bluuebunny/crossref_metadata_2025 huggingface dataset:
4D flow MRI of CSF dynamics: relations to CSF morphology and Aβ status
Authors: Vikner Tomas P. , Johnson Kevin M. , Hudson Sarah C. , Pompa Christian C. , Cadman Robert V. , Bevis William B. , Betthauser Tobey J. , Chin Nathaniel A. , Eisenmenger Laura B. , Johnson Sterling C. , Rivera‐Rivera Leonardo A.
Published: January 2025

Background

Cerebrospinal fluid (CSF) dynamics are increasingly studied to understand potential pathologic coupling with neurological disorders. In Alzheimer’s disease (AD), CSF dynamics may be altered secondary to AD‐related atrophy and enlarged CSF spaces. Additionally, animal studies suggest that altered CSF dynamics could impair clearance of metabolic waste, leading to accumulation of amyloid‐beta (Aß). However, assessment of human CSF dynamics has typically been limited to the cerebral aqueduct using 2D phase contrast MRI. In this work, we used 4D flow MRI to enable volumetric characterization of CSF flow dynamics in the human brain, to study its associations with CSF morphology and Aß burden from 11C‐PiB PET.

Method

Cardiac‐resolved 4D flow MRI was used to assess CSF motion in N=69 participants (age 69±8 years; 17 Aß+) from the Wisconsin Registry for Alzheimer’s Prevention, using a clinical 3T scanner (GE Premier) and a velocity encoding of 5 cm/s. Region‐averaged velocity waveforms were acquired in the spinal canal (SC), fourth ventricle (4V), cerebral aqueduct (CA), third ventricle (3V), the foramens of Monro (FMo), and the lateral ventricles (LV), segmented from T1‐weighted volumes. The waveforms were characterized by root‐mean‐square (RMS) velocity and were evaluated in relation to total CSF volume and Aß status from an established PiB global distribution volume ratio threshold >1.16.

Result

Velocity waveforms demonstrated cardiac‐pulsatility in all regions of interest (ROIs) (Figure 1), with RMS velocities ranging from high in the SC (6.56±2.29 mm/s) to low in the lateral ventricles (right LV 0.31±0.15 mm/s). RMS velocities were related to total CSF volume for the SC (R=‐0.24; p=0.043), CA (R=0.27; p=0.034), 3V (R=‐0.28; p=0.018), left LV (R=‐0.39; p=0.002), and right LV (R=‐0.35; p=0.009) (Figure 2). In preliminary analysis, RMS velocities were higher in Aß+ compared to Aß‐ for the SC (p=0.048) and right LV (p=0.024) (Figure 3).

Conclusion

4D CSF flow MRI is feasible for the assessment of CSF dynamics throughout the ventricular system. Total CSF volume was related to RMS velocities in 5/8 ROIs, highlighting the influence of CSF morphology on CSF dynamics. Finally, Aß status was related to RMS velocity in 2/8 ROIs, indicating that altered CSF dynamics could play a role in incipient AD.
Altered Regional and Whole‐Brain Excitation/Inhibition Balance Correlates with Alzheimer’s Disease Risk Factors
Authors: Burns Andrew P , Fortel Igor , Bendlin Barbara B. , Zhan Liang , Leow Alex
Published: January 2025

Background

Research indicates that the brain operates near a critical excitation/inhibition (E/I) balance point, which, when disrupted, correlates with Alzheimer’s Disease (AD) risk factors such as APOE genotype and sex. Utilizing our established multimodal imaging method (Fortel, Igor, et al. Network Neuroscience 6.2 (2022): 420‐444.), we investigated the E/I balance in cognitively normal and impaired individuals, focusing on factors like APOE status, amyloid status, age, sex, and dementia ratings.

Method

We analyzed 593 participants, aged 43‐92 (m = 62), including 495 cognitively intact and 98 impaired individuals, through 871 E/I ratio assessments (207 had multiple assessments). Participants underwent T1‐weighted, resting‐state, and diffusion‐weighted MRI to construct hybrid resting state structural connectomes for 105 regions using a recent multimodal connectome technique to detect whole‐brain and region‐specific E/I ratios. We employed two linear mixed models to correlate E/I ratios with age, sex, e4+/e4‐ status (binary) or APOE‐npscore (continuous), whole‐brain amyloid status (binary), and clinical dementia rating, adjusting for multiple comparisons. Patient IDs were used as random effects in the models to account for repeated measurements, with no interaction effects included. All imaging and variables were obtained from OASIS‐3: Longitudinal Multimodal Neuroimaging: Principal Investigators: T. Benzinger, D. Marcus, J. Morris; NIH P30 AG066444, P50 AG00561, P30 NS09857781, P01 AG026276, P01 AG003991, R01 AG043434, UL1 TR000448, R01 EB009352. AV‐45 doses were provided by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly.

Result

Both linear mixed models identified 26, significant E/I variations across the brain related to age, clinical dementia rating, and sex. Specific AD‐relevant regions such as the hippocampus and amygdala (Figure 1) show notable E/I changes. Whole brain E/I was negatively correlated with the APOE‐e4 allele in the binary APOE status model but not in the continuous APOE‐npscore model.

