bluuebunny/crossref_metadata_2025 huggingface dataset:
Vascular risk, WMH, pTau 181 and NfL, but not ApoE or Aβbeta 42/40, are associated with cognitive impairment in Latinos from the SOL‐INCA‐MRI study
Authors: Decarli Charles , Sapkota Shraddha , Márquez Freddie , Tarraf Wassim , Isasi Carmen R , Lipton Richard B. , Gallo Linda C , Talavera Gregory A , Daviglus Martha L , Testai Fernando Daniel , Ramos Alberto R , Rundek Tatjana , Thyagarajan Bharat , Gonzalez Hector M
Published: January 2025

Background

Serum AD biomarkers are becoming useful to the early and accurate diagnosis of neurodegenerative disease, but much of this work has been done with clinic‐based studies of mostly non‐Hispanic Whites. For this study, we examined relations between plasma biomarkers Aβ 42/40, pTau 181, NfL, GFAP, ApoE genotype and cognitive state in the SOL‐INCA‐MRI study. Given that prior work in SOL‐INCA found vascular risk to be associated with mild cognitive impairment1, we included vascular risk measured by the Framingham CVD risk score2 and white matter hyperintensity (WMH) burden from MRI as additional predictors.

Method

2288 individuals enriched for cognitive impairment (29%), mean age 64.5 ± 6.8 years of which 69% were female and 60% had at least a high school education were studied. All subjects had MRI as well as plasma measures of Aβ 42/40, pTau 181, GFAP and NfL and a diagnosis of normal (71%), questionable (16%), or mild cognitive impairment (13%). Multi‐variate linear regression adjusted for age, sex, heritage, and education was used to build models of associations between each of the measures and cognition. Finaly, structural equation modeling was used to assess the structural relationship between measured variables.

Result

Higher serum pTau181 and Nfl concentrations were significantly associated with diagnosis (Table 1). PTau181, NfL and GFAP were also associated with MRI measures, particularly WMH (Table 2). CVD risk also was significantly associated with pTau181 (β=1.23 ± 0.34, p <0.0001) and NfL (β=25.4 ± 2.8, p <0.0001). In a final model (Table 3), sex, CVD risk, WMH and pTau181 remained significantly associated with cognition. Best fit SEM summarizes the relationship of these measures to each other and cognition (Figure). ApoE4 genotype and Abeta 42/40 ratio were not associated with diagnosis in this group.

Conclusion

In a group of Latinos, enriched for cognitive impairment, vascular risk, WMH and pTau181 were significantly associated with diagnosis. The lack of association with serum Abeta 42/40 ratio suggest that vascular disease and not AD pathology are most strongly associated with cognition. The relationship between CVD risk, WMH, and pTau181is consistent with emerging evidence relating tau phosphorylation to vascular disease3, 4.
Midlife Periodontal Disease and Cognitive Functioning: Evidence from High School and Beyond
Authors: Warren John Robert , Demmer Ryan , Grodsky Eric , Muller Chandra
Published: January 2025

Background

Periodontal disease is a prevalent, preventable, and highly treatable oral infection that is (1) stratified by sociodemographic, educational, and spatial factors and (2) is believed to impact cognitive impairment and ADRD risk. However, there is very little information from community‐based, population‐representative, longitudinal studies about the association between periodontal disease and midlife cognitive functioning net of early life confounders.

Method

We use data from the U.S. High School and Beyond (HSB) cohort study, which has followed a nationally representative sample of ∼25,500 people from high school in 1980 through midlife in 2021‐22. HSB data from the 1980s includes rich information about educational contexts, opportunities, and outcomes; early life socioeconomic and family circumstances; spatial location; and demographic group memberships. HSB data from 2021‐22 include indicators of periodontal disease diagnosis and multiple measures of cognitive functioning.

Result

People who have been diagnosed with periodontal disease score worse on measures of memory, executive function, and other domains of cognitive functioning at midlife. These associations are only partly attributable to early life confounders. Some ─ but not all ─ of the association can be attributed to the mediating role of diabetes and CVD.

Conclusion

Periodontal disease is a preventable and treatable risk factor for subsequent cognitive impairment. Because risk of periodontal disease is stratified by demographic, educational, and other social factors, periodontal disease may also be important in shaping sociodemographic gradients in midlife cognitive functioning. This is the first population‐representative study using data from a community‐based cohort that has been followed from adolescence through midlife. As such, this work provides important evidence about the role of periodontal disease in stratifying cognitive outcomes.
Olfaction and blood‐based biomarkers of Alzheimer’s disease pathology and neurodegeneration in the ARIC Study
Authors: Shrestha Srishti , Zhu Xiaoqian , Sullivan Kevin J. , Palta Priya , Deal Jennifer A. , Schneider Andrea L.C. , Chen Honglei , Gottesman Rebecca F. , Thyagarajan Bharat , Windham B Gwen , Mosley Thomas H. , Griswold Michael E. , Kamath Vidyulata
Published: January 2025

Background

Olfactory impairment appears early in the course of Alzheimer’s Disease (AD) and may serve as a non‐invasive early marker of AD. Few studies have examined the association between olfaction and blood biomarkers of AD neuropathology in large, diverse, community‐based populations. Blood levels of amyloid‐beta (Aβ42 and Aβ40), phosphorylated‐tau (p‐tau) forms, glial fibrillary acidic protein (GFAP), and neurofilament‐light chain (NfL) appear to reliably reflect corresponding brain neuropathologies and neurodegeneration. Investigation of olfaction in relation to these biomarkers could provide insights into its utility in the early identification of individuals at high risk of progressing to AD.

