bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Cerebrospinal Fluid Flow in the Subarachnoid Space in Beta‐Amyloid Clearance
Authors: Kim Jeongchul , Barcus Richard A. , Lipford Megan E. , Yuan Hongyu , Hudson Jeremy Patton , Sai Kiran K. Solingapuram , Lockhart Samuel N. , Craft Suzanne , Whitlow Christopher T.
Published: December 2023

Background

Recent studies identified the lymphatic drainage system in the brain. Here, cerebrospinal fluid (CSF) carries waste from brain tissue. However, it is still not well understood how CSF flow in the brain affects waste removal. In this study, we hypothesize that CSF flow patterns in the subarachnoid space will be correlated with beta‐amyloid deposition in the brain.

Method

Thirteen participants (7 Cognitively Normal and 2 Mild Cognitive Impairment, Age = 68±7.7 yrs. M/F = 5/4) who had prior amyloid PET imaging were recruited for CSF flow MRI from the Wake Forest Alzheimer’s Disease Research Center. The CSF flow patterns during the cardiac cycle were measured using the phase‐contrast MRI at the cerebral aqueduct, pontine cistern and cerebellomedullary cistern (Fig. 1). Images were acquired for 40 cardiac cycles with a pulse oximeter and CSF flow profiles were estimated using the retrospective cardiac gating method. PET Amyloid burden in the whole gray matter (GM) was measured as the standardized update value ratio (SUVR, cerebellar gray matter as a reference region) from the prior PET imaging and corresponding MRI.

Result

CSF flow amplitude normalized by the brain tissue volume demonstrated moderate to strong correlations with beta‐Amyloid SUVR in GM (Fig. 2); Pearson’s correlation coefficient (rho) was ‐0.59 (p = 0.036) and ‐0.84 (p = 0.004) at pontine cistern and cerebellomedullary cistern, respectively. The lateral ventricle volume normalized by brain volume was also moderately correlated with GM SUVR (rho = 0.495).

Conclusion

At an early stage of AD, the CSF circulation in the subarachnoid space could be correlated with beta‐Amyloid deposition. Therefore, CSF flow in the subarachnoid space could be a useful imaging marker to predict the clearance of beta‐amyloid in the brain.
Self Perceptions of Stress in Caregiving Moderate Associations of Within and Between Caregivers’ Physical Health Symptoms
Authors: Ho‐yin Lai Frank
Published: December 2023

Background

The success of dementia care requires the full support from the caregivers with the goal of delaying the disease’s progress. Studies over decades have reinforced that the knowledge, attitude, and skills of caregivers are crucial parameters of the success of in‐community care for dementia. Nevertheless, studies have identified that many caregivers, across different culture and ethicity, are not well prepared emotionally or practically to be the caregivers and this will result in stress, particularly when their stress are ignored by medical professionals during this long journey of care.

Method

This is a mixed‐method research to examine how self‐perceptions of aging (SPA) moderated within‐ and between‐caregivers Self‐perceived stress (SPS) associations with physiological health symptoms (PHS) and daily physical health symptoms (DPHS). SPA was measured by the Philadelphia Geriatric Centre Morale scale. SPS was measured by Zarit Burden Interview Scale and Revised Memory and Behaviour Problem Checklist. DPHS was measured daily through an adapted symptom checklist.

Result

A pilot study of 20 caregivers reported significantly more physical health symptoms compared to individuals with lower perceived stress on average (p < .05). SPA significantly moderated associations between both within‐ and between‐persons perceived stress (SPS) and physiological health symptoms (PHS) (ps < .05).

Conclusion

More positive SPA significantly dampened the impact of perceived stress, suggesting the importance of SPA as an individual characteristic within stress processes. Future work should examine how daily changes in SPA may exacerbate or mitigate the impacts of daily stress processes and health outcomes.
Cognitive Performance in Relation to MIND and MEPA III Accordance among NHANES Participants
Authors: Derdiger Samara A , Friedeborn Sophia A , Tangney Christy C
Published: December 2023

Background

There is growing evidence from cohort studies and clinical trials that MIND and Mediterranean‐like diets are associated with better cognitive performance, but most rely on food frequency questionnaires that may not specify key food items consistent with these patterns.

Method

In this cross‐sectional sample from two NHANES cycles (2011‐2014), scores for the MIND dietary pattern (maximum score = 14) and those for the Mediterranean Eating Pattern for Americans III (maximum score = 22) were calculated based on reported foods consumed on two non‐consecutive 24‐hour dietary recalls. Only those adults with two completed recalls and cognitive tests were studied (n = 2598). Cognitive assessments included the word learning and recall components from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the Animal Fluency test (AFT), and the Digit Symbol Substitution test. The Complex Sample module in SPSS (version 26) was used to produce representative estimates of the older American population with the dietary weighting variable applied following the “least common denominator” rule.

