bluuebunny/crossref_metadata_2025 huggingface dataset:
Ten‐Year Trajectories of Cognitive Function and Their Lifestyle Predictors Among Older Koreans
Authors: Lim Seungju , Kim Ahram , Lim Young Myoung , Han Yebin , Park Ji‐Hyuk
Published: December 2023

Background

As the number of dementia patients increases, there is a growing concern regarding the cognitive decline of older Koreans. Lifestyle factors such as physical activity (PA), social engagement (SE), and adverse health behavior (AH) were considered as part of an engaged lifestyle that may effects of advanced age on cognitive function.

Objectives

To examined the ten‐year trajectories of cognitive function and associated lifestyle factors among young‐old (55‐64), middle‐old (65‐74), and old‐old (75+) Koreans.

Methods

Data came from the Korean Longitudinal Study of Ageing (KLoSA) between 2008‐2018 waves. Participants were classified as young‐old group (N = 2,346), middle‐old group (N = 2,407), and old‐old group (N = 1,436). Ten‐year cognitive function was assessed using a Korean version of the Mini‐Mental State Examination (K‐MMSE) score. Lifestyle factors, included as observed exogenous time‐invariant variables, were assessed through three domains : PA (regular exercise status, regular exercise duration); SE domain (the variety of social activities, the frequency of participating in); AH (alcohol consumption, smoking status). Latent growth curve modelling and multi‐group analysis were performed.

Results

This study found that older Koreans reported an average K‐MMSE score of 24.317 at baseline and experienced cognitive decline every years by −0.195. There were differences between the young‐old, middle‐old, old‐old age groups in cognitive trajectories and associated lifestyle factors. The cognitive trajectory of the old‐old groups, whose cognitive function decreased the fastest, was associated to a short exercise period (β = 0.437, p< 0.05) and inactive participation in social activities (β = 0.180, p< 0.01).

Conclusion

As the influence of lifestyle factors were differed by age groups, it suggests that age‐specific approaches to cognitive health promotion should be considered.

Keywords:

Cognitive trajectory, Latent growth model, Lifestyle, Older Koreans
Detection of behavioral, depressive, and anxious symptoms in patients with Subjective Cognitive Complaints
Authors: Berrios Waleska , Caporale Sofia , Deschle Florencia , Moreno Maria Cecilia , Bustos Claudia , Cervino Cecilia , Saglio Laura , Santajuliana Franco , Povedano Guillermo
Published: December 2023

Background

Subjective Cognitive Complaints (SCC) are frequent in Neurology. They may be defined as the self‐perception of cognitive decline without objective deficits in Neuropsychological tests. SCC have been associated with poorer cognitive performance, a higher risk of developing Cognitive Impairment or Dementia as well as neuropsychiatric symptoms such as depression and anxiety.

Depression and anxiety are frequent mental health issues, with a remarkable impact on cognitive function. An increase in prevalence in both of them is estimated during the COVID‐19 pandemic. Also, behavioral symptoms have a negative impact on quality of life. Nevertheless, they may remain unnoticed if not investigated or without a family report.

The objective is to report the frequency of depression, anxiety, and behavioral symptoms in a population with SCC.

Method

We selected patients with cognitive complaints and normal neuropsychological test performance. Demographic data, and behavioral, depressive, and anxious symptoms were collected. Anxious symptoms were assessed with the Beck Anxiety Inventory‐(BAI) and depressive symptoms with the Beck Depression Inventory‐(BDI‐II) and the Geriatric Depression Scale‐(GDS‐15). Neuropsychiatric Symptoms Inventory‐(NPI) was also investigated when an accompanist was available.

Result

166 patients were included. The mean age was 63.13 (SD 12.2) years, Mean Education was 11.25 (SD 3.62) years. In this sample the frequency of anxiety symptoms was 44.57% (n = 74) according to BAI; 48,64% (n = 36) were mild, 32.43% (n = 24) moderate and 18.93% (n = 14) severe. BDI‐II and GDS‐15 detected depression symptoms in 33.13% (n = 55) of the patients; 58.18% (n = 32) were mild, 32.72% (n = 18) moderate and 9.09% (n = 5) severe. In 59 cases we administer the NPI; 76.27% (n = 45) reported a symptom.

Conclusion

Our study showed a significant frequency of anxiety and depression symptoms as well as behavioral symptoms in patients with SCC. This reminds us how valuable it is to assess behavioral, depressive, and anxious symptoms in standard Neuropsychological Testing to take a comprehensive approach to the patients. Future studies will help to determine dementia‐developing predictors.
Hyperintensity on Diffusion‐Weighted MRI and Clinical Correlations in Probable Creutzfeldt‐Jakob Disease
Authors: Rhee Hak Young , Park Key Chung
Published: December 2023

Background

Although definite diagnosis for Creutzfeldt‐Jakob disease(CJD) requires tissue confirmation, diffusion‐weighted imaging (DWI) of the brain has an important role in the diagnosis of CJD. Also elevated CSF total tau (t‐tau) is considered as an useful CJD biomarker revealing neuro‐axonal damage although it is not specific for CJD. In this study, we attempted to find out the association between DWI abnormality and CSF t‐tau in CJD patients.

