bluuebunny/crossref_metadata_2025 huggingface dataset:
Myelin water imaging with clinically feasible scan time: The accelerated BMC‐mcDESPOT (aBMC‐mcDESPOT) method
Authors: Bae Jonghyun , Gong Zhaoyuan , Guo Alex , Laporte John P , Faulkner Mary E , Bouhrara Mustapha
Published: January 2025

Background

In 2016, we introduced the Bayesian Monte Carlo analysis of multicomponent‐driven equilibrium observation of T1 and T2 (BMC‐mcDESPOT) MRI method for myelin water fraction (MWF) mapping, a surrogate of myelin content. While BMC‐mcDESPOT has been extensively applied to study brain aging, dementias, and risk factors influencing myelination, it still requires a lengthy acquisition time (∼17 min) which hampers its integration in clinical studies and trials. In this study, we aim to accelerate the BMC‐mcDESPOT method for whole brain, high‐resolution, MWF mapping within clinically feasible scan time of ∼6 min.

Method

Data Acquisition

Reference data (ref‐BMC, no‐acceleration): Two subjects underwent the BMC‐mcDESPOT protocol consisting of SPGR and bSSFP images at 10 different FAs. For assessing reproducibility, three sets of fully‐sampled datasets were collected without any under‐sampling (total acquisition time =17 min).

Compressed sensing acceleration (cs‐BMC): Three sets of accelerated scans were acquired using compressed sensing (CS) with an acceleration factor of ∼2 (9 min) (Figure 1(a)).

Image domain acceleration (du‐BMC): The undersampling in the data domain was retrospectively performed on the bSSFP images by selecting only 2 optimal images instead of the full 10 images (12 min) (Figure 1(b)).

Combined accelerations (aBMC): The above two acceleration methods were combined and resulted in an acquisition time of ∼6min. (Figure 1(c))

Data Processing

We estimated MWF maps from the different undersampling methods described above. The accuracy was evaluated between the MWF from the reference and those from each undersampled dataset. The reproducibility was measured with the coefficient of variations (CoV) across different measurements for each sampling method. We also performed Bland‐Altman analysis to quantify bias and limits of agreement (LOA).

Result

Figure 2 shows a representative slice of MWF estimates from different sampling methods. The different acceleration methods showed similar regional patterns, with relatively low errors (du‐BMC/cs‐BMC/aBMC=10.8/9.8/13.7%) and CoV (ref‐BMC/du‐BMC/cs‐BMC/aBMC=9.0/14.3/10.7/15.3%). While a slight bias in the derived MWF values was observed (Figure 3), the LOA for aBMC was under 5% in white matter.

Conclusion

aBMC‐mcDESPOT is a practical MRI method for accurate determination of MWF within 6 min, offering unique opportunities to further integrate myelin imaging in clinical studies and trials.
ECT‐AD: Baseline Demographics of a Novel Therapeutic Intervention for Severe Agitation and Aggression in Dementia
Authors: Forester Brent P. , Merrill Julia G. , Hermida Adriana P. , Lapid Maria I. , Mueller Martina , Nykamp Louis J. , Patrick Regan E. , Mattingly Jefferson , Seiner Steve J. , Petrides Georgios
Published: January 2025

Background

Effect and Safety of Electroconvulsive Therapy plus Usual Care for the Acute Management of Severe Agitation in Dementia (ECT‐AD) is a multi‐site NIA‐funded FDA‐regulated pioneering clinical trial to investigate the effectiveness of electroconvulsive therapy (ECT) in treating severe and treatment‐refractory agitation and aggression among individuals with advanced dementia, a condition that has a profound negative impact on patient quality of life and caregiver burden. Here we present baseline demographics of the patient population in this ongoing trial.

Method

To date we have enrolled 18 participants, with a mean age of 74.1 years, where majority are male (61.1%). The racial composition is predominantly White (94.4%), with Asian representation (5.6%, 1/18), and with 11.1% (2/18) identifying as Hispanic or Latino. Dementia subtypes in our cohort include Alzheimer’s disease (AD, 77.8%), vascular dementia (VaD, 16.7%, 3/18), and frontotemporal dementia (FTD, 5.6%, 1/18).

Result

Baseline assessments reveal severe cognitive and functional impairment, as indicated by a mean Mini‐Mental State Examination (MMSE) score of 4.0, Barthel Index (BI) score of 52.2, and SIB‐8 score of 2.9, all consistent with advanced stages of dementia. High mean total scores on the Cohen‐Mansfield Agitation Inventory (CMAI, 75.8), Neuropsychiatric Inventory (NPI) agitation (15.1) and aggression (9.2) scales, and Pittsburgh Agitation Scale (PAS, 7.8), reflect the severe levels of agitation and aggression in our participants.

Conclusion

These baseline demographic and clinical data underscore the profound impact of advanced dementia, highlighting the need for innovative treatment approaches like ECT. The ECT‐AD trial offers a critical step towards understanding and improving the management of agitation in dementia, with implications that could enhance current clinical care practices.
Whispered Struggles in the Workplace: A Scoping Review of Cognitive and Interpersonal Challenges and Organizational Strategies for Employees living with Dementia
Authors: Jindal Shruti , Pit Sabrina , Hamiduzzaman Mohammad
Published: January 2025

Background

Dementia, including its younger‐onset variant, increasingly challenges diverse workplaces, affecting both employees living with dementia and their employers. With a growing global trend of individuals extending their working years, it becomes crucial to understand the specific challenges and implications for those with dementia within various employment contexts. This review delves into the cognitive, interpersonal, and organizational challenges faced by employees living with dementia across a broad range of workplaces, reflecting the evolving dynamics of today’s work environment.