Methods

We investigated cross‐sectional associations of olfaction (measured by a 12‐item odor identification test) with blood Aβ42/Aβ40 ratio, GFAP, NfL, p‐tau181, and p‐tau181/Aβ42 ratio (measured using Quanterix ultrasensitive single‐molecule array assays) in 1,565 Black and White participants from the community‐based ARIC Study and whether these associations differed by race and APOE ε4 genotype. Both olfaction and blood biomarkers were obtained at ARIC visit 5 (2011‐2013). Separate linear regression models were used to examine the association of continuous olfaction score and olfaction categories (anosmia: score ≤6; hyposmia: score 7‐8; moderate olfaction: score 9‐10, normal olfaction: score 11‐12) with each biomarker (all biomarkers were log‐transformed and measured in pg/mL), adjusting for relevant covariates (See Table).

Results

Among 1,565 participants (mean ± SD age:76±5 years, 60% women, 27% self‐reported Black), the mean ± SD olfaction score was 9.2±2.3; 14% had anosmia. Consistent with our hypotheses, higher olfaction score (i.e., better olfactory function) was significantly associated with lower levels of NfL, GFAP, p‐tau181, and p‐tau181/Aβ42, and higher Aβ42/Aβ40 ratio (See Table). Compared to normal olfaction, anosmia (i.e., poor olfaction) was significantly associated with higher NfL, GFAP, p‐tau181, and p‐tau181/Aβ42 ratio and lower (although not statistically significant) Aβ42/Aβ40 ratio. Associations of hyposmia and moderate olfaction with these biomarkers were not statistically significant. The associations did not differ by APOE ε4 status or race.

Conclusion

Our findings suggest that poor olfaction is associated with concurrent blood biomarkers of AD and neurodegeneration. Future analyses will examine associations of olfaction with prospective changes in these biomarkers and if these associations are explained by relevant neuroimaging markers.
An Imaging Marker for MCI to AD Conversion: Functional Dysconnectivity between Primary Olfactory Cortex to Default Mode Network
Authors: Pang Ran , Wang Jianli , Karunanayaka Prasanna , Kanekar Sangam , Eslinger Paul , Will Jens , Kalra Deepak , Ahmed Biyar , Elyan Rommy , Yang Qing
Published: January 2025

Background

Resting‐state functional MRI (rs‐fMRI) has been widely used for assessing disease progression in AD. It becomes, however, notoriously variable at disease’s prodromal stage when the cognitive functions are fluctuating while declining at the same time during this transitional period, which reduces its sensitivity in AD detection. Olfactory deficit has been shown to be an early sign of AD when the cognition decline is indistinguishable from normal aging. In this study, we investigated our hypothesis that functional connectivity (FC) between olfactory network and default mode network (DMN) will be disrupted in early AD.

Method

Longitudinal rs‐fMRI data of 42 clinically diagnosed MCI were collected at 1st‐time point from ADNI database (Table 1). The piriform cortex was manually segmented as the seed of POC (Figure 1A). The FC between POC and DMN was evaluated and analyzed within and between MCI‐AD converters and non‐converters.

Result

Compared to MCI non‐converters, AD patients’ FC between POC and DMN was significantly weaker (p<0.05, Table 1 and Figures 1‐2), while there was no significant difference in regards of POC‐DMN FC between MCI‐AD converters and non‐converters at the baseline (p>0.05). When the disease was progressed to AD, the FC between right piriform cortex and precuneus/PCC was significantly reduced (p=0.04). The FC of POC to DMN in MCI non‐converters was significantly correlated with cognitive score CDR‐cog, but not in MCI‐AD converters (Figure 2).

Conclusion

The FC between POC and DMN was disrupted in early AD. The observed disruption established a mechanistic link between olfactory deficits and cognition decline in AD. The functional dysconnectivity between POC and DMN could be an objective imaging marker for MCI conversion to AD.
Restoring Cognitive functions: Unveiling the Procognitive and Neurotrophic Impact of Chronic Administration of a Selective A5‐GABAA Receptor Positive Allosteric Modulator in Mouse Models of Amyloid Load and Tau Phosphorylation
Authors: Prevot Thomas D , Bernardo Ashley D , Wong Kayla D , Pina‐Leblanc Celeste , Marcotte Michael D , Sharmin Dishary , Mondal Prithu , Cook James M , Sibille Etienne
Published: January 2025

Background

Dysregulated GABA/somatostatin (SST) signaling has been implicated in psychiatric and neurodegenerative disorders. The inhibition of excitatory neurons by SST+ interneurons, particularly through α5‐containing GABAA receptors (α5‐GABAAR), plays a crucial role in mitigating cognitive functions. Previous research demonstrated that an α5‐positive allosteric modulator (α5‐PAM) mitigates working memory deficits and reverses neuronal atrophy in aged mice. Subsequently, we explored the behavioral and neurotrophic effects of this α5‐PAM in animal models reflecting β‐amyloid load and tau phosphorylation, hallmarks of Alzheimer’s disease progression.