Result

The average age of sample participants was 69.2 ± 0.3 years, with almost equal proportion of men and women. The average MIND score was (mean ± SD) 5.0 ± 0.0, whereas for MEPA III, this was 8.6 ± 2.1. There were positive associations between continuous MIND scores and education‐dependent standardized cognitive scores for each test as well as global cognition (β = 0.05‐0.10, all p‐values ≤ 0.002 when adjusted for covariates); these associations were not observed for MEPA III scores. Compared to those in the lowest MIND accordance tertile, those in the highest tertile were less likely to exhibit low cognitive performance on the AFT [odds ratio, 95% CI)] 0.45 (0.29–0.69)], CERAD Delayed Recall [0.52 (0.33–0.83)], and global cognition [0.50 (0.27–0.94)].

Conclusion

Older Americans in this sample were generally non‐accordant to MIND and MEPA III patterns. However, those who reported greater MIND diet accordance exhibited better cognitive performance.
Disparities in neuropsychiatric symptom clusters across dementia diagnoses within Lewy body dementia syndromes and Alzheimer’s dementia
Authors: Oliveira Fabricio Ferreira , Graça Naffah‐Mazzacoratti Maria , Smith Marilia Arruda Cardoso , Bertolucci Paulo Henrique Ferreira
Published: December 2023

Background

Behavioral clusters may differ in intensity and frequency across dementia syndromes and according to genetic variants.

Methods

Consecutive outpatients with probable dementia with Lewy bodies (fourth consensus report of the DLB Consortium), Parkinson’s disease dementia (PDD, Movement Disorder Society Task Force), or late‐onset Alzheimer’s dementia (AD, National Institute on Aging/Alzheimer’s Association, rs7412&rs429358 genotyped with TaqMan® Real‐Time PCR technology) were recruited (2010‐2018) and assessed for demographic features and scores on a 15‐item Clock Drawing Test (CDT), Mini‐Mental State Examination (MMSE), Index of Independence in Activities of Daily Living (ADL), Lawton’s Scale for Instrumental Activities of Daily Living, Clinical Dementia Rating (CDR) and Zarit Caregiver Burden Interview. According to the Neuropsychiatric Inventory, affective (anxiety,apathy,dysphoria,euphoria), hyperactive (aberrant motor behavior,agitation,disinhibition,irritability), and psychotic (delusions,hallucinations) clusters were associated with cognitive, functional and caregiver burden scores, and compared according to dementia diagnoses, p<0.05.

Results

All had similar education (p = 0.205): DLB (n = 38;57.9%♀), PDD (n = 14;64.3%♀), APOE‐ε4 carriers with AD (n = 117;72.6%♀), APOE‐ε4 non‐carriers with AD (n = 108;63.0%♀). Patients with AD used cholinesterase inhibitors (p = 0.004) and Memantine (p<0.0001) more often, had higher CDT (p = 0.027) and ADL (p<0.001) scores, and lower caregiver burden (p = 0.022);other score differences were non‐significant among groups. APOE‐ε4 carriers with AD had lower affective scores (p<0.0001), while APOE‐ε4 non‐carriers with AD had lower psychotic scores (p<0.0001);hyperactive scores were similar among groups (p = 0.146). Affective scores were associated with caregiver burden and inversely associated with MMSE scores only in AD, while inversely associated with functionality in DLB and AD;they were also associated with functionality and inversely associated with CDR Sum‐of‐Boxes scores in PDD. Hyperactive scores were inversely associated with functionality in all groups, while associated with cognitive scores in DLB, and inversely in PDD and AD;they were also associated with caregiver burden in DLB and AD, and inversely in PDD. Psychotic scores were associated with CDR Sum‐of‐Boxes scores in PDD and AD, while associated with caregiver burden and inversely with cognition and functionality in all groups.

Conclusions

The affective and hyperactive clusters have divergent associations with clinical features across dementia syndromes, while the psychotic cluster is most consistently associated with worsened cognition, functionality and caregiver burden. APOE‐ε4 carrier status may affect cluster intensity in AD.
Aligning the Alzheimer’s biomarker validation framework to technology readiness levels
Authors: Boccardi Marina , Savoini Adriano , Daussin Valérie , Alexandersson Jan , Teipel Stefan , Héder Miháli
Published: December 2023

Background

Technology readiness levels (TRL), used in technological R&D, also frame European Commission biomedical funding frameworks. Providing an adaptation to biomarker development would improve communication with industry, align stakeholders and professionals, reduce risk of development failure, costs and waste. Here, we aim to align TRLs with the Strategic Biomarker Roadmap (SBR) defined to validate biomarkers for Alzheimer’s disease (AD) and related disorders.

Method

We analyzed the NASA definition of TLR phases and a previously proposed adaptation to the biomedical field. We drafted an alignment of TRLs with the SBR Phases and Aims. We refined such alignment through discussion and consensus among coauthors and outlined discrepancies, gaps and SBR limitations relative to the TRL framework, to improve the development process for future biomarkers.

Result

The SBR covers all of the 9 TRLs. The demonstration of Analytical Validity entails TRLs_1‐4. Specifically, the SBR Phase_1 includes TRLs_1‐2; Phase_2 Primary Aim (PA) corresponds to TRL_3, and Phase_2 Secondary Aims (SAs) to TRL_4. Clinical Validity entails TRLs_5‐8. Specifically, the SBR Phase_3 corresponds to TRL_5, while TRLs_6‐8 correspond respectively to Phase_4 PA, SAs, and full completion. Demonstration of Clinical Utility corresponds to TRL_9. Despite such correspondence, the SBR entails only biomarker diagnostic performance and utility. Aspects like manufacturing and usability, fundamental in the TRL framework as well as in the previous biomedical adaptation, are still lacking. The definition of tools (e.g., Target Product Profile, introduced at TRL 3 in the biomedical adaptation) may help complement the SBR in this direction.

