bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of vocal biomarkers in detecting cognitive impairment: interim findings from US and Indian populations
Authors: Larsen Erik , Murton Olivia , Song Xinyu , Weiss Erica , Emmeline Ayers , Zwerling Jessica , Sharath Veena , Jacob Soumya , Sigamani Alben , Pradeep V.G. , Verghese Joe
Published: January 2025

Background

Vocal biomarkers are emerging as potentially meaningful health indicators in multiple domains, including cognition. Because voice‐enabled devices are widespread, automated vocal analysis could become a useful modality for early detection and monitoring of cognitive impairment. To assess the efficacy of vocal biomarkers in identifying cognitive impairment we evaluated prosodic speech features on vocal tasks in a research cohort from Kerala, India, and a referral cohort from the Montefiore‐Einstein Center for the Aging Brain in the Bronx, NY.

Methods

157 participants (38% female, mean age 67 (4.9)) in India, and 57 participants (65% female, mean age 76 (6.3)) in NY completed voice protocols and cognitive screening (Addenbrooke's Cognitive Examination‐III in India, mean 81 (13); Blessed Information Memory Concentration Test in NY, mean 6.0 (3.7)). Prosodic speech features on vocal tasks with low and high mental effort were compared to performance on cognitive screening. Speech feature values were characterized using means and standard deviations, and subgroup distributions were compared using ratio of means, Cohen’s d for effect size, and significance testing using independent sample t‐tests.

Results

Mean speech rate across conditions in syllables/minute was 100 (37) for the India and 107 (34) for the US cohort; pause duration in seconds was 0.68 (0.40) and 0.56 (0.33), respectively. Participants with worse performance on cognitive screening exhibited reduced speech rates and increased pause durations—23% variation in the Indian and 4% in the US cohort. Tasks with higher mental effort mirrored these effects, with about 25% variation in both cohorts. Mental effort had medium to large effect size (0.6‐0.9) and was statistically significant (p<0.01), while cognitive impairment achieved similar effect size and statistical significance for the India cohort only.

Conclusion

These preliminary findings reinforce the potential of vocal biomarkers, especially speech rate and pause duration, as potential indicators of cognitive impairment in older adults. The results align with our goals to develop accessible vocal biomarker technology and support continued investigation into their utility in clinical and everyday settings, development of predictive analytics, and incorporating these into existing vocal biomarker platforms.
Association between gene expression and neurodegeneration in dementia with Lewy bodies
Authors: Habich Annegret , Baumann Janna M. , Schwarz Christopher G. , Przybelski Scott A. , Pardini Matteo , Calizzano Francesco , Inguanzo Anna , Oppedal Ketil , Blanc Frédéric , Lemstra Afina Willemina , Hort Jakub , Brendel Matthias , Ochoa‐Figueroa Miguel A , Garibotto Valentina , Kramberger Milica G. , pilotto andrea , Boeve Brad F. , Aarsland Dag , Westman Eric , Dierks Thomas , Kantarci Kejal , Morbelli Silvia , Jonkman Laura E. , Ferreira Daniel
Published: January 2025

Background

Patterns of regional atrophy and hypometabolism have been observed in dementia with Lewy bodies (DLB). However, determinants of regional vulnerability to structural and functional neurodegeneration remain largely unexplored. First, we investigated the association between regional gene expression and grey matter volumes in probable DLB patients. Since hypometabolism presumably precedes overt brain atrophy, we additionally investigate the association between regional gene expression and hypometabolism in DLB.

Method

To investigate the association between gene expression and regional volumes, 165 DLB patients along with 165 age‐ and sex‐matched healthy controls from three European centres and the Mayo Clinic (USA) were included. Regional volumes were quantified from MRI using SPM12 in 112 cortical, subcortical, and cerebellar brain regions, and compared between groups, using w‐scores. Regional expression data of seven genes involved in the formation and degradation of pathological protein aggregates (APOE, APP, BIN1, GBA, MAPT, SNCA, TMEM175) was extracted from six healthy donors from the Allen Human Brain Atlas and correlated with regional volumetric w‐scores. To assess the predictive value of regional gene expression on regional volumes we used Gaussian stepwise backwards linear regression including all seven genes as predictors. To investigate the association between gene expression and hypometabolism, we are currently applying the same analysis pipeline to FDG‐PET data of 139 DLB patients from 8 European centres.

Result

Most brain regions showed lower volumes in DLB patients compared to healthy controls, with differences being most pronounced in occipital and parietal lobes. Regional expression of APOE correlated positively with regional volumes in DLB. Conversely, regional expression of MAPT correlated negatively with regional volumes. Both APOE and MAPT gene expression were significant predictors of regional volumes in the regression analysis. None of the other gene expression values was significantly associated with regional volumes in DLB.

Conclusion

Our findings show that regional expression of genes associated with the abnormal accumulation of amyloid and tau, common co‐pathologies in DLB, partially account for the brain atrophy pattern observed in DLB patients. Analyses are ongoing for the hypometabolism pattern. Our finding emphasises the relevance of co‐pathologies in predicting atrophy progression and identifying potential targets for future disease‐modifying treatments.
Relationship Between Social Support and Global Cognition by Level of Neighborhood Disadvantage in the HABS‐HD Cohort
Authors: Rhoads Tasha , Cobos Kimberly , O'Bryant Sid E. , Miller Justin B ,   the HABS‐HD Study Team
Published: January 2025

Background

Prior research has demonstrated the positive association between social support and cognition. Specifically, greater social support has been linked with improved cognitive performance and reduced risk of dementia. In particular, emotional support has been identified as a key dimension in the relationship between social support and cognition. This study examined how the relationship between social support and cognitive functioning varies by neighborhood disadvantage, as measured by the Area Deprivation Index (ADI), in a diverse sample of older adults.

