bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlations between monoaminergic biomarkers, classical biomarkers and the BPSD‐DSII behavioral scale in Down individuals with and without Alzheimer's dementia
Authors: Jacob Charlotte , Kachar Hanane , Heylen Annelies , Tollenaere Marleen , Verberk Inge M.W. , Teunissen Charlotte , Deyn Peter Paul De , Dam Debby Van
Published: January 2025

Background

Down syndrome (DS, trisomy 21) is the most frequent genetic cause of intellectual disability (ID), prevalent in approximately 1 in 900 live births (Loane et al., 2013). People with DS are at high risk to develop Alzheimer’s disease dementia (AD) (Lott & Head, 2001). Onset of clinical symptoms varies substantially in time. Consequently, predicting and monitoring decline and onset of dementia is a diagnostic challenge, while it is of essence in daily care and support. Behavioral and Psychological Symptoms of Dementia are an important and easily accessible tool for the prediction of dementia onset in the DS population. The BPSD‐DSII scale was developed to identify behavioral changes between the last six months and pre‐existing life‐long characteristic behavior in an (AD‐)DS population. Changes are assessed with the use of different behavior‐specific questions (items) which are categorized in different clusters (sections) (Dekker et al., 2018). We used the BPSD‐DSII to assess these symptoms and predict a potential diagnosis of dementia. BPSD‐DSII results are correlated with the serum levels of monoaminergic (epinephrine, norepinephrine, dopamine, serotonin and their metabolic products) and classical biomarkers, such as Ab40, Ab42, total tau, phosphorylated tau and neurofilament light chain.

Method

We used reversed‐phase ultra‐high performance liquid chromatography with electrochemical detection to determine the levels of epinephrine, norepinephrine, dopamine, serotonin and their metabolic products in serum. The Simoa platform was applied to detect the levels of Ab40, Ab42, total tau, phosphorylated tau and neurofilament light chain. Finally, we worked together with the caregivers of the (AD‐)DS individuals for the collection of BPSD‐DSII data.

Result

Preliminary data suggests correlations between different sections of the BPSD‐DSII questionnaire and serotonin levels, as well as correlations between different sections of the BPSD‐DSII questionnaire and classical biomarker levels. In addition, complementary data regarding the correlation between the different items of the BPSD‐DSII questionnaire and the different serum‐based biomarkers will be presented at the conference.

Conclusion

The results per section of the BPSD‐DSII correlate with the levels of monoamines and classical biomarkers in (AD‐)DS individuals. And could therefore be used as potential biomarkers for the development of AD within the population of DS patients.
Cardiovascular health is associated with social determinants of health in the LatAm‐FINGERS cohort
Authors: Delgado Carolina , Vergara Rodrigo C. , Pozo Natalia , Crivelli Lucia , Caramelli Paulo , Nitrini Ricardo , Sevlever Gustavo , Calandri Ismael Luis , Doren Carlos , Martin Consuelo San , Rodriguez Javiera , Gutiérrez Myriam , Bravo Jacinta , Moreno Maira , Márquez Carlos , Lara Oriana , More Jamileth , Lema Jose , Gomez Rodrigo , Allegri Ricardo , Lopera Francisco , Vellila Lina Marcela , Yassuda Monica , Sosa Ana Luisa , Salinas‐Contreras Rosa Maria , Suemoto Claudia Kimie , Consortium LatAM FINGERS
Published: January 2025

Background

Cardiovascular risk factors (CVRF) are among the main modifiable risk factors for dementia in Latin America (LA). Therefore, improving cardiovascular health (CVH) is one of the main objectives of the LatAm‐FINGERS trial, the largest non‐pharmacological (lifestyle improvement) randomized trial in LA. But, to fully comprehend CVH it is necessary to explore its relation with the social determinants of health (SDH), that are closely associated with lifestyle.

Methods

LatAm‐FINGERS is an initiative to develop a joint regional intervention protocol to prevent cognitive deterioration in 12 LA countries. Participants (between 60‐77 years old) should have high dementia risk (CAIDE >6), were evaluated clinically and cognitively at baseline and every 6 months for 2 years. At baseline, we measured the CVRF according to the Framingham risk score and the CVH with the “Life’s Essential 8 cardiovascular health index” (CVHI), a composed score that includes lifestyle’s (diet, physical activity, nicotine exposure, sleep health) and metabolic variables (body mass index (BMI), blood lipids, blood glucose, and blood pressure). Each score ranges from 0 to 100, with higher values meaning a healthier profile. SDH was characterized by years of education, race, and occupation. Occupation categorical data was transformed into an ordinal scale using the Hollingshead score. Partial correlations (controlled by age and sex) between CVHI and SDH measures were done.

Results

Preliminary data from 1,024 participants were analyzed, age = 67±5 years, education = 13±4 years, 72% women, 87% had high CVRF. The CVHI (60 ± 16) was obtained with 7 of the 8 variables, excluding sleep health (Figure 1). Diet (39±13) and physical activity (37±39) were the unhealthiest scores, while blood glucose (75±26) was the healthiest one (Figure 2). There were significant correlations between CVHI with years of education (r = 0.179, p<0.001) and occupation score (r = 0.169, p<0.001). Moreover, CVH individual components correlated with this SDH, except for blood lipids (Figure 3).

