bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation into the association between diet and dementia risk
Authors: Dobreva Ivelina , Mukadam Naaheed , Solmi Francesca
Published: December 2021

Background

The number of people living with dementia is rising. It is estimated that by 2030, the total number of people with dementia would reach 82 million. By 2050, the number would increase to 152 million. Modifiable risk factors are gaining increasing attention as means of prevention or delaying of the disease. A number of those factors relate to diet, however specific patient guidance has not been established due to inconsistent evidence, heterogeneity of samples, small effect and sample sizes.

We aimed to use a large sample with long follow up times to clarify links between dietary factors and dementia. We use data from the UK Biobank cohort [enrolment from years 2006‐ 2010] on dietary patterns and registered dementia cases to establish an association between diet and dementia risk.We investigate the association between adherence to the Mediterranean diet, as well as specific aspects such as vegetarianism and high versus low fat which could have an impact on dementia risk.This will help in establishing specific guidance for reduction in dementia risk.

Method

We will combine variables to form quantiles of low, medium and high adherence to the Mediterranean diet. We will also classify people into those adhering to a vegetarian/non‐vegetarian diet and those eating a low versus high fat diet. We will summarise characteristics of the sample and compare those developing and not developing dementia. Dementia diagnosis will be determined from self‐report and recorded diagnoses in electronic health records. We will conduct a Cox regression to investigate the effect of dietary factors on dementia risk, adjusting forage, sex, education, physical activity and cardiovascular risk factors.

Result

Results will be presented in the form of summary tables as well as results of Cox regression models. We will examine which dietary factors have the biggest impact on dementia risk and, if supported by the evidence, we will provide suggestions as to how to reduce dementia risk through dietary adjustments.

Conclusion

This project examines association between diet and dementia risk.
Anticipatory cue‐related alpha desynchronization reflects top‐down disinhibitory control during verbal working memory task
Authors: Mirjalili Mina , Zomorrodi Reza , Daskalakis Zafiris J. , Hill Sean , Rajji Tarek K.
Published: December 2021

Background

Working memory deficits are common in mild cognitive impairment (MCI) and cause troubles in routine activities. Frontal theta event‐related synchronization (ERS) and parietal alpha event‐related desynchronization (ERD) are known to be associated with working memory capacity. However, their association with working memory performance, including at the trial‐by‐trial level, has yet to be determined.

Method

54 healthy adults (mean age (SD) = 28.4 (7.4)) completed the N‐back working memory task at three conditions (N = 1, 2, and 3). Single‐trial ERS/ERD was measured during N‐back and in response to an anticipatory cue at the beginning of each trial. Anticipatory cue‐related power changes at the trial level were used to assess neural oscillation before target correct (TC) and target non‐correct (TNC) responses.

Result

2‐way ANOVA showed significant effect of response type (p=0.01) and interaction between N‐back condition and response type (p=0.03) on alpha ERD. Post‐hoc comparisons revealed less alpha ERD in TC vs. TNC responses during 2‐ and 3‐back conditions (p’s < 0.02), and less alpha ERD in TC trials of 2‐ and 3‐back compared to 1‐back condition (p’s < 0.001). Finally, no significant effect was observed in theta band.

Conclusion

Given that alpha ERD has been associated with top‐down disinhibitory control, our findings suggest that less anticipatory disinhibition prior to the processing of a working memory item of information promotes correct processing and high‐capacity working memory
Blood‐based multi‐omic signatures of blood‐brain barrier impairment and CSF‐defined Alzheimer disease in older adults
Authors: Clark Christopher , Bowman Gene L. , Dayon Loic , Raymond Frederic , Wojcik Jerome , Konz Tobias , Rezzi Serge , Masoodi Mojgan , Descombes Patrick , Popp Julius
Published: December 2021

Background

Blood‐brain barrier (BBB) breakdown and accummulation of Alzheimer disease (AD) pathology are risk factors for age‐related dementia. However, both require either lumbar puncture or advanced neuroimaging for detection that are not widely available. Less invasive ways to detect these risk factors early on could permit more targeted therapies for prevention. Multiple‐level molecular biomarker approaches (e.g., ‘multiomics’) may identify candidates for diagnostic development and help initiate earlier risk factor modificaion. We deployed multi‐omics spanning plasma or serum of non‐coding RNAs, proteins, and lipids to comprehensive nutrient biomarkers to distinguish BBB impairment and CSF defined AD pathology in older adults.