Method

We retrospectively analyzed the medical records reported as human prion disease.The patients who had been diagnosed and reported as human prion disease to Korea Disease Control and Prevention Agency (KDCA) by medical institutions in South Korea during the period of January 1, 2019 to December 31, 2019 were included in this study. The clinical information of the reported patients had been reviewed by a clinical review committee of KDCA for CJD and the patients who had fulfilled the criteria for probable CJD were evaluated for clinical, radiological, and laboratory findings.

Result

A total of 186 patients had been reported as suspected human prion disease during the one‐year period and 53 patients who satisfied the criteria for human prion disease were included in the analysis. The most common clinical presentation was cognitive change, followed by cerebellar dysfunction and extrapyramidal symptoms. Hyperintense lesions on DWI were observed in 52 patients (98%). The involvement of neocortex was observed in almost all patients (98%) and asymmetrical and bilateral hyperintensities on DWI were common. Among neocortex, the most commonly involved region was parietal lobe, followed by frontal lobe, temporal lobe, and occipital lobe. DWI abnormality in striatum and/or thalamus was observed in 65.3% of patients. CSF t‐tau was elevated in sporadic CJD patients (8998.3±11903.7 pg/ml) There was no significant association between the extent of the lesions on DWI and CSF t‐tau.

Conclusion

In this study,most of the patients with probable CJD showed DWI abnormality mainly on neocortex (parietal > frontal > temporal > occipital) but the association between the pattern of DWI abnormality and the level of CSF t‐tau was not observed.
Associations between glymphatic function and BBB water exchange rate and perfusion in a Latinx cohort
Authors: Shao Xingfeng , Liu Xiaodan , Barisano Giuseppe , Ringman John M , Wang Danny J.J.
Published: December 2023

Background

The glymphatic system is thought to clear waste products from the brain by facilitating the exchange of interstitial fluid (ISF) with cerebrospinal fluid (CSF) through aquaporin‐4 (AQP4) water channels present in astrocyte endfeet. A recent non‐invasive MRI method, diffusion tensor image analysis along the perivascular space (DTI‐ALPS), has been proposed for evaluating brain clearance function and has shown reduced glymphatic function in various neurological disorders such as Alzheimer’s disease. However, the role of microvascular perfusion and blood‐brain barrier (BBB) permeability in the glymphatic system remains unclear. In this study, we used a novel diffusion‐prepared arterial spin labeling (DP‐ASL) MRI technique to measure BBB water exchange rate (kw) and cerebral blood flow (CBF) and studied their relationships with the DTI‐ALPS score.

Method

44 Latinx subjects (20 male; age = 65.6±5.6 years) were recruited from the USC MarkVCID study. Imaging parameters for DP‐ASL were: resolution = 3.5×3.5×8mm3, 10 slices, scan time 10 mins. kw was calculated from the ratio of intra‐ and extra‐vascular perfusion signals with total‐general‐variation (TGV) regularized single‐pass approximation (SPA) modeling and CBF was calculated from PLD = 1800ms data using one‐compartment Kety model. kw and CBF maps were normalized into the MNI space and regional analysis was performed in the frontal/temporal/parietal lobe, and subcortical regions. Association between ALPS score and CBF/kw values were studied by linear regressions. P<0.05 was considered as significant.

Result

Fig.1 shows kw and CBF maps from three representative subjects with increasing ALPS scores (top to bottom). ALPS was significantly correlated with kw in MTL (β = 1.7e‐3,P = 0.04) and a positive trend was observed between ALPS and whole brain average kw (P = 0.11). While significant correlations were found between ALPS and CBF in multiple brain regions including frontal lobe (β = 7e‐3,P = 0.009), temporal lobe (β = 7e‐3,P = 0.002), parietal lobe (β = 4e‐3,P = 0.03), MTL (β = 8e‐3,P = 0.03), ACC (β = 6e‐3,P = 0.005), PCC (β = 4e‐3,P = 0.02), precuneus (β = 4e‐3,P = 0.04) and whole brain (β = 8e‐3,P = 0.01). Fig.2 shows scatter plots of ALPS versus kw (A) and CBF in MTL and whole brain, respectively.

Conclusion

This is the first study in Latinx population demonstrating positive correlations between ALPS score and both CBF and kw, suggesting a possible involvement of blood flow and BBB water exchange rate in the glymphatic system.
The retina in Alzheimer’s disease: Anatomy and Pathology
Authors: Koronyo‐Hamaoui Maya
Published: December 2023