Method

Data from 2811 participants (629 Non‐Hispanic Black, 1107 Hispanic, 1075 non‐Hispanic White individuals) from the community‐based Health & Aging Brain Study–Health Disparities (HABS‐HD) cohort were examined. Three composite social support subscales were computed based on self‐report questionnaire responses to describe the following dimensions: Companion support (e.g., accompanying an individual during activities), Emotional support (e.g., having others to confide in or turn to for advice), and Assistance support (e.g., providing help with household tasks). Separate regressions were stratified by ADI quintile. Each regression included all subscales as predictors along with age, sex, and education as covariates. The Mini‐Mental State Exam (MMSE) Total Score was used to reflect global cognition (outcome).

Result

Regressions indicated overall significant models for each level of neighborhood disadvantage. Within ADI 1 (least disadvantage), ADI 2, and ADI 5 (greatest disadvantage), Assistance support emerged as a significant predictor of global cognition. Within ADI 2, Companion support also significantly predicted global cognition. Finally, within ADI 3, Emotional support significantly predicted global cognition. There were no significant social support subscale predictors evident within ADI 4.

Conclusion

Overall, these findings highlight the generally robust, protective effect of social support on cognitive abilities in this large, diverse cohort of older adults. However, variations across subtypes of social support between neighborhood contexts were evident. This highlights the importance of social support for brain health among individuals across levels of socioeconomic status, although these effects may be somewhat weaker at higher levels of neighborhood disadvantage. This finding underscores the fact that greater resources to promote brain health should be directed towards individuals living in areas of greater neighborhood disadvantage.
MIND‐China in 2018‐2023: Multimodal interventions in rural communities
Authors: Qiu Chengxuan
Published: January 2025

Background

Worldwide, ∽40% of dementia cases are preventable by interventions to target major modifiable risk factors. In the multimodal interventions to delay dementia and disability in rural China (MIND‐China), we aim to test the effect of multimodal intervention programs on maintaining cognitive and physical function among rural‐dwelling older adults and discuss about challenges and opportunities for a multidomain intervention study in a rural population.

Method

MIND‐China targets people who are aged 60‐79 years and living in rural communities (52 villages) in Shandong. The study tested two intervention programs: The vascular intervention included treatment of hypertension, diabetes, and dyslipidemia; the multimodal intervention included vascular interventions plus non‐pharmacological intervention (e.g., group exercise, personalized leisure activities, and cognitive training). The control group received regular primary care. Baseline assessments and recruitment for interventions were performed in 2018‐2019. Follow‐up assessments were conducted in 2021 and 2023. The primary outcome is the composite cognitive z‐score from a neuropsychological test battery. Secondary outcomes are physical function, dementia, cardiovascular events, and mortality. Measures were taken to overcome barriers for study participation and to achieve high rate of participating interventions and follow‐up assessments.

Result

At baseline (March‐September 2018), 5765 persons (74.9% of all eligible persons; age ≥60 years; 57.2% women; 40.6% illiteracy; and 88.3% farmers) were recruited. In 2019, recruitment for interventions was performed aiming to recruiting 3000 participants who were aged 60‐79 years and free of dementia and disability. The cluster(village)‐based randomization method was used to assign participants into three groups. The intervention programs were organized by local coordinators and village doctors, even during COVID‐19 pandemic, whenever possible. Follow‐up assessments for intervention participants were conducted in 2021 and 2023. The interventions ended in October‐November 2023. The assessments and diagnosis of outcomes and data cleaning are ongoing. Factors associated with participation in and adherence to the interventions and follow‐up assessment are being analyzed.

Conclusion

MIND‐China successfully recruited a large sample of participants for a multimodal intervention in rural communities. The project is expected to clarify whether the personalized culture‐sensitive multimodal interventions may help maintain cognitive and physical function among rural elderly populations in China.
Proteomic Signature of The Cerebrospinal Fluid (CSF) in Preclinical and prodromal AD: A key role for adhesion proteins
Authors: Neal Reem M. , Yang zhiyi , Hajjar Ihab
Published: January 2025

Background

Alzheimer's Disease (AD) proteomic studies have focused on understanding the pathophysiology of AD during the late stages of AD. However, recent studies have suggested that the preclinical stage of AD represents a golden window for intervention. Yet, little is known about the influence of the cerebrospinal fluid (CSF) molecular environment on the mechanisms underlying the pathogenesis of AD during the preclinical stage.

Method

We performed targeted proteomics using Olink® platform that measured 276 proteins related to neuronal injury, endothelial function, and cardiometabolic pathways in samples from 354 participants recruited for the BSHARP study. Advanced bioinformatic pipeline for data reduction, protein‐protein interaction networks, and module development were used. Resultant Hub proteins that are associated with various clinical phenotypes and biological traits such as levels of CSF AD biomarkers (Aβ42, Tau, and pTau) and the Aβ42/Tau Ratio (TAR) were identified. We then ran the list of Hub proteins through the STRING database to identify critical proteins and performed a pathway enrichment analysis to understand their role in AD.