Method

CSF albumin index ≥ 9.0 indicated BBB impairment. CSF p‐tau181/abeta42 ratio > 0.0779 indicated AD pathology. miRNAs were measured with the HTG EdgeSeq technology; inflammatory biomarkers with MesoScale sandwich immunoassays; mass spectrometry was used for proteomics, lipidomics, metabolomics, measurements of amino acids, hydro‐and liposoluble vitamins, fatty acids, and minerals; mass spectrometry was coupled to liquid, supercritical fluid or gas chromatography where needed. LASSO logistic regression models selected multi‐omic signatures that best classified BBB impairment and AD pathology using formal diagnostic accuracy and area under the curve (AUC) statistical criteria.

Result

Cross‐sectional analysis was conducted in 120 subjects with a mean age of 70 years, 64% were female and the mean MMSE was 27. Prevalence of BBB impairment and AD pathology was recorded in 13.5% and 35%, respectively. A blood‐based multi‐omic signature, including 1 amino acid , 1 cholesterol ester, 1 mineral, 1 pro‐inflammatory cytokine, 3 proteins and 4 miRNAs produced a diagnostic accuracy of 93% for BBB impairment (AUC of 0.96 with 95% confidence interval (CI) of 0.91‐0.99; Figure 1). Another blood‐based multi‐omic signature, including 2 amino acids, ethanolamine and a phospholipid , 2 minerals, 3 inflammatory‐specific markers, 4 other proteins, 1 miRNA , APOE4 genotype and age diagnosed AD pathology with 86% accuracy and generated an AUC of 0.92 (95% CI of 0.86‐0.96; Figure 2)

Conclusion

We identified distinct blood‐based signatures of BBB impairment and CSF biomarkers of AD pathology in a cohort of predominantly non‐demented older adults using pre‐specified outcome criteria. Multi‐omic approaches in blood can provide novel insights into mechanism and improve detection of underlying risk factors for age‐related dementia.
Mass spectrometry approaches for the selection of primary calibrators in the development of reference method
Authors: Coppens Salomé , Dubois Christelle , McCullough Bryan , Hirtz Christophe , Quaglia Milena
Published: December 2021

Background

Neurofilament‐light chain (NF‐L) is a known early marker for neurodegeneration. This marker which is essential for the axonal structure, is quantifiable in biological fluids after neuronal damage but is not specific to a given pathology. Currently, the methods for detecting/quantifying this biomarker are mainly based on immunoassays. While the performance of immunoassay‐based assays is good in term of sensitivity and precision, mass spectrometry (MS) approaches are required to achieve standardisation. Those aiding to improved characterisation/quantification of the calibrator and potential for developing a reference measurement procedure traceable to the International System of Units. Furthermore MS has the potential of multiplexing NF‐L with other specific biomarkers for dementia. The characterization and quantification of a number of primary calibrators and their suitability for harmonization of immunoassay based results and development of a reference measurement procedure is here assessed.

Method

Microwaver hydrolysis and isotope dilution MS was used for quantification of NF‐L from different manufactures. An Orbitrap mass spectrometer (Q‐Exactive, Thermofischer) was used to provide high resolution intact protein analysis information. A QQQ mass spectrometer (Xevo TQ‐XS, Waters) was utilized to assess the potential of developing a reference measurement procedure for NF‐L.

Result

The quantitative analysis of the three NF‐L by amino acid analysis (AAA) showed for all samples discrepancy between the nominal concentrations and the experimental results with a general overestimation for the nominal concentration due to water and salt contents. Separation, identification and quantification of impurities present in the preparations was attempted to obtain a total protein content from the AAA and the NF‐L content from the AAA results corrected for the impurities. The sequence of NF‐L was verified by high resolution intact protein MS and tryptic digestion. A QQQ method was developed to monitor the tryptic digest peptides and assess their suitability to be used for the development of a reference measurement procedure. This was based on specificity, limits of detection and limits of quantification.