Method

In this scoping review, we employed Arksey and O’Malley’s framework, using a structured approach to explore the intersection of dementia and employment. Our methodology, shaped by the PRISMA‐P guidelines, involved a systematic search in PubMed and PsycINFO for studies published from 2000 onwards. We utilized a comprehensive set of search terms and Boolean operators, focusing on the experiences and challenges faced by employees living with dementia. This included assessing workplace adjustments, organizational support strategies, and employee well‐being. The selection criteria were defined to include studies that specifically addressed cognitive and interpersonal challenges in the workplace, avoiding broader dementia‐related topics to maintain focus on our research objectives.

Result

The review systematically identified key areas of concern and gaps in the current literature regarding dementia in the workplace. It underlined the necessity for workplace adjustments, including flexible hours and modified job responsibilities, to support employees with dementia. The role of organizations in facilitating appropriate workplace accommodations and support strategies, such as supportive supervision and access to tailored occupational health services, was also a significant finding. More importantly, this scoping review identified critical questions for future investigation, including the efficacy of current workplace adjustments, the role of policy in shaping organizational support, and the long‐term impact of such accommodations on both the employee with dementia and workplace dynamics.

Conclusion

This review underscores the need for comprehensive workplace strategies and policy reforms to support employees with dementia, highlighting the critical role of organizational support and flexibility.
Underlying mechanisms for altered reactivity of posterior cortical electroencephalographic alpha rhythms in DLB and PDD
Authors: Lizio Roberta , Percio Claudio Del , Noce Giuseppe , Lopez Susanna , Jakhar Dharmendra , Carpi Matteo , Arnaldi Dario , Güntekin Bahar , Yener Görsev , Ferri Raffaele , Frisoni Giovanni B. , Babiloni Claudio
Published: January 2025

Background

The amplitude of resting‐state electroencephalographic (rsEEG) rhythms is a promising neurophysiological biomarker to investigate the abnormalities of oscillatory neurophysiological thalamocortical mechanisms related to the general cortical arousal and vigilance in wakefulness in patients with dementia due to neurodegenerative diseases as Alzheimer’s disease (ADD), Parkinson’s disease (PDD) and Lewy Body disease (DLB). Here, we tested the hypothesis that the reactivity of posterior rsEEG alpha (about 8‐12 Hz) rhythms during the transition from eyes‐closed to ‐open condition may be lower in PDD patients than in DLB patients.

Methods

A Eurasian database provided clinical‐demographic‐rsEEG datasets in 35 ADD patients, 65 PDD patients, 30 DLB patients, and 25 matched cognitively unimpaired (Healthy) persons. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands, as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. The eLORETA freeware was used to estimate cortical rsEEG sources.

Results

Results showed substantial (i.e., greater than ‐10%) reduction (reactivity) in the posterior alpha source activities from the eyes‐closed to the eyes‐open condition in 88% of the Healthy seniors, 53% of ADD patients, 53% of the DLB patients, and only 37% of the PDD patients (Figure 1). In these alpha‐reactive participants, there was lower reactivity in the posterior alpha source activities in the three neurodegenerative (i.e., ADD, PDD, and DLB) groups than in the Healthy group. Furthermore, the reduction of the occipital alpha reactivity was stronger in the PDD and DLB groups than in the ADD group. Finally, the reduction of the parietal alpha reactivity was stronger in the PDD group than in the ADD and DLB groups (Figure 2).

Conclusion

These results suggest that ADD, PDD, and DLB patients may be characterized by very poor reactivity in the posterior cortical mechanisms desynchronizing rsEEG alpha rhythms in relation to increased vigilance levels as an interesting neurophysiological biomarker. This biomarker may be used as a primary endpoint for interventions with drugs or brain electromagnetic stimulations to improve vigilance regulation and quality of life in neurodegenerative patients, allowing them to follow TV programs and interactions in their social environment.
Ultra‐widefield retinal and choroidal vascular architecture in mild cognitive impairment and normal cognition
Authors: Joseph Suzanna , Haystead Alice , Robbins Cason B , Threlfall Adam , MacGillivray Tom , Stinnett Sandra , Grewal Dilraj S , Fekrat Sharon ,   iMIND research group
Published: January 2025

Background

Mild cognitive impairment (MCI) is currently a clinical diagnosis characterized by decline in memory and daily cognitive function from baseline. Exploratory studies using optical coherence tomography angiography have reported alterations in the retinal capillary plexus vessel density and attenuation of the retinal nerve fiber layer, but these results appear to be mixed. We used ultra‐widefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared to controls with normal cognition.

Method

A cross‐sectional comparison of patients with MCI compared to cognitively normal controls. Scanning laser ophthalmoscopy (SLO) (California, Optos Inc, Marlborough, MA) was used to obtain UWF fundus color images. Images were analyzed with the Vasculature Assessment Platform for Images of the Retina (VAMPIRE) software. Measured metrics included vessel width gradient, vessel width intercept, large vessel choroidal vascular density, vessel tortuosity, and vessel fractal dimension.