Growing evidence suggests that Alzheimer’s disease (AD) pathology is not confined to the brain but also appears in the neurosensory retina. Perceived as an extension of the brain, the retina is visible directly and noninvasively at the vascular, cellular and molecular resolution. Aβ accumulation, vascular amyloidosis, hyperphosphorylated (p)tau, microgliosis, astrogliosis, Müller glia changes, abnormal electroretinography patterns, and neuronal degeneration have all been described in the postmortem retina of AD patients, including in early‐stage cases. Although a few studies were unable to consistently repeat these findings, increased proportion of positive studies from subsequent histological, biochemical, and imaging studies validated the original findings. Several studies further provided data suggesting that the brain and retina follow a similar trajectory during AD progression, potentially due to their common embryonic origin and anatomical proximity. A host of retinal vascular abnormalities including reduced blood flow, foveal avascular zone and arteriole‐to‐venule ratio were observed by in vivo fundus imaging, optical coherence tomography (OCT) or OCT‐angiopathy in preclinical, prodromal and clinical AD patients. Further, retinal vascular platelet‐derived growth factor receptor‐β (PDGFRβ) expression and pericyte loss have been associated with retinal vascular amyloidosis and cerebral amyloid angiopathy in mild cognitively impaired (MCI) and AD patients. A recent proteomics profiling study revealed common molecular signatures in the AD retina and brain, with enriched pathways related to inflammation, vascular and photoreceptor vulnerability. Novel imaging techniques, such as curcumin fluorescence, have correlated increases in retinal amyloid burden with brain amyloid PET load and hippocampal atrophy in patients, and together with vascular changes predicted cognitive deficits. This perspective provides an overview on the evidence of AD pathology in the retina and current gaps in knowledge. Future studies exploring retinal pathology in AD and other neurodegenerative diseases may fundamentally contribute to the development of validated retinal biomarkers for improved noninvasive disease diagnosis and monitoring.
Modelling of Alzheimer’s disease pathology in the retina ‐ what can we learn from animal models?
Authors: De Groef Lies
Published: December 2023

Retinal neurodegeneration and visual dysfunction have been reported in the majority of Alzheimer’s patients, and, in light of the quest for novel biomarkers, the retina has been receiving increasing attention as an organ for diagnosing, monitoring, and understanding disease. Thinning of retinal layers, abnormalities in vasculature, and protein deposition can be imaged at unprecedented resolution, which offers a unique systems biology view on the cellular and molecular changes underlying AD. It makes the retina not only a promising target for biomarker development, but it also suggests that novel fundamental insights into the pathophysiology of AD can be obtained by studying the retina–brain axis.

This presentation will show how the visual system, together with retinal imaging techniques and available animal models of AD, constitutes a unique toolbox for fundamental and preclinical studies of AD; and explore how the retina‐brain axis has the potential to revolutionize preclinical research of AD. We will discuss the strengths of the rodent retina as a model organ to investigate Alzheimer’s disease mechanisms. Studies in different AD mouse models will be presented to showcase how retinal imaging can reveal information about the structure, function, and molecular composition of the retina and thereby aid in diagnosing, monitoring, and understanding AD. Furthermore, we will touch upon how the organotypic heterogeneity of the retina versus the brain may hold clues to understanding AD, and how the unique anatomical organization of the visual system offers opportunities to investigate disease propagation along neural connections.
Critical Next Steps for Translation of Preclinical and Ex Vivo Human Retinal Studies for Alzheimer’s Disease Diagnosis
Authors: Rissman Robert A , Ngolab Jennifer
Published: December 2023

Retinal ganglion cells are part of the CNS and as such many years of research has focused on determining and documenting how changes in retinal cells and layers may inform on disease diagnosis, display neuropathology and neurodegeneration. As noted in this session, degeneration of the retina and visual dysfunction occur in the majority of AD, with new and exciting imaging techniques being employed in both animal models and human ex vivo retinal tissues that suggest that the retina can act as a mirror to the brain. Unfortunately, consistency of methods and access to viable tissues has hampered the generalizability and speed of translatability of these exciting fundings. In addition, to date, no studies have directly linked observed neuropathology or neurodegeneration in the retina with more established biomarkers in CSF or blood which is ultimately needed to understand whether retinal imaging or analysis is viable for clinical use. Retinal imaging in live participants could serve as a minimally invasive biomarker to detect neurodegenerative disease. From recent anti‐amyloid studies, identifying individuals at risk for AD in the asymptomatic stage is critical for efficacy of treatments. If validation and establishment of retinal analyses continue as they have and consistency and consensus is obtained in retinal targets to focus on and these prove to mirror changes ongoing in brain, the timing of these changes in relation to brain changes will need to be determined so that a window of when retinal imaging and analysis is viable will need to be determined. Once the conditions, methods and timing of retinal imaging is determined, the ultimate goal would be to screen aged individuals in a primary care setting annually and then refer to specialty clinics or centers for follow up, confirmation and consideration for therapeutic trials.
The relationship between Structural, PET, and Plasma Alzheimer’s Disease Biomarkers and neuropsychological composites among Latino bilinguals and monolinguals
Authors: Rosselli Monica , Velez‐Uribe Idaly , Asken Breton M. , Barker Warren W , Coombes Stephen A. , Duara Ranjan , Smith Glenn E. , Curiel Rosie E , Loewenstein David A. , Adjouadi Malek
Published: December 2023

Background

Estimates from the Alzheimer’s Association indicate that approximately one in ten older adults in the US have Alzheimer’s disease (AD) dementia while 15 to 20% have mild cognitive impairment (MCI), projecting that about a third of those will develop dementia within five years. The Cognitive Reserve/ Resilience (CR/R) theory postulates that complex mental activity throughout the lifetime builds resilience to cognitive decline despite the biological risk (a neurodegenerative disease). Emerging evidence shows that bilingualism may be one of these neuroprotective factors in the aging brain, but results in bilingualism and CR/R remain inconsistent.