Conclusion

The SBR and TRLs follow a consistent sequence despite different pacing and granularity, SBR steps corresponding to one‐to‐multiple TRLs. Targeting such inconsistencies and upgrading the SBR validation roadmap into a development roadmap, entailing manufacturing, usability, and an integrated procedure to assess cost‐effectiveness and plan implementation requires a structured dialogue with industry partners and other stakeholders, like regulators. Such attempt to evolve the SBR from a linear to a multi‐dimensional model may help boost the efficiency of translational research and our response to the global priority of dementia.
Unsupervised detection of dementia based on longitudinal data from the Survey of Health, Ageing and Retirement in Europe
Authors: Gharbi‐Meliani Amin , Josse Julie , Husson François , Vandendriessche Henri , Bayen Eleonore , Yaffe Kristine , Bachoud‐Levi Anne‐Catherine , de Langavant Laurent Cleret
Published: December 2023

Background

In the Survey of Health, Ageing and Retirement in Europe (SHARE), a population‐based survey of aging in multiple countries, dementia status is self‐reported. However, more than half of dementia cases remain underdiagnosed, which may hinder the use of SHARE data to study dementia determinants and outcomes. We use unsupervised machine learning and longitudinal data from SHARE to discover clusters of patients with probable dementia.

Methods

We selected participants aged 50 or more with consecutive follow‐ups across all SHARE prospective waves. We chose variables informative of participants’ daily function and cognitive performance. We applied a Multiple Factor Analysis followed by a Hierarchical Clustering to the whole longitudinal data set. To evaluate our algorithm, we looked at its discrimination power by comparing it to the self‐reported dementia. We also checked if increased risk of transition to probable dementia was associated with non‐modifiable (age, sex) and modifiable (education, hypertension, obesity, hearing loss, diabetes, physical inactivity, smoking, drinking alcohol, social isolation, depression, air pollution) dementia risk factors. Finally, we replicated this study in the English Longitudinal Survey of Aging (ELSA).

Results

The baseline sample consisted of 15,278 initial participants across 12 countries. The algorithm identified a higher number of probable dementia cases compared with self‐reported cases. Its discriminative power was good discriminative power across all waves (Area Under the Curve > 0.75). Sensitivity attained its highest value at wave 4 reaching 0.71 [0.66–0.77]. Specificity remained high (> 0.9) in all waves. Both non‐modifiable and modifiable dementia risk factors were associated with increased risk of transition to probable dementia. These results were replicated in ELSA.

Conclusion

Detection of probable dementia with longitudinal data and unsupervised clustering could be used to study dementia in SHARE and ELSA cohorts. Further validation of this method is needed to apply it in other surveys of aging.
Impact on metamemory and cognitive measure of a multifactorial memory training program for older adults from Argentina
Authors: Feldberg Carolina , Barreyro Juan Pablo , Quian Rosario , Natalia Irrazabal , Ofman Silvia Deborah , Hermida Paula Daniela , Tartaglini María Florencia
Published: December 2023

Background

Several studies have suggested that cognitive training is a potentially effective way to improve cognition and metacognitive beliefs and postpone cognitive decline in older adults. The aim of the present study is to assess the impact of a multifactorial program on metamemory and cognitive measures of older adults from Argentina.

Method

Design: Comparative, pre‐post, longitudinal intervention study. Community dwelling older adults over 60 years. Memory training program participants (n = 50) (M = 68,68 years old; ds = 8.13 years) and controls (n = 50) (M = 69.03 years old; ds = 8,03 years) were assed at the begging and the end of the program. Instruments: questionnaire of social demographic data (built ad hoc), brief neuropsychological assessment for memory and attention and a metamemory questionnaire. Procedure: all the participants of the Intervention group took part in the memory training program. The program has a duration of 8 sessions of 90 minutes each, where theoretical and practical tools are provided to improve cognitive performance in everyday life. Program participants and controls were assed twice, with eight weeks of difference between the first and second evaluation.

Result

Multiple analyzes of variance (ANOVA) were performed. The results indicate an interaction effect between the training condition (training program participants and controls) and the longitudinal condition (pre‐test and post‐test condition) in the metamemory questionnaire (F(1,98) = 5.06, p = .03) and in the memory strategies subscale (F(1,98) = 15.58, p < .001). Post‐hoc analyzes indicate that the training group performed significantly better on both measures (p < .001), compared to the control group, which showed no differences. No differences were detected between the groups in measures of neuropsychological assessment.