Result

131 eyes of 82 MCI patients and 231 eyes of 133 cognitively normal participants were analyzed. Both retinal artery and vein width gradients were less negative in MCI vs. controls, demonstrating decreased rates of vessel thinning towards the periphery (p < 0.001, p = 0.027). Retinal artery and vein width intercepts, a metric that extrapolates vessel width at the center of the optic disc, were smaller in MCI patients vs controls (p < 0.001, p = 0.017). The large vessel choroidal vascular density was greater in MCI patients vs controls (p = 0.025).

Conclusion

When compared to controls with normal cognition, MCI patients had overall thinner retinal vasculature manifested in both the retinal arteries and veins. Furthermore, in MCI, these thinner arteries and veins attenuated at a lower rate when traveling towards the periphery, when compared to controls, perhaps because they were already more attenuated posteriorly. MCI patients also had increased choroidal vascular density.
Correlation between ERP and CSF biomarkers in Mild Cognitive Impairment and Dementia patients in a general neurological clinic population
Authors: Levy Igor
Published: January 2025

Background

We have recently reported on the use of Event‐Related Potentials (ERP) biomarkers to separate Amyloid PET positive vs Amyloid PET negative patients with mild cognitive impairment (MCI) and dementia.

A large body of evidence shows that low levels of beta amyloid and increased tau in the CSF are highly correlated with Alzheimer’s pathology in the brain. We investigated the correlation between amyloid and tau in the CSF, and ERP responses in patients with MCI and dementia.

Method

Patients with MCI and Dementia in a general neurological outpatient clinic underwent ERP testing. CSF analyses for Amyloid and TAU were also performed, and the results correlated with the output from the ERP test. When CSF studies were indeterminate, readings for brain amyloid brain load were obtained through PET analysis as part of the IDEAS (Imaging Dementia ‐Evidence for Amyloid Scanning) study when feasible

Result

Data will be presented at the conference with correlation between ERP markers and CSF amyloid and tau levels in patients with MCI and dementia.

Conclusion

Study results will provide valuable insights into the use of ERPs in a general neurological population with Alzheimer’s disease and cognitive impairment.
Cerebrospinal fluid proteomics identifies biomarkers for discriminating amyloid PET and tau PET stages
Authors: Wang Zhibo , Chen Yuhan , Jia Jianping
Published: January 2025

Background

Staging Alzheimer's disease pathology is critical for therapeutic trials and prognosis. Disease staging with amyloid and tau PET provides high accuracy, but this would be more practical with fluid biomarkers. However, current fluid biomarkers are deficient in tracking specific disease stages, especially in advanced stages.

Method

Participants (N=115) were enrolled from the Alzheimer’s Disease Neuroimaging Initiative who had available CSF proteomics and amyloid and tau PET. The proteomic analysis involved approximately 6000 unique CSF proteins measured by SomaScan 7K. A least absolute shrinkage and selection operator (LASSO) regression combined with machine learning approach was employed to develop proteomic predictive models for amyloid PET and tau PET stages. Finally, we compared the model's performance with established CSF Alzheimer's biomarkers (amyloid‐β [Aβ]42, phosphorylated tau [p‐tau]181, and total tau [t‐tau]).

Result

We identified 38 proteins associated with amyloid PET and 128 proteins with tau PET in the amyloid PET‐positive participants. These proteins are primarily related to glucose metabolism and neurotrophic function. Through machine learning, 17 proteins were selected for the panel to differentiate amyloid and tau PET stages. Of these, 9 proteins were specific for distinguishing between amyloid PET‐negative and tau PET‐negative (A‐T‐) and amyloid PET‐positive and tau PET‐positive (A+T‐) (e.g., SMOC1, NEFH), 4 for discriminating A+T‐ and amyloid PET‐positive and tau PET‐positive in the temporal neocortex (A+TNEO+) (e.g., TMOD2, CRNN), with 4 common to both categories (e.g., MMP10, PPIB). We found that a maximum of 8 and a minimum of 2 proteins effectively differentiated A+TNEO+ from A+T‐ (area under curve range: 0.9‐1), and a maximum of 13 and a minimum of 4 proteins discriminated A+T‐ from A‐T‐ (area under curve range: 0.82‐0.92) (Figure 1). The discriminative performance of these protein panels was significantly superior to the established CSF Alzheimer's biomarkers, with or without the addition of risk factors in the models (Figure 2), which we validated using autopsy data.

Conclusion

In conclusion, assessing a limited set of proteins can accurately determine distinct pathological stages of Alzheimer's disease, addressing the limitations of current fluid biomarkers in identifying specific disease stages.
Auranofin Alleviates Cognitive Deficit Induced by Cladribine in Experimental Rats
Authors: Aran Khadga Raj
Published: January 2025

Background

A purine nucleoside called cladribine has been shown to increase toxic amyloid protein and cause impaired cognition. Auranofin is a gold(I)‐containing drug with anti‐inflammatory, antioxidant, anti‐apoptotic, anti‐amyloidogenic, and neuroprotective properties. The goal of the current study was to find out the neuroprotective effects of auranofin against cladribine‐induced Aβ accumulation associated with AD‐like symptoms in experimental rats.

Method

1 mg/kg, p.o. Cladribine, followed by 5, 10 mg/kg, i.p. auranofin, was given to Wistar rats for 28 days, and behavioral parameters were performed. On day 29, Wistar rats were sacrificed, and the hippocampus part of the brain was isolated for estimation of pro‐neuroinflammatory markers, biochemicals, neurotransmitters, and molecular pathways analysis.

