We identified 1124 proteins that were dysregulated in AD plasma. Further, 22 panel proteins representative of the AD plasma protein profile were selected based on their association with the cognitive performance and cerebral regional SUVR of PiB‐PET imaging. The panel proteins, involved in the amyloid‐β protein production, metabolism and immune processes, have demonstrated high performance in distinguishing between early AD and HCs.

Conclusion

This study comprehensively profiled the AD plasma proteome and identified 22 dysregulated proteins as high‐performance biomarker candidates for early Alzheimer’s disease.
Gut Microbiome Multi‐Omics and Cognitive Function in a Large Latino Cohort
Authors: Palacios Natalia , Gordon Scot , Wang Tao , Huttenhower Curtis , Gonzalez Hector M , Knight Rob , Decarli Charles , Daviglus Martha L , Lamar Melissa , Tarraf Wassim , Cai Jianwen , Burk Robbie , Qi Quibin , Kaplan Robert C.
Published: January 2025

Background

Few large microbiome studies on Alzheimer’s Disease and Related Dementia (AD/ADRD) have been conducted, especially among US Latinos. We conducted a study within the Study of Latinos‐ Investigation of Neurocognitive Aging (SOL‐INCA) cohort to examine the role of the gut microbiota in cognitive function.

Methods

We analyzed the fecal metagenomes of 2,470 SOL‐INCA participants to, cross‐sectionally, identify microbial taxonomic and functional features associated with cognitive function. Global cognition was defined as an aggregate score based on a cognitive battery (executive function, working memory, among others). Omnibus (PERMANOVA) and feature‐wise analyses (MaAsLin2) were conducted to identify microbiome‐cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition. We assessed the accuracy of a Random Forest classifier to distinguish SOL participants with the best (>=1SD above mean) vs. the worst (>=1SD below mean) cognition. We also tested the association of identified taxa and KEGG modules with concurrently collected serum metabolites.

Result

We identified several taxa and pathways significantly associated with cognitive function in SOL. B. longum was the taxa most strongly associated with worse cognition, whereas Eubacterium species (E. siraeum and E.eligens), were associated with better cognition. Several KEGG modules, most strongly Ornithine and Serine biosynthesis, were associated with worse cognition. A microbiome species‐based Random Forest classifier had moderate accuracy (AUC = 0.62) to discriminate between high (1SD or more above mean) vs low (1SD or more below mean) cognition.

Conclusion

In a large Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition, further implicating the microbiome in AD/ADRD risk.
Unleashing the power of a willow bark‐derived tannin to alleviate behavioral deficits in a preclinical model of Alzheimer’s disease
Authors: Kahil Ezaldean A , Jackson Anisha , Patel Kruti , Coward Lori A , D'Souza Bernadette , Gorman Gregory , Jumbo‐Lucioni Patricia
Published: January 2025

Background

Despite some advances in treatment, a cure for Alzheimer’s disease (AD) remains elusive. Disease hallmarks include heightened neuroinflammation and oxidative stress, associated with progressive decline in mobility and cognitive functions. Natural compounds provide a valuable reservoir of novel bioactive substances with therapeutic potential, fewer side effects, and increased affordability. The plant‐derived tannin 1,2,3,4,6‐Penta‐O‐Galloyl‐β‐D‐Glucose (β‐PGG) displays potent antioxidant, anti‐inflammatory, and neuroprotective properties in vitro, but in vivo evidence is limited. This study assesses the dose‐dependent efficacy and therapeutic mechanisms of β‐PGG in mitigating age‐dependent mobility deficits in a Drosophila melanogaster model of AD.

Method

A fruit fly line overexpressing the human amyloid precursor protein (hAPP) and β‐site APP‐cleaving enzyme (hBACE), in neurons was used as AD model. Newly eclosed flies were supplemented with 0, 5, or 10µM β‐PGG and locomotion was assessed at 7, 14, 21, and 30 days via a negative geotaxis assay. The number of flies passing 2‐, 4‐, and 8 cm marks in 10 seconds was recorded by genotype, sex, age, and treatment. Oxidative stress sensitivity was measured by quantifying 48‐hour survival to paraquat exposure. Flies were homogenized to determine levels of β‐PGG metabolites by LC/MS/MS. Data were analyzed via a two‐way ANOVA to test the effects of genotype, treatment and their interaction in young (7‐ and 14‐days old) and old (21‐ and 30 days old) flies.

Result

Young non‐supplemented AD females (p<0.0001) and males (p<0.0001) moved significantly slower than controls. β‐PGG significantly ameliorated locomotion deficits in young AD flies. AD females (p<0.0001) and AD males (p<0.0001) supplemented with 10µM β‐PGG were significantly less movement impaired than their non‐treated counterparts. Regardless of genotype, old females supplemented with 10µM β‐PGG were significantly faster than untreated cohorts (p<0.05). Conversely, old AD but not control males supplemented with 10µM β‐PGG were significantly less movement impaired than their untreated counterparts (p<0.0001). At 48 hours, 2‐week β‐PGG supplementation significantly improved survival to paraquat among control females but not in males (p<0.01).