Result

We compared CSF and plasma proteomic profiles between participants who have normal cognitive function and those who have based on TAR status. As a result, we identified critical proteins that are associated with AD clinical phenotypes and levels of CSF AD biomarkers such as Aβ42, Tau, and pTau (all p‐values <0.05). We also found a significant difference in levels of 6 of the critical genes based on TAR status (HGF, ICAM1, VCAM1, NRP1, NRP2, SCARB2, CCL3). Pathway enrichment of the critical proteins using Gene Ontology (GO) Biological Process identified a series of pathways related to cell adhesion, inflammation, and endothelial function as well as response to Amyloid (all p‐value <0.05) pathways which are known to be related to AD.

Conclusion

Our findings reveal that adhesion and endothelial‐related pathways are highly associated with AD phenotypes, especially in the preclinical stage. This suggests a possible proteomic signature in the CSF of individuals with preclinical AD that is driven by adhesion molecules and contributes to the pathogenesis of AD. Future studies investigating this contribution might provide insight into the molecular mechanisms underlying AD.
Real‐world utilization of diagnostic tests for mild cognitive impairment, Alzheimer’s disease, and other dementias in Medicare fee‐for‐service beneficiaries
Authors: Yan Jessie T. , Dillon Allison , Meng Tong , Ramesh Viviktha , Sabbagh Marwan N. , Roth Sophie
Published: January 2025

Background

Use of neuroimaging [e.g. magnetic resonance imaging (MRI), positron emission tomography (PET), or computed tomography (CT) scan], cerebrospinal fluid (CSF), and blood biomarker tests can contribute to a more accurate and earlier diagnosis of Alzheimer’s disease (AD). This study aimed to examine real‐world utilization of existing diagnostic tests for mild cognitive impairment (MCI), AD, or other dementias in a large US elderly population.

Method

Using data from the Medicare 100% Research Identifiable files, this retrospective observational study included Medicare fee‐for‐service beneficiaries ≥ 67 years old and newly diagnosed with MCI, AD, or other dementias between 2015 and 2020. The study index date was the first disease diagnosis date. Descriptive analyses were conducted to examine the use of MRI, CT, PET, CSF, and any blood tests within 1 year before the index date in the overall study group and by three cohorts (MCI, AD, and other dementia). To understand test utilization patterns over time, test rates were also stratified by index year.

Result

The final study sample consisted of 653,420 patients (9.1% MCI, 30.3% AD, and 60.6% other dementias). Overall, during the 1 year before the index date, 71.9% had at least one blood test, 53.9% had any neuroimaging test, 46.4% had CT, 17.7% had MRI, 0.7% had PET, and 2.2% had CSF. Across cohorts, the other dementia cohort had the highest utilization of any neuroimaging test (56.2% vs. 51.4% in AD vs. 46.9% in MCI). The MCI cohort had the highest utilization of CSF (3.5% vs. 2.2% in other dementias vs.1.8% in AD). The use of these diagnostic tests increased slightly from 2015 to 2020 (see Figure 1).

Conclusion

In the six years prior to the availability of disease‐modifying therapies (DMTs), blood tests, MRI and CT were the predominant diagnostic tests, while the use of CSF and PET was very infrequent. Despite the modest increasing trends, substantial improvements are needed in the use of confirmatory tests, especially PET and CSF which will be necessary for increased utilization of new DMTs.
Digital Clock Assessment in South Asian Setting: Insights from the P‐CARRS study
Authors: Jagannathan Ram , Mohan Deepa , Komal Rani , Kondal Dimple , Subramani Poongothai , Pai Rima , Ali Mohammed K , Mohan Sailesh , Alladi Suvarna , Tandon Nikhil , Prabhakaran Dorairaj , Mohan V , Levey Allan I. , KM Venkat Narayan , Goldstein Felicia
Published: January 2025

Background

Detection of presymptomatic individuals or those with subtle cognitive changes in midlife may prevent or slow the course of Alzheimer's Disease by identifying candidates for disease‐modifying treatments. Utilizing newer delivery approaches involving digital measures shows promise for cognitive phenotyping, early detection, ease of administration, and scoring, particularly in low‐resource settings. However, the feasibility of these approaches, along with their association with demographics and their effectiveness in detecting fine‐grained aspects of cognitive performance in low‐resource settings, remains unclear. We conducted a pilot study evaluating digital cognitive screening using an iPad‐administered clock drawing test in a diverse South Asian population residing in India.

Methods

Individuals ≥ 50 years old (median: 61.0 years; range: 50‐89 years; female: 56%; education: up to primary schooling: 8%; high school to secondary: 65%; graduation and above: 27.4%) nested within the ongoing population‐based longitudinal Precision‐CARRS study representing socio‐demographically and linguistically diverse adults from Delhi and Chennai in India (n=300; 150/site) were studied. Participants were administered the FDA‐approved, iPad‐based clock drawing test using a commercially available Linus Health Digital Clock (DCTclock) screening tool. The DCTclock summary score, ranging from 0 to 100, was derived through AI analytics and provided various features, including drawing efficiency, information processing, simple motor skills, and visuospatial reasoning. Performance on the traditionally administered paper/pencil version of the Mini‐Cog test incorporating clock drawing and three‐item recall was used to classify participants as cognitively impaired (0‐2 points) or intact (3‐5 points).