Result

Rats administrated with cladribine showed elevated cytokine release, oxidative stress, biochemical changes, and a dysbalanced concentration of neurotransmitters. However, auranofin treatment dose‐dependently increased concentrations of antioxidant enzymes decreased the release of proinflammatory cytokines and neurotransmitters and enhanced recognition and spatial memory in rats. Auranofin downregulated tau phosphorylation, Aβ (1–42) levels and regeneration of hippocampal cells. Moreover, the auranofin restoration of the neuroprotective mechanism includes anti‐inflammatory, antioxidant, anti‐apoptotic, anti‐amyloidogenic, and neurotransmitter restoration. Auranofin treatment improved spatial and recognition memory in Wistar rats, restored concentrations of neurotransmitters, antioxidant enzymes and slowed down the release of proinflammatory cytokines in a dose‐dependently way. Additionally, auranofin cleared the accumulation level of Aβ (1–42) and enhanced the Na+/K+‐ATPase activity in the hippocampal cells. Additionally, the histopathological results showed that auranofin mitigates the neuronal death caused by cladribine in the hippocampus.

Conclusion

We can conclude that auranofin reduced amyloid‐β (1–42), tau phosphorylation levels, and neurotransmitter balance and improved Na+/K+‐ATPase activity.
Association of Cerebrospinal Fluid BACE1 with Amyloid pathology and Neurodegeneration in Alzheimer disease
Authors: Gao Feng , Shen Yong , Zhang Mengguo
Published: January 2025

Background

The exact impacts of β‐site APP cleaving enzyme (BACE1) on brain atrophy and cognitive decline in the Alzheimer’s disease (AD) remain not fully understood. This study aimed to investigate the relationship between BACE1 in cerebrospinal fluid (CSF) and amyloid‐β (Aβ) pathology, neurodegeneration and cognitive function.

Method

This study involved 359 participants from original individuals of the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort, who underwent measurements of AD biomarkers. Among them, 259 individuals underwent baseline structural magnetic resonance imaging (MRI) scans, 101 individuals underwent 18F‐labeled florbetapir (AV45) positron emission tomography (PET) scans and 117 individuals received 18F‐labeled fluorodeoxyglucose (FDG) PET scans. Additionally, 95 participants underwent follow‐up cognitive tests, and 81 participants received follow‐up structural MRI scans.

Results

Out of the 359 participants, 216 (60.17%) were women. The mean [SD] age was 62.18 [8.48] years, and the mean [SD] follow‐up times for MRI and cognitive tests were 1.52 (0.55) years and 1.79 (0.87) years, respectively. CSF BACE1 levels were elevated in patients with mild cognitive impairment caused by AD or AD. CSF BACE1 levels were correlated with soluble Aβ40 (β = 0.469, p < .001) and Aβ42 (β = 0.174, p = .001), but not AV45‐PET signal. Furthermore, CSF BACE1 levels were positively associated with cortical thickness in specific brain regions, including the insula and supramarginal areas. BACE1 was also linked to cortical glucose metabolism in frontal and supramarginal areas after adjusting regional Aβ burden. Additionally, the longitudinal study revealed that elevated BACE1 levels were associated with reduced cortical thinning in specific brain regions and less cognitive decline (β = ‐0.219, p = .05) over time.

Conclusions

While increased CSF BACE1 is involved in promoting Aβ production, higher levels of BACE1 are associated with better cortical thickness and cognitive function. Maintaining the normal physiological function of BACE1 in the brain is important for cognitive function.
Functional connectivity patterns among clinical variants of progressive supranuclear palsy
Authors: Sintini Irene , Ali Farwa , Stephens Yehkyoung C. , Clark Heather M. , Stierwalt Julie A.G. , Josephs Keith A. , Whitwell Jennifer L.
Published: January 2025

Background

Progressive supranuclear palsy (PSP) can present with different clinical variants which show distinct, but partially overlapping, patterns of neurodegeneration and tau deposition in a PSP network of regions, including cerebellar dentate, superior cerebellar peduncle, midbrain, thalamus, basal ganglia, and frontal lobe. We sought to determine whether disruptions in functional connectivity within this PSP network measured using resting‐state functional MRI (rs‐fMRI) differed between PSP‐Richardson’s syndrome and the cortical and subcortical variants of PSP.

Method

Structural MRI and rs‐fMRI scans were collected for 40 PSP‐RS, 24 PSP‐cortical (12 speech and language; 10 corticobasal syndrome; 2 frontal) and 36 PSP‐subcortical (18 parkinsonism; 11 progressive gait freezing; 6 postural instability; 1 oculomotor) participants who met the Movement Disorder Society PSP clinical criteria (Table 1). Ninety‐six participants underwent flortaucipir‐PET scans. MRIs were processed using CONN Toolbox. Functional connectivity between seeds placed throughout the PSP network was compared between each PSP group and 83 healthy controls, and between the PSP groups, covarying for age and sex.