Conclusion

These results coincide with previous studies that point out the importance of assessing and intervening on metacognitive aspects in multidimensional cognitive training programs for older adults. The inclusion of cognitive training is an approach that can help cognitively vulnerable older adults and promote healthy cognitive aging.
Narrative Ethnography in Analysis Caring Demand of Spousal Caregivers for Older People with Dementia : A Qualitative Study
Authors: Ho‐Yin Lai Frank , Hai Eddie , Chan Catherine
Published: December 2023

Background

With deteriorated cognitive condition and age‐related disease, care for older adults becomes a global challenge. This challenge care is further aggravated with decreased fertility and increased longevity in an ageing population. Being an informal carer of a person with dementia can have a negative effect on the caregiver’s health and quality of life. Spouse caregivers (SC) have been found to be especially vulnerable as they need to simultaneously fulfil their supportive roles and manage the burden brought about by the demands of caregiving with the disease progression of their spouse. Nevertheless, relatively little is known about the needs of SC at different stages of the caring.

Method

With the framework of caregiving by Cameron and Gignac (2008), this paper explores the topic of caregiving with focus on specific needs of SC in caring for the spouse with different stages of the dementia. Narrative ethnography, the qualitative research technique, was selected as a methodology to study stories in the context of SC telling and use stories to interpret the caregiving phenomenon. Participant inclusion criteria were: (a) SC aged between 65 and 80, and (b) being able to understand verbal and written instructions. To eliminate the co‐founding care‐giving burden, participants with major physical dysfunctions, such as stroke and head injuries, were excluded.

Result

Forty‐five SC were recruited through poster advertisements. With adaptation of the stage of change model of Cameron and Gignac (2008), there were identified 5 major themes of experience from the spousal caregivers, namely a) seeking understanding, b) stabilization, c) preparation, d) implementation, and e) adaptation. Several sub‐themes and constructs to address different needs of SC, such as concern on their deteriorating physical health condition cannot further cope with both physical and mental demand in taking of their progressively deteriorated relatives with dementia. Mental well‐being of SC changed over the course of changing cognitive function and functional impairment of older adults with dementia.

Conclusion

Narrative ethnography indicated poor cognitive function and functional dependent were the most difficult mental burden for the SC. These two components are crucial part for the further grounded theory development.
Objectively‐measured physical behaviors, peripheral cytokines, and plasma neurofilament light chain in older adults: a population‐based study
Authors: Wang Yongxiang , Han Xiaolei , Dong Yi , Hou Tingting , Cong Lin , Du Yifeng , Qiu Chengxuan
Published: December 2023

Background

Evidence has linked self‐reported sedentary behavior (SB) and physical activity (PA) with cognitive impairment; however, the underlying neuropathological mechanisms are poorly understood. We examined the dose‐response associations of the accelerometer‐measured daily SB and PA time with plasma neurofilament light chain (NfL) among older adults and the role of systemic low‐grade inflammation in the associations.

Method

This population‐based study included 1,029 dementia‐free older adults (age ≥60 years, 59.48% women) who undertook the ActiGraph substudy (March 2018‐December 2020) in MIND‐China. Plasma NfL and serum cytokines were measured on SIMOA and MSD platforms, respectively. Movement parameters were assessed with an accelerometer. Data were analyzed using the restricted cubic splines, general linear, and mediation models.

Result

There were J‐shaped associations of daily SB and PA time with plasma NfL concentration, such that more daily SB time or less daily light‐intensity physical activity (LPA) and moderate‐to‐vigorous‐intensity physical activity (MVPA) time were significantly associated with increased plasma NfL only when SB time ≥8.00 hours/day or LPA time <5.00 hours/day or MVPA time <2.00 hours/day. Furthermore, more daily SB time or less daily LPA and MVPA time was significantly associated with higher serum inflammation scores (P<0.05). Finally, serum biomarkers of low‐grade inflammation could account for 15% to 19% of the associations between movement behaviors and plasma NfL level.

Conclusion

More daily SB and less PA time are associated with peripheral biomarker for neurodegeneration and systemic low‐grade inflammation in older adults. The association of movement behaviors with neurodegeneration is partially mediated by systemic low‐grade inflammation.
Causal association of cardiovascular risk factors with Alzheimer’s disease
Authors: Tripathi Shailendra Mohan , Murray Alison D. , Wischik Claude M , Schelter Bjoern
Published: December 2023

Background

Alzheimer’s Disease (AD) frequently coexist with cerebrovascular disease (CVD) and makes it difficult for researchers to delineate the two pathologies with available diagnostic criteria. Neuroimaging techniques, especially FDG‐PET can help differentiate the two pathologies based on the characteristic temporo‐parietal metabolic deficitsin AD and regional patchy deficits in CVD. Co‐occurrence of the both patterns can be seen in mixed cases.Existing literature supports a possible role for cardiovascular risk factors in AD pathogenesis. This study aims to determine whether cardiovascular risk factors have a causative association with typical AD pathogenesis or it has an association with mixed AD.

Method

Baseline brain FDG‐PET images of participants with a diagnosis of AD from two large clinical trials of hydromethylthionine were classified into “typical AD” and “mixed” patterns through visual analysis. Causal association of independent variable age and dependent variables cardiovascular risk factors, White matter hyperintensities (WMH), AD subtypes and severity of cognitive impairment depicted with ADAS Cog scores were analysed using Structural equation modelling (SEM).