Conclusion

These studies allow us to characterize three NF‐L proteins from different suppliers and to perform a first selection of the most relevant ones as primary calibrators for the development of a reference method.
“Nothing more will be changed here”: A qualitative study on the needs of people with dementia
Authors: Kowe Antonia , Panjaitan Hentry , Brokop Lisa , Teipel Stefan J.
Published: December 2021

Background

To prepare nursing students optimally for their future daily working life as formal caregivers of people with age‐related diseases such as dementia, the needs of this target group must be identified. We explored the needs of people with dementia based on Maslow’s need hierarchy theory to systematically identify requirements of nursing professionals as part of the project Digital Training of Nursing and Health Management (DigiCare).

Method

We conducted semi‐structured interviews with people with dementia (n = 10) and caregivers of people with dementia (n = 32). We asked for their daily routines, favoured living spaces, leisure activities and experience of care. We analysed the data with qualitative content analysis according to Mayring. Categories were formed deductively based on the need levels defined by Maslow.

Results

The survey showed that the deficiency needs (physiological needs, safety and security, love and belonging) were mostly met in people with dementia, although some respondents described that social needs were not sufficiently met. People with dementia felt loneliness caused by the loss of social contacts due to disease symptoms such as language impairment. The respondents made very ambivalent statements regarding growth needs (esteem, and self‐actualization) of people with dementia. Some people with dementia and their relatives dealt openly with the disease, others described the stigmatisation of dementia and the resulting social rejection of those affected by the disease. Dementia, but also old age in general, was a barrier to cover the need of self‐actualization. The majority of people with dementia we interviewed showed little willingness to accept external help and preferred a high degree of independence. Maintaining good health was mentioned as the most important wish for the future. The identification of further wishes was challenging, as the majority of respondents wanted to continue with their usual life without any changes.

Conclusion

Our survey suggests that people with dementia need support in particular to cover the needs for belonging, esteem, and self‐actualization. The systematic identification of needs carried out in this study can help to inform formal caregivers to deliver demand‐oriented and person‐centred care.
LANGaware: Introducing the right solution for the early detection of neurodegenerative and psychiatric diseases
Authors: Rentoumi Vassiliki , Vassiliou Evangelos , Demiraj Admir , Pittaras Nikiforos , Mandalis Petros , Alexandridou Martha , Kemp Hollie , Eleftheriou Ioanna , Danezi Maria , Hatzopoulou Maria , Kamtsadeli Vasiliki , Paliouras George , Papatriantafyllou John D
Published: December 2021

Background

There are multiple neurodegenerative diseases that directly affect speech [1]. However, its utilization as a robust indicator for cognitive impairment is under‐investigated. In many cases, mild cognitive decline progresses to a neurodegenerative disease and its detection is of utmost importance, since it is at this stage that treatment is most effective. One of our core goals is developing techniques for differentiating between patients with cognitive decline and healthy cohorts, by utilizing only speech samples [2]. Such samples are obtained from verbal elicitation tasks designed for cognitive assessment, e.g. picture descriptions and narration of everyday activities.

Method

Audio recordings from cognitive assessment tasks are fed through our platform to a Natural Language Processing and Machine Learning pipeline, employing an automatic discovery procedure of predictive salient biomarkers, to train an advanced classification system. The biomarker collection includes features that characterize voice, speech, language structure, composition and usage, and are engineered to highlight symptoms of neurodegenerative disorders. Biomarkers undergo multiple stages of filtering, processing and transformation to train and fine‐tune the final model. Diagnostic performance of the output classifier is obtained on an unseen test set, to ensure a robust generalization of the platform.

Result

Our platform utilizes the set of automatically selected, cross‐linguistic digital biomarkers to obtain sensitivity and specificity scores of 81% and 84% respectively, compared against medical expert diagnosis. The most salient biomarkers with respect to identifying our pathological cohort, relate to feature categories of Syntactic Complexity, Content Word usage, Lexical Repetition, Syntactic Errors and Function Words, with weight contributions of ∼ 16%, 14%, 13%, 12% and 11% respectively. Our platform provides additional, detailed population and patient‐based descriptive analytics to enhance transparency and explainability of the results.