Results

Connectivity was reduced throughout the network in PSP‐RS compared to controls (Figure 1A), involving cerebellar dentate, midbrain nuclei, subthalamic nuclei, basal ganglia, thalamus, and frontal regions. Frontal regions showed reduced connectivity to other regions in the network in PSP‐cortical, including substantia nigra and superior cerebellar peduncle. Disruptions in connectivity in PSP‐subcortical were less pronounced, with the strongest disruption between the pallidum and putamen. When PSP groups were compared to each other (Figure 1B), PSP‐RS had lower connectivity from the thalamus and cerebellar dentate to the cortex compared to PSP‐subcortical and from the thalamus to substantia nigra than PSP‐cortical. PSP‐subcortical had lower connectivity from the subthalamic nucleus to caudate than PSP‐RS and from the subthalamic nucleus to substantia nigra than PSP‐cortical and higher connectivity from the thalamus to the prefrontal cortex than both the other variants. Voxel‐based analyses replicated these patterns. There was moderate evidence that tau uptake in the PSP network regions influenced connectivity between these regions in PSP.

Conclusions

Patterns of disrupted functional connectivity revealed both variant‐specific and shared disease pathways among PSP variants, providing insight into the disease heterogeneity beyond patterns of atrophy.
Multi‐omic blood biomarkers and cognitive profiles discriminate causes of younger‐onset neurocognitive symptoms: a cohort study
Authors: Bhalala Oneil G , Beamish Jessica , Summerell Patrick , Porter Tenielle , Laws Simon M , Kang Matthew , Huq Aamira , Eratne Dhamidhu , Walterfang Mark , Farrand Sarah , Evans Andrew H , Kelso Wendy , Watson Rosie , Yassi Nawaf , Velakoulis Dennis , Loi Samantha M
Published: January 2025

Background

Younger‐onset neurocognitive symptoms result from a heterogenous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the BeYOND (Biomarkers in Younger‐Onset Neurocognitive Disorders) cohort, a study of individuals less than 65 years old presenting with neurocognitive symptoms for a clinical diagnosis and who have undergone cognitive and biomarker analyses.

Method

65 participants were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia. Specific diagnoses were clinically determined and categorised as either early‐onset Alzheimer’s disease (AD, n=18), non‐AD neurodegeneration (nAD‐ND, n=23) or primary psychiatric disorders (PPD, n=24). Using Simoa technology, blood levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated‐tau at threonine 181 (p‐tau181), amyloid‐β1‐40 (Aβ40), Aβ42 and Aβ42/40 ratio were measured. Apolipoprotein E (APOE) genotypes and polygenic risk scores (PRSs), based on genome‐wide association studies for late‐onset AD, were determined. Generalized linear and multinomial models, as well as information‐theoretic model selection, were used to identify discriminatory factors, adjusted for age and sex.

Result

NfL, GFAP and p‐tau181 levels were up to 3‐fold higher in individuals with AD compared to nAD‐ND and PPD (Dunn‐adjusted p<0.05). Aβ‐species levels were not significantly different between the groups. While the PRS was not associated with diagnostic categories (p=0.25), a higher PRS was associated with increased NfL and GFAP levels (OR=1.08, p<0.05). Multi‐omic model selection identified various combinations of NfL and p‐tau181 levels, APOE genotype and global cognitive function as parsimonious models that discriminated between AD and PPD with AUC≥0.975 (95% CI: 0.925–1.000). A model containing only p‐tau181 significantly discriminated between AD and nAD‐ND causes (AUC=0.950, 95% CI: 0.877–1.000). Multinomial regression models identified NfL, GFAP and p‐tau181 as significant variables for discriminating between the three diagnostic categories (p<0.0005).

Conclusion

Discriminating between AD, nAD‐ND and PPD causes of younger‐onset neurocognitive symptoms is possible using a combination of cognitive profiling with protein and genetic biomarkers. These results support utilising blood biomarkers for work‐up of younger‐onset neurocognitive symptoms as well as highlight the need for the development of a younger‐onset AD‐specific PRS.
Association of serum‐based mitophagy biomarkers and spatial navigation performance in Alzheimer´s disease
Authors: Laczó Martina , Veverova Katerina , Svacova Zuzana , Katonova Alzbeta , Fang Evandro Fei , Hort Jakub , Vyhnalek Martin , Laczó Jan
Published: January 2025

Background

Mitophagy is a process of intracellular protein homeostasis through which cells eliminate senescent and dysfunctional mitochondria. Altered mitophagy contributes to Alzheimer´s disease (AD) pathology and is associated with worse cognitive functions. We evaluated association of levels of mitophagy proteins (ULK1, BNIP3L, PINK1, and TFEB in serum and ULK1 and PINK 1 in cerebrospinal fluid [CSF]) with spatial egocentric (body‐centered) and allocentric (world‐centered) navigation performance, which is typically impaired in early stages of AD.

Method

Participants with AD aMCI (n=39), mild AD dementia (n=19), and cognitively normal (CN) older adults (n=20) underwent cognitive assessment and brain MRI. Diagnosis of AD was supported by positivity of AD biomarkers in CSF or amyloid PET imaging. Spatial navigation assessment was performed using real‐space and computerized versions of a human analog of the Morris Water Mate Test (hMWM). The hMWM had four tasks: first, with start position and landmarks (combined allocentric‐egocentric), second, only with start position (egocentric), third, only with landmarks (allocentric), and fourth, with landmarks after 30 minutes (allocentric delayed).

Result

Levels of mitophagy proteins in the CN group were not associated with performance in any of the spatial navigation tasks (ps > .091). In the AD aMCI group, higher levels of CSF PINK1 were associated with more accurate spatial navigation performance in the computerized egocentric‐allocentric task (r = ‐0.39; p = .030) and the association of higher levels of CSF ULK1 with worse spatial navigation performance in computerized allocentric delayed task approached statistical significance (r = 0.36; p = .054). Levels of mitophagy proteins in the AD dementia group were not associated with performance in any of the spatial navigation tasks (ps > .068).