Conclusion

We demonstrated significant E/I ratio alterations in the whole brain and known AD relevant regions, such as the hippocampus and amygdala, against the largest risk factor of AD (age), clinical dementia rating, and binary APOE status. Our findings are consistent with past studies exhibiting correlations between altered E/I metrics and known AD risk factors.
Visual memory is primarily impacted by tau load in the right hemisphere
Authors: Arias Jaime Fernandez , Therriault Joseph , Servaes Stijn , Macedo Arthur C. , Wang Yi‐Ting , Rahmouni Nesrine , Socualaya Kely Monica Quispialaya , Aumont Etienne , Trudel Lydia , Hosseini Seyyed Ali , Hall Brandon J , Chan Tevy , Kunach Peter , Mathotaarachchi Sulantha , Vitali Paolo , Rosa‐Neto Pedro
Published: January 2025

Background

Classical literature has pointed at lateralization of the relationship between memory scores and cerebral hemisphere injury. Epilepsy studies have suggested an association between left hippocampal damage and verbal memory deficits, and between right hippocampal damage and visual memory deficits. We aimed to explore this concept in the context of tauopathy due to Alzheimer’s disease.

Method

we assessed 132 cognitively unimpaired (CU) older adults, and 44 cognitively impaired (CI), amyloid‐ß positive individuals from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort. All participants had amyloid‐PET with [18F]AZD4694 and tau‐PET with [18F]MK6240, verbal memory assessments with Rey Auditory Verbal Learning Test (RAVLT), and visual memory assessments with Aggie Figures Learning Test (AFLT). We conducted voxel‐wise analyses to explore the relationship between tau PET and memory modality. In addition, we run regression models with right or left tau temporal metaROI as predictor and memory scores as outcome variables. We entered global amyloid (PET), sex, age, years of education, ApoE status, grey matter volume and handedness as covariates. Finally, we used the laterality index (LI) to investigate correlations with memory modality. Right laterality is indicated by an LI below 0, while left laterality would be signaled by an LI above 0.

Result

voxel‐wise analyses suggested a lateralized relationship between tau and visual memory scores on the right hemisphere, whereas tau and verbal memory scores were bilaterally associated. Regression analyses showed a trend towards a stronger relationship between temporal tau on the right and visual memory scores. The LI was significantly associated with visual memory performance. Further analyses showed that this relationship seems to be driven by tau positive individuals.

Conclusion

visual memory performance might be more prominently affected by tau load on the right hemisphere in Alzheimer’s disease. Furthermore, a hemispheric imbalance in the amount of tau is related to visual, but not verbal, memory scores.
Amyloid‐PET in patients with a clinical diagnosis of sporadic early‐ versus late‐onset AD: comparison of the LEADS and ADNI cohorts
Authors: Lagarde Julien , Maiti Piyush , Schonhaut Daniel R. , Zhang Jiaxiuxiu , soleimani‐meigooni David N. , Zeltzer Ehud , Windon Charles , Raya Maison Abu , Vrillon Agathe , Hammers Dustin B. , Dage Jeffrey L. , Nudelman Kelly N. , Eloyan Ani , Koeppe Robert A. , Landau Susan M. , Carrillo Maria C. , Touroutoglou Alexandra , Vemuri Prashanthi , Dickerson Bradford C. , Apostolova Liana G. , Rabinovici Gil D. , La Joie Renaud
Published: January 2025

Background

Large‐scale studies comparing sporadic early‐onset AD (EOAD, age<65) and late‐onset AD (LOAD, age = 65) are lacking. We compared amyloid‐PET outcomes (positivity rate and amyloid burden) between patients clinically diagnosed with sporadic EOAD vs LOAD, leveraging data from the Longitudinal Early‐Onset AD Study (LEADS) and the Alzheimer’s Disease Neuroimaging Initiative 3 (ADNI3).

Method

731 patients meeting the 2011 NIA‐AA criteria for AD dementia or MCI were included (505 early‐onset from LEADS, 226 late‐onset from ADNI3, Table 1). All participants underwent amyloid‐PET with [18F]Florbetaben or [18F]Florbetapir. Amyloid positivity was centrally determined by a process involving a visual read by a trained expert and PET‐only quantification; in case of a discrepancy, a read from an independent physician acted as a tiebreaker. Logistic regressions in each cohort examined relations between amyloid positivity and age, sex, MMSE and APOE4 genotype. Amyloid burden was independently quantified in Centiloids using an MRI‐based pipeline. Mean Centiloids in LEADS and ADNI were compared with two‐way ANOVA, for visually positive and visually negative scans.

Result

Amyloid positivity rate was higher in LEADS (76%) than ADNI (64%, p<0.001, Figure 1A). Lower MMSE and APOE4 genotype increased odds of amyloid positivity in both cohorts, although the APOE4 effect was stronger in ADNI than LEADS (OR = 10.1 versus 2.4, p = 0.007, Table 2). Amyloid positivity was more common in females across cohorts, but this effect was only statistically significant in LEADS (Table 2). Centiloids were bimodally distributed in both cohorts, although the separation between positive and negative scans was more prominent in LEADS (Figure 1B). Visually positive scans had significantly higher Centiloids in LEADS than in ADNI, whereas no cohort difference was observed for visually negative scans (Figure 1C). Sensitivity analyses showed that this effect was driven by patients with MCI (CDR = 0.5; Figure 1D‐E).