Conclusion

Early detection of cognitive decline facilitates early intervention, treatment and proactive care, delaying disease progression and reducing symptom severity. We believe that our platform provides an effective solution for risk factor estimation and our findings incentivize further research into speech analysis techniques for the prediction of cognitive decline.

[1] Boschi, Veronica, et al.,Frontiers in psychology 8 (2017): 269.

[2] Vassiliki Rentoumi et al., Alzheimer's & Dementia, Wiley, volume 16, 2020.
An unexpected risk: Surgical procedures are common in patients with prion disease
Authors: Prusinski Christian C , Porter Amanda , Lazar Evelyn , Yuh Clara , Bucelli Robert C , Day Gregory S
Published: December 2021

Background

Patients with prion disease commonly present with visual, sensorimotor or gait complaints that may prompt surgical interventions for related disorders (e.g., cataracts, carpal tunnel syndrome and joint disease). To prevent iatrogenic transmission of prion disease, surgical instruments used on patients with possible prion disease must be decontaminated or decommissioned. This is only done when the diagnosis of possible prion disease is recognized by the healthcare team. We considered the frequency with which patients with definite or probable prion disease underwent surgeries within one year of the symptomatic onset of prion disease diagnosed.

Method

The Mayo Clinic’s Advanced Cohort Explorer was used to identify patients with prion disease diagnostic codes assessed since 1/1/2014 (n=296). Patients with prion disease enrolled in prospective studies of rapidly progressive dementia beginning 2/14/2015 at Washington University School of Medicine (St. Louis, MO) were also included (n=14). Charts were independently reviewed by two team members, and demographic and clinical details extracted.

Result

108 patients with probable or definite prion disease were identified, including 62 (57%) with autopsy‐ or genetically‐proven prion disease (57 sporadic, 4 familial, 1 fatal familial insomnia). The majority of patients experienced a rapidly progressive course (mean symptom‐duration 10.0±9.7 months). Twenty‐nine patients (26.9%) underwent 36 surgeries or invasive procedures using durable instruments, including 3 high‐risk procedures directly involving the central nervous system, and 13 intermediate‐ (e.g., joint replacement) and 20 low‐risk procedures (e.g., endoscopy). Surgeries were performed a median of 10.2 months before death (range: 0.8‐62.3), with 16 (44%) performed after symptom onset. Surgical operators were unaware of the diagnosis of possible prion disease in all but one case (diagnostic brain biopsy).

Conclusion

Surgeries were common in patients with prion disease in this series and were commonly performed by operators who were unaware of the diagnosis. Coordinated approaches to screening and reporting may be needed to reduce the risk of iatrogenic spread of prion disease.
Clinical phenotypes of behavioral variant frontotemporal dementia by age at onset
Authors: Fieldhouse Jay L.P.
Published: December 2021

Background

Behavioral variant frontotemporal dementia (bvFTD) is generally considered a young‐onset dementia, although late‐onset is not uncommon. BvFTD knows a large clinical variability and an age range varying from 21 to 85 years of age at onset. This heterogeneity challenges diagnostics, patient management and trial cohort design. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. We aimed to examine behavior, cognition and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic or histopathological confirmation and exclusion of positive Alzheimer’s disease biomarkers.

Method

In total, 321 patients with a clinical diagnosis of probable or definite bvFTD from the Amsterdam Dementia Cohort were included and grouped into quartiles by age‐at‐diagnosis. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory and the Geriatric Depression Scale. Cognitive functioning was assessed with a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Continuous associations of clinical features with age‐at‐diagnosis, group differences between age quartiles, and mortality risk were examined in two models (M1: unadjusted, M2: adjusted for sex).

Result

Age‐at‐diagnosis ranged between 26‐85 years and established quartiles with mean ages of 52±6, 60±2, 66±2 and 74±3 years. In the total sample, 44.2% exceeded an age of 65 years at time of diagnosis, 50% were deceased at time of analysis and mean survival time from date of diagnosis was 4±3 years. Earlier age‐at‐diagnosis was associated with more severe behavioral symptoms of primarily euphoria, apathy and depression, while later age‐at‐diagnosis was associated with more memory deficits. This was mainly explained by the youngest subgroup. Unexpectedly, mortality risk was not associated with age‐at‐diagnosis and was equal within age quartiles (Figure 1).