Results

DCTclock was administered in ∼3‐4 minutes, and only 0.7% of clocks were unanalyzable due to missing components. Older age and lower education (p<0.0001) were associated with worse DCTclock summary scores. There were no sex differences in performance (p=0.90). Compared to those cognitively intact based on the Mini‐Cog scores (n=252), the impaired group (n=48) performed significantly worse on the DCTclock summary score and spatial reasoning components (Table).

Conclusion

Screening for cognitive status using digital clock measurement is highly feasible and takes a short amount of time to administer in low‐resource settings. The DCTclock provides fine‐grained measures of performance not available on traditional paper/pencil measures, which may prove sensitive to early detection of cognitive impairment.
Insights From A Super Seniors Population: Plasma Biomarkers Increase In Magnitude And Variability With Age
Authors: Cooper Jennifer G , Stukas Sophie K , Ghodsi Mohammad , Leach Stephen , Brooks‐Wilson Angela , Wellington Cheryl L
Published: January 2025

Background

Plasma biomarkers such as neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau‐181 (p‐tau‐181) have been thoroughly investigated in Alzheimer’s disease and other dementias. However, further investigations into how biological variables can influence biomarker concentrations in both normative and cognitively resilient populations will be important for more robust interpretations of biomarker levels. This study investigates how ageing modifies plasma biomarkers in a normative, epidemiologically representative Canadian population and in cognitively healthy seniors over 80 years old.

Method

Biomarkers were analysed on the Quanterix Simoa HD‐X analyzer using Neurology 4‐plex E and p‐tau‐181 assays. N=900 Canadian Health Measures Survey plasma specimens were analyzed as a normative population. Using smoothed quantile regression, the 5th, 50th and 95th percentiles from ages 3‐79 years were determined. The percentiles from 50, 60, and 70 years old were extracted here for analysis. N=480 plasma specimens were analyzed from cognitively healthy Super Seniors Study participants with a median age of 88 years old (IQR= 87‐90y), who had never been diagnosed with dementia, cancer, diabetes, cardiovascular or major pulmonary disease.

Result

In the normative population, between 50 to 70 years old, median concentrations increased by 88% for NfL, 79% for GFAP, and 38% for p‐tau‐181. When compared to 50‐year‐olds in the normative population, the median biomarker concentration in Super Seniors were also higher; 3.4 times for NfL, 3.3 times for GFAP, and 2.2 times for p‐tau‐181. The variability of plasma biomarkers, measured as the range between the 5th and 95th percentiles, also increased with age. Compared to 50 years old, the ranges at age 70 were 2.8 times larger for NfL, 2.2 times larger for GFAP, and 1.5 times larger for p‐tau‐181; While the ranges observed in Super Seniors, compared to 50 years old, were 5.3 times larger for NfL, 3.4 times larger for GFAP, and 2.8 times larger for p‐tau‐181.

Conclusion

Cognitively healthy seniors over 80 years have higher and more variable plasma biomarker concentrations than a normative 50‐year‐olds. These data indicate that age, regardless of cognitive status, modifies biomarker concentrations over the age of 80 years.
Age‐Related Structural and Vascular Changes in the Choroid Plexus: Insights from the HCP Dataset
Authors: Sun Zhe , Li Chenyang , Wisniewski Thomas , Ge Yulin
Published: January 2025

Background

The choroid plexus (ChP) plays a vital role in CSF production and waste clearance. While existing imaging studies have established connections between ChP volume changes and age‐related neurodegenerative diseases, a comprehensive investigation into the microstructural and vascular changes associated with aging remains insufficient. This study aims to explore ChP changes in normal aging using diffusion and perfusion MRI in the HCP‐Aging dataset to enhance our understanding of age‐related microstructural and vascular changes in the ChP.

Method

Our analysis included 641 healthy participants (age: 36‐90 years; mean±SD = 60±16 years; 282 males) with the following MRI parameters: (1) T1 MPRAGE for ChP segmentation[1]; (2) Diffusion MRI for quantification of mean diffusivity (MD); (3) PCASL MRI for quantification of cerebral blood flow (CBF) and arterial transit time (ATT). The ChP mask was co‐registered with MD, CBF, and ATT maps to extract corresponding values. Pearson's correlation and one‐way ANOVA were used for age effects and perfusion property comparisons among gray matter (GM), white matter (WM), and ChP, respectively.

Result

ChP imaging revealed increased volume, increased MD, and decreased CBF across different age groups (Figure 1). Figure 2 demonstrated a positive correlation between ChP volume and age (r = 0.31, p<0.0001), while ChP CBF declined with age (r = ‐0.41, p<0.0001) and MD positively correlated with age (r = 0.56, p<0.0001). Adjusting for age and sex, ChP CBF negatively correlated with volume (r = ‐0.26, p < 0.0001). One‐way ANOVA analyses indicated significant differences in CBF and ATT among ChP, GM, and WM (p<0.0001 for all comparisons), with ChP exihbiting the highest CBF and shortest ATT (Figure 3).