Conclusion

The lower amyloid positivity rate in ADNI might be due to AD‐mimicking pathologies being more common at an older age. The higher amyloid burden in early‐onset, amyloid‐positive patients could reflect younger patients being diagnosed later in the disease course compared to typical, late‐onset patients. Alternatively, younger patients might tolerate higher neuropathology burden due to higher brain reserve or fewer co‐pathologies.
Differences between high‐precision Alzheimer’s disease plasma and PET biomarkers among cognitively normal older Black and White adults
Authors: Bubu Omonigho M , Boutajangout Allal , Debure Ludovic , Vedvyas Alok , Briggs Anthony Q , Bernard Mark A , Gills Joshua L , Valkanova Elena , Mbah Alfred , Ghuman Mobeena , Jean‐Louis Girardin A , Betensky Rebecca A , Marsh Karyn , Rusinek Henry , Osorio Ricardo S. , Wisniewski Thomas , Masurkar Arjun V.
Published: January 2025

Background

We evaluated whether baseline differences existed in various plasma Alzheimer’s disease (AD) biomarkers in cognitively normal participants racialized as Black or White.

Method

This cross‐sectional study included 203 (n = 83 non‐Hispanic Black [NHB] and n = 120 non‐Hispanic White [NHW]) cognitively unimpaired older adults from the NYU Alzheimer’s Disease Research Center. Of the 203, 115 (39NHB, 76 NHW) had tau‐PET (PI‐2620/MK‐6240) data; 195 (85 NHB, 110 NHW) had amyloid‐PET (florbetaben); 98 (39 NHB, 59 NHW) had plasma Aß40 and Ab42 data, 93 (37 NHB, 56 NHW) had data for total tau, 135 (55 NHB, 80 NHW) had neurofilament light (NfL) and glial fibrillary protein (GFAP) data and 139 (57 NHB, 82 NHW) had pTau181 data. Plasma biomarkers assay Aß 40, Aß42, total tau [t‐tau], neurofilament light [NfL], glial fibrillary acid protein [GFAP], ubiquitin carboxyl‐terminal hydrolase L1 [UCH‐L1] and pTau181 were measured were measured using Quanterix SIMOA HD‐1.

Result

Overall, mean (SD) age was 75.6 (6.5) NHW vs. 68.9 NHB (p = .008), BMI was 27.4 (9.7) vs. 32.4 (11.2) (p = .161), and education 17.0 (2.1) vs. 16.4 (2.32) (p = .273) for NHW vs. NHB respectively. Overall, 135 (66.5%) were females, of which 61 (73.5%) were NHB, and 62 were APOE e4 carriers [30.5%], of which 27 were NHB. Compared to NHW, NHB subjects had significantly lower plasma Aß40 (One‐tailed t‐test p = .006), NfL levels (p = .0005), Tau (p = .0313), pTau181 (p = .0015), and GFAP (p = .0005). NHB subjects had lower amyloid‐PET SUVR levels compared to NHW subjects (p = .0014). Baseline plasma Aß42/40 and pTau181/Aß42 levels were higher in NHB versus NHW participants (p = .002), consistent lower levels of amyloid pathology in NHB participants. There were no significant differences in levels of plasma Aß42, tau‐PET SUVR, and UCH‐L1.

Conclusion

In this sample of cognitively normal older adults, NHB participants had biomarker measures suggestive of lower levels of cerebral amyloid pathology. This warrants further correlation with brain imaging and cognitive outcomes, and examination of the potential impact of demographic, socio‐structural and genetic factors on observed differences. Additionally, this may imply that racial variability in amyloid threshold possibly exists before clinical AD onset, potentially lowering the proportion of NHB patients eligible for AD therapies and trials.
Comparison of reference region stability for longitudinal amyloid PET in Down syndrome
Authors: McLachlan Max , Rouanet Jeremy P. , Garimella Arun , Price Julie C , Tudorascu Dana , Laymon Charles M , Keator David B. , Betthauser Tobey J. , Kreisl William Charles , Lao Patrick J. , Minhas Davneet S , Klunk William E , Cohen Annie , Handen Benjamin L , Fryer Tim D , Zaman Shahid , Koeppe Robert A. , Head Elizabeth , Mapstone Mark , Bettcher Brecca , LeMerise Lisette , McVea Andrew K , DiFilippo Alexandra H , Zammit Matthew D , Hartley Sigan L , Christian Bradley T.
Published: January 2025

Background

The cerebellum is frequently used as the reference region for amyloid PET analysis. However, this reference region has been shown to demonstrate longitudinal variability, particularly with [18F]florbetapir (FBP) PET (Landau, JNM 2015). For investigations in individuals with Down syndrome (DS), cerebellar atrophy and rapid disease progression may increase these longitudinal variabilities. Although white matter possesses different non‐displaceable uptake properties, the relative lack of specific binding makes white matter a suitable reference region for longitudinal studies. This work compares the observed longitudinal change when using whole cerebellum and white matter reference regions in [18F]FBP and [11C]PiB scans of adults with DS.

Method

Participants with DS, recruited through the ABC‐DS study, underwent longitudinal PiB or FBP PET imaging and T1w MRIs (Table 1 lists cohort differences). PET images were smoothed to 8mm resolution, summed 50‐70 min, co‐registered with the MRI, and normalized to a common DS MRI template (LeMerise, 2022). GAINN whole cerebellum (WC) VOI was applied to create SUVRWC. Whole brain white matter was segmented in native space using SPM, smoothed to PET resolution, and eroded to 90% tissue probability. The resulting eroded white matter (EWM) mask was used as reference to create SUVREWM. Average SUVR was calculated for GAINN global cortex (CTX). Longitudinal scans were assessed for correlations between reference region strategies and average rate of SUVR change: % Change/year = (SUVR2‐SUVR1)/(SUVR1*Δt).

