bluuebunny/crossref_metadata_2025 huggingface dataset:
Concordance between biomarkers in cerebrospinal fluid (CSF), brain positron emission tomography with 18‐fluorodeoxyglucose (18F‐FDG‐PET) and clinical diagnosis in patients with cognitive impairment
Authors: Mimenza Alberto Jose , del Ángel Karen Leon , Martínez Rodrigo Hernández , Aguilar‐Navarro Sara Gloria
Published: January 2025

Background

The diagnosis of neurodegenerative diseases such as dementia due to Alzheimer's Disease (AD) and other dementias continues to be a challenge. The use of complementary studies in diagnosis is recommended in the main clinical guidelines for this pathology. Biomarkers in CSF (Aβ42, tTau and pTau) and by brain [18F]FDG‐PET are useful for diagnosis, since they increase its certainty. Objective: Establish diagnostic agreement between biomarkers in CSF, PET and clinical evaluation.

Method

Cohort, retrospective and comparative study. Patients with biomarkers were included for the diagnostic approach of cognitive impairment due to any cause in the INCMNSZ from July 2018 to September 2023. An analysis of concordance was carried out with the Kappa coefficient between the result of the biomarkers and the clinical assessment.

Result

77 patients were evaluated, with an average age of 71 years (SD ± 10.19) and 53.2% were men; 27.3% with a diagnosis of mild cognitive impairment (MCI) and 72.7% with dementia. The agreement between the initial diagnosis and the hypometabolism patterns by PET was moderate (kappa 0.461, p=0.011). The overall agreement between the biomarkers to differentiate between AD and other dementias was 88% (kappa 0.694, p=0.002). The change in diagnosis after taking the biomarkers occurred in 46% of the patients.

Conclusion

This study demonstrates that the agreement between the use of CSF and PET biomarkers to differentiate between AD and other dementias is good. There was disagreement in 12% of the patients, which suggests that in cases with diagnostic doubt it is advisable to perform both biomarkers.
Complement proteins C1q, C3, and Factor H are associated with early tau pathology and synaptic integrity in persons with pre‐symptomatic Alzheimer’s disease
Authors: Loncke Julia , Picard Cynthia , Labonté Anne , Zetterberg Henrik , Blennow Kaj , Brinkmalm Ann , Breitner John C.S. , Poirier Judes ,   The PREVENT‐AD Research Group
Published: January 2025

Background

The immune complement system is key to the elimination of redundant neural connections in the brain through a process called synaptic pruning. In neurodegenerative diseases such as Alzheimer's disease (AD), this system may result in excessive synapse loss, leading to brain atrophy and cognitive impairment. While increased cerebrospinal fluid (CSF) levels of complement proteins have been observed in patients with AD dementia, no studies have yet investigated the role of complement in the pre‐symptomatic phase of AD, nor throughout its progression.

Method

We used Luminex technology to assess complement protein levels in 566 CSF samples obtained over five years from 160 high‐risk asymptomatic subjects with familial history of AD [the PREVENT‐AD cohort; Breitner et al, 2016: JPAD 3,(4) 236]. Baseline complement levels were contrasted with CSF biomarkers of AD pathology (Aβ42, p(181) and total tau, NFL) and markers of synaptic dysfunction (GAP‐43, SYT1, SNAP‐25, ADAM22, ADAM23). Analyses were stratified by sex and ApoE4 carrier status. Currently pending are additional longitudinal analyses probing complement levels versus PET‐quantified cerebral amyloid and tau deposition, MRI volume of AD‐implicated structures, and cognitive ability (RBANS).

Result

Preliminary analyses revealed significant positive associations between complement proteins and p‐(181)tau (C1q: R2 = .238, p < .0001; C3: R2 = .041, p = .0099; C3b: R2 = .027, p = .0384; Factor H: R2 = .128, p < .0001) and total tau levels (C1q: R2 = .247, p < .0001; C3: R2 = .023, p = .0543; Factor H: R2 = .128, p < .0001). Complement relationships with synaptic protein levels were more significant overall in females, which showed the following associations [GAP‐43 (C1q: R2 = .389, p < .0001; Factor H: R2 = .315, p = .0002); SNAP‐25 (C1q: R2 = .367, p < .0001; C3: R2 = .106, p = .0459; Factor H: R2 = .278, p = .0072); SYT1 (C1q: R2 = .316, p = .0002; Factor H: R2 = .246, p = .0015)].

Conclusion

There is a clear association between complement levels, tau pathology, and synaptic markers in the asymptomatic phase of AD, especially in women. Longitudinal and multimodal investigation is ongoing to further characterize these relationships.
Culturally adapted intervention regarding decision‐making on feeding options for Chinese American dementia caregivers: A human‐centered approach
Authors: Pei Yaolin , Wang Jing , Schulman‐Green Dena , Fried Terri , Hanson Laura , Wu Bei
Published: January 2025

Background

Studies show that tube feeding does not improve clinical outcomes, and professional guidelines recommend against its use for individuals with advanced dementia. Yet, our preliminary work demonstrates a preference for tube feeding among Chinese‐American dementia caregivers. We propose linguistic and cultural adaptation of “Making Choices: Feeding Options for Patients with Dementia (MCFODA) to create the Chinese version of this efficacious decision aid intervention. The study aims to inform the process and domains of the cultural adaptation.

Method

The first step of the adaptation process is interviews with Chinese‐American dementia caregivers to learn about their decision‐making experiences around feeding options. To identify participants, we collaborated with Caringkind, an agency of servicing dementia caregivers, and used purposive sampling. We began conducting semi‐structured interviews via Zoom with a target sample of 25. Participants completed a brief demographic questionnaire. Audio recordings were transcribed in Chinese and translated into English by a multilingual research assistant. Thematic analysis was used in this study.