Method

Two studies were conducted with approximately 12 mice per group, including 50% females: 1) 5xFAD transgenic mice exhibiting progressive amyloid‐related cognitive decline; 2) PS19 transgenic mice displaying progressive tau‐tangle‐cognitive decline. Chronic administration of GL‐II‐73 (30mg/kg, p.o, for 4 weeks) was employed to assess its efficacy in rescuing cognitive deficits across three domains. Working memory, spatial memory, and cognitive flexibility were evaluated through an alternation task, water maze, and set‐shifting assay, respectively. Golgi‐Cox staining of brains (n = 4brain/group; 8cell/brain) facilitated the quantification of dendritic length and spine density in the prefrontal cortex and hippocampus using NeuroLucida. In the 5xFAD cohort, the impact of treatment on spine maturation steps was also examined.

Result

Chronic treatment in both models reversed cognitive deficits across domains (ps<0.01), demonstrating a robust effect on working memory. Furthermore, it significantly mitigated amyloid‐induced and tau‐related dendritic shrinkage and reduction of spine density at apical and basal dendrites (p<0.001 in PFC and CA1). Notably, this effect extended to all maturation steps in the 5xFAD model.

Conclusion

The findings collectively indicate that selectively targeting α5‐GABAA receptors overcomes amyloid‐ or tau‐related cognitive deficits and neuronal morphology detriments. This marks the first intervention addressing the GABAergic system with both symptomatic and disease‐modifying therapeutic potential across various disorders. This breakthrough suggests a promising avenue for clinical development, offering hope to patients grappling with cognitive deficits across a spectrum of brain disorders.
Dysphagia‐Related Burden in Caregivers of Persons with Early‐Stage Dementia: Impact of Disease Stage and Diet Level
Authors: Todd Marissa , Mackowicz‐Torres Meredith , Gustafson Sara , Shune Samantha , Namasivayam‐MacDonald Ashwini , Rogus‐Pulia Nicole M.
Published: January 2025

Background

Caregiver burden, or the impact of caregiving, commonly occurs in caregivers of persons with dementia (PWD); however, prior research focused on caregiver burden in this population has not considered the impact of dysphagia. Therefore, the purpose of this study was to measure dysphagia‐specific burden in caregivers of PWD and examine its relationship to general caregiver burden, as well as the PWD’s current diet level and dementia severity.

Method

Data were collected from PWD‐caregiver dyads participating in a prospective, dysphagia‐focused clinical trial at the initial study visit. The Clinical Dementia Rating (CDR) scale was administered to dyads to determine dementia severity. The Zarit Burden Interview (Zarit) and Caregiver Analysis of Reported Experiences with Swallowing Disorders (CARES) were administered to caregivers. Functional Oral Intake Scale (FOIS) scores were recorded for the PWD.

Result

Twenty‐nine dyads were included. Caregivers were 93% female with a mean age of 65 years. PWD were 21% female with a mean age of 80 years. The mean CARES score was 2.86 (range = 0‐26; SD = 3.43) and the mean Zarit score was 28.1 (range = 5‐65; SD = 16.64). The median FOIS score for PWD was 7 (range = 5‐7). The highest CARES values were reported for the following experiences: being worried about the future, fear of their care recipient choking, and feeling “anxious.” A one‐way analysis of variance revealed no differences in CARES scores based on CDR stage. A Kendall tau rank correlation coefficient revealed a significant moderate, negative association between FOIS and CARES scores (r = ‐0.52; p<.002); while the moderate, positive association Pearson correlation between CARES and Zarit scores (r = .40; p = .03) was also significant.

Conclusion

Findings revealed that dysphagia‐associated caregiver burden may trend similarly as general burden (Zarit) but is generally low in earlier stages of dementia. However, the more restrictive the PWD’s diet (lower FOIS scores), the greater the dysphagia‐related burden reported by caregivers. Higher ratings on specific CARES items can guide clinical decision‐making regarding support needed by caregivers of PWD with early‐stage disease. The relationship between dysphagia‐related burden and general burden may change with disease progression, warranting continued investigation.
Construction and Validation of the modified visual index of parietal atrophy by brain magnetic resonance imaging in Alzheimer's Disease in a memory clinic
Authors: Aguilar‐Navarro Sara Gloria , Martínez Daniel Herrera , Ortega Jhonatan Ruvalcaba , Putoy Michelle Gonzalez , Mejía Ivonne Uscanga , Jiménez Irvin Abharca , Mimenza Alberto Jose
Published: January 2025

Background

Magnetic resonance imaging (MRI) has been very useful in evaluating brain atrophy related to Alzheimer's Disease (AD), so it is important to have scales that allow objective evaluation specifically of parietal atrophy. The objective of this study was to develop and validate a modified visual scale for the assessment of parietal atrophy (APM Scale) by brain MRI in a single slice (axial T2‐FLAIR), with focus on the measurement of the posterior cingulate sulcus to differentiate between Mild Cognitive Impairment (MCI), AD and other forms of dementia (OD not AD).

Method

retrospective validation study carried out in a memory clinic of a tertiary hospital in Mexico City, in a period from March 2015 to June 2023. Patients with a complete clinical and cognitive evaluation were included, including: MMSE, MoCA, brain MRI, Comprehensive Geriatric Evaluation, who met the diagnostic criteria for AD and other dementias and who, according to the evaluation carried out by the group of specialists, were classified into the following groups: Cognitively Healthy (CS), MCI, AD and OD non‐AD. A descriptive statistical analysis to characterize the population, normality tests, ANOVA for continuous variables and chi‐square tests for categorical variables. To demonstrate interobserver agreement, Cohen's Kappa test and the construction of ROC curves were used to determine the sensitivity and specificity of the APM Scale, as well as a logistic regression model to search for its association according to the Gold standard for AD.