Methods

We studied 238 Latino older adults (age 71.8 ± 8.0 years old, 65% female) from the 1Florida Alzheimer’s Disease Research Center who were diagnosed as clinically normal, MCI, or dementia. Of these, 158 were Spanish‐English bilinguals and 80 were Spanish monolinguals. Bilingualism was assessed by a proficiency questionnaire. Six cognitive composites were developed (Figure 1). We investigated cognitive test correlates of plasma P‐tau181 (Quanterix simoa), hippocampal volume, and amyloid PET (Centiloid) biomarkers in both language groups, using 2×3 ANCOVAs (controlling for age and level of education). We analyzed correlations between biomarkers and cognition and performed multiple regression analyses within each language group.

Results

The main effect of the diagnostic group was significant for all biomarkers (ps < .001). There was no main effect of the language group and no significant interactions. The correlations between biomarkers were equally significant for both language groups but differences in the association of biomarkers with cognitive tests emerged between language groups. Bilinguals showed a stronger negative association between hippocampal volume and cognitive test scores than monolinguals. In bilinguals, higher PTau181 was associated with lower visuomotor composite scores, while amyloid PET positivity and lower hippocampal volume were associated with cognitive stress and working memory. In monolinguals, higher PTau181 was associated with worse inhibitory control, and amyloid PET positivity and lower hippocampal volume were associated with worse memory.

Conclusion

Results demonstrated discrepancies between bilingual and monolingual Latinos in the associations between cognitive composites and AD biomarkers. Further exploring the relationship between bilingualism, cognitive test scores, and biomarker patterns is warranted, especially longitudinally.
Automatic analysis of skull thickness, scalp‐to‐cortex distance and association with age and sex in cognitively normal elderly
Authors: Zhang Junhao , Treyer Valerie , Gietl Anton F. , Hock Christoph , Razansky Daniel , Nitsch Roger M. , Ni Ruiqing
Published: December 2023

Background

Transcranial brain stimulation has been a potential treatment for many brain diseases. The skull compartment exerts a strong influence on the delivery of stimulation, implying the need to accurately examine its geometry and alterations in the population. In addition, personalized neurostimulation requires better understanding of skull geometry and scalp‐to‐cortex distance for optimization.

Method

Here, we developed an open source efficient pipeline BrainCalculator based on BrainSuite Skullfinder for automatically computing the skull thickness map to locate the position of minimum thickness, SCD, and brain volume based on structural T1‐weighted MRI 3T data. We examined the influence of age and sex cross‐sectionally in 407 cognitively normal older adults (71.93±7.98 years, 60.2% female) from the ADNI on the minimum skull thickness, SCD and brain volume of the whole‐head MR data. We demonstrated the compatibility of BrainCalculator with available preprocessing toolboxes, including FSL Brain Extraction Tool (BET) 2 and Statistical Parametric Mapping (SPM)12‐based unified segmentation, and compared their performance.

Result

Our pipeline was able to compute automatically the skull thinkness, SCD and brain volume using T1 MR data in 8 minutes. We found that the sphenoid bone and temporal bone were thinnest among the skull regions. There was no increase in minimum skull thickness at different regions with increasing age except in the female sphenoid bone. No sex difference in minimum skull thickness or SCD in different age groups was observed. Positive correlations between age and SCD in both males and females were observed, and the slope was higher in the temporal cortex SCD in females (0.307%/y) than in males (0.216%/y) but comparable in other regions. A negative correlation between age and whole brain volume computed based on brain surface in both males and females was observed, and the slope was slightly higher in females (‐1.031%/y) than in males (‐0.998%/y).

Conclusion

We developed a pipeline for MR‐based skull thickness and SCD brain volume automatic analysis and demonstrated the sex‐dependent association between minimum regional skull thickness, SCD and brain volume with age. This pipeline is potentially useful for personalized neurostimulation.
White matter hyperintensity features differentially contribute to dementia subtypes as shown by machine learning
Authors: Campo Cecilia Gonzalez , Guardia Camila Sol , Saracco María Antonia , Fraile‐Vazquez Matias , Altschuler Florencia , Ibanez Agustin , Moguilner Sebastian
Published: December 2023

Background

White matter hyperintensities (WMH) are frequently observed on MRI scans of older people. Usually interpreted as a sign of cerebrovascular disease (CVD), they are also associated with an increased risk of cognitive impairment and dementia. WMH are prevalent in Alzheimer’s disease (AD) and in behavioral variant frontotemporal dementia (bvFTD). However, the total and spatial differential burden of WMH between these two pathologies is not well understood. Furthermore, the differential contributions of WMH across both conditions is unknown.

Method

Here we assessed the total and tract‐specific WMH burden features to classify the two dementia subtypes. We used a gradient boosting (GB) machine learning algorithm with a multi‐feature approach (demographic, neuropsychological, and magnetic resonance imaging (MRI) data). A total of 66 patients (43 AD, 23 bvFTD) and 66 controls (CN) from the ReDLat consortium underwent high‐resolution brain MRI and neuropsychological examination. WMH were extracted from Flair images using automated segmentation algorithms (LST) to perform analyses of total volume and white matter (WM) tract spatial distribution using the JHU atlas. As input data, three different approaches were tested: cognitive data only (MoCA and IFS scores), structural data only (total and tract‐specific WMH, from 20 different WM tracts) and mixed data (cognitive, structural, and demographic data (age, gender and years of education)). Then, we employed the GB algorithm to classify between AD vs CN, bvFTD vs CN, and AD vs bvFTD.