Result

Caregivers reported various strategies to prevent choking and ensure patients’ healthy eating, including adding thickness, blending food, and making soup. Caregivers and other family members participated in decision‐making regarding feeding options. To maintain family harmony, timely communication about patients’ health status is one of the important strategies they used for the family decision‐making about feeding options. Factors affecting family decision‐making of whether to use tube feeding included the PLWD’s health status, other people’s end‐of‐life experience of using tube feeding, PLWD’s preferences toward tube feeding and personality, the cultural importance of food, and caregivers’ perception of comfort in feeding options. PLWD’s wishes were perceived as important in decision‐making. However, family were often unaware of these wishes, as they had not been discussed, although some PLWDs expressed their wishes indirectly by discussing other people’s experience in movies or TV drama. Chinese translators were reported as critical during discussions between Chinese families and health care providers.

Conclusion

Engaging end‐users in the adaptation of MCFODA will optimize development of the culturally adapted intervention. For Chinese Americans, we plan to summarize caregivers’ practices used to manage PLWD’s eating, provide suggestions for good family communication, and how to identify PLWD’s wishes.
Importance of Speed of First Attempted Contact in Alzheimer’s Trial Participation
Authors: Starling Sarah , Sanz Madeleine , Chukwu Chiamaka , Albano John , Evans Miriam , Rutrick Stephanie
Published: January 2025

Background

Identifying strategies to engage with potential participants is critical for efficient enrollment in Alzheimer’s Disease (AD) trials. Previous studies link faster speed of first contact with successful phone interview completion for Major Depressive Disorder (MDD) participants. This has not been examined in AD participants. We explored how first contact speed impacts the likelihood of AD participants completing a phone screen and how quickly that phone screen happened following initial contact.

Method

Our sample includes prospective AD trial participants recruited from January to November 2023 via Facebook and Google ads. Contact information was submitted online, followed by a recruiter‐conducted phone interview. A voicemail was left for non‐responsive participants, along with an automated text and additional follow‐up calls in the following days. This analysis investigates how time lag between online submission and the first attempted recruiter call impacts completion rates of phone screens and how quickly that phone screen occurred following initial contact.

Result

From January to December 2023, 6881 individuals applied to participate in AD trials through online advertisements. Time to first attempted call ranged from under an hour to 227 days, with 95.4% occurring within 72 hours. 46% of applicants eventually communicated with a recruiter. Longer delays to first call decreased the likelihood of reaching the potential participant across all calls (β = ‐.001, p<.001) and just those made in the first 72 hours (β = ‐.024, p<.001). Calls made within 24 hours yielded a 47.9% success rate, compared to 42.7% for 24‐48 hours, and 39.4% for 48‐72 hours. Unlike for MDD, time to the first attempted call wasn’t predictive of participants answering the first call (p = .334). It did, however, positively correlate with the number of business days between first call and eventual communication with the participant (r = .136, p<.001).

Conclusion

These findings suggest that minimizing delay from a participant’s online submission to a recruiter’s first attempted call increases the likelihood of the participant completing a phone screen and shortens the time between that call and when the phone interview occurs. As fewer than half of potential participants ever spoke with a recruiter, future efforts should explore additional outreach strategies.
Evaluation of the prospective use of blood biomarkers for Alzheimer’s disease in primary and secondary care
Authors: Palmqvist Sebastian , Salvadó Gemma , Mattsson‐Carlgren Niklas , West Tim , Smith Ruben , Ossenkoppele Rik , Schindler Suzanne E. , Blennow Kaj , Monane Mark , Verghese Philip B. , Braunstein Joel B. , Janelidze Shorena , Stomrud Erik , Tideman Pontus , Hansson Oskar
Published: January 2025

Background

An accurate blood test for Alzheimer’s disease (AD) could streamline the diagnostic work‐up and treatment of AD. Our aim was to evaluate an AD blood test in primary and secondary care, using predefined biomarker cutoffs and prospective analyses of plasma samples.

Method

940 prospective and unselected patients seeking medical evaluation for early cognitive symptoms were included. Plasma %p‐tau217 and Aβ42/40 was measured using mass spectrometry and the Amyloid Probability Score‐2 (APS2) combining these values was calculated. Predefined cutoffs were established in an independent training cohort and were applied to primary (n=307) and secondary care (n=300) cohorts comprised of patients undergoing cognitive evaluation where plasma samples were analyzed in single batches. The blood test was then evaluated prospectively in primary (n=100) and secondary (n=234) care patients where plasma samples were analyzed bi‐weekly. The main outcome was amyloid status as determined by cerebrospinal fluid AD biomarker positivity.

Results

In primary care, 51% of patients were AD pathology positive and were diagnosed with the following: 25% subjective cognitive decline (SCD), 47% mild cognitive impairment (MCI), and 28% dementia. In secondary care 49% were AD pathology positive and diagnoses were 21% SCD, 43% MCI, and 36% dementia. Using single batch analyses in primary care, the AUC for APS2 was 0.97 (95% CI 0.95–0.99), PPV 91% (87–96%), and NPV 92% (87–96%); in secondary care, the AUC was 0.96 (0.94–0.98), PPV 88% (83–93%), and NPV 87% (82–93%). When samples were analyzed prospectively in primary care, the AUC was 0.97 (0.95–1.00), PPV 90% (81–99%), and NPV 90% (82–98%); in secondary care, the AUC was 0.97 (0.94–0.99), PPV 92% (86–97%), and NPV 89% (83–94%). Primary care physicians accurately identified AD in 58% of patients after a standard work‐up versus 89% (83–95%) for APS2 (p<0.001). Dementia experts had a diagnostic accuracy of 74% (69–80%) versus 90% (86–94%) for APS2 (p<0.001). At AAIC, we will also present prospective data using plasma p‐tau217 immunoassay‐based tests.