Conclusions

In the LatAm‐FINGERS cohort, better socioeconomic position is associated with a healthier cardiovascular index at baseline, being important to explore the role of SDH in CVH modification across the trial.

Funded by Alzheimer Association
Digital assessment of turning behaviours in Alzheimer’s disease and Lewy body disease and their association with cognitive function
Authors: Ardle Ríona Mc , Din Silvia Del , Rehman Rana Zia , Galna Brook , Thomas Alan J , Rochester Lynn , Alcock Lisa
Published: January 2025

Background

Digital mobility outcomes (DMOs) can be captured using body‐worn inertial measurement units (IMUs) in lab‐based and real‐world environments. DMOs may support differential diagnosis of dementia; for example, Alzheimer’s disease (AD) and Lewy body disease (LBD) show unique signatures of gait impairment. Growing evidence suggests that turning impairments are related to cognitive decline. Turning outcomes can be captured via IMUs and may complement use of existing DMOs. This study aims to assess differences in turning outcomes between AD, LBD and older adult controls, and explore their clinical and cognitive correlations.

Method

Participants completed six intermittent 10‐metre walks while wearing a IMU (APDM, Opal 128Hz) attached to their lower back. Following each walk, they made a 180degree turn. Two spatiotemporal (turn duration, angular velocity) and two acceleration‐based (combined direction [anterior‐posterior/medio‐lateral/vertical] Root Mean Square (RMS) and Jerk RMS) turning outcomes were extracted using validated algorithms. Analysis of covariance assessed between‐group differences in turning outcomes, controlling for age and sex. Tukey HSD tests for multiple comparisons determined where differences occurred. Correlations (Spearman’s rho) between significant turning outcomes and age, motor disease severity (MDS Unified Parkinson’s Disease Rating Scale III), global cognition (standardised Mini Mental State Examination; sMMSE), information processing (Trail Making Task A), and executive function (FAS Verbal Fluency Test) were assessed.

Results

98 eligible participants from the GaitDem study were included: 28 controls (Age (mean±SD):74±9 years, sMMSE:29±1), 35 AD (Age:77±6, sMMSE:23±4), and 35 LBD (Age:76±6, sMMSE:24±3). Both dementia disease subtypes demonstrated lower jerk RMS compared to controls (p<.05), while people with LBD also showed lower angular velocity, RMS and Jerk RMS (p<.05; Figure 1). For AD, turning impairments were associated with greater motor disease severity (Figure 2). For LBD, slower angular velocity was associated with greater motor disease severity, slower information processing and worse executive function (Figure 3).

Conclusions

Results suggest that dementia disease subtypes have significant turning impairments compared to normal ageing, but not compared to each other. However, turning impairments were related to discrete motor‐cognitive profiles in dementia disease subtypes. Further work should explore other turning characteristics (i.e. related to turn phase, signal direction, turn strategy) as differential markers of dementia.
Evaluating handwriting characteristics as a novel assisted screening approach for Mild Cognitive Impairment in community settings
Authors: Shi Lulu , Ren Yinxia , Wei Zhuqin , Qi Hengnian , Zhang Ruoyu , Wang Lina
Published: January 2025

Background

Older adults with Mild Cognitive Impairment (MCI) show decreased flexibility, speed, and fluency in writing, suggesting the feasibility of using quantitative handwriting analysis for MCI detection. Given task variability and the complexities of Chinese versus English characters, investigating Chinese handwriting characteristics is crucial for refining MCI screening approach.

Method

259 participants (109 with MCI, 150 controls) were engaged to completed six handwriting tasks using a dot‐matrix digital pen, encompassing four Chinese characters tasks and two graphical drawing tasks. Kinematic handwriting parameters were collected and analyzed using Light GBM, XGBoost, RF, and SVM machine learning models to assess their effectiveness in MCI recognition.

Result

A total of 48 handwriting characteristics were extracted, of which 12 characteristics derived from graphical drawing tasks and 18 from Chinese characters writing tasks exhibited significant differences between the two groups (P<0.05). Compared to the control group, the MCI group demonstrated a significantly longer mean lag time (Z = ‐2.991, P = 0.003 for graphical drawing tasks; Z = ‐6.441, P<0.001 for Chinese characters tasks), lower average writing velocity for graphical drawing tasks (Z = ‐3.263, P = 0.001), shorter single stroke lengths (Z = ‐2.352, P = 0.019), and decreased writing correctness scores (Z = ‐9.388, P<0.001 for graphical drawing tasks; Z = ‐5.949, P<0.001 for Chinese characters tasks). The accuracy of XGBoost, Light GBM, RF, and SVM machine learning models constructed based on handwriting characteristics were 81.35%, 83.28%, 81.03%, and 63.02%, respectively, with their Area Under the Curve (AUC) values being 0.888, 0.896, 0.895, and 0.570.

Conclusion

Handwriting characteristics in Chinese writing tasks showed promise for MCI screening in older adults, with the Light GBM model offering improved predictive accuracy, potentially enhancing MCI detection among community‐dwelling older adults.

Trial registration: The trial was registered at Chinese Clinical Trials Registry on 05/02/2022 (www.chictr.org.cn; Number Registry: ChiCTR2200059499).