Result

The model using only total and tract‐specific WMH data yielded the highest area under the curve classification values between AD and bvFTD (0.92 (±0.8)), in comparison with only cognitive (0.86 (±0.1)) and mixed inputs (0.81 (±0.12)). Feature importance analysis revealed specific tract affectation for each dementia subtype. Demographic features were not relevant for the classification, discarding possible sample biases.

Conclusion

The model using only WMH data accurately identified dementia subtypes using readily available measures in patients with dementia. We gained biological insights into WMH pathophysiological profiles differentiating AD and bvFTD. If confirmed and replicated in future studies, this approach could be of complementary use for diagnosing and phenotyping dementias.
Predicting early Alzheimer’s disease from diffusion tensor imaging using machine learning techniques
Authors: Bezerra Thais Maria Santos , Balthazar Marcio Luiz Figueredo , Rizzi Liara
Published: December 2023

Background

The major current challenge in Alzheimer’s disease (AD) is the identification of individuals likely to develop dementia. Non‐invasive imaging techniques that reflect the integrity of the brain’s white matter are potential parameters to study the pathogenesis of AD. Diffusion tensor imaging (DTI) provides tools to analyze AD‐related brain changes despite the large amount of data generated. To process large amounts of data, computational methods capable of finding relationships among large and complex data sets are needed. In this context, machine learning (ML) techniques have been extended to address this issue. This study aimed to evaluate whether DTI features could predict future AD in non‐AD patients using ML techniques.

Method

Sixty‐two subjects, with mild cognitive impairment and healthy controls, were enrolled and followed for approximately eleven months. At the first assessment, MRI, neuropsychological tests, and cerebrospinal fluid analysis were performed. At the second assessment, ten had progressed to Alzheimer’s dementia. The clinical diagnosis was used to train the ML classification models. Five data sets were generated with different missing data strategies. Feature selection strategies measured by information gain were implemented and compared. Twenty ML algorithms distributed over several mathematical approaches were used in model training. A deep learning model was also implemented for comparison with ML results.

Result

The best model for predicting AD by DTI was Random Forest with kNN missing data imputation and features selected by information gain. This model achieved a test accuracy of 88.72%. The most relevant DTI tract that contributed to the prediction of the model was the fractional anisotropy (FA) of the cingulum ‐ hippocampus . When other categories of data, such as neuropsychological tests, were included in the model, the accuracy hardly changed (90.26%), suggesting that DTI alone is a good predictor of Alzheimer’s disease. When the deep learning model was run, the constructed neural network achieved 92.31% accuracy.

Conclusion

Our results suggest that DTI measures analyzed by ML models, such as Random Forest, may predict AD in non‐AD patients. Furthermore, DTI measure of cingulum ‐ hippocampus tract may be a sensitive marker of early AD pathology.
A Rule‐Based Framework to Identify Severity of Dementia from Unstructured Electronic Health Record Data
Authors: Prakash Ravi , Dupre Matthew E. , Ostbye Truls , Xu Hanzhang
Published: December 2023

Background

The severity of Alzheimer’s disease and related dementias (ADRD) is mostly documented in unstructured textual data in electronic health records (EHR). This information is important for clinical decision‐making yet is often “hidden” in free text fields and then not as readily available as information in the structured fields for clinicians to act upon. This study assessed the feasibility and potential bias in using keywords and rules‐based matching for obtaining information about severity of ADRD from EHR.

Method

We used EHR data from a large academic healthcare system that included patients with a primary discharge diagnosis of ADRD based on ICD‐9/10 codes between 2014 and 2020. The severity of ADRD was determined using clinicians’ notes based on (1) scores from the Mini Mental State Examination and Montreal Cognitive Assessment, and (2) explicit terms for ADRD severity (e.g., “mild dementia”, “advanced AD”). A list of common ADRD symptoms, cognitive test names and diagnosis stage terms was compiled and iteratively refined based on prior literature and clinical expertise. We used the list together with rule‐based pattern matching to identify the context in which the word/phrase was mentioned. The algorithm was developed in python 3.8 using spaCy and pandas library. We assessed the prevalence of the documented ADRD severity and used logistic regression to examine whether the severity varies by patient characteristics.

Result

A total of 9,115 patients with over 65k providers’ notes were evaluated. Overall, 16.85% (N = 1,536) of patients were documented with mild ADRD, 17.95% (N = 1,636) were documented with moderate or severe ADRD, and 65.20% (N = 5,942) did not have any documentation of the severity of their ADRD. Compared with patients with mild ADRD, those documented with more advanced ADRD were older, more likely to be female, black, and receive their diagnoses in a primary care or in‐hospital setting. Relative to patients with undocumented ADRD severity, those documented with ADRD severity had a similar distribution regarding sex, race, and rural/urban living environment.