Conclusions

Highly accurate AD blood tests might improve the diagnostic work‐up of individuals with cognitive symptoms in primary and secondary care. Future studies are needed to further evaluate these tests prospectively in primary care of other countries.
Plasma Tau Biomarkers for Alzheimer's Disease Staging
Authors: Montoliu‐Gaya Laia , Salvadó Gemma , Ashton Nicholas J. , Janelidze Shorena , Nilsson Johanna , Mattsson‐Carlgren Niklas , Weiner Sophia , Palmqvist Sebastian , Rodriguez Juan Lantero , Brinkmalm Gunnar , Stomrud Erik , Zetterberg Henrik , Gobom Johan , Blennow Kaj , Hansson Oskar
Published: January 2025

Background

Plasma phosphorylated tau (p‐tau), particularly p‐tau217, has demonstrated its reliability as a biomarker for diagnosing Alzheimer's disease (AD). Coming challenges in the field include determining whether quantifying additional plasma phosphorylated, and non‐phosphorylated tau species could enhance diagnostic accuracy, prognosis, and improve patient monitoring by effectively staging the disease.

Method

We used a mass spectrometric targeted method to simultaneously quantify the levels of six different phosphorylated (p‐tau 181, 199, 202, 205, 217 and 231), and six non‐phosphorylated (0N CNS‐specific, 1N CNS‐specific, tau195‐209, tau212‐221, PNS‐specific 7‐14, PNS‐specific 151‐167) tau peptides in plasma. We analyzed a total of 553 samples from participants in the BioFINDER‐2 cohort, with available amyloid‐PET ([18F]flutemetamol, n=358) and/or tau‐PET ([18F]RO‐948, n=458). We studied how plasma levels were increased in participants based on amyloid‐ and tau‐PET status (A‐/A+, T‐/T+) and PET stages based on amyloid positivity and tau positivity in early (medial temporal lobe [MTL]) and intermediate regions (neotemporal [NeoT]).

Result

Visual inspection of locally estimated scatterplot smoothing (LOESS) analyses showed that the levels of specific plasma tau markers became abnormal (z‐score>2, >95%CI of CU‐) at different stages in relation to Tau‐PET SUVR (ordered: p‐tau217, p‐tau205, 0N CNS‐specific, and tau212‐221). We then created a 5‐step disease staging model based on the positivity for these biomarkers and compared them with stages based on amyloid and tau PET status (Figure 1) and PET‐based stages (Figure 2). In stage‐1 (negative for all plasma biomarkers), 80.8% of participants were A‐T‐ and 19.2% were A+T‐. In stage‐2 (p‐tau217+), only 3.4% were A‐T‐, 40.9% were A+T‐ and 55.7% were A+T+. Specifically, 22.6% were MTL+NeoT‐, 22.6% MTL+NeoT+, and 31% MTL+NeoT++. In stages‐3 and ‐4 (p‐tau217+ p‐tau205+, and p‐tau217+ p‐tau205+ 0N CNS‐specific+) all participants were A+MTL+, and 83.3%‐86.7% were also NeoT+ or NeoT++. Finally, in stage‐5 (all markers positive), 100% of the participants were A+T+ and they all were A+MTL+NeoT++.

Conclusion

Plasma tau species exhibit sequential changes, and our data supports the notion of staging AD using fluid biomarkers. The stages identified in plasma may not necessarily correspond to PET imaging stages. Future analyses will focus on determining the utility of plasma‐based staging model for prognosis.
Multi‐analyte measurement of blood biomarkers for Alzheimer's disease: enabling concurrent analysis of affected pathophysiological processes
Authors: Zeng Xuemei , Lafferty Tara K , Sehrawat Anuradha , Chen Yijun , Ferreira Pamela C.L. , Bellaver Bruna , Povala Guilherme , Kamboh M. Ilyas , Klunk William E , Lopez Oscar L. , Pascoal Tharick A. , Villemagne Victor L , Ganguli Mary , Cohen Ann D , Karikari Thomas K
Published: January 2025

Background

Alzheimer’s disease (AD) is a multifaceted condition associated with various brain pathologies, necessitating diverse biomarkers for precise prognosis, diagnosis, clinical management, and therapeutic development/evaluation. The integration of multiple biomarkers into a single test can enhance efficiency, reduce analytical errors, and save on specimen volume. Alamar Biosciences recently introduced the NULISAseq CNS disease panel, a multiplex NUcleic acid‐linked Immuno‐Sandwich Assay (NULISA) targeting ∼120 analytes. This includes classical amyloid, tau, and neurodegeneration biomarkers and allows for key proteins defining various disease hallmarks. However, its performance in assessing AD pathologies remains undetermined.

Method

The NULISAseq CNS disease panel was applied to 264 plasma samples from two independent cohorts (Human Connectome and MYHAT‐NI), encompassing cross‐sectional and longitudinal specimens. Wilcoxon rank sum tests and Spearman rank‐based correlations were used to determine the significance of the association between NULISAseq measurements and neuroimaging‐based assessment of AD pathologies. Classical AD biomarkers (p‐tau181, p‐tau217, p‐tau231, GFAP, NEFL, and amyloid beta peptides Aβ40 and Aβ42), along with cytokines IL6 and TNF, were also measured using alternative immunoassays (Simoa and Quest) in a subset of samples for cross‐platform validation.