Funding: National Natural Science Foundation of China (NO.72174061; NO.71704053), China Scholarship Council Foundation (NO. 202308330251).
Is the countryside still inside? Exploring long‐standing effects of childhood rurality for dementia risk in the PROAME Study
Authors: Rocha João Victor de Faria , Friedlaender Clarisse Vasconcelos , Tomaz Kelle Luisa dos Santos , Ruppert Emma Patrice , Lourandes Aida , Zacarias Ana Paula , Assenção Joanna de Castro Magalhães , Rincon Luciana Paula , Ribeiro Norton Gray Ferreira , Rosen Howard J. , Grinberg Lea T. , Maciel Francisca Izabel Pereira , Caramelli Paulo , Resende Elisa de Paula França ,   Cognitive and Behavioral Neurology Research Group (CogNeuro_UFMG)
Published: January 2025

Background

Dementia prevalence in Latin America is higher in rural than urban areas. This discrepancy may be explained by inequities over the lifespan in access to health and educational services. However, there is no evidence of potential adverse long‐standing effects of living in rural areas during childhood in current urban adults. This work investigates whether being born in rural areas (Rurality) increases exposure to dementia risk factors in adulthood among individuals who have emigrated to urban centers early in life.

Method

130 individuals aged 40+ years were screened across 11 schools offering a late‐life educational program in Belo Horizonte. Participants underwent a comprehensive neuropsychological evaluation, sociodemographic interviews, literacy assessment, and serum neurofilament light chain (sNfL) exam. Participants were classified as originally from the metropolitan region (BH), or born in countryside regions (CS). The groups were compared in terms of sociodemographic features, cognitive performance, Dementia risk factors, and neurodegeneration.

Result

108 met the inclusion criteria. Mean age was 58 (9.7) years, 71% women, and 90% non‐whites. CS (80% of the sample) and BH had similar sociodemographic characteristics. Cognitive performance was not significantly different. Concerning dementia risk factors, there was no difference in the frequency of sedentarism and depression (X², p = 0.38, for both), and for self‐reported hypertension, diabetes, dyslipidemia, smoking, alcohol consumption, hearing impairment, and severe head trauma. (X², p > 0.3 for all). Participants in the BH group were 4 times more likely to attend formal school during life, (p = 0.017), and had more years of schooling (p = 0.001). Education in childhood was positively associated with literacy level in adulthood (p = 0.024). Literacy level, but not education, was associated with global cognition, Executive functioning, and sNfL levels (p‐value = 0.003, 0.001, and 0.032).

Conclusion

Decreased educational attainment in childhood was the main difference between the groups. This difference might be perpetuated over their lifespan in urban areas by a persistent disparity in basic literacy level. Our study suggests that low literacy/illiteracy might be an underlying mechanism linking rural origins to increased dementia risk, even among Brazilians currently in urban areas.
The Role of ApoE4 in The Acceleration of Tau Aggregation
Authors: Steward Anna , Biel Davina , Roemer Sebastian Niclas , Zhu Zeyu , Pescoller Julia , Wagner Fabian , Gross Mattes , Dichgans Martin , Ewers Michael , Dehsarvi Amir , Brendel Matthias , Franzmeier Nicolai
Published: January 2025

Background

Understanding modulators of Alzheimer's disease’s (AD) progression is crucial for determining optimal treatment windows and targets. Apolipoprotein E ε4 (ApoE4), i.e. a key AD risk factor, is associated with earlier tau accumulation at lower Aβ levels (Steward et al. 2023), yet, the mechanisms driving this connection remain unclear. Thus, we assessed whether ApoE4 accelerates initial Aβ‐related tau secretion measurable in CSF or subsequent tau aggregation as determined via PET (Figure 1A).

Method

We combined cross‐sectional CSF measures of phosphorylated tau (p‐tau181) and Aβ‐PET in 287 APOE genotyped non‐demented (cognitively normal [CN]; mildly cognitively impaired [MCI]) ADNI participants. P‐tau181 was adjusted to Aβ40 to account for inter‐individual variability in CSF protein concentrations. Using linear regression, we investigated i) whether ApoE4 was related to accelerated Aβ‐related p‐tau secretion (i.e., Aβ‐PET by ApoE4 interaction on p‐tau181), ii) whether ApoE4 accelerated the p‐tau‐induced fibrillisation of tau (i.e. p‐tau181 by ApoE4 interaction on tau‐PET) and iii) whether regional effects of ApoE4 on p‐tau‐related tau fibrillisation were associated with ApoE4 mRNA expression levels.

Result

ApoE4 did not moderate the relationship between Aβ‐PET and p‐tau181 (Figure 1B, p=0.76) but strengthened the effect of p‐tau181 on global Tau‐PET increase (Figure 1C, β=0.7, p<0.001). At the regional level, this ApoE4 x p‐tau181 interaction on tau‐PET was correlated with regional APOE mRNA expression in CN (Figure 2B, r=0.5, pspin<0.001), but not in MCI (p=0.141), suggesting that ApoE4 drives earliest p‐tau‐induced tau aggregation. Supporting this further, we found that the regional effect of p‐tau181 on Tau‐PET was more strongly correlated with APOE mRNA expression in CN ApoE4 carriers (Figure 2C, r=0.54, pspin<0.001) than in CN non‐carriers (r=0.4, pspin=0.05). Lastly, we confirmed that the effect of Aβ on tau aggregation is mediated by p‐tau increases (Figure 1D, ACME: B=0.28; p<0.001; ADE: B=0.206; p=0.008) which is strengthened in ApoE4 carriers (B=0.21, p=0.006).