Result

Out of a total 794 participants, 533 (67.1%) were classified as typical AD and 261 (32.8%) were classified as mixed. Overall, the people with a mixed pattern were significantly younger than the people with a typical AD pattern. Age significantly influenced cardiovascular risk factors, WMH and typical AD subtype. The severity of cognitive impairment was significantly influenced by cardiovascular risk factors, WMH and typical AD subtype. Interestingly, cardiovascular risk factors had a statistically significant positive influence on typical AD subtype in comparison to mixed.

Conclusion

It is well known fact that the cardiovascular risk factors are commonly associated with cerebrovascular disease but contrary to our expectations cardiovascular risk factors have a causal association with typical AD.
Neurocognitive study of bodily and traumatic memory in a Moroccan novel on Alzheimer’s disease
Authors: Taiebine Mohamed
Published: December 2023

Background

Person‐centered care in dementia focuses on empowering patient’s wellbeing and quality of life. In this context, Ben Jelloun’s novel About My Mother (2016) addresses multiple issues related to social justice, hegemony, ageism, and women’s health conditions by combining literary, fictional autobiography and factual biography in a critical period of Moroccan colonial and post‐colonial history. We will study Lalla Fatma as a prototype carrying a triple burden: early traumatic events of life, weight of tradition, and Alzheimer’s disease (AD).

Method

Text mining was used for lexical‐semantic analysis and to develop patterns of themes across the novel’s corpora. A neurocognitive approach has been used to describe gendered aesthetics, antero‐retrograde amnesia, traumatic and bodily memory.

Result

Theoretical framework from Tulving descriptions of noetic and autonoetic memory disorders have been used to classify Lalla Fatma amnesia. Alzheimer’s disease is an incentive to adopt the narrative of filiation and reconstruction that brings into life distant memories. Ben Jelloun’s novel gives the subjectivity “insight of disease” more time and space in order to express all states of memory in a stream of consciousness until its abolition. Moreover, the question of the genesis of psychogenic‐organic memory disorders through early trauma in the life of Lalla Fatma could favor a triple stress at a physiological level “a declined global health,” a microstructural level “microaggressions from her caregivers,” and macrostructural level “the trauma of the colonial past and successive widowing”.

Conclusion

This study characterized AD using a mixture of fictional and factual autobiography. The anguish of successive widowing may reactivate psychic traces and an intrapsychic conflict between the desire of Lalla Fatma to preserve the lost object “body and memory” and the weight of society “culture and tradition”. The person‐centered care was successfully implemented thanks to the involvement of multiple caregivers around the main character.
Integrative single‐nucleus multi‐omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer’s disease brains
Authors: Chiba‐Falek Ornit , Gingerich Daniel , Shwab Elliot Keats , Gamache Julia , Garrett Melanie E , Crawford Gregory , Ashley‐Koch Allison
Published: December 2023

Background

The genetic underpinnings of late‐onset Alzheimer’s disease (LOAD) are yet to be fully elucidated. Although numerous LOAD‐associated loci have been discovered, the causal variants and their target genes remain largely unknown. Since the brain is composed of heterogenous cell subtypes, it is imperative to study the brain on a cell subtype specific level to explore the biological processes underlying LOAD.

Methods

In this study we performed a parallel single‐nucleus (sn) multi‐omics analysis to simultaneously profile gene expression (snRNA‐seq) and chromatin accessibility (snATAC‐seq) using nuclei from 12 normal and 12 LOAD brains. We developed a pipeline based on integrative analysis of multimodal datasets that utilizes several bioinformatics packages to catalogue cis‐ and trans‐ regulatory network and their target genes.

Results

We identified cell subtype specific LOAD‐associated differentially expressed genes (DEGs), differentially accessible peaks (DAPs) and cis co‐accessibility networks (CCANs). Integrative analysis defined disease‐relevant CCANs in multiple cell subtypes and discovered LOAD‐associated cell subtype specific candidate cis regulatory elements (cCRE), their candidate target genes, and trans‐interacting transcription factors (TF), some of which were LOAD‐DEG, for example, ELK1 in a specific sub type of excitatory neurons and ATF7 and JUN, found in multiple cell subtypes. Overall, our analysis discovered 53 new candidate LOAD genes and validated 16 gene previously implicated in LOAD. Finally, we focused on a subset of cell subtype‐specific CCANs that overlap known LOAD‐GWAS regions and catalogued putative functional SNPs disrupting TF motifs within LOAD‐cCREs linked to LOAD‐DEGs including, APOE and MYO1E in a specific subtype of microglia.

Conclusions

In this study we identified candidate cis‐ and trans‐ regulatory factors and their target genes that contribute to the pathogenesis of LOAD. To our knowledge, this study represents the most comprehensive systematic interrogation of regulatory networks underlying gene dysregulation in LOAD at an unprecedented cell‐subtype resolution. Collectively, our findings provide a rich dataset for future mechanistic experiments, confirm known LOAD‐GWAS loci while also identifying novel loci, and suggest the disease‐relevant cell types and subtypes for follow‐up validation studies using in vitro and in vivo disease model systems. This information is important for the development of new therapeutic targets and interventions for LOAD.
The complex relationship between anticholinergic medication, frailty, and hospitalization in patients with early‐stage dementia
Authors: Wyman‐Chick Kathryn A , Chrenka Ella A , Miller Michael J , Barrett Matthew J , Sabayan Behnam , Werner Ann M , Rossom Rebecca C
Published: December 2023

Background

Anticholinergic medications are associated with frailty and hospitalization in patients with dementia. It is unclear if anticholinergic burden mediates the relationship between frailty and hospitalization or if specific dementia syndromes moderate the direct and indirect relationships between these three factors.