Result

The NULISAseq CNS disease panel measured a total of 116 targets with robust reproducibility, showing mean intra‐plate and inter‐plate coefficients of variation (CVs) of 5.2% and 7.6%, respectively. Consistent concordance was observed between NULISAseq measurements and those obtained with Simoa or Quest assays, with Spearman’s correlation coefficients up to 0.874. NULISAseq measurements demonstrated strong predictive capability for amyloid burden and neurodegenerative status and, to a lesser extent, for tau pathology. Specifically, NULISAseq measurements of p‐tau217, p‐tau231, and GFAP exhibited strong correlations with amyloid burden, while GFAP and NEFL displayed robust correlations with neurodegeneration. In addition to these classical AD biomarkers, several NULISAseq targets, such as TIMP3, SOD1, and SQSTM1, demonstrated significant associations with AD pathologies.

Conclusion

The NULISAseq CNS panel provides reliable and comprehensive measurement of classical AD biomarkers and other key proteins in neurodegenerative diseases, establishing it as a valuable tool for AD biomarker discovery and validation studies. Concurrent evaluation of markers will be critical to the implementation of the revised AT(N) framework to include an expanded set of multiple biological processes.
TMS‐EEG excitability measures are related to global and local cognitive function in early symptomatic AD
Authors: Buss Stephanie S. , Ozdemir Recep , Passera Brice , Fried Peter J. , Manning Daniel , Woods Isabelle , Desmond Grace , Shaughnessy Lynn , Press Daniel Z. , Shafi Mouhsin
Published: January 2025

Background

Cortical excitability is elevated in Alzheimer’s disease (AD). Transcranial magnetic stimulation‐evoked responses on electromyography (EMG) and electroencephalography (EEG) have captured this increased excitability in motor brain regions. However, it is not yet known if increased excitability is also present in the parietal lobe or the extent to which excitability is related to cognition.

Method

TMS‐EEG data from 29 participants with biomarker‐confirmed AD (CDR 0.5‐1, age 57‐81, 45% female) and 38 cognitively unimpaired older controls (CDR 0, age 57‐89, 59% female) were analyzed. Single‐pulse TMS was applied to left motor cortex (M1) and inferior parietal lobule (IPL) at 120% of resting motor threshold (RMT) and 135% of RMT (in 12 AD and 22 controls). The early (15‐40 msec) TMS‐evoked local mean field amplitude (LMFA) was assessed from electrodes near each TMS target. Group differences in LMFA were assessed separately for each site and intensity, controlling for age, sex, and scalp‐to‐cortex distance. A subset of AD participants had cognitive testing scores available for the Assessment Scale‐Cognitive subscale (ADAS‐Cog, n=10) and a Parietal Composite Score (averaged z‐scores of Benton Judgement of Line Orientation, ADAS‐Cog Maze 3 time, and WRAT 4 Math, n=13). Cognitive scores were related to LMFA at each site and intensity using separate linear models.

Result

In M1, 135% RMT evoked a larger LMFA in AD than in older controls (R2adj=0.17, p=0.036). Visual inspection of the M1 135% RMT evoked responses also revealed higher local responses in AD (Figure 1). There were no between‐group differences for other conditions (p‐values > 0.100). In AD, higher M1 LMFA at 135% RMT was related to worse global cognition on the ADAS‐Cog (R2adj=0.68, p=0.002, Figure 2a), but not the Parietal Composite Score. Higher IPL LMFA at 120% RMT was related to worse performance on the Parietal Composite Score (R2adj =0.38, p=0.015, Figure 2b), but not the ADAS‐Cog.

Conclusion

TMS‐EEG reveals elevated motor‐area excitability in AD. Excitability measures showed a double‐dissociation with cognition: motor excitability is related to global cognition and parietal excitability is related to parietal function. TMS‐EEG may be useful to measure target engagement for future therapies seeking to restore normal neuronal excitability in AD.
White Matter Hyperintensities and Cholinergic Degeneration as Lewy Body Disease
Authors: Kang Sungwoo , Jeon Seun , Ye Byoung Seok
Published: January 2025

Background

To investigate the relationship between basal forebrain (BF) cholinergic activity, dopaminergic degeneration, white matter hyperintensities (WMHs), and their effects on clinical manifestations of Alzheimer’s disease (AD) and Lewy body disease (LBD).

Method

A total of 407 subjects who underwent 3‐T MRI, dopamine transporter (DAT) positron emission tomography, neuropsychological tests, and assessments for parkinsonism, cognitive fluctuation (CF), visual hallucination (VH), and rapid eye movement sleep behavior disorder (RBD) were evaluated for probable AD, LBD, or both (AD+LBD). General linear models were used to investigate the relationships between BF volume (BFV), striatal DAT uptake, WMHs, and clinical manifestations after controlling for age, sex, education, vascular factors, and intracranial volume. Quantitative analyses of DAT uptake in the anterior caudate (AC), posterior caudate (PC), anterior putamen (AP), and posterior putamen (PP) and assessment of WHMs in the anterior/posterior periventricular (PWMH‐A/PWMH‐P) and deep regions (DWMH‐A/DWMH‐P) were performed.

Result

DAT‐AC was positively associated with BFV. DAT‐AC was negatively associated with PWMH‐A, but not with DWMHs, independent of BFV. Both DWMHs and PWMHs were associated with hypertension and the number of microbleeds and lacunae. Lower BFV and DAT‐AC were independently associated with increased risk of CF and VH, whereas lower DAT‐AC was additionally associated with an increased risk of RBD and higher parkinsonian severity. Lower BFV and DAT‐AC were independently associated with widespread cognitive impairment, whereas higher PWMH‐A was associated with executive dysfunction.