Conclusion

This study demonstrated the value of unstructured EHR data and the feasibility of using pattern matching algorithm in identifying severity of ADRD. Still, differences in the documentation may introduce bias in the algorithm.
Remote and in‐clinic digital cognitive screening tools outperform the MoCA to distinguish cerebral amyloid status among cognitively healthy older adults
Authors: Dion Catherine , Kunicki Zachary J. , Emrani Sheina , Strenger Jennifer , De Vito Alyssa N. , Britton Karysa J. , Harrington Karra D , Roque Nelson A , Sliwinski Martin J. , Salloway Stephen , Correia Stephen , Jones Richard N , Thompson Louisa I
Published: December 2023

Background

Existing cognitive screening measures fall short in capturing preclinical AD, and cognitive impairment is unrecognized or misdiagnosed in 27‐81% of older adult primary care patients. Digital assessment technology has the potential to deliver more efficient and sensitive cognitive screening, but requires rigorous validation first. We aimed to determine the accuracy of remote (M2C2 mobile app) and clinic‐based (TabCAT and DCTclockTM) digital tests to distinguish between older adults with and without AD pathologic change. We used the Montreal Cognitive Assessment (MoCA) as a reference standard comparison test.

Methods

We recruited 73 cognitively normal participants with Aß PET status (Aß+, n = 25; Aß‐, n = 48, determined by clinical read) from the Butler Hospital Alzheimer’s Prevention Registry (mean age = 69.2 and education = 16.5; 71% female; 89% White). Participants completed M2C2 tasks at home 3 times per day for 8 days, followed by the TabCAT tasks, DCTclockTM, and MoCA at an in‐person study visit. We calculated the area under the curve (AUC) to compare cognitive task accuracy to distinguish Aß status. Multi‐day learning curves were used to examine differences in M2C2 task performance by Aß status over time.

Results

Among the M2C2 tasks, average performance on the Prices task (episodic memory) over 8 days showed the highest accuracy (AUC = .77) to distinguish Aß status. The Aß+ group tended to perform worse than the Aß‐ group on the Prices task over time (Figure 1). On in‐person screening measures (single time‐point), accuracy to distinguish Aß was greatest for the TabCAT Favorites task (AUC = .76), relative to the DCTclockTM (AUC = .72) and the MoCA (AUC = .71).

Conclusions

We showed that several brief digital screening approaches (memory‐specific tasks on the M2C2 and TabCAT) outperform the MoCA in distinguishing between cognitively healthy individuals with and without elevated cerebral Aβ. Although further validation in community and clinic‐based samples is needed, these results suggest that these digital cognitive assessments may be suitable for more widespread screening to detect early pathological changes in neurodegenerative disorders.

Figure 1. M2C2 task performance over time (3 sessions daily for 8 days) by Aβ status.
Glomerular filtration rate, neurofilament light, and phospho‐tau 181 in a community‐based cohort: the Shanghai Aging Study
Authors: Wu Jie , Xiao Zhenxu , Wu Wanqing , Wang Mengjing , Ma Xiaoxi , Liang Xiaoniu , Zheng Li , Ding Saineng , Luo Jianfeng , Hong Zhen , Chen Jing , Zhao Qianhua , Ding Ding
Published: December 2023

Background

The blood‐based biomarkers are approaching the clinical practice of Alzheimer’s disease (AD). Chronic kidney disease has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers.

Method

Plasma phospho‐tau181 (P‐tau181), and neurofilament light (NfL) were assayed via the Simoa HD‐X platform in 1189 dementia‐free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between blood markers and renal function was analyzed.

Result

Plasma NfL significantly increased as the eGFR descended (median = 12.27,15.50,20.70pg/mL in the high, medium, and low eGFR groups, respectively, P<0.001). The same trend was observed for plasma p‐tau181, but insignificant after adjustment (P = 0.485). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction< 0.001). Among participants older than 70 years old, the association between plasma NfL and eGFR was stronger (B = ‐0.222, P < 0.001).

Conclusion

In a community‐based cohort, renal function differentially impacted blood NfL and P‐tau 181 levels. Plasma NfL level was markedly influenced, whereas P‐tau 181 was a relatively robust marker to comorbidities.
SPATIAL WORKING MEMORY IN PRODROMAL STAGE: AN EYE TRACKING STUDY
Authors: Ekin Merve , Koçoğlu Koray , Boz Hatice Eraslan , Akkoyun Müge , Tüfekci Işıl Yağmur , Yalınçetin Berna , Bora Emre , Akdal Gülden
Published: December 2023

Background

Individuals at ultra‐high risk for psychosis and bipolar disorder (UHR‐P and UHR‐BD) have shown cognitive abnormalities and sub‐threshold clinical features (de Paula et al., 2015; Metzler et al., 2014). Assessing saccadic eye movements is one of the useful methods for investigating high cognitive functions like spatial working memory and inhibition (Pierrot‐Deseilligny et al., 2005; Winograd‐Gurvich et al., 2008). Memory‐guided saccade (MGS) may be described as short‐term maintenance of attention both when a peripheral target is presented, and a delay screen. The purpose of this study was to examine the differences between clinical risk groups and healthy controls (HCs) based on the memory‐guided saccade.

Method

The study was included 33 UHR‐P (age: 21.61 ± 3.24), 28 UHR‐BD (age: 21.64 ± 4.02), and 28 HCs (age: 22.11 ± 4.03). Participants were selected from cases of clinical‐high‐risk criteria in interviews made with The Structured Interview of Psychosis Risk Syndromes and Bipolar Prodrome Symptom Interview and Scale. The memory‐guided saccade was measured with the number of the correct, incorrect, anticipatory and express saccades, also latency, peak velocity and amplitude for the correct saccades. Eye movement data were recorded from the right eye using an EyeLink 1000 Plus eye‐tracker. All results were analyzed with SPSS software.