Result

Figure 1 displays the averaged EWM reference template. Figure 2 displays longitudinal PET data and regressions between SUVRs. Across participants, SUVRWC shows 78/90 (PiB) and 50/83 (FBP) between‐scan increases. SUVREWM shows 66/90 (PiB) and 71/83 (FBP) between‐scan increases. For A+ individuals (18CL cutoff), the average difference (% ChangeEWM ‐ % ChangeWC)/year is ‐0.5%/year [‐1.2,0.3] (PiB) and 1.9%/yr [0.5,3.3]** (FBP). FBP group SD in % Change/year decreases from 5.6% (WC) to 2.9% (EWM).

Conclusion

As observed in LOAD, SUVREWM demonstrates lower group variability and greater longitudinal change in FBP. SUVREWM shows strong agreement with SUVRWC in PiB. These data suggest that an EWM reference region can reduce variability in longitudinal FBP studies in DS.
Neuroinflammation potentiates the effect of amyloid‐β on longitudinal tau changes
Authors: Rahmouni Nesrine , Wang Yi‐Ting , Therriault Joseph , Servaes Stijn , Tissot Cécile , Macedo Arthur C. , Arias Jaime Fernandez , Hosseini Seyyed Ali , Stevenson Jenna , Kunach Peter , Hall Brandon J , Trudel Lydia , Gauthier Serge , Jeromin Andreas , Zetterberg Henrik , Blennow Kaj , Zimmer Eduardo R. , Ashton Nicholas J. , Benedet Andrea L. , Pascoal Tharick Ali , Rosa‐Neto Pedro
Published: January 2025

Background

It has been proposed that microglia release of proinflammatory factors reactive to amyloid plaques constitutes an early event leading to tau pathology. Here, we assessed how the rate of progression of tau‐PET and the rate of change in plasma pTau217 are affected by baseline levels of amyloid‐ß and neuroinflammation.

Methods

We included 93 individuals from TRIAD cohort: 11 young individuals, 57 cognitively unimpaired elderlies, 15 with mild cognitive impairment and 10 individuals with Alzheimer’s Disease. Neuroinflammation, tau tangle and amyloid‐ß (Aß) deposition were assessed via [11C]PBR28‐PET, [18F]MK6240‐PET and [18F]AZD4694‐PET, respectively. Individuals also had plasma pTau217 quantified using the Alzpath assay. [11C]PBR28‐PET positivity was defined as a SUVR of 2.5SD above the mean of the young individuals in the precuneus and posterior cingulate. Voxel‐based regression models evaluated the interaction of TSPO‐ and Aß‐PET with annual change in tau‐PET and plasma pTau217. The effect of the interaction on tau‐PET was also evaluated at the region‐of‐interest level using Braak regions. All models were corrected for age, sex and RFT corrected. Comparison of models was made using the Akaike Information Criterion (AIC) and the models’ goodness‐of‐fit was evaluated using R2 analyses. Models used [18F]MK6240‐PET SUVR yearly change as the outcome and used as predictors [11C]PBR28‐PET SUVR in the precuneus and posterior cingulate and [18F]AZD4694‐PET SUVR in the neocortical region.

Results

Positive associations were found between the interaction of Aß‐ and TSPO‐PET at baseline predicting the yearly change in tau‐PET (Figure 1A). At the ROI level, the interaction significantly predicts tau load in Braak regions III‐IV in [11C]PBR28 positive individuals (Figure 1B). Positive associations were also found between the interaction of Aß‐ and TSPO‐PET at baseline predicting the yearly change in plasma pTau217 (Figure 2A), which is driven by [11C]PBR28 positive individuals (Figure 2B). In addition, the interaction between Aß‐ and TSPO‐PET predicting the yearly change in tau‐PET is the model with the highest R2 and the lowest AIC values in Braak regions III‐IV‐V‐VI (Figure 3).

Conclusion

These results support the hypothesis that microglial activation potentiates the effect of Aß plaques on tau tangle progression and the pTau217 increases across the aging and AD spectrum.
Relationship between cortical diffusivity and neuropathological substrates in Alzheimer’s disease
Authors: Debatisse Justine , Leng Fangda , Edison Paul
Published: January 2025

Background

Pathological alterations in Alzheimer’s disease (AD) begin several years before the onset of symptoms. Grey matter mean diffusivity (MD) may be used as a measure of early grey matter damage in AD as it reflects the breakdown of microstructural barriers, which precede volumetric changes and affect cognitive function. In this study, we investigated the changes in MD early on in the disease trajectory, and relate them to the amyloid and tau deposition.

Method

We analysed multimodal PET, DTI and MRI data of 90 participants, stratified into amyloid‐ß negative and positive, cognitively normal (CN), mild cognitive impaired (MCI) and AD patients.

Result

We found that MD was significantly increased in Aß‐positive MCI and AD compared with CN in frontal, parietal, temporal cortex, hippocampus, and medial temporal lobe. We also found that cortical MD is significantly correlated with cortical thickness only in patients without amyloid deposition and is not significant in Aß‐positive patients.

Conclusion

Our results suggest that cortical MD is an early marker of neuronal damage as it is observed simultaneously as Aß deposition and as it is correlated with cortical thickness when there is no Aß deposition. This suggests that cortical MD provides information about early microstructural changes before macrostructural changes.
Patterns of Association of Tau Across Cortical Regions Differ Between [18F]MK6240 and [18F]Flortaucipir
Authors: Hosseini Seyyed Ali , Rahmouni Nesrine , Therriault Joseph , Servaes Stijn , Tissot Cécile , Aumont Etienne , Arias Jaime Fernandez , Macedo Arthur C. , Wang Yi‐Ting , Stevenson Jenna , Lussier Firoza Z , Chan Tevy , Zheng Yansheng , Trudel Lydia , Gauthier Serge , Baker Suzanne L. , Pascoal Tharick A. , Rosa‐Neto Pedro
Published: January 2025

Background

This study aims to investigate the differential patterns of association in tau protein imaging across cortical regions using two distinct Tau imaging agents: [18F]MK6240 and [18F]Flortaucipir. The underlying hypothesis posits that variations in the properties of these tracers, such as affinity and off‐target effects, influence the observed patterns of association in neuroimaging.