Conclusion

Cholinergic degeneration in the BF and PWMH‐A levels are closely associated with dopaminergic degeneration. PWMH‐A may be a manifestation of axonal alterations caused by the interplay between LB‐related degeneration and vascular pathologies.
Evidence‐based comprehensive overview of research quality, effectiveness of interventions, and practice‐based principles for clinicians supporting people who present with changed behaviours associated with dementia and for family care partners
Authors: Burns Kim , Casey Anne‐Nicole S. , Brodaty Henry
Published: January 2025

Background

Guidelines that provide current and comprehensive overviews of the evidence quality and effectiveness of interventions that address behaviours and psychological symptoms associated with dementia (BPSD, also known as Changed Behaviours) are needed for clinicians, professional care staff and family care partners. With funding provided by the Australian Government Department of Health and Aged Care, we aimed to update the existing Behaviour Management: A Guide to Good Practice, Managing Behavioural and Psychological Symptoms of Dementia (2012) text and app resources to reflect findings from the most recent literature and other sources.

Methods

We systematically searched PubMed, Medline, Embase, and PsycINFO for psychosocial and environmental and biological and pharmacological interventions published between 2012‐2021 that addressed BPSD. We reviewed identified studies, rated research quality using predetermined criteria, calculated effect sizes where possible, and synthesised the moderate to strong quality evidence and advice from the most recent clinical guidelines. The final updated resource was reviewed by frontline expert advisors and dementia support specialists working with people with lived experience.

Results

We identified 420 studies of psychosocial and environmental interventions and 221 studies of biological/pharmacological interventions for review and rating. The final updated resource A Clinician’s BPSD Guide 2023: Understanding and helping people experiencing changed behaviours and psychological symptoms associated with dementia includes moderate to strong quality evidence from 348 studies of psychosocial and environmental interventions and 178 studies of biological/pharmacological interventions. Sections detailing additional considerations for Aboriginal and Torres Strait Island peoples and those from culturally and linguistically diverse backgrounds with dementia are included.

Conclusions

Published research evidence relating to interventions to support people living with dementia who experience changed behaviours has increased dramatically in volume and quality since 2012. Future advances will necessitate ongoing evidence updates. The 2023 Clinician’s BPSD Guide provides a comprehensive overview of evidence and practice‐based principles for supporting people who present with behaviours and psychological symptoms associated with dementia (BPSD) and their family care partners. Travel size summary versions A Clinician’s Field Guide 2023 and A Guide for Carers 2023, and mobile apps A Clinician’s BPSD Guide and CareForDementia (c4d) are also available. All are free to download1.
The Role of Social Support for Caregivers of Persons Living with Dementia (PLwD) in Hospice: A Secondary Analysis
Authors: Cho Hannah , Huang Liming , Oliver Debra Parker , Washington Karla , Demiris George
Published: January 2025

Background

There are 55 million persons living with dementia (PLwD) today, projected to 139 million by 2050. As they progress towards dementia’s advanced stages, hospice care becomes crucial to manage their symptoms and the caregiver burden. Solo family caregivers, particularly lacking in social support, are vulnerable to deteriorating physical and mental well‐being. Previous studies highlighted adequate social support as one factor consistently related to better caregiver outcomes; yet there is a significant gap in our understanding of their experiences in hospice settings. This study examines the moderating factors for hospice family caregivers, exploring the relationship between social support, anxiety, depressive symptoms, and physical health.

Method

This is a secondary analysis of baseline data from an ongoing study testing a behavioral intervention for caregivers. Participants were adult caregivers of PLwD who completed the Generalized Anxiety Disorder – 7, the Patient Health Questionnaire – 9, the Medical Outcome Study‐ Social Support Survey, and demographic information. A statistical analysis including descriptive statistics, Pearson correlation and linear regressions was performed.

Result

One hundred fifty‐seven adults were enrolled in the time frame of this study. Most caregivers were female (63.05%) and average age was 60 (SD 13.52). By regressing physical health, anxiety and depressive symptoms on social support respectively, we found that having more social support is significantly associated with less depressive symptoms (b = ‐.047, p = .029) and improved physical health (b = .273, p = .0001) and the direction and significance of these relationships still hold after adjusting for employment changes (i.e., quitting or reducing working hours) (p = .013, p = 0.001). Controlling for caregiver age, depressive symptoms decrease when social support increases (b = ‐.053, p = .034).

Conclusion

In a hospice setting, inadequate social support significantly elevates depression risk for caregivers of PLwD. Being a primary caregiver, having more hours of caregiving, and seeking support and resources from reducing or quitting a job could affect their physical and mental well‐being. Further examination of these findings will inform supportive strategies for families of PLwD.
Tapping into a new hand‐motor biomarker of the dementia continuum ‐ integration and validation in a cognitive clinic
Authors: Wang Xinyi , Bindoff Aidan , George Rebecca J St , Lawler Katherine , Noyce Alastair J , Bai Quan , Tran Son , Salmon Katharine , Vickers James C , Alty Jane E
Published: January 2025

Background

The process for assessing cognitive symptoms in clinic is time consuming, expensive and usually requires multiple clinicians. There is an urgent need for accessible, quick and low‐cost methods to aid identification of people at the early stages of the dementia continuum. Emerging evidence shows that simple hand movement tests could aid risk stratification. We evaluated the classification accuracy of the new online TAS Test alternate tapping test in the ISLAND Cognitive Clinic in Tasmania, Australia, for dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) from control subjects.