Method

We analyzed electronic health record and claims data for member‐patients diagnosed with dementia with Lewy bodies (DLB), Alzheimer’s disease (AD), or vascular dementia (VD) from an integrated healthcare system in the U.S. between October 2015 and August 2022. The Anticholinergic Cognitive Burden Scale (ACB), Claims‐based Frailty Index (frail ≥0.20), and number of hospital admissions were calculated for the 12‐month period prior to dementia diagnosis. Patient demographics, ACB score, frailty status, and hospitalization frequency were compared between dementia syndromes. Baron and Kenny regression‐based method was used to evaluate if ACB is a mediator between frailty and hospitalization. DLB, AD, and VD were included as interactions with ACB and frailty in stratified mediation models to determine if dementia syndrome moderated the relationship. Significant interaction terms indicate a moderating effect of dementia syndrome. All models included patient age and sex as covariates.

Result

We identified 3166 patients (DLB n = 175; AD n = 2478; VD n = 513). Approximately 23% of patients with DLB were prescribed 5+ anticholinergic medications (17.2% with VD; 9.9% with AD; p<.001). Two or more hospitalizations were documented in 12.5% of patients with VD (10.3% with DLB; 5.5% with AD; p<.001). The ACB score was 3.7 greater for patients with frailty compared to those without (3.2, 4.4, p<.001). The relationship between frailty and hospitalization was mediated by ACB (higher ACB was associated with increased utilization; Table 1). A diagnosis of AD or VD moderated the indirect relationship between frailty and hospitalization, but the specific dementia syndrome did not moderate the path between ACB and hospitalization (Table 2; Figure 1).

Conclusion

In the year prior to dementia diagnosis, frailty was associated with a higher number of anticholinergic medications, which, in turn, was associated with a greater number of hospitalizations. A diagnosis of VD increased the expected rates of hospitalization for frail patients, while an AD diagnosis decreased the magnitude of the association between frailty and hospitalization.
Detecting early Alzheimer’s disease using neuropsychological assessment and structural neuroimaging
Authors: Quek Yi‐En , Fung Yi Leng , Bourgeat Pierrick , Vogrin Simon J , Collins Steven J , Bowden Stephen C
Published: December 2023

Background

Alzheimer’s disease (AD) can be challenging to diagnose early as cognitive changes are mild. Neuropsychological assessment, in contrast to cognitive screening or isolated cognitive tests, are more sensitive to the mild cognitive changes in early AD. Magnetic resonance imaging (MRI) can detect early structural brain changes in AD, particularly entorhinal cortex, transentorhinal cortex, and hippocampal atrophy. Combining neuropsychological assessment with MRI examination may yield improved ability to detect early AD. The current study examined combining neuropsychological and MRI measures to detect patients with mild cognitive impairment (MCI) in a memory clinic sample.

Method

Neuropsychological assessment and entorhinal cortex, transentorhinal cortex, and hippocampal volume measurement were conducted in memory clinic patients, including 38 with memory symptoms, 16 with MCI, and 16 with dementia due to AD, and in 40 healthy controls. Backward stepwise multinomial logistic regression was used to compare the neuropsychological measures and MRI measures.

Result

Among the neuropsychological measures, memory and processing speed were the most important measures that contributed to group membership prediction. All MRI measures contributed to group membership prediction. The neuropsychological measures were more accurate than the MRI measures at detecting patients with MCI. Combining the MRI measures with the neuropsychological measures did not improve group membership prediction.

Conclusion

Neuropsychological assessment is an important tool to support MCI diagnosis. MRI measures contribute little diagnostic value over and above neuropsychological assessment. Further advancement in deriving MRI‐based measurements is required to achieve clinical utility.
Passive logging of smartphone interactions as a feasible and reliable measure to monitor everyday cognition in Alzheimer’s Disease
Authors: Keijzer Matthijs J. , Glind Marie‐Christine M.A.B.J Van De , Twose James , de Kloet Sybren F. , Redeman Erwin G.M. , Meijer Kim A. , van der Flier Wiesje M. , Sikkes Sietske A.M.
Published: December 2023

Background

As cognitive assessments can be burdensome to patients, new approaches are emerging to assess symptomatic changes in Alzheimer’s Disease (AD). Since typing on smartphones requires a variety of cognitive functions, passively and remotely collected typing behaviour has the potential to provide day‐to‐day insights into cognitive decline in AD. We investigated therefore the feasibility and reliability of a keyboard application for smartphones (Neurokeys) that passively collects keystroke dynamics (KD) to monitor cognition in people with preclinical and clinical AD.