Conclusion

ApoE4 promotes p‐tau‐induced tau aggregation, particularly in early disease stages and in regions that express high APOE. This suggests that ApoE4 can trigger earlier Aβ‐related tau spreading most likely due to facilitated p‐tau induced tau aggregation. This suggests that preventing soluble p‐tau increases may attenuate tau aggregation and therefore dementia.
Associations of CAIDE dementia risk score with glucose and lipid‐related metabolic blood biomarkers in the FINGER study participants
Authors: Rocha Ana Sabsil Lopez , Stephen Ruth , Solomon Alina , Ngandu Tiia , Lehtisalo Jenni , Laatikainen Tiina , Mecocci Patrizia , Tuomilehto Jaakko , Kivipelto Miia , Mangialasche Francesca
Published: January 2025

Background

The Cardiovascular risk factors, aging, and dementia (CAIDE) risk score is a validated tool estimating dementia risk. We investigated the association of CAIDE score with 12 markers of glucose and lipid metabolism, in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) participants.

Methods

The FINGER trial had 1260 participants, aged 60–77 years, with a CAIDE score ≥6, without substantial cognitive impairment. At baseline, a panel of 12 glucose and lipid metabolism blood markers (adiponectin, adipsin, c‐peptide, ghrelin, gastric inhibitor polypeptide (GIP), glucagon‐like‐peptide (GLP‐1), glucagon, insulin, leptin, plasminogen activator in plasma (PAI‐1), resistin, and visfatin) were measured using Bio‐Plex‐200. CAIDE dementia risk score (age, sex, education, blood pressure, body mass index (BMI), cholesterol, physical activity) was also available. Linear regression models were fit using CAIDE score as the outcome, metabolic markers as predictors and APOE4 as covariate. We also tested the interactions between the metabolic markers and APOE4.

Results

Participants with the metabolic markers (n=813) were younger (p=0.01), had lower levels of HDL (p=0.01) and higher levels of systolic blood pressure (p= 0.02), HbA1c (p=0.00), BMI (p=0.00), CRP (p=0.02) and higher CAIDE risk score (p=0.02) but slightly better memory (p=0.00) compared to those without the metabolic markers (n=447).

Initially, CAIDE score was tested with each metabolic marker separately. Interactions between metabolic markers and APOE4 were also tested. Higher CAIDE score was associated with lower adiponectin (β coefficient= ‐0.01, p=0.01), ghrelin (β = ‐0.13, p<0.001), and higher insulin (β =0.16, p<0.001), leptin (β=0.15 p<0.001), PAI‐1 (β =0.14, p<0.001) and c‐peptide (β=0.15 p<0.001). No interactions between metabolic markers and APOE were significant except for glucagon x APOE4 (β= ‐2.10, p=0.021).

Next, the metabolic markers with the significant associations were added to a mutually adjusted model. The associations of CAIDE score with ghrelin (β= ‐0.22, p<0.001) and insulin (β=0.124, p=0.03) remained significant.

Conclusion

Increased dementia risk in older people is linked to glucose and lipid imbalance. The identification of phenotypes through different metabolic markers and the role of genetic factors on these metabolic markers can lead to a better stratification of the population at risk of developing dementia.
The effects of socioeconomic deprivation on long‐term outcomes in Parkinson’s disease and frontotemporal lobar degeneration syndromes
Authors: Dreyer Anna Jane , Murley Alexander G , Coyle‐Gilchrist Ian , Stockton Katherine , Holland Negin , Camacho Marta , Rouse Matthew A , Naessens Michelle , Brayne Carol , Barker Roger A , Williams‐Gray Caroline H. , Rowe James B
Published: January 2025

Background

Socioeconomic deprivation has been associated with shorter survival and an earlier loss of functional independence in patients with Alzheimer’s disease and dementia. However, the effect of deprivation on outcomes in Parkinson’s disease (PD) and syndromes associated with frontotemporal lobar degeneration (FTLD) are largely unknown. Prognosis in these neurodegenerative diseases is variable and difficult to predict despite multiple known sociodemographic, clinical and genetic predictors. Using data from three long‐term prospective incident cohorts in the UK, we conducted a survival analysis to investigate the association of the deprivation in one’s residential area with outcomes after symptom onset and diagnosis.

Method

Within known geographical settings patients with FTLD‐associated syndromes (bvFTD, PPA, PSP, CBS; N = 283) were recruited in three waves (2013‐2014, 2017‐2018, 2021‐2022) as part of PIPPIN. Similarly, patients with PD were recruited as part of CamPaIGN (N = 140) from 2000‐2002, and PICNICS (N = 280) from 2008‐2013. The Index of Multiple Deprivation (IMD) centile was assigned to each participant according to their residence at the time of diagnosis and dates of care home admission and death recorded from NHS records. Using Cox proportional hazards regression, we investigated the univariable and multivariable associations between IMD and (1) absolute survival (time to death) (2) independent survival (time to care home admission/death) (3) remaining cognitively healthy in PD (time to dementia diagnosis).