Method

212 participants (69.0 ± 9.3 years old) were recruited: 130 from the Clinic (50 diagnosed with dementia, 54 with MCI, 26 with SCD) and 82 cognitively healthy controls. All Clinic participants had a gold‐standard interdisciplinary consensus diagnosis after detailed neuropsychological tests and completed a 60‐second alternate key tapping test on the TAS Test website during their standard clinic visit. Healthy controls completed the Addenbrookes Cognitive Examination with a score of 95 or higher and TAS Test in clinic. Frequency, variability, key press duration and accuracy scores were calculated. Regression models comprising all motor features, adjusted for age and sex, were compared to their respective null models, comprising age and sex, with area under ROC curves (AUC).

Result

Compared to the baseline model, tapping motor data improved classification of people with dementia (AUC = 0.89, 95% CI = [0.84,0.95], p=0.025), MCI (AUC = 0.8, 95% CI = [0.73,0.87], p=0.002) and SCD (AUC = 0.75, 95% CI = [0.63,0.86], p = 0.004) from cognitively healthy controls. The motor features also helped distinguish dementia (AUC = 0.9, 95% CI = [0.84,0.97], p = 0.024) and MCI (AUC = 0.79, 95% CI = [0.67,0.91], p = 0.022) from SCD, but not dementia from MCI (p = 0.221).

Conclusion

A 60‐second simple keyboard tapping test helped distinguish people with SCD, MCI, or dementia from cognitively healthy controls and holds potential as a new low‐cost and clinically‐accessible motor biomarker.
Digitial memory test for detecting and assessing cognitive impairment in parkinson's disease
Authors: Pei Zhong
Published: January 2025

Background

The objectives of the study is to assess the clinical utility of the MemTrax Memory Test for detection of cognitive impairment in patients with PD.

Method

The MemTrax and Montreal Cognitive Assessment (MoCA) were administered to 61 healthy controls (HC), 102 PD patients with normal cognition (PD‐N), 74 PD patients with mild cognitive impairment (PD‐MCI) and 52 PD patients with dementia (PD‐D). The MemTrax performance, MTx‐%C, MTx‐RT and MTx‐Cp, and the MoCA scores were comparatively analyzed. The MemTrax performances were assessed according to the areas under the receiver operating characteristic curve.

Result

The MoCA scores were similar between HC and PD‐N, however, MTx‐%C and MTx‐Cp were lower in PD‐N than HC(p<0.05). MTx‐%C, MTx‐Cp and the MoCA scores were significantly lower in PD‐MCI versus PD‐N and in PD‐D versus PD‐MCI (p ≤ 0.001), while MTx‐RT was statistically longer in PD‐D versus PD‐MCI (p ≤ 0.001). For the PD groups, the MemTrax performance strongly correlated with the MoCA scores. To detect PD‐MCI, the optimal MTx‐%C and MTx‐Cp cutoff were 75% and 50.0, respectively. To detect PD‐D, the optimal MTx‐%C, MTx‐RT and MTx‐Cp cutoff were 69%, 1.341s and 40.6, respectively.

Conclusion

The MemTrax provides rapid, valid and reliable metrics for assessing cognition in patients with PD that could have practical clinical utility for identifying PD‐MCI at early stage and monitoring cognitive function decline during the progression of disease.
Relationship between Health Decision‐Making Roles and Subjective Memory Ability among Older Adults in Rural Community
Authors: Park Myonghwa , Kim Jinju , Kim Heejung , Seo Eunkyung , An Wonmi
Published: January 2025

Background

Older adults in rural areas often face the challenge of managing their health decisions due to limited access to medical services. Cognitive function, particularly the awareness and assessment of one’s memory abilities, plays a significant role in the decision‐making process. This study investigates the relationship between subjective memory ability and health‐related decision‐making among older adults in rural areas.

Methods

This research was conducted as a secondary analysis using data from a broader health advancement project in a rural South Korean locality. It examined the roles in health decision‐making, categorizing them into three: active (making decisions independently), shared (making decisions with family members), and passive (having decisions made by family members). Subjective memory ability was assessed on a scale from 0 to 10, reflecting perceived memory ability.

Results

The study involved participants with an average age of 75 years. It found that 47.0% assumed active roles, 48.3% shared roles, and 4.6% passive roles in health decision‐making. Women predominantly assumed active roles (51.7%), while men were more likely to be in shared (50.1%) and passive roles (6.1%). Active roles peaked among those aged 70‐79 (48.1%), shared roles were most common under 70 (50.2%), and passive roles increased after 80 (10.0%). Regarding education, active roles were most frequent among college‐educated individuals, shared roles among middle/high school graduates, and passive roles among those with the least education. The average subjective memory ability scores varied with decision‐making roles: 5.85 for active roles, 5.77 for shared roles, and 4.57 for passive roles. Lower subjective memory ability scores were associated with a higher likelihood of assuming passive roles (p = .001).

Conclusion

The study demonstrates that those with lower subjective memory ability scores tend to adopt passive roles, underscoring the influence of perceived autonomy on decision‐making. Therefore, developing support strategies that empower older adults, particularly those with cognitive challenges, to actively participate in their healthcare decisions is essential. Involving families in this process is also important, considering the preferences and cognitive capabilities of older adults.
Effect Of Horseradish (Moringa Oleifera) Seeds on Biochemical and Molecular Parameters in Paraquat‐Induced Parkinson Disease‐Like Symptoms in Fruit Flies
Authors: Aro Olayemi Philemon , Adefegha Adeniyi Stephen , Ogunsuyi Opeyemi Babatunde , Oboh Ganiyu
Published: January 2025

Background

In recent decades, epidemiological and experimental studies have looked into the role of pesticides, particularly the herbicide paraquat, in the development of Parkinson’s disease. Horseradish tree (Moringa oleifera) is an ethnobotanical plant with lots of therapeutic potential, but there is a dearth of information on the bioactive properties of the seed alkaloid extracts.