Method

Participants with preclinical AD (N = 8) and patients with a clinical AD diagnosis (N = 8, Table 1) were included from the Amsterdam Dementia Cohort. Participants used Neurokeys for 28 consecutive days in the context of the ‘A Personalized Medicine Approach for Alzheimer’s Disease’ (ABOARD)‐project. The retention rate (active users on day 28) and the average number of daily keystrokes were calculated to determine feasibility. KD were aggregated into two commonly investigated features: time between keystrokes (flight‐time) and duration of a keystroke (hold‐time), which were standardized into z‐scores. Intra‐class correlations (ICC) between first and last 14 days of data collection for both features were determined to assess reliability. Finally, KD features were correlated to scores on the Mini‐Mental State Examination (MMSE) to explore the association between KD and global cognition.

Results

The retention rate was 93.75% for all participants (Figure 1). Participants with preclinical AD used the keyboard for 26.25±2.12 days with 653.67±305.61 keystrokes each day, and clinical AD patients used the keyboard for 22.63±4.10 days with 409.44±288.73 daily keystrokes. For all participants, the ICC for flight‐time and hold‐time are 0.85 and 0.89 respectively. MMSE is negatively correlated with flight‐time (r = ‐0.68, p = 0.003), but not with hold‐time (r = ‐0.20, p = 0.45, Figure 2).

Conclusion

The number of daily keystrokes is sufficient to obtain reliable KD features in preclinical and clinical AD. The results show that people with better global cognition type faster, indicating that passive logging of keystrokes can be a feasible measure for cognition in AD. To elaborate on these first findings, a larger validation study can further explore the utility of smartphone interactions and aid the development of digital biomarkers in AD.
ApoB‐related Sulcal depth Patterns Contributed to Executive Function and Plasma Biomarkers of Alzheimer’s disease
Authors: Wang Ziqi , Wang Jiayu
Published: December 2023

Background

As the cerebral cortex is an important indicator of the pathological changes of AD, ApoB, ApoA1, ApoB/ApoA1 and blood Alzheimer’s biomarkers have been proved to be important markers of AD.

Method

We analyzed data from 21 patients with SCD enrolled in the 500 nm light therapy cohort who filled a battery of neuropsychological tests and had apolipoproteins, plasma Alzheimer’s biomarkers, and gene levels assessed at the time of their baseline 3T MRI scans. The sulcal depth and cortical thickness were obtained using the vertex‐based approach with the CAT12 toolbox (in SPM12).

Result

At corrected thresholds (p < 0.05, FWE‐corrected), there were significant positive correlations between ApoB and sulcal depth in the lateral occipital cortex, and between ApoB/ApoA1 and sulcal depth in the left lateral occipital cortex. In addition, we found a significant negative correlation between shape trails test part B (STT‐B) time and sulcal depth in the left lateral occipital cortex (β = ‐0.502, p = 0.040). Moreover, the plasma Aβ42 was positively related to sulcal depth (β = 0.493, p = 0.044) and plasma p‐tau181 was negatively related to the sulcal depth (β = ‐0.592, p = 0.012) in the left lateral occipital cortex. There was no relationship between cortical thickness and apolipoproteins or any of the biomarkers.

Conclusion

ApoB and ApoB/ApoA1 influence sulcal depth in the left lateral occipital cortex where the sulcal depth may relate to the executive function and plasma Alzheimer’s biomarkers in SCD.
Estimating the Prevalence of Dementia in a sample of Australian Prisoners: The Cohort Study Design, Results and Implications for Public Health and Prison Sectors
Authors: Modini Ella L , Nixon Margaret , Fullam Rachael , Macfarlane Stephen
Published: December 2023

Background

The number of older prisoners within our prison system is increasing. The health challenges faced by prisoners in general contribute to prisoners being considered ‘old’ within the prison system once they reach the age of 50. The prison lifestyle, combined with the risk factor profiles of those incarcerated (higher rates of low educational attainment, smoking, substance use, head injury, psychiatric illness, unmet chronic health needs) suggests that older prisoners are likely to be at significantly higher risk of developing dementia than those of similar ages in the general population.Surprisingly, however, we know very little about the prevalence of dementia within prison systems both internationally and locally, with no Australian data being available. This study aimed to estimate the prevalence of dementia among older prisoners within prisons in Victoria, Australia. Cognitive screening was conducted on a large sample of older prisoners housed within 3 correctional facilities in Victoria, such that the overall prevalence of dementia within this vulnerable group could be ascertained, as a first step towards appropriate service planning.

Method

Dementia assessments of over 100 prisoners aged over 50 years, were conducted across three prison sites in Victoria, Australia. Each assessment included a demographic interview to capture the presence of risk factors and an Addenbrooke’s Cognitive Examination 3rd edition. All assessment data were reviewed by a psychogeriatrician for quality and to identify false positive dementia screens.

Result

The total sample of prisoners 114 reported higher rates of risk factors than those seen in the general population. Conservative dementia prevalence rates based on psychogeriatrician review of self‐reported medical history and patterns of responding on the ACE‐III suggest that dementia is more prevalent in prison populations than in the Australian general population. The overall sample of 95 included assessments suggested prisoners were up to eight times more likely to have dementia than population estimates of 1.1%.