Results

400 files were reviewed, 238 were excluded due to lack of data. The average age was 77 SD: 3.2 years, 55.6% were women. Diagnoses by groups included: 12.9% CS, 22.6% MCI, 50% AD dementia and 15.4% other non‐AD dementias. The interobserver agreement for the APM Scale was 0.880 for observer 1 and observer 2, 0.73 for observer 1 and observer 3 and 0.60 for observer 1 and observer 4 (p < 0.001). The AUC for EA was 0.748, with a sensitivity of 72% and a specificity of 71%. (p< 0.001).

Conclusion

This study demonstrates that the APM Scale based on MRI in axial T2 FLAIR sequence is a useful and valid tool to support the diagnosis of AD.
Cultural and linguistic diversity in dementia: data from an Australian memory clinic
Authors: Chin Kai Sin
Published: January 2025

Background

Australia has a rich migration history, with one in three older people coming from a culturally and linguistically diverse (CALD) background. Patients from CALD backgrounds tend to present at later stages of their diseases but face difficulties accessing appropriate dementia care compared to English‐speaking patients. Limited literature exists on the clinical experience among CALD patients who have been historically underrepresented in dementia research. This study therefore aimed to investigate and describe the clinical characteristics and service provision for CALD patients presenting to the Memory Clinic at the Royal Melbourne Hospital, a tertiary hospital which serves a significant proportion of CALD patients.

Method

A retrospective analysis was conducted. All consecutive patients who presented to the Memory Clinic between September 2016 and June 2018 were included. Data collected included patient demographics, medical history, cognitive test scores, neuropsychiatric symptoms, other clinical scales, clinical diagnoses, and length of follow up.

Result

A total of 301 patients (mean age 78.8 ± 8.2; 55.8% female) were included and 48.5% were from a CALD background, the majority being Italian. Patients from CALD backgrounds were more likely to be living with family (73.3% vs 57.4%, OR [odds ratio] 2.1) and less likely to have attended education beyond primary level (26.7% vs 83.9%, OR 14.3). Cognitively, CALD patients had poorer performance on MMSE (median MMSE 18 vs 25) and were more likely to be diagnosed with dementia (46.6% vs 31.0%, OR 1.9) at their initial assessments. Additionally, CALD patients were less likely to be referred for neuropsychology (28.8% vs 50.3%, OR 0.40).

Conclusion

The study findings highlight the differences in clinical characteristics as well as inherent issue of inequality in healthcare among patients from CALD backgrounds in an Australian clinical setting. Given the recent approval of disease‐modifying anti‐amyloid therapy in mild Alzheimer’s disease, more research is warranted to help diagnose dementia at earlier stages in CALD patients and ultimately promote more equitable and culturally inclusive dementia care.
The Markers in Neuropsychiatric Disorders Study (The MiND Study): progress of a large nationwide Australian blood biomarker study and platform for collaborations to improve diagnosis and care of dementia and other brain conditions
Authors: Eratne Dhamidhu , Lewis Courtney , Dang Christa , Grewal Jasleen , Kang Matthew , Zetterberg Henrik , Blennow Kaj , Santillo Alexander , Velakoulis Dennis ,   The MiND Study Group
Published: January 2025

Background

The Markers in Neuropsychiatric Disorders Study (The MiND Study) is investigating the diagnostic and wider utility of blood based biomarkers such as neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau (p‐tau), as well as other markers, to improve timely and accurate diagnosis of dementia and distinction from non‐neurodegenerative and primary psychiatric disorder (PPD). This in‐progress study has expanded significantly, becoming a robust platform for Australian and international collaborations.

Methods

Participants have been recruited and blood samples collected across Australia. Longitudinal clinical/diagnostic, questionnaire, cognitive, and health utilisation data is collected. Second timepoint bloods (24 months) are now underway. Samples have been been analysed for NfL, GFAP, p‐tau217, p‐tau181, amyloid beta, and genetics.

Results

As of January 2024, over 1500 referrals have been received, and over 1000 participants recruited from diverse specialist and community settings. Partnering with public and private pathology services, blood sample collection and storage processes have been developed across most of Australia. Approximately 2/3 of participants have volunteered to participate in the second timepoint blood samples. Findings thus far include plasma NfL reference ranges, strong diagnostic utility of blood and cerebrospinal fluid NfL to distinguish dementia from PPD, and GFAP and ptau217 to distinguish Alzheimer from non‐Alzheimer disease with very high accuracy, and high value placed on NfL testing by participants. Numerous collaborations and sub‐studies have developed, investigating cognitive and neuroimaging markers.

Conclusions

The MiND Study is large biobank and platform supporting collaborations, pioneering research to lead to clinical translation, with particular focus on clinical translation in to broad clinical settings, younger onset dementia, primary care settings, and non‐AD and neurodegenerative mimics such as primary psychiatric disorders.
MG‐PE3 bioinspired nanoparticle treatment for clearing amyloid with no toxicity
Authors: Kim Hyuck , Yoon Jeong‐Kee , Lee Wooseung , Jeon Miyeon , Lee Hyunju , Kang Somang , Kang Ee‐Seul , Lee Ji Eun , Kim Seyeon , Rho Hoon Suk , Levey Allan I. , Kim YongTae
Published: January 2025

Background

Impaired Aβ clearance plays a key role in the common, late‐onset AD. Anti‐Aβ immunotherapies are controversial, in part because of high rates of serious side effects including edema, microhemorrhages, and siderosis, highlighting the importance of the development of alternative Aβ clearance strategy. Here, we introduce a bioinspired nanoparticle named MG‐PE3 crossing the human blood‐brain barrier (BBB) and clearing Aβ with no adverse effect. We used a human BBB chip to test the BBB‐crossing capability in vitro and AD mouse model (5xFAD) to evaluate the Aβ clearance efficacy and the potential toxicity. The good BBB penetration, enhanced glial uptake, and high Aβ affinity of MG‐PE3 resulted in effective clearance of Aβ with no toxicity, thus providing an excellent potential to overcome the current challenges for AD treatment.