Result

IMD did not predict absolute or independent survival, in any of the three cohorts, in univariable or multivariable analyses. In univariable models, IMD predicted time to PD dementia diagnosis in PICNICS, but not in the other cohorts. Multivariable models showed that poorer outcomes were associated with sociodemographic (older age, being male), clinical (disease severity, cognitive deficits, depression, FTLD diagnosis) and genetic variables (APOE, GBA), but not IMD.

Conclusion

To live in an area of higher socioeconomic deprivation is not associated with poorer long‐term survival in patients with FTLD‐associated syndromes or PD. In patients with PD, living in an area of high deprivation predicted shorter time to dementia diagnosis. These reassuring results might reflect universal healthcare coverage (i.e., NHS), with specialist services for patients able to mitigate deprivation effects.
Evaluating the potential of teleneurology in a low‐resource setting for dementia: An exploratory study on patient and healthcare provider satisfaction
Authors: Alexander Pullumpallil Thomas , Ansari Mohammad Farhan , Rao Girish N , Arshad Faheem , Menon Deepak , Thomas Priya Treesa , Ramakrishnan Subasree , Parthasarathy Rajani , Alladi Suvarna
Published: January 2025

Background and Objectives

Telemedicine, including teleneurology, has emerged as a valuable tool for providing healthcare services remotely, particularly in situations where distance plays a critical role. Teleneurology has the potential to increase access to care, improve patient outcomes, and reduce healthcare costs, especially for patients in rural and underserved areas. We aimed to investigate patients and health care providers satisfaction with teleneurology for dementia.

Methods

We recruited 15 patients with dementia as a part of a public health initiative on Brain Health in the state of Karnataka in India. Patients resided across different districts of the state and had undergone an initial consultation at the specialist centre. Follow up teleconsultations were conducted using the Zoom Video Conference application and included a brief neurological examination. Patient and/or caregiver satisfaction was assessed using Telemedicine Satisfaction Questionnaire (TSQ) and healthcare provider satisfaction was assessed using Patient and Physician Satisfaction with Monitoring Questionnaire (PPSM).

Results

Of the 15 patients with dementia enrolled in the study, mean age of the cohort was 65 years. All 15 patients [8 men] or caregivers completed the Teleneurology Satisfaction Questionnaire (TSQ), yielding a mean score of 4.47±0.41. The mean duration of teleconsultation was 43 minutes. Additionally, the Patient Perception of Satisfaction with Method (PPSM) questionnaire was completed by the neurologist for all 15 patients, resulting in a mean score of 4.33±0.44. Among these patients, 12 consultations were initiated by a primary care physician, and all of them completed the PPSM questionnaire, which had a mean score of 4.04±0.51. Paired patient and neurologist agreement was 60% for quality of care provided, 98% for time saving benefit and 95% for willingness for future use.

Discussion

Overall, patients or their caregivers expressed satisfaction with the quality of care provided through teleneurology and agreed that it was comparable to face‐to‐face encounters. Primary care physicians also reported positive experiences with teleneurology, including a good understanding of patients' health status and the belief that teleneurology was a valuable addition to regular care. Both patients or caregivers and neurologists agreed for the quality of care provided, the time saving benefits and the willingness for future use of teleneurology.
Longitudinal neurodegeneration in relation to amyloid pathology among cognitively unimpaired individuals
Authors: Stephenson Henry Gilreath , Betthauser Tobey J. , Hulle Carol A. Van , Du Lianlian , Langhough Rebecca E. , Jonaitis Erin M. , Kollmorgen Gwendlyn , Quijano‐Rubio Clara , Chin Nathaniel A. , Okonkwo Ozioma C , Carlsson Cynthia M. , Asthana Sanjay , Christian Bradley T. , Johnson Sterling C. , Blennow Kaj , Zetterberg Henrik , Bendlin Barbara B.
Published: January 2025

Background

The timing of neurodegeneration in relation to the onset of Alzheimer’s disease pathology is not fully known. This study examined the association of longitudinal atrophy derived from T1‐weighted MRI with 1) cerebrospinal fluid (CSF) amyloid‐tau (AT) groupings and 2) Pittsburgh compound B (PiB) PET‐derived estimates of amyloid duration among cognitively unimpaired (CU) individuals.

Method

CU participants in the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center (N = 297) underwent longitudinal MRI, APOE genotyping, and lumbar puncture to determine CSF Aβ42/40 (A) and pTau181 (T) concentration at baseline using in‐house cutoffs. CSF measurements were performed using the NeuroToolKit, a panel of robust prototype biomarker assays (Roche Diagnostics International Ltd). Image segmentation was performed using a longitudinal pipeline in SPM12. Grey matter volumes from AD‐associated regions (adjusted for intracranial volume) were z‐scored according to age‐associated predictions from a robust longitudinal A‐T‐/APOE4‐/CU control group. Differences in longitudinal atrophy relative to controls were tested in linear mixed‐effects models using contrasts between A+T‐ and A+T+ groups and A‐T‐ controls and interactions with time (years from baseline). In the PiB PET subset, sampled iterative local approximation was used to estimate time‐to‐positivity at baseline relative to a PiB DVR threshold of 1.16. CSF A+ individuals were grouped as CSF A+ only, early PiB+ (PiB+ <= 5 years), and established PiB+ (PiB+ > 5 years). Differences in longitudinal atrophy were tested with A+ group/A‐T‐ contrasts and interactions with time. All analyses were FDR‐corrected. See Table 1 and Figure 1 for participant characteristics and model details.