Conclusion

Dementia is likely to be more prevalent in prison systems due to increased risk factors profiles. This poses a significant challenge for corrective services as the ageing prisoner population continues to increase. This study provides rationale for review of planning and service provision to older prisoners.
Examining the measurement equivalence of Alzheimer’s Disease Centre Neuropsychological Test Battery (Version 3) across two distinct cultures
Authors: Tay Sze Yan , Koay Way Inn , Liew Tau Ming
Published: December 2023

Background

Neuropsychological assessments are important in clinical diagnostic process for dementia as it help early detection of cognitive difficulties. Prior to using neuropsychological test batteries across different populations, it is critical to standardize the battery to ensure consistency in the assessment process, as well as valid and comparable results across different settings. The Alzheimer’s Disease Centre Neuropsychological Test Battery (Version 3) (ADCNTB3) is a widely used battery that had shown sensitivity in detecting cognitive decline in MCI and early dementia, with minimal test repetition effects (Boccardi et. al., 2022). While norms are available in America, harmonization efforts are currently in place to adapt ADCNTB3 for European populations.

Method

This study examined whether ADCNTB3 could be adapted to Singapore (multi‐ethic Asian population), a culture distinctly different from America, and whether ADCNTB3 demonstrates measurement equivalence when adapted to the Singapore population. Following the qualitative process of cultural adaptation, the ADCNTB3 was administered to 266 community‐dwelling older persons with normal cognition in Singapore. Scores from these participants were then compared with 1064 random samples with normal cognition from National Alzheimer’s Coordinating Centre (NACC) to evaluate whether the ADCNTB3 has equivalent scores across the two distinct populations. Score‐difference between the 2 populations was computed using multiple linear regression (adjusted for age, education, gender, family history of dementia, cardiovascular conditions, psychiatric and neurological history, smoking, untreated hearing loss, obesity, MoCA total score, CDR sum of boxes, NPI‐Q total score) and equivalence scores are considered to be present if the 90% confidence interval of the adjusted score‐difference fall within the equivalence margin. A priori, we defined the equivalence margin as 0.5 Standard Deviation of tests from ADCNTB3, as this often defines the minimally important clinical significance (Sloan et al., 2005).

Result

Other than working and delayed memory tasks, all other tests from the ADCNTB3 are not directly equivalent. Notably, Asians performed better in visuospatial task, but consistently performed poorer in most other tasks.

Conclusion

Other than working and delayed memory tasks, all other tests from the ADCNTB3 are not directly equivalent. Notably, Asians performed better in visuospatial task, but consistently performed poorer in most other tasks.
Associations between Anxious‐Depression and Cognitive Change, Function, and Impairment: Results from the Hispanic Community Healthy Study/Study of Latinos‐Investigations of Neurocognitive Aging
Authors: Gonzalez‐Prado Roberto , Paredes Alejandra Morlett , Tarraf Wassim , Stickel Ariana M , Kuwayama Sayaka , Zeng Donglin , Gallo Linda C , Testai Fenando D , Daviglus Martha L , Penedo Frank J , González Hector M
Published: December 2023

Background

Anxiety and depression often co‐occur and both are risk factors for Alzheimer’s disease and related dementias (ADRD). This study sought to examine associations between anxiety and depressive symptoms with cognitive change, function and impairment among middle‐aged and older Hispanics/Latinos.

Method

Data included 6,162 middle‐aged and older Hispanic/Latinos adults (Age M = 63.4 years, SD = ±8.2 years; 55% female) enrolled in the Study of Latinos‐Investigation of Neurocognitive Aging study (SOL‐INCA), an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Participants completed the Spielberger State‐Trait Anxiety Inventory 10‐item (STAI‐10) and Center for Epidemiology Scale for Depression 10‐item (CESD‐10) at HCHS/SOL Visit 1 (2008‐2011). Outcomes of interest include cognitive function at Visit 2, change in cognition from Visit 1 to 2 (approximately 7‐years later in SOL‐INCA), and mild cognitive impairment status (MCI; NIA‐AA diagnostic criteria) at Visit 2. Latent class analysis (LCA) was used to derive phenotypes of anxious‐depression using both STAI‐10 and CESD‐10 items. The phenotypes were used as exposures in survey generalized linear regression models for cognitive function, change, and MCI. Covariables included age, sex, education, income, heritage, center, and antianxiety/antidepressant medication use.

Result

LCA results demonstrated 3 classes of anxious‐depression (Low; 62%, Moderate; 30%, and High; 8%). We found consistent negative associations between the Moderate and High group with cognitive function, from baseline. Participants in the High group had more pronounced associations (p<.001) than the Moderate group (p<.01) vs. the Low group, after covariate adjustments. We found consistent negative associations with MCI whereby both Moderate (OR = 1.62, CI = [1.12; 2.33], p<.05) and High (OR = 1.64, CI = [1.25; 2.16], p<.001) groups were associated with higher odds ratios for MCI. However, there were no associations with cognitive change.

Conclusion

This study demonstrated the utility of the anxious‐depression construct when investigating the relationships between co‐occurring anxiety and depressive symptoms with cognitive aging among Hispanics/Latinos. Anxious‐depression was negatively associated with cognitive function and MCI status, demonstrating unique effects of co‐occurring anxiety and depressive symptoms among older Hispanic/Latinos. However, further replications are required to evaluate the longitudinal effects of anxious‐depression on cognitive outcomes.