Result

The anticipatory and express saccades in the cue screen, the anticipatory saccade in the delay screen and the total error response were significant between groups (p<0.05). There was a significant increase in UHR‐BD compared to controls in the error responses (p = 0.018). The anticipatory saccades in UHR‐BD were higher than in both UHR‐P and HC on the cue screen (p = 0.005 and p = 0.014), and controls on the delay screen (p = 0.027). In addition, the express saccades in the cue screen showed statistical differences between the risk groups (p = 0.032).

Conclusion

Memory‐guided saccades are used to assess the top‐down mechanism, including perceptual organization and goal‐directed behaviors, and are related to frontal lobe functions like spatial working memory and inhibitory control (Ostendorf et al., 2004). The elevation of incorrect saccades and predictive parameters like anticipatory saccades have indicated that individuals at the prodromal stage may appear spatial problems in inhibitory and exhibitory functions.
Engagement in Meaningful Activities Among Residents with Dementia in Assisted Living
Authors: Holmes Sarah D , Scherr Susan , Vigne Erin , Levy Sorah , Koenig Marcie , Galik Elizabeth , Resnick Barbara
Published: December 2023

Background

Engagement in meaningful activities is beneficial for the physical and psychological well‐being of persons with Alzheimer’s disease or related dementia (ADRD). Meaningful activities are a critical dimension of person‐centered care, although challenges exist in providing them for persons with ADRD in long‐term care settings. The purpose of this study was to describe engagement in meaningful activities among residents with ADRD in assisted living.

Method

This study included baseline data collected from the first cohort of the randomized controlled trial, Meaningful Activities for Managing Behavioral Symptoms of Distress (MAC‐4‐BSD). Assisted living residents were eligible if they were ≥55 years old, live in a participating setting, and screen positive for dementia based on the Saint Louis University Mental Status exam (SLUMS) and AD8 Dementia Screening Interview. Residents were excluded if they were enrolled in hospice, admitted for short term respite, or had a significant neurological condition not related to ADRD. Residents’ engagement in meaningful activities was evaluated based on the Engagement in Meaningful Activities Survey (EMAS). Descriptive statistics were used to summarize sample characteristics and describe engagement in meaningful activities.

Result

A total of 38 residents from 3 assisted living communities were included in the sample. Most participants were female (71%), White (82%), and mean age was 81 years old (SD = 7.9). Average score on the SLUMS was 4.5 (SD = 4.9). The EMAS mean score was 43.57 (SD = 10.9) with a range of 25 to 60. Participation was endorsed most frequently for activities that give them pleasure (60.7%) and a sense of satisfaction (64.3%). Participation was endorsed least frequently for activities that help other people (35.7%), contribute to feeling competent (42.9%), and have the right amount of challenge (42.8%).

Conclusion

Findings from this study offer preliminary insights into residents’ engagement in meaningful activities in assisted living and suggest there is limited participation in activities that help others, help with feeling competent, and have the right challenge level for those with ADRD. Although limited by small sample size, this study highlights the need for increasing engagement in meaningful volunteer activities to help others which recent research demonstrates could positively impact physical and cognitive health outcomes.
Metabolic pathways associated with multi‐morbidity among Black caregivers of persons living with dementia
Authors: Brewster Glenna S , Houser Madelyn , Yang Irene , Wells Jessica , Carlson Nicole
Published: December 2023

Background

Black adults have the highest prevalence of obesity and hypertension, and these multiple chronic conditions increase their risk of morbidity and mortality. Black adults also represent the second largest group of caregivers of persons living with dementia. Gaps exist in our understanding of the physiologic changes associated with multiple chronic conditions in Black caregivers. This study used metabolomics to compare the metabolic profiles of Black caregivers with obesity, with or without hypertension. Our goal was to identify physiologic pathways for targeted interventions to improve morbidity/mortality in this group.

Method

High‐resolution, untargeted metabolomics assays were run on stored serum samples from Black caregivers (n = 26) with obesity (BMI > = 30kg/m2), among whom 18 also had a diagnosis of hypertension. Linear regression using the xmsPANDA package was employed to identify metabolites differentiating multi‐morbidity. Two‐way hierarchical clustering analysis was used to visualize metabolome‐wide associations with multi‐morbidity. Additionally, metabolic pathways differentially impacted in multi‐morbidity were identified using mummichog.

Result

On average, caregivers were 62.9 (±6.5) years. 88.5% were female and 43% were married. Caregivers had been providing care for about 4.33 (±4) years. A total of 129 metabolites differentiated multi‐morbidity status at a p value < .05. Among these, key metabolic pathways associated with obesity and hypertension were butanoate metabolism and fatty acid activation. Among caregivers with only obesity, metabolites in the butanoate pathway were downregulated, compared to caregivers with both obesity and hypertension. Two exceptions were butyric acid and 2‐hydroxybutyric acid, which were both upregulated in caregivers without multi‐morbidity. In the fatty acid activation pathway, caregivers with only obesity had upregulated metabolites with the exception of icosatrienoic acid and dihomo‐gamma‐linolenic acid, which were down‐regulated.