Method

To test this hypothesis, a comprehensive study was conducted involving 104 subjects part of the HEAD study at McGill University: 53 cognitively normal (CN), 19 with mild cognitive impairment (MCI), 9 with Alzheimer’s Disease (AD) and 23 non‐AD. A key methodological aspect of the study was the selection of seed cortical regions based on the highest standardized uptake value ratios (SUVR) obtained in population average images. These regions included the trans‐entorhinal area, parietal, posterior cingulate cortices, and two off‐target binding regions: the choroid plexus and substantial nigra. This approach allowed for a nuanced analysis of tracer associations in both target and off‐target regions.

Result

The results revealed notable differences between the two tracers. Specifically, [18F]MK6240 exhibited higher associations between cortical regions, with similar slopes in these associations across different areas. In contrast, the associations between the off‐target binding regions (Choroid Plexus and Substantia Nigra) and the established Braak regions were found to be non‐significant. This finding is particularly revealing, as it underscores the differential binding affinity and specificity of the two tracers.

Conclusion

In conclusion, the study substantiates the initial hypothesis by demonstrating that distinct tau tracers exhibit unique patterns of cortical associations, which can be attributed to their specific properties. This insight has significant implications for the interpretation of tau imaging in neurodegenerative diseases, particularly in AD. It highlights the necessity of considering tracer‐specific characteristics when analyzing neuroimaging data and suggests that a one‐size‐fits‐all approach may not be appropriate in the nuanced field of neuroimaging. The findings of this study pave the way for more refined and accurate diagnostic practices in neurology, particularly in the context of neurodegenerative diseases where tau protein plays a pivotal role.
Developing a machine learning stack model to forecast the progression of mild cognitive impairment to Alzheimer’s dementia, using the Australian Imaging, Biomarker & Lifestyle (AIBL) Study dataset
Authors: Chu Chenyin , Wang Yihan , Maruff Paul , Masters Colin L. , Goudey Benjamin , Jin Liang , Pan Yijun
Published: January 2025

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative condition, with considerable variation in disease progression from the mild cognitive impairment (MCI) stage. Predicting disease progression will support prognostic decisions and patient management. Here we designed a machine learning (ML) stack model, where a classifier was used to differentiate MCI progressors from non‐progressors (i.e. whether an individual with MCI progress to AD), and different regression models were then applied to each category to forecast their Mini‐Mental State Examination (MMSE) score after 3 years.

Method

Demographic and neuropsychological data from 2428 participants of the AIBL study was used for model construction and validation. The model was validated via a stratified 3‐fold cross‐validation approach. Support vector machine (SVM), gradian boosting (GB), random forest (RF) was experimented, and their performance were compared. MMSE score was a predicted variable indicating cognition.

Result

The performance of RF‐stack model was superior to SVM‐ and GB‐stack models. Largest area under the receiver operating characteristic curve (0.85) when RF‐stack model was employed (compared with SVM 0.79 and GB 0.70), signifying the highest accuracy in classify MCI progressors and non‐progressors. RF‐stack model achieved the best performance in predicting MMSE score after 3 years), evidenced by the smallest median mean average error (MAE) (RF 1.51, SVM 1.52, GB 2.51). The MAE indicated how much the predicted MMSE score deviated from the AIBL record. Representative prediction results from RF‐stack model for AIBL participants were presented in Table 1.

Conclusion

Our RF‐stack model relies on neuropsychological test scores and demographic data to predict the probability of an individual progressing from MCI to AD and accurately forecast the MMSE score after 3 years. This model achieved is comparable if not better prediction accuracy than the existing ML models using neuroimaging data. Further model optimization and validation using data collected from other longitudinal AD cohort studies are required.
Clinical Success of Biophoton Therapy in Improving Cognition of Alzheimer’s Disease
Authors: Liu James Z
Published: January 2025

Background

Alzheimer’s disease (AD) poses a significant global health challenge, which demands innovative therapeutic approaches. The strong biophoton field generated by breakthrough medical devices has preliminarily shown a high rate of success in improving cognition and life quality of the patients with AD.

Method

This was a randomized triple blinded placebo controlled clinical study to verify if biophotons can improve cognition of AD. The clinical trial was to enroll a total of 30 participants diagnosed with moderate to severe AD. All participants continued their standard care if any.

Result

During a 4‐week observational period, 16 participants in the treatment group used the biophoton generators daily. Cognitive function, life quality and EEG were assessed using standardized measurements. Additionally, bioenergy of brain was determined using a non‐linear bioenergy scanner. Preliminary analysis reveals a remarkable improvement in cognitive performance among participants in the biophoton therapy group compared to the control group. Seventy‐five percent (75%) participants reduced the Alzheimer’s Questionnaire severity; 88% increased life quality SF‐36 score; and 94% increased brain bioenergy. All were significantly different from the Control group (P < 0.01). EEG test also showed that the “missed response” was reduced in the Treatment group. Caregivers reduced the stress and difficulty in caring for their seniors. No adverse effects were observed.