Conclusion

In addition to volume changes, we found significant age‐related diffusion and perfusion changes in the ChP in this large dataset. The decline in CBF and the increase in MD with aging suggest vascular degeneration and compensatory dystrophic hyperplasia of surrounding tissues of ChP. These findings in normal aging set a crucial normative reference for future studies on cognitive impairment in abnormal aging processes

References: 1. Tadayon, E., et al. J Alzheimers Dis (2020).
Short‐term Sirolimus Treatment Increases Cerebral Blood Flow in Asymptomatic APOE4 Females Determined by 3T MRI
Authors: Neher Caitlin M. , Khegai Oleksandr , Overschmidt Jessica , Cassani Joanne , Xing Xin , Flemister Abeoseh , Green Stefan J. , Kurt Mehmet , Beversdorf David Q. , Xu Feng , Grinstead John W. , Balchandani Priti , Altes Talissa A. , Lin Ai‐Ling
Published: January 2025

Background

Apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for late‐onset Alzheimer’s disease (AD) with females having higher risk than males. Compared with non‐carriers, cognitively normal, middle‐aged APOE4 carriers have lower cerebral blood flow (CBF) decades before clinical symptoms appear. Early intervention to protect CBF would be critical for APOE4 carriers to mitigate AD progression. We have shown in APOE4 mice that Rapamycin (a.k.a. Sirolimus), a FDA‐approved mTOR‐inhibitor, can restore CBF. Here, in the first human study, our goal is to determine whether the findings translate to human APOE4 carriers by measuring CBF with MRI.

Method

The study was performed at the University of Missouri. Low dose Sirolimus (1 mg/day) was given for 4 weeks to two middle‐aged, cognitively normal APOE4 females (45‐65 yrs; MOCA>28). APOE status was determined by oral swabs. 3T MRI‐based pseudo‐continuous arterial spin‐labeled (PCASL, 1.7x1.7x4mm resolution) images were acquired at four time‐points: baseline (pre‐treatment), 2nd and 4th week into treatment, and washout (2 weeks post‐treatment). PCASL data was processed with FSL BASIL toolbox and regionally analyzed using FreeSurfer segmentation of T1‐weighted images.

Result

Average values of CBF (ml/100g/min) increased in all areas of investigation. When compared to baseline values, we observed an average 34.8±2.1% increase in washout CBF in the cortex across subjects (Figure 1). Within the cortex, there was an average increase of 41.5±8.9, 28.2±6.2, 37.4±1.7, and 33.1±0.3% in the frontal, parietal, temporal and occipital lobes, respectively. White matter CBF showed a similar trend, increasing by 33.7±4.9% across subjects from baseline to washout (Figure 2). Smaller AD‐associated regions were evaluated and also showed CBF improvement: the entorhinal cortex showed a 25.1±4.3% increase, while the hippocampus and amygdala showed a 21.4±1.1 and 23.6±9.8% increase, respectively (Figure 3). No side effects were observed, and no changes in blood glucose and HbAc1 levels were found in the participants.

Conclusion

Short‐term Sirolimus treatment can effectively increase CBF for asymptomatic APOE4 females, who have the highest risk for AD. Future work will include APOE4 males, increase the sample size and compare CBF with non‐carriers (e.g., APOE3/APOE2). Restoration of CBF may pave a way to mitigate or prevent AD developments for APOE4 carriers.
Perivascular space enlargement and cerebrovascular and Alzheimer’s diseases
Authors: Moyano Jose Bernal , Menze Inga , Yakupov Renat , Kaya Pinar , Aki Cagla , Pfister Malte , Geisendörfer Jonas , Peters Oliver , Priller Josef , Schneider Anja , Fließbach Klaus , Wiltfang Jens , Buerger Katharina , Perneczky Robert , Teipel Stefan , Laske Christoph , Spottke Annika , Heneka Michael T. , Wagner Michael , Ramirez Alfredo , Wolfsgruber Steffen , Kleineidam Luca , Jessen Frank , Schreiber Stefanie , Düzel Emrah , Ziegler Gabriel
Published: January 2025

Background

Perivascular spaces (PVS) can become large enough to be visible in magnetic resonance imaging (MRI). The exact aetiology of PVS enlargement in humans remains, however, elusive and under continuous debate [1‐5]. Here, we tracked PVS volumes longitudinally over three years in 525 individuals along AD syndromal cognitive stages, namely cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer’s disease (AD), to pinpoint conditions related to PVS enlargement.

Method

We studied centrum semiovale (CSO) and basal ganglia (BG) PVS computationally over three to four annual visits in 525 DELCODE participants (CU/MCI/AD 417/72/36; 49.52% female, mean age 70.85 (SD 5.78)) [6]. We segmented PVS using a multimodal Hessian‐based filtering method [7] leveraging T1w and FLAIR imaging, which we validated against clinical visual ratings. We used linear mixed‐effect modelling to study temporal PVS volume changes. First, we tested whether PVS volumes increased over follow‐ups in CU. Second, we explored whether longitudinal PVS enlargement was associated across ROIs, and predicted by individual white matter hyperintensities (WMH), Amyloid and Tau positivity status at baseline in the entire cohort. We adjusted all analyses by age, sex, years of education, and total intracranial volume.