Result

Based on CSF assays, both A+ groups showed longitudinal atrophy relative to controls in a majority of ROIs, suggesting that A+, regardless of pTau+, is associated with neurodegeneration. Further analysis incorporating PET showed that CSF A+ in the absence of PiB+ was not associated with atrophy, but early PiB+ was associated with atrophy in medial temporal ROIs and precuneus. The largest and most widespread atrophy was observed in the established PiB+ group (Figure 2).

Conclusion

Neurodegeneration appears to begin soon after the onset of PET‐measurable amyloid‐positivity. Clinical intervention at the earliest signs of amyloid deposition may be needed to delay neurodegeneration.
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‐ε4 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.
Quantitative transport mapping estimated blood flow velocity is more sensitive to the perfusion change in Alzheimer's disease than the conventional cerebral blood flow, estimated from multiple delay arterial spin labeling
Authors: Zhou Liangdong , Guo Yihao , Li Yi , Wang Yi , Liu Tao , Chen Huijuan , Huang Weiyuan , Chiang Gloria , de Leon Mony J. , Chen Feng
Published: January 2025

Background

Quantitative transport mapping (QTM) has been developed for estimation of blood flow velocity with 4D dynamic tracer concentration data (Zhou et. al., Magn. Reson. Med. 2021;85: 2247–2262; Zhang et. al., Magnetic Resonance Imaging 2022; 86: 86–93). We investigated the QTM and CBF in human brain for Alzheimer's disease using multiple post‐labeling delay arterial spin labeling (mPLD‐ASL) MRI.

Method

A total of 131 subjects (28 AD, 82 patients with mild cognitive impairment (MCI), and 21 normal controls (NC)) were prospectively recruited in this study. All participants underwent magnetic resonance imaging (MRI) examination and neuropsychological evaluation. CBF and QTM maps were computed from ASL with multiple PLD (Wang et al Neuroimage: Clinical 2013; 3:1‐7). Group differences of regional CBF and QTM analysis were performed and compared. The associations between perfusion and cognition were assessed.

Result

Regional analysis showed decreased QTM value in occipital lobe, and hippocampus in MCI compared with NC as shown in Figure 1 (D)‐(F). CBF only decreases in AD patients compared to NC in cerebral cortex and hippocampus and was not able to distinguish MCI and NC as shown in Figure 1 (A)‐(C). CBF and QTM in hippocampus were both positively correlated with cognition, including global cognition, memory, executive function, and language function.

Conclusion

This study demonstrated a reduced QTM of occipital lobe and hippocampus in MCI compared with NC, suggesting QTM as a potential early biomarker for AD. QTM in the hippocampus are correlated with cognitive deterioration. These findings contribute to a clear comprehension of perfusion change, glymphatic clearance deficit and cognitive decline in AD. QTM performs superior to CBF in distinguishing MCI and NC could be due to its accurate biophysical nature where arterial input function (AIF) is not required, and local mass conservation is satisfied. Global AIF used in CBF estimation could be not sufficiently sensitive to the physiological change at the early stage of AD.
Genetic contribution to the sex differences of tau pathologies in Alzheimer’s disease –APOE and beyond
Authors: Wang Yi‐Ting , Therriault Joseph , Rahmouni Nesrine , Macedo Arthur C. , Servaes Stijn , Arias Jaime Fernandez , Mathotaarachchi Sulantha , Stevenson Jenna , Gauthier Serge , Rosa‐Neto Pedro ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

Background

Alzheimer's disease (AD) disproportionately impacts females, who exhibit a higher tau load compared to males. Existing literature suggests that biological sex may alter the impact of APOE on tau pathology in AD. Nevertheless, the genetic factors contributing to sex differences in AD tau pathology, beyond the influence of APOE, have been minimally investigated.

Methods

This study included 2 well‐characterized AD cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD, n=359) cohort and the ADNI cohort (n=283). All participants underwent APOE genotyping and PET imaging with radioligands targeting Aβ plaques and tau tangles respectively. Polygenic hazard score (PHS) was computed using 31 AD‐associated SNPs identified from a stepwise Cox proportional hazards model for each ADNI participant. Low and high PHS is defined as low: −1 SD, ∼16 percentile; and high: +1 SD, ∼84 percentile.

Results

Sex‐disaggregated voxel‐based analyses revealed higher tau‐PET SUVRs in female subjects with APOE4 allele(s) and high PHS (Figure 1). ANOVA tests also showed a significant difference in tau load in Braak I‐II ROIs between female E4 carriers and both male E4 carriers (P<0.05) and non‐carriers (P<0.0001). To illustrate the relationship between Aβ and tau, modulating by APOE4carriage status, non‐linear Locally Weighted Scatterplot Smoothing (LOWESS) trendlines were applied, demonstrating an initial rise in tau among female E4 carriers, succeeded by male E4 carriers (Figure 2). Subsequently, linear Ordinary Least Squares (OLS) regression analyses were conducted to explore the influence of PHS on the Aβ‐tau relationship. Notably, female individuals in the high PHS group exhibited the highest tau load under a comparable Aβ load compared to other groups (Figure 2). In line with this, regression analyses unveiled a modulating effect of PHS and sex on tau load in AD‐associated regions, and this effect remained statistically significant after adjusting for APOE4 carriage status (Table 1).