Method

Microfluidic technology was used to produce MG‐PE3 with uniform physicochemical properties. MG‐PE3 was tested in vitro for its binding affinity to Aβ, clearance ability with Aβ aggregates, and degradation by glia. MG‐PE3 (vs. saline) was then tested in vivo for Aβ clearance performance, in which MG‐PE3 was intravenously injected to 3‐month‐old wild type (WT) and 5xFAD mice at every third day for 3 months. The BBB penetration was examined by IVIS and the chronic efficacy on AD pathology was assessed by analyzing Aβ levels in CSF and plasma, Aβ load, and neuroinflammation.

Result

Aβ aggregation was significantly inhibited in vitro by MG‐PE3. Further, IVIS imaging presented that MG‐PE3 was delivered into the brain of WT and 5xFAD in a concentration‐dependent manner and superior BBB permeability of MG‐PE3 than apoE3. Compared to saline‐treated groups, MG‐PE3‐treated 5xFAD groups showed significantly lower levels of Aβ40 and Aβ42 in plasma and CSF and, more importantly, reduced Aβ burden in cortex and hippocampus, leading to decreased expression of cytokines. Moreover, no evidence of abnormality and toxic effects were observed in major organs in MG‐PE3‐treated 5xFAD.

Conclusion

MG‐PE3, a bioinspired nanoparticle manufacturable with good homogeneity, showed enhanced BBB penetration, effective brain Aβ clearance, and low risk of adverse effects, with excellent potential for ameliorating amyloidosis and AD pathogenesis. Overall, MG‐PE3 is the first therapeutic nanomedicine for promising disease‐modifying treatment for AD.
Exploring the Nexus between Physical and Cognitive Status in Older Adults in South Brazil
Authors: Haas Aline Nogueira , Gonçalves Andréa Kruger , Kanitz Ana Carolina , Martinez Flávia Gomes , Peyré‐Tartaruga Leonardo Alexandre , Martins Valéria Feijó , Castilhos Raphael Machado
Published: January 2025

Background

Low‐middle income countries in Latin America, including Brazil, face a higher prevalence of cognitive decline compared to high‐income countries, leading to social‐economic and healthcare implications. Several studies have showed an association between reduced physical function and cognitive decline. However, there remains a gap in the understanding of this relationship within the older Brazilian population. The main objective of this study is to evaluate the physical function of older adults in South Brazil across different cognitive states.

Method

A cross‐sectional analysis was conducted using baseline data from the “CREM ‐ Center for Aging and Movement Reference: a Controlled Clinical Trial” developed in the Brazilian South Region. A total of 336 community‐dwelling older adults over 60 years of age were categorized into three cognitive states based on established cutoffs points of the Montreal Cognitive Assessment (MoCA): No Cognitive Impairment (NCI), Mild Cognitive Impairment (MCI), and Cognitive Impairment (CI). Timed up and go was used to assess functional mobility; Single‐leg Stance Test to assess static balance; 10‐meter walk test to assess gait; Arm‐curl and 30‐second chair‐stand test, Back Scratch Test and Chair it‐and‐Reach Test, to assess upper and lower‐limb flexibility. The ANOVA was used to determine the main effects of the cognitive level groups (NCI, MCI and CI). A Tukey correction for multiple comparisons was used for the comparisons between groups.

Result

NCI group exhibited superior functional mobility (p<0.001), balance (p<0.001), gait speed (p = 0.002), muscular endurance (p = 0.002), and flexibility (p = 0.007) compared to those with MCI and CI. All physical assessments modalities were able to differentiate the three groups: NCI was the group with better results and the MCI group showed better results than the CI group.

Conclusion

This study strengthens the evidence that cognitive status influences physical function in Brazilian older adults. Identifying specific physical indicators associated with cognitive decline may enhance screening efforts in clinical trials. Longitudinal studies are recommended to elucidate the causal relationship between physical function and cognitive abilities.
Diagnostic Performance of Plasma Biomarkers for A/T/N Image Classification in Alzheimer's disease
Authors: Kim Han‐Kyeol , Lee Jae Hoon , Chun Joong‐Hyun , Lee Jeong‐Ha , West Tim , Kirmess Kristopher M. , Verghese Philip B. , Braunstein Joel B. , Connell Daniel , Ryu Young Hoon , Lyoo Chul Hyoung , Cho Hanna
Published: January 2025

Background

We aimed to validate the ability of Alzheimer’s disease plasma biomarkers to predict clinical diagnosis and the ability to predict image‐based A/T/N biomarkers positivity in Asian population. We also sought to define the optimal cut point for each biomarker.

Method

232 participants were enrolled, all of whom underwent 18F‐florbetaben (FBB), 18F‐flortaucipir (FTP) PET, volumetric MRI, and neuropsychological assessments. Their plasma samples, collected at the time of the imaging scans and stored at ‐80 degrees Celsius, were tested for plasma p‐tau217/np‐tau217 ratio, p‐tau217, Aβ42/40 ratio, and APS2 score at C2N Diagnostics. FBB and FTP positivity were determined based on the SUVR value through a Gaussian mixture model. The presence of hippocampal atrophy was defined as the mean minus 2 standard deviations of amyloid‐negative cognitive unimpaired participants. ROC analysis was conducted to assess the predictive ability and determine the optimal cut‐off point.