Result

We observed PVS volume increase over follow‐ups in healthy ageing with a significant individual difference of change (Figure 1; BG: B=0.06 [95%‐CI 0.04‐0.08], p<0.001; CSO: B=0.06 [95%‐CI 0.04‐0.09], p<0.001). PVS enlargement in BG was associated with that in CSO (ρ=0.17, pFDR<0.001). Participants with greater baseline WMH volumes tended to have faster BG‐PVS enlargement (ρ=0.05, pFDR=0.06). Participants with both Amyloid and Tau positive tended to have faster CSO‐PVS enlargement than those with neither (Figure 2; Χ²(2)=5.07, p=0.079, η²=0.014).

Conclusion

Given our findings, ageing is a primary driver of PVS enlargement. Associations between PVS and WMH underline shared cerebrovascular mechanisms. Detrimental cycles driven by neurotoxic waste accumulation might also contribute to PVS enlargement. Further research is needed to disentangle pathological cascades, their concurrent dynamics, and their unique contribution to disease progression.

References

10.1016/j.neurobiolaging.2022.01.006

10.18632/oncotarget.17724

10.1002/ana.26475

10.1161/STROKEAHA.117.017526

10.1016/j.clineuro.2019.05.002

10.1186/s13195‐017‐0314‐2

10.1007/BFb0056195
Training of formal caregivers in geriatric mental health and dementia care: Experiences and challenges from the Indian context
Authors: Sivakumar Palanimuthu Thangaraju
Published: January 2025

The population of older adults in India is projected to increase from the current estimate of 150 million to 350 million by the year 2050. The prevalence of older adults with mental health problems including dementia is also increasing rapidly. The socio‐cultural changes in the joint family system have necessitated the increasing requirement of formal caregivers for supporting the care of older adults in home as well as residential care institutions. Home care services providing caregiver assistance, day care, old age homes, residential care institutions for persons with mental illness or dementia are available predominantly in major cities. However, there is a huge variability in the profile of formal caregivers ranging from those with no training to qualified nurses as caregivers depending on the affordability. The need for training of formal caregivers in geriatric mental health and dementia care is acknowledged by most of the the stakeholders in the care of older adults. However, there are no minimum standards of training for the formal caregivers. The lack of trained caregivers has contributed to the increase of elder abuse, higher stress, and burnout for the caregivers with adverse impact on the quality of care of older adults. This presentation will summarize the experience and challenges related to the implementation of the training of formal caregivers in geriatric mental health and dementia care. The training initiatives for the formal caregivers conducted by the Government and Non‐Governmental organizations ranges from brief sensitization program for half a day to formal certificate course for 3 months. Most of the training programs are focused on the basic aspects of geriatric care with inadequate component of practical training. High rates of discontinuation and change of jobs, poor working conditions, lack of motivation among the caregivers and employers, lack of mandatory requirement of training are some of the important challenges limiting the progress in ensuring trained formal caregivers.
Development and application of empowerment assessment tools for caregivers: a scoping review
Authors: wu junhong
Published: January 2025

Background

To systematically analyze the current situation and application of caregiver empowerment assessment tools at home and abroad, to provide a reference for the future development of caregiver empowerment assessment tools and the assessment of caregiver empowerment level.

Method

According to the research method of scope review, the relevant literature from the establishment of the database to October 2023 was searched, and the references of the included literature were traced, and the relevant literature of the caregiver empowerment assessment tool was comprehensively collected.

Result

A total of 856 articles were retrieved. According to the inclusion and exclusion criteria, 14 articles were finally included. After data extraction, a total of 13 kinds of caregiver empowerment assessment tools were summarized, mainly from China and the United States. The application group was mainly the caregiver group with limited behavioral activities or cognitive impairment, and the overall reliability and validity level was good.

Conclusion

There are many kinds of caregiver empowerment assessment tools at home and abroad. Different tools have their own scope of use. Nearly half of the tools have not been further applied, and the reliability and validity test indicators are different. Follow‐up researchers should pay attention to the full test of reliability and validity when developing the caregiver empowerment assessment tool, and evaluate it with recognized standards, focusing on the application and promotion of the tool.
Preclinical Dementia Risk Estimation: Attitudes and Views of Relatives of Dementia Patients – The PreTAD‐Study
Authors: Gerards Michelle , Baumeister Annika , Hübner Constanze , Ribaldi Federica , Cantero‐Fortiz Yahveth , Braun Julia , Boada Mercè , Frisoni Giovanni B. , Schmitz‐Luhn Björn , Schwegler Carolin , Woopen Christiane , Jessen Frank , Rostamzadeh Ayda
Published: January 2025

Background

Due to further development of diagnostic methods of early‐stage diagnosis of Alzheimer’s disease (AD) and new disease‐modifying treatment options that require early diagnosis, a new focus on predictive and preventive medicine arises. With progress in AD dementia risk estimation, guidelines for counseling, considering individual aspects of those affected, are becoming more important. As part of the trinational project PreTAD (The Predictive Turn in Alzheimer’s Disease: Ethical, Clinical, Linguistic and Legal Aspects) anticipated effects of AD dementia risk estimation for first‐degree relatives of people with AD dementia are evaluated.

Method

In the PreTAD project, the topics risk understanding, and anticipated effects of risk estimation were surveyed. First‐degree relatives of people with AD dementia were confronted with one of the following hypothetical AD dementia risk scenarios: 1) higher risk due to abnormal biomarker results or 2) a lifetime risk comparable to the general population. First results of the main study with 50 participants in Germany are reported.