Conclusion

These promising results highlight the potential of biophoton therapy as a novel and safe intervention for Alzheimer’s disease. Further investigations are warranted to elucidate the underlying mechanisms. This clinical study represents a significant step forward in treating Alzheimer’s disease.
Intelligent dementia friendly environment: A Preliminary Study on the Feasibility of Integrating Assistive Humanoid Robots, Wearable Sensors, and Spatial Technology for maintaining quality of life
Authors: Khan Arshia A , Das Rupak Kumar , Imtiaz Rana Z
Published: January 2025

Background

Integrating humanoid robots, wearable sensors, and spatial technology into an intelligent dementia‐friendly living space is crucial for tailoring personalized and supportive environments, thereby addressing the unique needs of individuals affected by dementia and maintaining quality of life.[1‐10].

Methods

We programmed Pepper, a humanoid robot, for independent verbal communication to interact, tell jokes, and offer medications. To validate our assistive robot integrated with a sensor‐based system, we built a specifically designed living space optimized for sensor functionality and conducted a 90‐minute study involving 32 healthy participants. The participants performed various activities after consenting, filling pre and post‐experiment surveys and pre, during, and post‐sensor readings. The activities comprised of administration of a placebo sugar pill by the robot, treadmill exercises following the Bruce submaximal treadmill protocol, engagement in cognitively stimulating activities, wandering detection using spatial sensors, media presentation to induce higher arousal state, performance of some daily tasks such as preparing short meals, folding towels, cleaning the floor, and an interaction with the robot. These activities aimed to assess sensor functionality, simulate real‐world scenarios, and monitor physiological responses during various tasks, contributing to the evaluation of the integrated sensor system. Various physiological data, including Electrodermal Activity (EDA), blood pressure, and Electrocardiogram (EKG), were gathered using distinct wearable sensors throughout the experiment. To gauge the subjective experiences of participants, two surveys were employed: the Presentation survey, conducted during the International Affective Digital Sound (IADS) presentation, and the Post‐Study survey, distributed on paper after the study’s completion.

Results

By incorporating pressure sensors in chairs and the robot’s emotion detection system, participants' moods were accurately assessed, aligning with self‐reported moods in 95% of cases. Furthermore, door sensors consistently identified exiting behavior, and wall‐mounted PIR sensors successfully recognized wandering behavior. Wearable sensors, such as EDA and blood pressure sensors, in conjunction with robot interactions, detected physiological changes during diverse activities, with the most notable impact observed during interactions with the robot. Conclusion The findings suggest that an intelligent living space specifically designed for dementia care can effectively preserve the quality of life for affected individuals, particularly through robot interactions, showcasing promising effectiveness.
Applying the eHealth Literacy lens to evaluate a virtual assistant to support family carers of people with dementia
Authors: Nguyen Tuan Anh
Published: January 2025

Background

We have co‐produced with carers of people with dementia (hereafter carers) a culturally tailored iSupport Virtual Assistant (VA), namely e‐DiVA, to support English‐, Bahasa‐ and Vietnamese‐speaking carers in Australia, Indonesia, New Zealand and Vietnam. The presented research reports qualitative findings from the e‐DiVA user‐testing study.

Method

Family carers and healthcare professionals working in the field of dementia care were given the e‐DiVA to use on their smartphone or handheld device for 1‐2 weeks. They tested all functions and content of the VA and provided feedback in a ‘Think‐aloud' session, either in person or online. Data was analysed thematically, guided by the eHealth Literacy Framework (eHLF).

Result

Eighteen family carers and nine staff of aged care providers were recruited. Participants discussed all seven domains of eHLF, which were evidenced in the e‐DiVA. They include: 1) ability to process information, i.e. the VA contains information in a format that can easily be understood, e.g. animations; 2) engagement in own health, i.e. providing tailored lessons through need assessments and ‘chatbot'; 3) ability to engage actively with digital services, i.e. providing user manuals; 4) feeling safe and in control; i.e. secure login; 5) motivation to engage with digital services, i.e. providing quick responses/solutions to carers' queries; 6) having access to systems that work, i.e. ability to access to the VA anytime anywhere; and 7) digital services that suit individual needs, i.e. available in users' preferred language. Participants highly ranked domains 1, 2 and 5. They suggested further improvements including making content into audiobooks and messages (domain 1), as well as pointed out some potential barriers to use, especially on domains that require interactions between individuals and the digital system (domains 3, 5 and 7).

Conclusion

Findings show the high acceptance of the VA by both the carers and aged care providers, as well as a need for enhancement to improve accessibility.
Facilitating Conversations about Supportive Care Options in the Context of Cognitive Impairment using an Online Visual Elicitation Tool
Authors: Turner Anne M , Chen Annie T. , Child Claire E. , Miller Lyndsey M.
Published: January 2025

Background

Persons with cognitive impairment may experience difficulties with language and cognition that interfere with their ability to make and communicate decisions. We developed an online visual tool to facilitate conversations about their preferences concerning supportive care.

Methods

We conducted Zoom interviews with persons with mild cognitive impairment (MCI) and mild to moderate dementia, using storytelling and a virtual tool designed to facilitate discussion. Each interview sought to discuss decision‐making in the context of three scenarios, one concerning a past decision about supportive care, and two hypothetical scenarios based on decreasing abilities and increasing care needs. Interviewers shared their screen with the visual tool, which used the visual diagramming platform draw.io (https://www.drawio.com/) to create an online “canvas.” Interviewers could drag icons (representing people, places, safety, emotions, activities, and issues) or type text onto the canvas to communicate concepts. We developed the tool with a multidisciplinary team of designers and researchers, and with input from people with cognitive impairment. Key user‐centered design goals for the tool included focusing on simplicity, minimizing cognitive load, and using concepts and images that resonated with participants. We also used pilot interviews to refine interviewers' techniques for eliciting preferences with the tool. We examined the utility of the tool for engaging participants in dialogic interactions with the interviewer, and the cognitive and communicative processes exhibited by participants.