Conclusion

Our findings provide strong evidence that β‐PGG supplementation mitigates age‐associated mobility deficits in our preclinical model of AD. Benefits from this supplementation may delay physiological aging in a sex‐specific manner.
Genetic and Sex Associations with Earlier Estimated Onset of Amyloid Positivity from over 4000 Harmonized Positron Emission Tomography Images
Authors: Castellano Tonnar , Wang Ting Chen , Nolan Emma , Archer Derek B. , Cody Karly , Harrison Theresa M. , Wu Yiyang , Durant Alaina , Janve Vaibhav A , Engelman Corinne D. , Jagust William J. , Albert Marilyn S. , Johnson Sterling C. , Resnick Susan M. , Sperling Reisa A , Bilgel Murat , Saykin Andrew J. , Vardarajan Badri N , Mayeux Richard , Betthauser Tobey J. , Dumitrescu Logan C. , Mormino Elizabeth , Hohman Timothy J. , Koran Mary Ellen I.
Published: January 2025

Background

New techniques have been developed to estimate the age when someone converted to amyloid positivity (EAOA) from PET, oftentimes offering information Aβout a participant decades before they joined a research study. EAOA is variable across populations but we do not know the causes for these differences. This study aims to validate APOE associations with EAOA and explore genetic and sex‐based factors with EAOA.

Methods

Data from six cohorts were analyzed. Our analysis included 4220 non‐Hispanic white people (57.6% women; 86.7% cognitively unimpaired at baseline scan). Amyloid PET data were harmonized using gaussian mixture models. EAOA was calculated using the sampled iterative local approximation (SILA) algorithm. Sex differences in EAOA were compared using t‐tests amongst amyloid positive individuals. A genome‐wide association study of EAOA was performed. Gene analyses were conducted using MAGMA.

Results

Average EAOA was 81.1 years across all individuals regardless of amyloid status. APOE e2 homozygotes had slightly later EAOA than e3/e3 homozygotes. APOE e4 homozygotes converted to amyloid positivity 8.2 years before e3/e4 heterozygotes and over two decades earlier than e3 homozygotes. APOE e2/e4 converted to positivity roughly three years later than e3/e4 and nearly ten years earlier than e3 homozygotes. APOE genotype differences in EAOA described were statistically significant (p < .01). There were significant sex differences between men and women when examining amyloid positivity. Men converted to amyloid positivity over 2 years later than women (65.3 vs 63.2 years, p=3.23x10‐5). The rs12981369 polymorphism in ABCA7 was associated with EAOA (β = 2.14, p=9.27×10−9). Brain eQTL databases indicate associations between rs12981369 and gene expression of ABCA7. Gene‐level analyses revealed significant associations for ABCA7, HMHA1, and KIF13B.

Conclusion

This study further describes the role of APOE and reveals roles for ABCA7 and KIF13B on amyloid onset. We identified a novel variant on chromosome 19 correlating with later amyloid onset conversion and highlight important differences between sexes. These findings highlight EAOA as a powerful endophenotype of AD and offer insights into potential drug‐targetable mechanisms for early AD intervention.
Luteolin and curcumin in rodent models of cognitive disorders: a dose‐response perspective
Authors: Führ Giulia A , Zimmer Aline R.
Published: January 2025

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common form of dementia. Although AD is characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs), it’s estimated that nearly half of AD cases might be attributed to modifiable risk factors and lifestyle‐based interventions may offer promising preventative strategies to delay disease onset and progression. Polyphenolic derivatives easily found in foods like luteolin and curcumin have shown beneficial effects to counteract cognitive decline.

Method

A systematic review was conducted to determine the oral therapeutic doses of curcumin and luteolin used in experimental models of cognitive disorders in rodents, presenting beneficial effects. Public databases, including PubMed, Embase, Web of Science and Scopus were searched. Original research and review papers published between 2009 and 2023 using the following keywords: “luteolin,” “curcumin,” “oral administration,” “cognitive disorder,” “mice,” and “rats” were included in the search.

Result

Eleven articles for luteolin and twenty‐seven for curcumin fit the inclusion criteria. For luteolin, the oral doses range from 1.25 mg/kg to 200 mg/kg, with treatment length from 7 days to 5 months. For curcumin, oral doses range from 0.4 mg/kg to 400 mg/kg, with treatment length from 2 days to 6 months. The studies demonstrated that luteolin reduces the deposition of Aβ, oxidative stress, neuroinflammation, neuronal damage and neuronal insulin resistance, improving learning and memory and rescuing cognitive impairment. Curcumin reduces oxidative stress and Aβ production and promotes hippocampal neurogenesis, improving spatial learning, memory and cognitive function. None of the studies evaluated reported toxic effects at the tested doses. The use of both compounds in combination was not found in the literature. The most promising doses for improving cognitive function in experimental models ranging 10 – 20 mg/kg for luteolin and 25 – 50 mg/kg for curcumin.

Conclusion

Luteolin and curcumin exhibit multi‐target pharmacological properties, suggesting the potential to prevent cognitive disorders, including AD. The neuroprotective effect of these agents in combination and whether this would lead to a dose reduction and an improvement in effect is still a subject to be explored.