Conclusion

In caregivers with obesity, pathways associated with butanoate metabolism and fatty acid activation significantly differentiated hypertensive status. Healthcare interventions targeting caregiver education on diet/exercise may help optimize fatty acid activation in Black caregivers, thereby helping to reduce their risk of developing multi‐morbidities with hypertension. In addition, expanded health assessment of Black caregivers should be considered, as they may be at high risk for metabolic syndrome due to perturbed fatty acid and butanoate pathway functioning.
Depletion of microglia with CSF1R inhibitor prevents tau aggregation in the mouse model Thy1P301S
Authors: Lombardo Sylvia , Stanek Agathe , Wuest Carolin , Reich Thomas , Secker Philipp , Sefrin Julian , Biber Knut , Mezler Mario , Klein Corinna
Published: December 2023

Background

Neuroinflammation and microglia proliferation are central in Alzheimer’s disease pathology. However, the role of microglia in the accumulation and spreading of plaques and tau tangles is not yet well understood.

Method

In this study, we depleted the microglia population in the brain of Alzheimer’s disease (APP PS1) tauopathy (Thy1P301S) and dual pathology (APPPS1 Thy1P301S) mice models using a colony stimulating factor 1 receptor (CSF1R) inhibitor to achieve microglia ablation. Consequences of compound treatment on brain pathology were analyzed.

Result

Reduced number of microglia cells in the brain was successfully achieved in the mouse model Thy1P301S. In a chronic treatment study of 3 months, mice treated with the CSF1R inhibitor showed a significant decrease in tau aggregation and deposition compared to the control group.

Conclusion

Here we show that inhibition of microglia proliferation induces attenuation of tau pathology. This work demonstrates that intervention on microglia is a potential therapeutic approach in Alzheimer’s disease.
The bidirectional associations between cognition and depression in mid‐life and older adults in the CLSA
Authors: Stinchcombe Arne , Hopper Shawna
Published: December 2023

Background

Existing evidence suggests that depression may be a risk factor for subsequent cognitive impairment and dementia. Concurrently, other evidence suggests that cognitive impairment may precede depression symptoms. We investigated the relationship between depression symptoms and memory performance over a three‐year time period in a sample of mid‐life (45 ‐ 64 years) and older adults (65 ‐ 85 years).

Method

Data were drawn from the Canadian Longitudinal Study on Aging (CLSA), a large longitudinal study of health and aging. Depression symptoms were assessed with the Centre for Epidemiological Studies Depression Scale (CESD‐10) and memory was captured using the Rey Auditory Verbal Learning Test (RAVLT). Two time points were analyzed: baseline (completed in 2015) and first follow‐up (completed in 2018). We used multigroup cross‐lagged structural equation modelling (SEM) to estimate the bidirectional relationships between depression and cognition over time, based on age group: participants aged 45‐64 years (n = 26,605) and 65 years and above (n = 17,986). Sex, education, ethnicity, sexual orientation, and general health were controlled for at baseline.

Result

The results confirmed a bidirectional association between depression symptoms and memory over time, a relationship that was moderated by age group (difference test: p = .02). Results showed that the association between depression at baseline and memory at follow‐up was stronger for the younger cohort (r = ‐.039, p<.001) compared to the older cohort (r = ‐.015, p = .026).

Conclusion

The results confirm the bidirectional relationship between depression symptoms and memory. This work also highlights the role of age group as a moderator of this relationship, insofar as depression is a stronger correlate of memory for mid‐aged adults in comparison to older adults.
Microglia and neuron derived extracellular vesicles show distinct small RNA patterns in Alzheimer’s disease
Authors: Arbaciauskaite Skaiste , Allelein Susann , Scholz Alexander , Loeffler Dennis , Reiche Kristin , Blumert Conny , Kuhlmeier Dirk
Published: December 2023

Background

Extracellular vesicles (EVs) are nano‐sized membranous particles that are released by almost all cells in the human body. EVs carry different cargo (e.g. protein, lipid, nucleic acids) that differs based on the EVs biogenesis and state of the cell during the release. Therefore, EVs are excellent for identifying disease patterns and biomarkers. The need to understand the pathogenetic patterns and biomarkers in neurodegenerative diseases is crucial for early diagnosis as well as potential therapeutic intervention.

Studies show that small RNA, especially miRNA participate in pathologic processes connected to neurodegeneration, therefore we have specifically looked into microglia and neuron derived EVs small RNA content of patients with Alzheimer’s disease (AD) and control patients. The aim of the study was to find AD patterns coded in small RNA.

Method

EVs were isolated specifically from microglia and neurons by immunomagnetic precipitation from blood plasma and cerebrospinal fluid (CSF) collected from patients with AD and healthy aged‐matched controls. Western blots were used to characterize EVs composition and assess purity. Small RNA isolation was performed on the isolate EVs and then sequenced using commercial kits. Quantitative PCR (qPCR) was performed for validation.

Result

We found that neuron‐ and microglia‐derived EVs are present in blood plasma as well as CSF and they carry a big variety of small RNA biotypes. Looking specifically into miRNA, distinct groups of miRNA were expressed only in AD patients and only in healthy controls. Also, differences between genders was observed.

Conclusion

We showed distinct miRNA patterns in neurodegeneration, specifically in AD. The results of our study suggest that miRNA could be used to elucidate the pathological processes involved in AD development and help to diagnose neurodegenerative changes earlier.