Results

We conducted fifteen interviews with persons with MCI, and mild or moderate dementia [mean age 77.8 years ± 7.1 (SD), 9 male, 6 female]. With respect to dialogic interactions, interviewers actively used the visualization technique to facilitate the conversation; participants engaged with the interface to varying degrees. Common communicative issues included participants being unresponsive to the question or providing unclear responses. During the sessions participants also exhibited uncertainty, introspection, and self‐awareness.

Conclusion

We present a visual technique to engage persons with cognitive impairment in dialogue about complex decisions. We hope to explore the potential use of this technique in research, clinical, and community settings.
A machine learning approach to predict tau positivity using clinical features in amyloid‐positive individuals
Authors: Arnold Daniel , Borelli Wyllians Vendramini , Machado Luiza Santos , Rahmouni Nesrine , Therriault Joseph , Servaes Stijn , Stevenson Jenna , Macedo Arthur C. , Schumacher‐Schuh Artur Francisco , Mattjie Christian , Barros Rodrigo C. , de Bastiani Marco Antônio , Lussier Firoza Z , Chamoun Mira , Bezgin Gleb , Benedet Andrea L. , Pascoal Tharick , Rosa‐Neto Pedro , Zimmer Eduardo R. ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: January 2025

Background

Anti‐amyloid therapy appears to have an increased effect on reducing cognitive decline in amyloid‐ and tau‐positive individuals. However, clinical trials inclusion criteria require solely amyloid positivity. Herein, we developed a machine‐learning prediction model to identify tau positivity in amyloid‐positive individuals using clinical variables.

Method

We selected 1191 amyloid‐positive participants and tau status from ADNI, TRIAD, PPMI databases. Commonly shared clinical features selected between datasets were age, total MOCA scores, clinical diagnosis, sex, education, BMI, heart disease, stroke, hyperlipidemia and diabetes. Amyloid positivity was defined by amyloid‐PET (PIB‐PET, FBB‐PET or AZD4694‐PET) or CSF AB42 and Tau positivity defined by Tau‐PET (MK6240‐PET or AV1451‐PET) or CSF p‐tau181. The dataset was split into training (49%), validation (21%), and testing datasets (30%). A XGBoost model was tuned, and then used to predict the tau status outcome in the testing dataset.

Result

A total of 647 men and 544 women were included with mean age 66.1 ± 10.4 (mean ± SD) years, MOCA 25.1 ± 4.1 scores and education 16.1 ± 3.2 years (Table). The population consisted of 794 controls, 271 MCI and 126 dementia individuals. Tau status was negative for 854 individuals and positive for 337. The receiver‐operator characteristic (ROC) analysis showed that the area under the curve (AUC) was 0.81 for discriminating tau‐negative vs. tau‐positive, with 0.76 as sensitivity, specificity as 0.86, and accuracy as 0.83. The top 3 most impactful features were found to be age, diagnosis‐CN and MOCA score through a SHAP value analysis (Figure).

Conclusion

Predicting tau positivity with clinical and cognitive variables may improve the selection of individuals for AD trials. A two‐step workflow using this approach may significantly reduce the need for tau‐PET exams in trials by screening individuals using clinical variables. The following steps should include adding more individuals and other clinical variables through different cohorts to optimize the model applicability and test their performance in outcomes of clinical trials.
Optimizing Dynamic White Lighting for practical application
Authors: Ansari MD. Azaharuddin , White Jonathon David
Published: January 2025

Background

Effect of dynamic lighting on sleep were studied since 1980’s. Traditional light sources were used due to lack of advancement in technology and also researchers assumed illuminance as cause of melatonin suppression. This led researchers to use high illuminance to suppress melatonin at day time. Later, it was discovered that intrinsic photoreceptor retinal ganglion cell (ipRGC), sensitive to specific wavelength, has direct impact on the level of melatonin, that shifted the attention to the actual wavelength of the stimulating light. With the invention of LEDs, having various emission profiles has allowed researcher to propose numerous LED using 5 to 8 types of LED for appropriate delivery of dynamic light to control melatonin secretion whole day. Better lighting has been shown to improve sleep, reduce anxiety/depression, and improve mood in dementia patients.

Method

A C‐program was developed to calculate various lighting parameters of combined spectra of LED strips. Brute force optimization was used to calculate the power to be supplied to each of the input LED strips to obtain a combined white light for dawn, day and dusk based on the required visual (e.g. CRI>90, Duv < 0.001) and non‐visual parameters for minimum power consumption and lowest material cost.

Result

We investigated 3 red, green, blue, ice blue, and warm white (R‐G‐B‐IB‐WW) systems from different manufactures. Only in one system, did the blue LED allow increased efficiency (<1%), demonstrating that a 4 LED system (R‐G‐IB‐WW) is sufficient i.e. blue LED is unnecessary. We added a monochromatic Cyan LED strip, its spectra overlap the action spectra of ipRGC, hoping it could help to achieve better stimulation of ipRGC cells with lower power consumption. While m‐EDI increased, but m‐EDI/W input power did not. Cyan is thus unnecessary.