Result

The ability to predict FBB PET positivity was excellent for p‐tau217/np‐tau217 ratio, p‐tau217, and APS2 (AUC=0.964, 0.963, and 0.958, respectively) while Aβ42/40 ratio showed lower performance with an AUC of 0.726. The Aβ42/40 ratio did not have the ability to predict FTP positivity, but p‐tau217/np‐tau217 ratio, p‐tau217, and APS2 all exhibited excellent performance with AUC = 0.926, 0.937, and 0.907, respectively. The Aβ42/40 ratio also did not have the ability to predict hippocampal atrophy, while p‐tau217/np‐tau217 ratio, p‐tau217, and APS2 demonstrated good performance (AUC=0.809, 0.815, and 0.811, respectively). Similarly, only the p‐tau217/np‐tau217 ratio, p‐tau217, and APS2 had the ability to differentiate clinical diagnosis while Aβ42/40 ratio failed to distinguish. The AUC‐ROC for p‐tau217/np‐tau217, p‐tau217, and APS2 all showed no significant difference in DeLong’s test when predicting X Y Z. The optimal cutoffs for predicting amyloid, tau and neurodegeneration by p‐tau217/np‐tau217 ratio, p‐tau217 and APS2 showed increases following the progression of AD.

Conclusion

The plasma biomarker using p‐tau217 reflects the clinical status well on its own and is excellent at predicting the positivity of image‐based biomarkers and diagnostic performance. Among the image‐based A/T/N biomarkers, the predictive power was excellent in the order of A, T, and N. The p‐tau217 alone was not inferior to the p‐tau217/np‐tau217 ratio or APS2
Relation Between Educational Attainment and Cerebral Small Vessel Disease: the Framingham Heart Study
Authors: Kang Matthew C , Pinheiro Adlin A , Aparicio Hugo J. , Beiser Alexa S , Pase Matthew P. , Manchanda Riya , Decarli Charles , Seshadri Sudha , Demissie Serkalem , Romero Jose Rafael
Published: January 2025

Background

Socioeconomic factors have an impact on long‐term neurovascular health. Education attainment (EA) is a socioeconomic factor which may be related to vascular risk factors and brain health. We investigated the relation of EA and cerebral small vessel disease (CSVD) in community dwelling participants free of stroke and dementia.

Method

We evaluated 3367 Framingham Heart Study Original and Offspring Cohort participants, categorizing EA into four levels (less than high school, high school graduate, some college, or more). CSVD was assessed via MRI, considering covert infarcts, cerebral microbleeds, cortical superficial siderosis, high perivascular space burden, and extensive white matter hyperintensities, with 1 point assigned for each, to categorize CSVD scores as 0, 1, or 2+. We related education level to the CSVD score using logistic regression analysis with a generalized logits model adjusted for age, sex, and cohort.

Result

Participants without high school degrees had higher CSVD scores (23% had CSVD score 2+ vs 7% in college graduates) and a higher proportion of hypertension and diabetes. There were slightly higher odds of CSVD scores 2+ in those without high school degrees (OR 1.30, 95% CI 0.62 ‐ 2.73 vs. OR 0.81, 95% CI 0.59‐1.12 in participants with some college or more), but not statistically significant after multivariable adjusted analyses. There was a non‐statistically significant suggestion of higher odds of CSVD 2+ among participants with low EA with APOE‐𝜺4 alleles (OR 2.88, 95% CI 0.57‐14.45).

Conclusion

Our findings suggest that lower EA may be linked to CSVD burden, but analyses were limited by a small sample of participants with highest CSVD burden and low EA. Further studies are needed to characterize the role of education, a modifiable risk factor, on vascular brain injury.
qEEG as Biomarker for Alzheimer’s Disease: Investigating Relative PSD Difference and Coherence Analysis
Authors: Simfukwe Chanda , Youn Young Chul , An Seong Soo
Published: January 2025

Background

Electroencephalography (EEG) is a non‐intrusive technique that provides comprehensive insights into the electrical activities of the brain’s cerebral cortex. The brain signals obtained from EEGs can be used as a neuropsychological biomarker to detect different stages of Alzheimer’s disease (AD) through quantitative EEG (qEEG) analysis. This paper investigates the difference in the abnormalities of resting state EEG (rEEG) signals between eyes‐open (EOR) and eyes‐closed (ECR) in AD by analyzing 19‐ scalp electrode EEG signals and making a comparison with healthy controls (HC).

Method

The rEEG data from 534 subjects (ages 40–90) consisting of 269 HC and 265 AD subjects in South Korea were used in this study. The qEEG for EOR and ECR states were performed separately for HC and AD subjects to measure the relative power spectrum density (PSD) and coherence with functional connectivity to evaluate abnormalities. The rEEG data were preprocessed and analyzed using EEGlab and Brainstorm toolboxes in MATLAB R2021a software, and statistical analyses were carried out using ANOVA.