Conclusions

In the trajectory of Alzheimer's disease, early‐stage tau deposition was more pronounced in female individuals with the APOE4 allele. Our findings suggest exploring the polygenic architecture aids in identifying female individuals at the highest risk of developing tau pathology. This may be valuable for stratifying AD risk and as an enrichment strategy in clinical trials.
Providers’ Experiences Implementing Cognitive Care Planning: Barriers and Facilitators
Authors: Britt Katherine Carroll , Xiao Xaviera , Sun Kevin H , Huang Bin
Published: January 2025

Background

Cognitive care planning—the process of regularly and systematically assessing patient needs and documenting recommendations to address them—improves health and quality of life among patients with cognitive impairments, like Alzheimer’s disease and related dementias (ADRD). A cognitive care plan may promote physical exercise, social engagement, healthier eating, medication recommendations, and overall improvement in care management (e.g., advance care planning), which translates to lower health facility use and better quality of life. As dementia is progressive, even short‐term improvements in quality of life, emotional health, and resource use can significantly alleviate the disease burden. With limited pharmaceutical treatments, cognitive care planning is likely to remain one of the most effective ways to promote care among patients with ADRD. Despite significant potential benefits for patients and caregivers, formal and individualized cognitive care planning remains underutilized.

Method

We conducted a qualitative study exploring providers’ perceptions and experiences implementing cognitive care planning in their practice. A purposive sample of 8 primary care providers actively caring for older adults including patients with ADRD participated in semi‐structured teleconference interviews. Iterative inductive content analysis was used to analyze data.

Result

Our preliminary results indicate several barriers and facilitators for implementing cognitive care planning into practice by providers. Providers reported some familiarity with general cognitive care and assessment but lacked a clear systematic approach and thorough understanding of the cognitive care planning process and steps. Across patient‐ and caregiver‐related, organization‐related, clinical care team‐related, and provider‐related focused areas, we identified five categories: (1) perceptions (buy‐in or reluctance), (2) family presence (context, support, communication, provider‐patient relationship), (3) logistics and priorities (time, schedule, staffing, priorities), (4) structure/systemized approach (standardization, templates, clear roles, referrals), and (5) experience and training (confidence or unfamiliarity).

Conclusion

Providers expressed the value of a structured approach for successfully implementing cognitive care planning. Buy‐in at multiple levels (patient, caregiver, organization, and clinical team) may prompt prioritizing this care approach in practice to restructure the assessment process for older adults. In addition, caregiver and family accompaniment to patient visits can increase contextual knowledge and provider communication for tailoring cognitive care plans.
Building a dementia care effectiveness trial to facilitate and anticipate widespread intervention adoption
Authors: Fortinsky Richard H , Robison Julie T
Published: January 2025

Background

This presentation maps the journey of an evidence‐based dementia care program from effectiveness trial design to adoption by policymakers as an ongoing program available to eligible older adults living at home with dementia and their care partners. Care of People with Dementia in their Environments (COPE) is a non‐pharmacologic program that seeks to maximize physical function and quality of life in people with dementia and build dementia management skills in care partners. Efficacy trial results showed that, compared to controls, people with dementia receiving COPE had greater functional independence in activities of daily living and care partners receiving COPE reported improved well‐being and increased confidence using dementia management skills.

Methods

From 2014‐2020, COPE was tested in Connecticut, USA, using an effectiveness‐implementation hybrid design. The target population was people with dementia receiving services from Connecticut’s Medicaid‐funded home and community‐based services (HCBS) program and their care partners. Several study features were designed to anticipate the possibility that COPE might be adopted for widespread use if the study were successful. First, a translational advisory committee met annually to help guide the study and interpret findings with an eye toward offering COPE within Connecticut’s HCBS program throughout the state. Advisory committee members included leaders from Connecticut’s Medicaid program and from the state’s largest HCBS service coordination organization. Second, this service coordination organization co‐designed study recruitment procedures with the study team, including use of its electronic health record system to identify and invite people with dementia and care partners to join the study. Third, qualitative data were used to give voice to stakeholders about how well COPE was implemented within the HCBS program workflow. Fourth, extensive cost data were captured enabling economic analyses to be presented to policymakers.

Findings

Care partners receiving COPE reported more improved well‐being, and total healthcare costs were lower among older adults receiving COPE, compared to those not receiving COPE.

Conclusions

Based on study findings, COPE is being incorporated into Connecticut’s HCBS program pursuant to public policy opportunities that arose in the wake of the COVID pandemic, which has provided funding for a variety of new Medicaid HCBS initiatives.
“Continu‐A‐Mente”: continuity of care between hospital and community for people living withdementia and their caregiver with Tailored Activity Program
Authors: Pozzi Christian , Staglianò Andrea , De Ponti Chiara , Ballabio Claudia , Bartoli Federica , Antolini Laura , Ferrara Maria Cristina , Morandi Alessandro , Cavalli Stefano , Gitlin Laura N. , Bellelli Giuseppe
Published: January 2025

Background

Nonpharmacological approaches have been identified as first line treatments for the behavioral and psychological symptoms (NPS) of persons living with dementia (PLWD).