Result

Almost all participants would undergo AD dementia risk estimation if offered. The preferred method was blood sampling compared to other diagnostic methods. Anticipated effects of AD dementia risk estimation were disadvantages at work, on one’s financial situation and when taking out insurance policies. Fewer disadvantages were expected on relationships with close others. Participants confronted with a higher risk of developing AD dementia were more likely to feel diagnosed with a disease and were less likely to share test results with close others. Those confronted with a higher risk were more likely to be willing to change their lifestyle, and make changes in further life planning. Anticipated effects on mental health (e.g. depressed mood, increased anxiety) were higher when confronted with a higher risk of AD dementia.

Conclusion

First results show that dementia risk estimation is desired by first‐degree relatives of people with AD dementia and may have an effect on various elements of personal life, including lifestyle, further life planning and mental health. Findings of the PreTAD project will help to inform the process of counseling and clinical management within preclinical predictive AD diagnosis.
Prognostic value of neuroinflammation [11C]PK11195 PET on longitudinal cognitive decline and survival up to 15 years after PET in Alzheimer's disease
Authors: Rikken Roos M. , Yaqub Maqsood , Coomans Emma M. , van der Vlies Anne E. , Barkhof Frederik , Windhorst Albert D. , Pijnenburg Yolande A.L. , van der Flier Wiesje M. , Boellaard Ronald , Vijverberg Everard G.B. , van de Giessen Elsmarieke
Published: January 2025

Background

Neuroinflammation plays a key role in Alzheimer’s disease (AD) pathophysiology. However, whether neuroinflammation has a prognostic effect on disease progression is largely unknown. Therefore, we aim to investigate the role of neuroinflammation as measured using PET on longitudinal cognition and survival.

Method

We included 29 amyloid‐positive participants (N=10 MCI, N=19 AD dementia) from a historical cohort who underwent dynamic [11C]PK11195 (TSPO) PET to quantify neuroinflammation (Table 1). [11C]PK11195 BPND was obtained using supervised cluster analysis and quantified in the parietal and temporal cortex. [11C]PK11195 BPND values were z‐scored to young healthy controls (N=12). Longitudinal MMSE covering a period up to 11 years was used to measure cognitive decline (median: 3.9, range: 0.3‐11.6 years). We used linear mixed models with random intercept and slope corrected for age, sex and education to investigate the effect of neuroinflammation on cognition. Survival data were available for all participants, up to 15.7 years after PET. To examine the influence of neuroinflammation on survival time, we used age, sex, and diagnosis adjusted cox proportional‐hazards models for both regions.

Result

Demographic characteristics and mean [11C]PK11195 BPND can be found in table 1. Overall, the group showed a mean annualized decline of ‐1.86±1.42 points on MMSE and had a median survival time of 7.6 years (range: 0.4‐15.7) after PET. Temporal or parietal [11C]PK11195 BPND did not predict longitudinal MMSE (parietal: β=0.15, p=0.438; temporal: β=‐0.11, p=0.660) (Figure 1). Higher parietal [11C]PK11195 BPND was marginally associated with shorter survival (HR = ‐0.39, P=0.043) (Figure 2A). There was no significant difference in survival time with higher temporal [11C]PK11195 BPND (HR= ‐0.42, P=0.053) (Figure 2B).

Conclusion

In this initial set of analyses covering up to 11 years of cognitive follow‐up and survival information of 15 years after PET, we found preliminary evidence of a shorter survival with increasing parietal neuroinflammation, but no associations between neuroinflammation PET and the rate of cognitive decline. Future research could explore the effect of neuroinflammation PET on more specific cognitive domains and biological measures such as cortical thickness.
Multi‐modal AI screening for MCI and Alzheimer's Disease: results from an Argentine Cohort
Authors: Belloli Laouen , Keller Greta , Carello Agostina , Gauder Lara , Juantorena Gustavo , Corvalan Nicolas , Allegri Ricardo , Crivelli Lucia , Slezak Diego Fernandez
Published: January 2025

Background

Early detection of Mild Cognitive Impairment (MCI) is crucial for effective prevention. Traditional methods like expert judgment, clinical evaluations, and manual linguistic analyses are now complemented by Artificial Intelligence (AI). AI offers new avenues for identifying linguistic, facial, and acoustic markers of MCI. The exploration of these markers for MCI research is just beginning, especially in regions like Argentina. The effectiveness of AI‐methodologies hinges on local data calibration and validation prior to deployment. This study focuses on designing AI‐based neuropsychological instruments to differentiate healthy individuals from MCI subjects, emphasizing local data calibration and validation.

Method

We recruited 42 participants (30/12 healthy/MCI according to Petersen's criteria, 2016) aged 60 to 89 (mean ± SD: 70.95 ± 6.8) in Fleni, Argentina. During the assessment, which included neuropsychological tests (UDS‐3), participants were video and audio recorded while performing a language task on a web platform. They were required to describe two target images ('Cookie Theft' and 'Firefighter‐Oasis.') and two tasks without any target image (description of their favorite sandwich and reading a story). Markers were extracted from 5 modalities: Speech (automated speech transcription), Acoustics (audio), Face mesh (video), Blend shapes (video) and Emotion recognition (video and audio).