Result

Based on the Welch method, the relative PSD of the EEG EOR and ECR states difference in the AD group showed a significant increase in the delta frequency band of 19 EEG channels, particularly in the frontal, parietal, and temporal, than the HC groups. The delta power band on the source level was increased for the AD group and decreased for the HC group. In contrast, the source activities of alpha, beta, and gamma frequency bands were significantly reduced in the AD group, with a high decrease in the beta frequency band in all brain areas. Furthermore, the coherence of rEEG among different EEG electrodes was analyzed in the beta frequency band. It showed that pair‐wise coherence between different brain areas in the AD group is remarkably increased in the ECR state and decreased after subtracting out the EOR state.

Conclusion

The findings suggest that examining PSD and functional connectivity through coherence analysis could serve as a promising and comprehensive approach to differentiate individuals with AD from normal, which may benefit our understanding of the disease.
Memory Café in Rural Communities: Reflection from Participatory Action Research (PAR)
Authors: Li Eric
Published: January 2025

Background

Memory Café, introduced by Dr. Bere Miesen in 1997, has become a global initiative fostering connections among individuals affected by dementia. This community‐based platform facilitates interactions between dementia patients, caregivers, professionals, and the wider public, allowing for open sharing of experiences. Despite its global success, there remains a gap in research regarding its implementation in rural and remote regions.

Method

Our participatory action research aimed to investigate the impact of Memory Café in interior British Columbia, Canada, over a six‐month period. A multi‐disciplinary team collaborated with stakeholders in three rural communities, employing a multi‐method design to explore various experiences and insights. The research identified three key themes.

Results

Firstly, the study highlighted the importance of “listening” and the creation of “inclusive spaces” in rural and remote communities. Due to heightened social isolation, patients and caregivers expressed a need for spaces like Memory Café, enabling them to openly share challenges. Emphasizing the significance of listening in Indigenous settings, this theme underscored the health benefits for both individuals and communities.

Secondly, operational challenges faced by initiatives like Memory Café were revealed. Uncertainties related to financial and human resources, including volunteers, significantly impacted sustainability in resource‐limited areas. Gaps in government programs and policies were identified, emphasizing a lack of comprehensive support for patients and caregivers.

Lastly, the research highlighted the role of creativity and intergenerational outreach. Arts‐based methodologies were well‐received by participants, presenting an opportunity for innovation.

Conclusion

In conclusion, our research sheds light on both the benefits and challenges of Memory Café in rural and remote communities. Future studies should prioritize exploring mechanisms to sustain community‐based initiatives and develop holistic support systems for dementia patients and caregivers in non‐urban settings.
Differentiating Parkinson‐Plus Syndromes from Other Neurodegenerative Diseases Using Automated T1 MRI Quantification
Authors: Bonke Elena M , Koikkalainen Juha , Tolonen Antti , Hakumäki Juhana , Mecocci Patrizia , Hasselbalch Steen G. , Meester Hanneke F.M. Rhodius‐ , Jasperse Bas , Lemstra Afina Willemina , van der Flier Wiesje M. , Barkhof Frederik , Lötjönen Jyrki
Published: January 2025

Background

Accurate differential diagnosis of neurodegenerative diseases is challenging, but crucial for the management and treatment, particularly given the development of disease‐modifying drug therapies for Alzheimer’s disease (AD). In this work, we investigate imaging biomarkers derived from T1‐weighted magnetic resonance imaging (MRI) with a focus on differentiating Parkinson‐plus syndromes from other relevant diagnostic groups in dementia and Parkinson’s disease (PD).

Method

MR scans from 1206 subjects and three cohorts were used: Parkinson’s Disease Biomarkers Program (PDBP), Amsterdam Dementia Cohort (ADC) and PredictND cohort (PND) (Table 1). The following imaging biomarkers were quantified using an automated image quantification tool: computed medial temporal lobe atrophy score (MTA), computed global cortical atrophy score (GCA) [1], anterior vs. posterior score (APS) [2], the midsagittal areas of the midbrain and pons and midbrain/pons ratio, the volumes of the cerebellum and putamen. Percentiles versus age, sex and head size normalized data were used to calculate sensitivity and specificity. As Parkinson‐plus syndromes are quite rare, a cutoff for each marker was chosen to ensure high specificity and avoid false positives.

Result

Figure 1 shows boxplot visualizations for all investigated imaging biomarkers and diagnostic groups. Table 2 shows the performance in differential diagnosis. 1) The midbrain area best differentiated progressive supranuclear palsy (PSP) from all other diagnostic groups. 2) The combination of pons area and putamen volume best differentiated multiple system atrophy (MSA) from other PD forms. 3) The combinations of pons area and MTA best differentiated MSA from several dementia forms.

Conclusion

Automatic MRI quantification of brain structures such as the midsagittal area of the midbrain and pons, putamen volume and MTA rating can help clinicians to differentiate between common neurodegenerative diseases like AD, vascular dementia and frontotemporal dementia and more Parkinson‐related neurodegenerative diseases like MSA, PSP, and dementia with Lewy bodies.

References:

[1] Koikkalainen et al., European Radiology, 2019

[2] Bruun et al, NeuroImage Clinical, 2019
Associations of resting heart rate with incident dementia, cognition, and brain structure: a prospective cohort study of UK biobank
Authors: Yue‐Ting Deng
Published: January 2025

Background

Resting heart rate (RHR) has been linked with an increased risk of dementia. However, evidence characterizing the associations of RHR with different dementia subtypes and their underlying mechanisms remains scarce. This study aims to investigate the relationships of RHR with different dementia types, cognitive function, and brain structural abnormalities.