Conclusion

Higher level of CSF PINK1 was associated with more accurate egocentric‐allocentric spatial navigation performance in computerized task and higher levels of CSF ULK were associated with worse allocentric navigation performance. These findings support the hypothesis that normal cognition requires efficient mitophagy and more research is needed to evaluate the role of various mitophagy markers in AD.
Correlations between white matter microintegrity and risk level of allostatic load in cognitive complaint subjects
Authors: Contreras Patricio Riquelme , Henriquez Fernando , Godoy Claudio Román , Buller‐Peralta Ingrid , Campo Cecilia Gonzalez , Thumala Daniela , Lillo Patricia , Okuma Cecilia , Demanet Michele , Damm María Francisca , Alvez Pamela Guevara , Wael El‐Deredy , Muniz‐Terrera Graciela , Chonchol Andrea Slachevsky
Published: January 2025

Background

Chronic exposition to stressor factors has been postulated as a cause of structural changes in the brain in the context of dementia. One of these changes can be the fiber integrity loss, that can be measured by diffusion tensor imaging (DTI). We obtained DTI whole brain metrics to relate them with allostatic load in subjects of a chilean cohort of cognitive complaint subjects.

Method

We selected 135 subjects of a chilean cohort of cognitive complaint subjects and classified based in MoCA test in subjects with (58) (MCI) and without (77) (SCC) cognitive decline groups. To measure AL, we selected 15 metabolic, cardiovascular and immunitary biomarkers and the subjects were categorized in low, medium, and high‐risk categories of AL. DTI was calculated using a deterministic tractography algorithm and the relationships were established using a correlational tractoghraphy tool, based in DSIstudio, calculating the FDR (≤ 0,05) of whole brain fasciculus. Age and education was regressed out. After that, fasciculus with significance were segmented based on HCP 1065 atlas.

Result

we obtained significative correlations in many fibers, depending on the parameter studied. Is interesting to note that bilateral cingulum bundles, and corpus callosum integrity are within the fibers that have relationship with allostatic load in both cognitive groups. Additionally, MCI group presents more compromised tracts than SCC group.

Conclusion

In this study, a relationship between allostatic load and DTI integrity measurements in MCI and SCC groups was found. An interesting correlation exists in fornix and bilateral cingulum bundles, that can be supported by findings in previous studies based in human and animal models where the stress effects in white matter were studied. These results open an interesting research area to explore the role of stress response and mediators in early steps of dementia, who until today, has been poorly studied.
Adapting the Care Partner Hospital Assessment Tool for Dementia Care
Authors: Fields Beth
Published: January 2025

Background

Care partners commonly support patients living with dementia (PLWD) during and post‐hospitalization, however, they frequently report feeling excluded from care and unprepared for their caregiving tasks. While the evidence‐informed and validated Care Partner Hospital Assessment Tool (CHAT) was designed to better include and prepare family members and friends, it has not yet been adapted for the growing number of care partners supporting PLWD.

Objective

To adapt and finalize the CHAT for care partners of hospitalized PLWD.

Setting

Hospitals in the United States.

Study Population

We selected hospital‐based clinicians who had at least 5 years of professional experience working with PLWD and their family/friends, and care partners who were at least 18 years old and provided support to a PLWD who experienced a hospitalization. A total of 7 clinicians and 5 care partners were recruited. Clinicians were White (100%), female (85%), and represented social work, nursing, occupational therapy, medicine, and pharmacy. Care partners ranged in age from 41 to 73 years, were White (100%), female (100%), and provided support to a mother or mother‐in‐law (30%), spouse/partner (20%), and other relative (50%).

Methods

Two design teams each consisting of clinicians and care partners respectively—were formed to suggest adaptations to CHAT and share satisfaction with the final tool. Teams completed 5 co‐design videoconference sessions, with 2‐3 weeks between each session. Sessions lasted approximately 60 minutes and were audio recorded. The Rapid Identification of Themes from Audio‐recordings method was used to identify suggestions for adaptation between sessions, and thematic analysis was used to code the transcripts in NVivo.

Results

Adaptations to the CHAT included (a) providing options for dementia specific educational resources, (b) identifying power of attorney and care partner roles and responsibilities (c) using more comprehensive response options and simple language. After making adaptations, participants (100%) reported that they were satisfied or very satisfied with the final Dementia CHAT (i.e., D‐CHAT). Participants described the D‐CHAT as ‘empowering’, ‘comprehensive’, ‘collaborative’, and ‘helpful’.

Conclusion

The converged‐upon D‐CHAT is ready for feasibility testing in the hospital setting and may help guide clinicians’ inclusion and preparation of care partners of PLWD.
Formal and informal care use before, during, and after detection of cognitive disorders: a population‐based longitudinal study
Authors: Sakakibara Sakura , Dove Abigail , Guo Jie , Grande Giulia , Sjölund Britt‐Marie , Agerholm Janne , Fratiglioni Laura , Xu Weili
Published: January 2025

Background

Dementia is strongly linked to increased care use, but the use of formal and informal care throughout dementia journey remains unclear.

Method

Within a population‐based cohort study, we identified 240 older adults (aged ≥78 years) with who developed CIND and 155 with incident dementia. These participants were matched to 480 and 310 cognitively intact participants, respectively, and their formal and informal care use and care hours were compared with a control groups before and after diagnosis of cognitive disorders.