Conclusion

We have shown that an LED system with only 4 types of LEDS (2 monochrome and 2 broadband) can generate dawn to dusk dynamic white light suitable for both visual and non‐visual needs of dementia patients (as widely accepted by researchers over the world) with high electrical to optical efficiency. This approach, using fewer LED strips and lower energy consumption, is more financially appealing.
Precision Phenotyping of Mild Behavioral Impairment and the Early Detection of Dementia
Authors: Vahia Ipsit V
Published: January 2025

There is growing recognition of the importance of changes in behavior as an early clinical marker of the onset of Alzheimer’s disease. Behavior symptoms may precede the onset of cognitive symptoms by as many as three years. However, these symptoms are often confused for primary psychiatric pathology and there is an urgent need for markers that can help quantify behaviors with the eventual goal of helping distinguish behavior changes related to psychiatric pathology from behavior changes related to the onset of dementia. This talk will summarize the state of knowledge on mild behavioral impairment, and present data from three studies demonstrating how a range of sensor‐derived biomarkers can quantify subtle changes in behavior with precision. The talk will include case presentations around detection of apathy, agitation, pacing. It will also demonstrate how these markers can identify response to medications, which may be one way of distinguishing the presence of psychiatric versus neurodegenerative pathology. Finally, the talk will present data from ongoing clinical trials around how these biomarkers may translate into research and eventually practice.
Testing Measurement Invariance Across Gender in a Low Resource Setting Using the Computerized Battery for Neuropsychological Evaluation of Children (BENCI)
Authors: Maina Rachel W , Wicherts Jelte
Published: January 2025

Background

Developing culture‐fair tests that measure constructs equivalently across different ethno‐lingual groups is challenging, given the diverse cultural variations that impact neurocognitive measurement. Multi‐level measurement invariance must be established before interpreting scores similarly across groups, both within and between cultures for meaningful comparisons.

Method

We set out to test whether a neurocognitive tool (BENCI) behaves the same way across the males (n = 311) and the females group (n = 291) using measurement invariance testing with multigroup confirmatory factor analysis. We used a four factor model that had an excellent fit in a Kenyan pooled sample when modified to have four correlated first‐order factors i.e., Fluency, Reasoning, Memory, and Flexibility. We evaluated configural, metric, scalar and lastly strict invariance model and then tested whether the different restraint in the models resulted in a significant chi‐square difference.

Result

The four‐factor model showed good model fit (RMSEA = .034, CFI = .959, TLI = .930, χ2 (92, n = 604) = 154.309, p < .001), with metric measurement invariance (RMSEA = .033, CFI = .957, TLI = .933, χ2 (100, n = 604) = 164.368, p < .001; Δχ2 = 10.059, DF = 8, p = 261, ΔCFI = 0.002), scalar measurement invariance (RMSEA = .032, CFI = .957, TLI = .938, χ2 (108, n = 604) = 172.831, p < .001; Δχ2 = 8.463, p = .390, ΔCFI = 0.000), and the strict measurement invariance (RMSEA = .031, CFI = .955, TLI = .940, χ2 (118, n = 604) = 186.563, p < .001; Δchi‐square = 22.195, df = 18, p = .223, ΔCFI 0.002) between the females and males.

Conclusion

Metric, scalar and strict invariance is achieved indicating that indicator items, indicator intercepts (same starting point on the BENCI) and residuals (except Visual Memory Delayed CA residuals) of the BENCI are comparable across the male and female samples, and we can compare the association of BENCI with other invariant constructs across the two groups, including the latent mean comparisons. These results are promising and suggest that cross‐gender comparisons may also be tenable for other clinical group comparisons in Kenya and cross‐cultural data harmonization in multi‐national research programs.
People with dementia as exercise video game testers: Gathering end‐user perspectives
Authors: Dove Erica , Wang Rosalie H. , Patterson Kara K. , Astell Arlene J.
Published: January 2025

Background

Commercially available exercise video games (‘exergames') can be used by people with dementia with the right (human) prompting and support. However, more information is needed about what makes these systems and games technologically accessible for this population, considering their cognitive difficulties. This study explores what works and doesn’t work for people with dementia when introducing new exergame systems and games to broaden opportunities for physical activity.

Methods

Thirty‐two people living with dementia (mean Montreal Cognitive Assessment score: 12.75/30) were recruited from four community‐based adult day programs in Canada. Participants were recruited as ‘game testers' once weekly for six weeks at each day program. Participants with dementia tried different exergame systems (e.g., Xbox Kinect, Nintendo Switch) and games (e.g., darts, boxing, dancing, etc.). Concurrently, gameplay video recordings and feedback via the talk‐aloud protocol and audio‐recorded post‐game group debriefs were collected. Data were analyzed descriptively and are currently undergoing analysis using behavioural coding software to examine in‐game prompts and player movements.

Results

In total, 292 gameplay turns occurred across the sessions. Some participants declined to play certain games after watching their peers experience accessibility challenges. Common reasons for ending a turn (beyond completing the game objective) included boredom, frustration, confusion, fatigue, and soreness. Systems with handheld controllers (e.g., Nintendo Wii) were less accessible for participants than gesture‐based controls due to the need to push buttons and attend to the controller while simultaneously performing physical motions. Additionally, games requiring multiple coordinated movements and those not accommodating additional age‐related impairments (e.g., range of motion impairments, mobility devices) were not widely accessible to this diverse group of participants.

Conclusions

This study highlights the importance of involving people living with dementia in game development. The findings reveal which elements of current exergames make them accessible or inaccessible for people living with dementia. These findings can help design new exergames to increase access to physical activity for people with dementia. The findings will also interest dementia service providers who want to use exergames to increase physical activity for people with dementia.