Method

This study examined the modulatory effects of various concentrations of an alkaloid extract from the seeds of Horseradish Tree (Moringa oleifera) on the survival rate of flies exposed to paraquat, as well as certain biochemical and molecular markers related to Parkinson’s disease in the heads of the flies.

Result

The findings showed that the survival rate of the treated flies was significantly (p<0.05) higher than that of paraquat‐induced flies. The catalase and total thiol content of the flies were found to be significantly lower in the paraquat‐induced flies, but this was ameliorated in the treated groups. In addition, when compared to their elevated levels in paraquat‐induced flies, monoamine oxidase and acetylcholinesterase activities in the treated groups were found to be significantly (P<0.05) reduced. In addition, the enhanced reactive oxygen species (ROS) of the paraquat‐induced groups were significantly reduced after being treated with alkaloid extracts. The findings of gene expression demonstrate that catalase and tyrosine hydroxylase (TH) mRNA expression levels were downregulated in the induced group but elevated in the treated groups, with the seed showing a significant upregulation in catalase expression compared to tyrosine hydroxylase (TH) mRNA expression.

Conclusion

According to the findings of this study, alkaloid extracts from Moringa seeds ameliorated impaired biochemical indices and, at the same time, upregulated genetic expression in paraquat‐induced flies. The results of this research indicate that extracts from M. oleifera seeds have neuroprotective potential, especially as it relates to Parkinson’s disease.
APOEε4 drives microglial activation in the medial temporal cortex in individuals across the AD spectrum
Authors: Ferrari‐Souza João Pedro , Lussier Firoza Z , Leffa Douglas Teixeira , Therriault Joseph , Tissot Cécile , Bellaver Bruna , Ferreira Pamela C.L. , Povala Guilherme , Benedet Andrea L. , Servaes Stijn , Stevenson Jenna , Rahmouni Nesrine , Macedo Arthur C. , Soucy Jean‐Paul , Gauthier Serge , Souza Diogo O. , Zimmer Eduardo R. , Rosa‐Neto Pedro , Pascoal Tharick Ali
Published: January 2025

Background

Microglial activation is an early phenomenon in Alzheimer’s disease (AD) that may occur prior to and independently of amyloid‐β (Aβ) aggregation. Compelling experimental evidence suggests that the apolipoprotein E ε4 (APOEε4) allele may be a culprit of early microglial activation in AD. However, it is unclear whether the APOEε4 genotype is associated with microglial reactivity in the living human brain. In individuals across the aging and AD spectrum, we tested the hypothesis that APOEε4 associates with microglial activation.

Method

We studied 118 individuals (79 cognitively unimpaired [CU], 23 with mild cognitive impairment [MCI], and 16 with AD dementia) from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort. Individuals had available [18F]AZD4694 Aβ PET, [18F]MK6240 tau PET, [11C]PBR28 microglial activation PET, and magnetic resonance imaging (MRI), as well as APOE genotyping. To increase the reliability of our results, we only included high‐affinity binders for the [11C]PBR28 radiotracer. In a subgroup of 42 individuals with longitudinal clinical and MRI data, we further assessed longitudinal hippocampal atrophy and clinical deterioration.

Result

Voxel‐wise analysis revealed that APOEε4 carriership was associated with increased [11C]PBR28 uptake mainly in the medial temporal cortex (Figure 1A and B), and this effect of APOEε4 was independent of Aβ and tau accumulation. Region‐wise analyses demonstrated that APOEε4 carriers presented increased [11C]PBR28 SUVR relative to noncarriers only in Braak I‐II regions (Figure 1C), which further supports that APOEε4‐related microglial activation occurs specifically in medial temporal structures. Lastly, we found that [11C]PBR28 uptake in brain regions vulnerable to APOEε4 effects is associated with subsequent hippocampal atrophy and clinical decline over 2 years (Figure 2).

Conclusion

These results support a model in which APOEε4 plays a role in early AD progression by contributing to microglial activation in medial temporal regions. Our findings provide a rationale for the development of novel AD therapies targeting the interplay between ApoE and neuroinflammation.
Generation and validation of anti‐TREM2 agonistic antibodies to enable the advancement of drug targets in the TREM2/DAP12 signaling pathway for the treatment of Alzheimer Disease
Authors: Moussaif Mustapha , Javens‐Wolfe June , Palkowitz Alan D. , Richardson Timothy I.
Published: January 2025

Background

TREM2 signaling has been implicated in Alzheimer’s Disease (AD). TREM2 regulates microglial states and functions such as phagocytosis. The most prominent TREM signaling adapter is DAP12, encoded by TYROBP. Understanding functional changes of this complex, and downstream effectors such as SHIP1, PLCG2 and the Scr family kinases Lyn and Hck, is required to evaluate a broad range of therapeutic hypotheses and drug targets for prioritization and enablement. The lack of available, well validated, and openly distributed experimental tools can limit early drug discovery efforts. Therefore, the IUSM Purdue TREAT‐AD Center has generated and validated TREM2 activating antibodies to enable the advancement of drug targets in the TREM2/DAP12 signaling pathway.