Method

Three hundred thirty‐nine thousand nine hundred one participants with no prior diagnosis of dementia from the UK biobank were analyzed. Cox regression and restricted cubic spline models examined the associations between RHR with all‐cause dementia (ACD) and its major subtypes—Alzheimer’s disease (AD) and vascular dementia (VaD). Logistic regression models assessed the associations of RHR with cognitive function, and linear regression models estimated the associations with hippocampal subfield volume and white matter tract integrity indexed by magnetic resonance imaging data.

Result

During an average of 3148 (± 941.08) days of follow‐up, 4177 individuals were diagnosed with dementia, including 2354 AD and 989 VaD cases. RHR ≥ 80bpm was associated with ACD (HR: 1.18, 95% CI: 1.08–1.28, P < 0.001) and VaD (HR: 1.29, 95% CI: 1.08–1.54, P = 0.005) but not AD in multi‐adjusted models. A 10‐bpm increment of RHR demonstrated non‐linear effects in VaD, consisting of J‐shape relationships. Several heterogeneities were indicated in stratified analysis, in which RHR measures only showed associations with dementia incidents in relatively younger populations (age ≤ 65) and females. Apart from dementia analysis, elevated RHR was associated with worsening performance in fluid intelligence and reaction time of cognitive tasks, decreased hippocampal subfields volume, and poor white matter tract integrity.

Conclusion

RHR is associated with increased risks of ACD and VaD but also presented with few heterogeneities across different sex and age groups. Elevated RHR also appears to have deleterious effects on cognitive function and is distinctively associated with volume reduction in hippocampal subfields and impaired white matter tract integrity.
PFTAIRE peptide degrading cyclin Y and ameliorating cognitive deficits in mouse models of Alzheimer’s Disease
Authors: Cho Illhwan , Cha Minhae , Kim Hye Yun , Kim YoungSoo
Published: January 2025

Background

Cyclin Y (CCNY) is a member of cyclin protein family inhibiting long‐term synaptic plasticity, which is related to the learning and memory function in neuronal system. Recently, CCNY has been reported to associate with the cognitive deficits in Alzheimer’s disease (AD).

Method

In this study, we discovered PFTAIRE peptide to diminish CCNY protein level and to ameliorate cognitive dysfunction in AD. This peptide is derived from the domain of cyclin‐dependent kinase 14, a kinase degrading CCNY protein, and this domain is essential for the binding to CCNY. Utilizing solid‐phase peptide synthesis, PFTAIRE peptide was produced.

Result

We observed that PFTAIRE peptide binds to CCNY protein in in vitro studies. We confirmed the plasma and liver microsomal stability of the peptide and the ability to penetrate blood brain barrier. We intravenously injected PFTAIRE peptide to AD mouse models and performed behavior tests. PFTAIRE peptide prevents memory impairments in AD mouse models. In the proteomic analysis of the cortical brain section of mouse models, we observed the alteration of 93 proteins by the PFTAIRE peptide compared to non‐treated groups. Utilizing gene ontology, PFTAIRE peptide up‐regulated proteins related to release/transport neurotransmitter in brain synapse and down‐regulated proteins related to oxidative stress.

Conclusion

Overall, the discovery of PFTAIRE peptide suggests new approach for the development of therapeutics targeting AD.
Chrysin loaded Nanostructured lipid carrier (NLC) drug delivery system: Harnessing neuroprotective effects in the management of Alzheimer’s Disease
Authors: Khandale Nikhil B , Birla Devendra S , Bashir Bushra , Singh Sachin Kumar , Vishwas Sukriti , Gulati Monica , Dua Kamal
Published: January 2025

Background

Alzheimer’s Disease (AD) poses a substantial global health burden, necessitating innovative therapeutic strategies. This study investigates the neuroprotective potential of a chrysin‐loaded Nanostructured Lipid Carrier (NLC) drug delivery system in AD management. Employing the high‐pressure homogenization method, chrysin‐loaded NLCs were meticulously formulated to optimize drug delivery efficiency. The research explores the multifaceted neuroprotective effects of chrysin, a naturally occurring flavonoid, within the context of AD pathology. The intricate mechanisms of action underlying the chrysin‐loaded NLCs are elucidated, shedding light on their potential to modulate key pathways implicated in AD progression. This study advances our understanding of tailored drug delivery systems, specifically highlighting the therapeutic promise of chrysin‐loaded NLCs for the nuanced management of Alzheimer’s Disease.

Method

To overcome these challenges, a Nanostructured lipid carrier (NLC) for Chrysin was devised, employing quality by design (QbD) based Box‐Behnken design (BBD). NLC offers numerous advantages, encompassing increased drug loading, facile preparation, exceptional stability, as well as enhanced bioavailability and permeability across the blood‐brain barrier.

Result

The optimized Chrysin‐loaded NLC formulation exhibited Particle Size, PDI, zeta potential, and drug loading as 66.45nm, 0.19, ‐22mV, and 98% respectively. The formulation was found to be stable after six months in accelerated stability studies. The formulation underwent various pharmacodynamic studies. Pharmacodynamic studies assessed cognitive and motor functions in rats, revealing significant improvements in cognition with both low and high doses respectively. Additionally, the biochemical investigations revealed that the Chrysin‐loaded NLCs effectively decreased the levels AChE enzyme, amyloid β, oxidative stress, and neuroinflammation.

Conclusion

This study explores Chrysin‐loaded NLCs as a solution for challenges in Alzheimer’s Disease (AD) treatment. The optimized formulation overcomes Chrysin’s solubility issues, demonstrating improved bioavailability and permeability. Chrysin‐loaded NLCs hold promise as a neuroprotective for AD.