Result

Compared to cognitively intact participants, those with CIND were more likely to use formal care at the detection (odds ratio [OR] 2.06, 95% confidence interval [95%CI] 1.19‐3.58). Compared to cognitively intact participants, those with dementia were more likely to use formal care before (OR 2.55, 95% CI 1.21‐5.39) and at the wave of (OR 4.38, 95% CI 1.99‐9.65) diagnosis, while informal care use was greater at the wave of (OR 3.75, 95% CI 2.01‐6.99) and after diagnosis (OR 5.05, 95% CI 1.00‐25.64). In linear regression analysis, CIND and dementia were related to a faster increase in informal care hours (β: 5.52, 95% CI 2.87, 8.17/ β: 30.26, 95% CI 24.40, 36.12) compared to controls. Among individuals with CIND/dementia, older age, female sex, secondary educational attainment, and impairments in activities of daily living (ADL) at baseline were significantly associated with formal/informal care use.

Conclusion

Compared to cognitively intact individuals, those with CIND were associated with increased formal care use at detection, while people with dementia were associated with increased use of formal care already before diagnosis and informal care from diagnosis. CIND and dementia are associated with increased informal care hours. Age, sex, education, and ADL may predict greater care use among people with CIND/dementia.
Engaging people with lived experience in a national research network: Experience from the Canadian Consortium on Neurodegeneration in Aging
Authors: Bethell Jennifer , Myers Karen , Norman Myrna , Snowball Ellen , McGilton Katherine S
Published: January 2025

Engagement of People with Lived Experience of Dementia (EPLED) was a new cross‐cutting program introduced as part of the Canadian Consortium on Neurodegeneration in Aging (CCNA) for their second 5‐year phase (from 2019 to 2024). The initiative was supported by the Alzheimer Society of Canada as part of their commitment to the CCNA. EPLED had three objectives: (1) support persons with dementia and care partners to be actively involved in the CCNA research process; (2) work with CCNA research Teams, Cross‐cutting Programs and Partners to develop novel mechanisms and formats to further this collaboration; and, (3) advance the methods of patient engagement in research by embedding evaluation. One of the main activities of EPLED was to recruit and support an Advisory Group of people from across Canada with diverse lived experiences of dementia. Since 2020, EPLED Advisory Group members became involved in various CCNA central and research team activities as well as contributing as co‐presenters and co‐authors in academic and non‐academic venues and as co‐applicants and co‐investigators on research grants. Advisory Group members also took on roles advocating for more people living with dementia in research roles. Key factors described for the success of the Advisory Group were developing trusting relationships, providing education, offering support, being flexible and acknowledging tensions between research, practice and lived experience. Ongoing challenges often related to the gap between research and practice and balancing EPLED’s research objectives with aspirations for advocacy and system‐level change. Looking forward to the third phase of the CCNA, key challenges will include: developing capacity to meet increasing research funding expectations of engagement while also ensuring meaningful engagement, engaging new perspectives by recruiting new Advisory Group members while also retaining expertise from existing members, evaluating the impact of engagement and initiating EPLED‐driven research initiatives.
Synergic effect of tau tangles and cortical thinning on cognitive decline in aging and Alzheimer’s disease
Authors: Trudel Lydia , Therriault Joseph , Rahmouni Nesrine , Aumont Etienne , Wang Yi‐Ting , Servaes Stijn , Macedo Arthur C. , Chan Tevy , Arias Jaime Fernandez , Hall Brandon J , Hosseini Seyyed Ali , Socualaya Kely Monica Quispialaya , Mathotaarachchi Sulantha , Stevenson Jenna , Lussier Firoza Z , Gauthier Serge , Pascoal Tharick A. , Rosa‐Neto Pedro
Published: January 2025

Background

Tau burden has been found to be involved in brain atrophy during aging, especially in regions such as the parahippocampal gyrus. However, how tau levels at baseline are associated with trajectories of tau accumulation, cortical thinning and cognitive impairment remains poorly understood. The goal of this study was to assess tau rate of change in patients between baseline Tau+ and Tau‐ patients. We also aimed to determine if tau status at baseline or rate of accumulation of tau interacted with the rate of cortical thinning of the parahippocampal regions, leading to an increased rate of change in cognition.

Method

We assessed 133 participants from the TRIAD cohort (mean age = 68.5 ± 8.9, 85 females) with at least two visits with tau‐PET using [18F]MK6240 and cortical thickness extracted using FreeSurfer 7. Average time between visits was 25.6 months. Patients were classified according to clinical status, Amyloid‐β status and tau status at baseline (CU AB‐Tau‐, CU AB+Tau‐, CU AB+Tau+, MCI AB+Tau‐, MCI AB+Tau+, AD AB+Tau+). The tau‐PET rate of change was calculated for each participant, voxelwise and with temporal meta‐ROI. The MMSE rate of change was calculated to quantify cognitive decline over follow‐up period. We assessed the voxelwise relationship between baseline tau status and tau‐PET rate of change.

Results

We found a voxelwise positive association between rate of accumulation of tau and tau status at baseline in both anterior temporal lobes. Furthermore, we found an interaction effect between tau‐PET at baseline and parahippocampal rate of atrophy on MMSE rate of change (standardized β = 0.48, p < 0.0001).