Methods

This is a single‐arm study to evaluate the feasibility of the TAP approach to promote continuity of care between hospital (S. Gerardo hospital ‐ Italy) and community. Inclusion criteria were presence of NPS; autonomy in activities of daily living (Katz’s index ≥ 2); presence of caregiver. On recruitment, PLWD underwent a multidimensional assessment, Clinical Frailty Scale (CFS), Neuropsychiatric Inventory (NPI), Katz’s Index, Timed‐Up‐and‐Go‐test (TUG), number of drugs taken by the patient and caregiver’s sense of competence (SCQ questionnaire). After recruitment, the dyad PwD+caregiver received 8 TAP sessions performed by two occupational therapists, at hospital (two sessions) and at home (6 sessions). Follow‐up was set after 4 mouths. The attrition rate (% of dropouts) was the primary outcome.

Results

51 patients identified as potentially eligible, 21 declined to participate in the project. Currently, 30 dyads have been recruited, with 16 having completed the follow‐up. Overall, there were 6 (20%) dropouts. The mean patient’s age was 81 ±4.8 years. The median CFS patient’s score was 6 and half of patients were taking more than 7 medications per day. Wilcoxon signed‐rank test was conducted on the 16 dyads. From baseline to follow‐up (median, IQR 75%‐25%), there was a significant reduction in the NPI total score (NPI baseline = 17 (10.7‐33.2) NPI follow‐up 15.7 (8‐2 – 24.0), p = .002), caregiver distress (NPI caregiver distress baseline = 9.5 (6.0‐17.0); NPI caregiver distress follow‐up 6.5 (2.2‐11.5); p = .003) and TUG score (TUG baseline = 18.0 (13.0 – 35.5); TUG follow‐up 13.4 (10.5‐21.5); p = .007). Moreover, there was a significant decrease in the SCQ scale (SCQ baseline = 49.0 (44.0‐64.5) SCQ follow‐up 43.0 (36.5‐56.5); p = .001). No patient experiences hospital admissions at follow‐up while 3 patients had accessed emergency department.

Conclusions

Preliminary data are very promising and in line with what was hypothesized in the clinical trial design phase. TAP may be a valuable aid in monitoring the BPSDs of PLWD and avoiding re‐hospitalizations.
Depression and cardiovascular symptoms in a diverse Frontotemporal Dementia cohort, enriched for Caribbean Hispanic patients
Authors: Martinez Anisley , Gu Tianjie , Illanes‐Manrique Maryenela Z. , Tejada Sergio J. , Mena Pedro R. , Acosta Heriberto , Camargo Christian , Sun Xiaoyan , Alfonso Michelle Marrero , Baumel Bernard , Cornejo‐Olivas Mario , Castro‐Suarez Sheila , Vance Jeffery M. , Cuccaro Michael L. , Pericak‐Vance Margaret A , Nuytemans Karen
Published: January 2025

Background

Most biomedical data currently available for any disease is derived from studies in non‐Hispanic white (NHW) populations. Specifically, clinical information, genetics as well as biomarkers for frontotemporal dementia (FTD) have been studied predominantly in those NHW populations. For example, a role for depression and cardiovascular symptoms in increased risk for cognitive impairment has been reported; but little information is available on their risk effect in (diverse) FTD.

Method

Our current cohort consists of 135 FTD patients (71% Hispanic, 21% NHW, 6.5% Black/African American), with continuing enrollment from University of Miami (FL), Caribbean Center for the Study of Memory and Cognition (PR) and Instituto Nacional de Ciencias Neurologicas (Peru). All patients were evaluated using NACC Uniform DataSet or equivalent in their preferred language; ∼53% of the cohort also completed the FTD module forms. We compared clinical presentation (age‐at‐onset, ratio behavioral to language variant) in NHW versus Hispanic patients. Additionally, we studied association of Clinical Dementia Rating (CDR) scores with cardiovascular symptoms and depression (Geriatric Depression Score or Cornell Score for Depression).

Result

We did not identify a significant difference in age‐at‐onset, global CDR or ratios of behavioral FTD (bvFTD) versus primary progressive aphasia (PPA) as first symptoms between the NHW and Hispanic patients. We observed association of depression with global CDR≥2, across all patients (p = 0.003) and in Hispanic or Black/African American patients specifically (both p∼0.04). This difference was not driven by bvFTD or PPA subtypes specifically. No significant association was observed for global CDR with diabetes, hypertension or hyperlipidemia in all, Hispanic or NHW patients.

Conclusion

Biomedical research of FTD in underrepresented population groups is necessary as data from research in NHW is not always generalizable across race/ethnicity. Our data suggests that the reported association of depression with higher CDR scores is valid in diverse FTD patient groups; whereas we see less evidence for cardiovascular symptoms being associated with risk for FTD. We are working to expand our efforts characterizing the full clinical and biological presentation of FTD in non‐NHW population groups. The biomedical characterization of FTD across race/ethnicity will help the understanding of disease mechanisms in all patients, ultimately preventing further health disparities.