Result

Unimodal analysis was performed to study shared information between proposed AI‐markers and traditional neurocognitive tests. Speech markers were correlated with language and memory, and overall, we obtained a total of 204 significantly correlated AI‐markers to traditional tests of a total of 432 (47%). Univariate AUC for MCI diagnosis was measured for all markers obtaining an average above chance performance of (0.57 ± 0.062). Finally, a multivariate random forest classifier was used to extract the performance of the modalities altogether, an AUC of 0.91

Conclusion

The results of this preliminary study show the validity of the AI algorithms applied to the local argentine population. Validation of algorithms using data in Spanish language and with Latin American population is a key element for de dissemination and the diversification of AI tools. The next step of this research is to include more patients with MCI to gain a comprehensive understanding of differential communicational patterns.
Deciphering the enigma of atypical forms of Alzheimer's disease by employing connectomics in the context of early and late‐phase Amyloid PET and [18F]FDG PET Imaging
Authors: Cirone Alessio , Kreshpa Wendy , Garbarino Sara , MASSA FEDERICO , Raffa Stefano , Sambuceti Gianmario , Piana Michele , Chincarini Andrea , Roccatagliata Luca , Uccelli Antonio , Morbelli Silvia , Pardini Matteo
Published: January 2025

Background

Alzheimer's disease (AD) is the most common form of dementia, predominantly manifesting as amnestic impairment. However, atypical presentations such as logopenic variant of primary progressive aphasia (lvPPA), posterior cortical atrophy (PCA), corticobasal syndrome (CBS) and frontal AD pose diagnostic challenges. This study presents preliminary data from a retrospective analysis investigating brain functional differences between typical and atypical AD forms. Specifically, a structural connectome, a comprehensive map of anatomical white matter connections in the brain, was employed alongside late‐phase amyloid [18F]FBB PET, which resembles focal regional amyloid uptake. Additionally, the research aims to examine whether early‐phase amyloid [18F]FBB PET can serve as a surrogate for glucose metabolism throughout various brain regions, similar to [18F]FDG PET.

Method

Thirty patients have been recruited, including 13 with atypical AD (median age 70; median MMSE 21) and 17 with typical amnestic phenotype (median age 71; median MMSE 23). Neuropsychological tests, 3D isotropic T1 MRI, [18F]FDG PET, and [18F]FBB PET (consisting of 3 early frames and 1 late frame) were performed for each subject. Structural and functional images underwent spatial registration, segmentation, and intensity normalization, using a custom Python pipeline based on FreeSurfer and ANTs tools. Basic statistics were employed to establish functional patterns and assess their statistical significance. Structural connectomes derived from probabilistic tractography on DWI images of 30 healthy subjects were employed.

Result

Results revealed a significant preservation of the hippocampus in atypical AD phenotypes (p<0.05). The connectome analysis demonstrated variations in interconnections among late‐phase amyloid PET uptake regions, distinguishing between atypical and typical AD forms. Additionally, there is support for the hypothesis that early‐phase amyloid PET serves as a reliable marker for synaptic dysfunction.

Conclusion

In conclusion, these preliminary findings suggest that structural connectomes in PET imaging can unveil unique neurodegenerative pathways in atypical AD patients. Moreover, the study supports the notion that early amyloid PET phases can provide insights into neurodegeneration among patients with atypical AD, akin to [18F]FDG PET.
Genetic Spectrum Features and Diagnostic Performance of Four Plasma Biomarkers in 245 Patients with Frontotemporal Dementia
Authors: Shen Lu , Xu Tianyan , Zhou Yafang , Zhang Cong , Tang Beisha , Jiao Bin , Weng Ling
Published: January 2025

Background

Frontotemporal dementia (FTD) exhibits clinical phenotypic and genetic heterogeneity. However, reports on the clinical phenotypic characteristics and the frequency of genetic mutations in large‐sample Chinese populations with FTD are lacking. Furthermore, the FTD diagnostic performance of plasma neurodegenerative biomarkers remains unclear.

Method

This study included 245 clinically diagnosed FTD patients for an analysis of clinical characteristics. All FTD patients and 1,000 gender‐ and age‐matched healthy controls underwent targeted gene sequencing or whole‐genome sequencing. Additionally, plasma samples were analyzed for GFAP, α‐Syn, NfL, and P‐tau181 levels.

Result

It was found that 44.5% (109/245) of patients were diagnosed with bvFTD, 21.2% (52/245) with SD, 15.5% (38/245) with PNFA (20/245), 10.6% (26/245) FTD‐PD, and 8.2% with FTD‐ALS. After gene sequencing, 53 pathogenic or likely pathogenic (P/LP) variants in FTD‐related genes were identified in a total of 19.2% of the patients (47/245). The most common mutation was MAPT (4.9%, 12/245), followed by C9orf72 (3.3%, 8/245), CHCHD10 (2.4%, 6/245), and GRN (1.6%, 4/245) mutations. Other rare variants together were found in the other eleven genes. Elevated levels of GFAP, α‐Syn, NfL, and P‐tau181 were significantly observed in FTD patients compared to controls (P < 0.05), and among them, a combination of GFAP, α‐syn, and Nfl demonstrated high diagnostic value for varied FTD subtypes, with AUCs of 0.83‐0.93. We further confirmed that the gene variants could not have an impact on plasma biomarkers level.

Conclusion

This research enhances comprehension regarding the genetic and phenotypic spectrum of FTD within the Chinese population, and underscores the diagnostic utility of biomarkers such as GFAP, α‐Syn, and NfL in identifying FTD.