Method

To establish and validate anti‐TREM2 agonist antibodies, heavy and light chain variable sequences were identified from multiple publications including patent applications. Antibodies were formatted as either human IgG1, Fc null mutant IgG1 or antibody transport vehicle (ATV) Fc null mutant IgG1. They were expressed in mammalian ExpiCHO cells and tested ex vivo for agonism based on their ability to activate AKT and Syk phosphorylation in THP1 cells and TREM2/DAP12 overexpressing cells respectively. The strongest agonistic candidate was scaled, purified, and further characterized biophysically and functionally.

Result

Several agonistic antibodies were identified. AL2p31 antibody showed binding specificity to human versus murine TREM2. Biophysical characterization using biolayer interferometry showed that binding kinetic parameters (KD, Kon, and Koff) were not significantly affected in LALAPG null mutant Fc background. AL2p31 specifically induced Syk phosphorylation in comparison to an isotype control. Analysis of antibodies formatted as bispecific IgG1 targeting both TREM2 and the human transferrin receptor (hTfR), confirmed that RS9‐F6 can bind both human and murine TREM2 and revealed the ATV 35‐21‐16 variant sequence as a binder for the hTfR.

Conclusion

The mission of the IUSM Purdue TREAT‐AD Center is to enable and advance the next generation of drug targets for the treatment of AD. The validation of anti‐TREM2 agonistic antibodies as research tools will enable comprehensive studies of the TREM2/DAP12 signaling and potential drug targets within the pathway including SHIP1, PLCG2 and the Scr family kinase Lyn and Hck.
Confabulation and Fluctuating Memory: A Case of Alzheimer’s Dementia in a Culturally Diverse Patient
Authors: Dahroug Nada , Siddig Nidhal , Mezzoni Mayra , Abdelrahman Nadir G
Published: January 2025

Background

Confabulation, the fabrication of details with short lucid intervals, hinders the diagnosis of Alzheimer’s and other dementias. This case report explores the complexities of diagnosing and managing Alzheimer’s dementia in a culturally diverse patient exhibiting fluctuating memory and confabulation, emphasizing challenges heightened by cultural and linguistic factors.

Case

An 84‐year‐old African descent man resided with his family in the United States, independent in his basic daily activities but struggling with instrumental tasks due to memory impairment. While demonstrating clear recollection at times, closer examination revealed fabricated details and disorientation regarding his current environment. Confabulation in this trilingual patient (English, German, and Arabic) posed additional challenges, necessitating a closer look at his cultural background, language barriers, and family dynamics. The patient was born and raised in Africa. He relocated recently to join his family in the US. The family was involved in managing medication adherence and therapeutic interventions. A specialist evaluated the patient, and the Montreal Cognitive Assessment (MoCA) indicated a score of 12/30, signifying moderate cognitive impairment. The assessment considered language nuances, cultural influences, and familial support. Laboratory tests were grossly unremarkable. Donepezil and Vitamin B12 were prescribed to the patient. Family members were educated regarding the use of storytelling as a therapeutic approach.

Result

Family involvement played a pivotal role in holistic care coordination. Despite prescribed medications, the family has not initiated treatment due to the risks of side effects. Melatonin was used as needed for sleep disturbances. Predominantly non‐pharmacological treatment approaches were implemented, including reorientation and redirection. Storytelling as a therapeutic approach was effective.

Conclusion

This case underscores the significance of culturally sensitive approaches in cognitive assessment and holistic care coordination, emphasizing the need for continued research on Alzheimer’s presentation in diverse populations. The abstract serves as an invitation to discuss effective strategies for diagnosing and managing Alzheimer’s dementia in culturally diverse patients, promoting inclusivity and optimal care.
Correlation between blood biomarkers and neuropsychiatric symptoms: Siriraj cohort, Thailand
Authors: Senanarong Vorapun , Rattanabannakit Chatchawan , Nanthasi Witsarut , Wongkom Natthamon , Dujada Pathitta , Phoyoo Paphawadee , Wachirutmangur Lertchai
Published: January 2025

Background

We explored the relationship of neuropsychiatric symptoms (assesses by NPI) and Alzheimer disease pathophysiology from blood AB42/40, GFAB, NFL, and pTau181. We also investigated if age and cognition were related to these neuropsychiatric symptoms.

Method

222 subjects included 96 dementia, 66 MCI, and 60 normal controls (NC). Spearman correlation was used to calculation the correlation coefficient. Mann‐Whitney U test is used to compare biomarkers of those with and without subitem symptoms of NPI.

Result

Mean ages were 71.26±9.82 years old in dementia group, 68.83±8.01 years old in MCI group, and 59.28±9.22 years old in NC group. Sum of 12 NPI subscale scores showed significant low correlation (r=0.20‐0.29) were correlated with blood AB42/AB40, Ptau 181, NFL, and GFAB. Sum of 12 NPI subscale scores showed significant moderate correlation with age and global cognition (assessed by Thai mental state examination, TMSE). Blood pTau181 displayed low correlation with hallucination, depression, anxiety, apathy, and irritability subscale scores. There was a significant low correlation between blood AB42/AB40 and delusion and irritability subscale scores. Blood NFL showed low correlation with euphoria, a, apathy, disinhibition, irritability, and aberrant motor activity. Inflammation process appeared to be significantly related with psychosis, apathy, disinhibition, and irritability. After controlled by age and TMSE; only apathy and AMA NPI subscale scores were correlated to NFL and GFAB accordingly.

Conclusion

We discovered that psychosis and mood factors of NP symptoms were related to blood pTau. While most frontal factors of NP symptoms showed significant relationship with axonal destruction and microglia activation/inflammation.

This study was supported by grants from Health Systems Research Institute (HSRI), Thailand.