Conclusion

Our results suggest that tau status at baseline might impact the rate of accumulation of tau, and that higher baseline levels of tau interact with cortical thinning of parahippocampal regions, leading to faster rates of cognitive decline. Our results emphasize the importance of preventing tau burden to prevent faster pace of cognitive decline during the disease’s trajectory.
Comparison of amyloid positron emission tomography, hippocampal volume, and plasma biomarkers in predicting conversion to mild cognitive impairment
Authors: Bilgel Murat , An Yang , Shah Ishaan , Walker Keenan A. , Moghekar Abhay , Ashton Nicholas J. , Kac Przemyslaw Radoslaw , Karikari Thomas K , Blennow Kaj , Zetterberg Henrik , Thambisetty Madhav , Resnick Susan M.
Published: January 2025

Background

We examined whether brain amyloid PET, hippocampal volume, or plasma biomarkers are better predictors of conversion to mild cognitive impairment (MCI).

Method

In the Baltimore Longitudinal Study of Aging (BLSA), plasma Aβ42, Aβ40, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) concentrations were measured using Quanterix Simoa Neurology 4‐plex E. Plasma p‐tau181 and p‐tau231 concentrations were measured using in‐house Simoa assays at University of Gothenburg. Brain amyloid was quantified using mean cortical 11C‐Pittsburgh compound B PET distribution volume ratio (mcDVR). Hippocampal volume was calculated from T1‐weighted MRI and adjusted for intracranial volume. Of 178 cognitively unimpaired (CU) participants with both plasma and neuroimaging measurements at baseline, 33 developed MCI during follow up (median time to MCI onset: 3.7 [interquartile range (IQR) 2.1–6.2] years), 17 of whom had elevated brain PET amyloid at baseline. We used Cox proportional hazards models to examine the association between risk of conversion to MCI (time to conversion right‐censored at death or last visit for CU participants) and baseline plasma or neuroimaging biomarker, adjusting for age, sex, race, and education. To enable comparison of hazard ratios (HRs), we negated plasma Aβ42/Aβ40 and hippocampal volume, and standardized each biomarker using statistics calculated in a cross‐sectional dataset of CU individuals aged 60–80 (preferring the visit closest to age 70 per participant) drawn from the larger BLSA. For standardization, we examined subtracting the median and dividing by the IQR and binarization (top tertile vs. not).

Result

In analyses using IQR normalized scores, mcDVR and plasma Aβ42/Aβ40 and GFAP had statistically significant HRs (Table 2). In binarized biomarker analyses, mcDVR and plasma GFAP, p‐tau181, and p‐tau231 were statistically significant. Using all plasma biomarkers together yielded the highest concordance: 0.877±0.026 and 0.861±0.026 for the continuous and binarized biomarker analyses, respectively.

Conclusion

Plasma biomarkers provide information beyond demographics regarding the prediction of MCI conversion within 4 years. Risk prediction conveyed by several individual plasma biomarkers exceeded that of brain amyloid PET. Plasma GFAP was consistently identified as contributing to the prediction of MCI conversion, with Aβ42/Aβ40 and p‐tau exhibiting statistically significant associations in a subset of analyses.
Can neuroimaging methods help us to disentangle WMH etiology in AD?
Authors: Dadar Mahsa , Parent Olivier
Published: January 2025

White matter hyperintensities (WMHs) are frequently observed in ageing individuals, and have a higher prevalence in neurodegenerative disorders such as Alzheimer’s disease. Ex‐vivo assessments of the microstructural alterations within WMHs have reported heterogeneous tissue alterations, with demyelination, axonal loss, and inflammation presenting with various degrees of severity. There is a crucial need to better assess the severity of WMH microstructural alterations in vivo, in particular with the emergence of anti‐amyloid immunotherapies and the associated risk of Amyloid Related Imaging Abnormalities (ARIAs) in individuals with comorbid vascular disease. Recent in‐vivo and ex‐vivo investigations have revealed important aetiology differences in regional WMHs, linking frontal WMHs to more vascular factors (e.g. ischaemia) and posterior WMHs to neurodegenerative processes. Regional WMH features might therefore reveal additional information regarding their potential aetiologies in absence of postmortem neuropathology information. Novel neuroimaging techniques such as diffusion‐weighted imaging (DWI) and quantitative magnetic resonance imaging (qMRI) can also provide further insight into the specific pathophysiological properties of the WMHs. These microstructural MRI metrics allow for the characterization and measurement of iron and myelin density, axonal integrity, and water content, paving the way for deep phenotyping of the pathophysiology of WMHs in‐vivo. Using DWI and qMRI data from the UKBiobank, we assessed the differences in baseline volume, mean diffusivity (MD), isotropic volume fraction (ISOVF, an index of relative extracellular water diffusion), fractional anisotropy (FA), intracellular volume fraction (ICVF, an estimate of neurite density), orientation dispersion (OD, reflecting the directional complexity of diffusion), T2* relaxation, and quantitative susceptibility mapping (QSM, sensitive to myelin and iron) of periventricular, anterior, and posterior WMHs between those with a diagnosis of AD (N=15) and cerebrovascular disease (N=95) in their future visits (mean interval: 3.3years). Our results show differences in their baseline WMH pathophysiological and spatial patterns (Figure 1), with cerebrovascular pathologies having a higher WMH burden on most metrics, especially in anterior regions. Figure 2 shows the standardized beta coefficients of the models, controlling for age and sex. Combined, regional volumetric and signal measures might therefore be able to provide important additional information regarding the aetiology of WMHs at an individual level.