Conclusion

In bvFTD, symptom profile is associated with age‐at‐diagnosis. This should be taken into account with regard to diagnostics, patient management and trial design. Furthermore, our findings suggest that late disease onset and memory deficits are more frequent in bvFTD than generally thought.
Associations between late‐life cardiometabolic risk factors and dementia
Authors: Ren Dianxu , Lopez Oscar L , Lingler Jennifer H , Conley Yvette
Published: December 2021

Background

Late‐life cardiometabolic risk factors (overweight/obesity, hypertension, hypercholesterolemia, and diabetes) have been inconsistently reported to associate with dementia, with both increased and decreased risks. The purpose of this study was to examine such associations with incident dementia using the large national dataset from National Alzheimer’s Coordinating Center (NACC).

Method

We used NACC dataset from 2005 to December 2020 and restricted our analysis to patients who were 65 years and older at initial visit, had an APOE genotype available, first visit with dementia free and had a minimum of one follow‐up visit. The cardiometabolic risk factors were measured at initial visit. Piecewise multivariable Cox proportional hazard models accounting for non‐proportional hazards were performed to examine the associations of the 4 cardiometabolic risk factors with incident dementia, controlling for age, gender, race, education and APOE genotype. Adjusted hazard ratio (aHR) and 95% confidence interval (CI) were reported.

Result

For the defined cohort (N=13,068), mean age at enrollment was 74.9 years, participants were more female (59%), and non‐Hispanic white (76.9%). Over an average of 4.8 years follow‐up, 2817 (21.6%) developed dementia. Both diabetics and hypertension demonstrated the increased risk of dementia compared to non‐diabetics (aHR=1.26, 95% CI (1.12, 1.41), P<0.0001), and to non‐hypertension (aHR=1.09, 95% CI (1.01, 1.19), P=0.026). However, hypercholesterolemia was not associated with dementia (aHR=1.03, 95% CI (0.95, 1.11), P=0.65). Differential BMI effects on incident dementia were observed over the length of follow‐up before dementia diagnosis. During the time of 0‐4 years and 4‐8 years before dementia, increased BMI significantly associated with reduced risk of dementia [aHR=0.96, 95% CI (0.95‐0.97), P<0.001; aHR=0.98, 95% CI (0.96‐0.99), P=0.016], and no effect during the time of 8‐12 years (aHR=0.99, 95% CI (0.96‐1.02), P=0.54). However, for the time longer than 12 years before dementia, higher BMI exhibited a trend of increased risk of dementia (aHR=1.05, 95% CI (0.99‐1.10), P=0.08).

Conclusion

Our analyses showed baseline diabetes and hypertension in late‐life are associated with dementia. The BMI‐dementia association likely attribute to a harmful effect of higher BMI with the onset of dementia over a long follow‐up and a potential reverse‐causation effect when the follow‐up is short.
Concordance and diagnostic accuracy between Innotest and two fully automated platforms: Elecsys and Lumipulse
Authors: Ortega Ricard López , Dakterzada Faride , Arias Alfonso , Llena Iolanda Riba , Julián Maria Ruiz , Huerto Raquel , Tahan Nuria , Piñol‐Ripoll Gerard
Published: December 2021

Background

Manual ELISA assays are the most commonly used methods for quantification of CSF AD biomarkers; however, they show inter‐ and intra‐laboratory variability. We compared the Innotest ELISA method with two fully automated platforms (Lumipulse and Elecsys) to determine whether these new methods can provide effective substitutes for ELISA assays.

Method

We included 149 males and females with AD (n = 34), MCI (n = 94) and non‐AD dementias (n = 21). Aβ42, T‐tau, and P‐tau were quantified using the ELISA method (Innotest, Fujirebio Europe), CLEIA method on a Lumipulse G600II, and ECLIA method on a Cobas e 601 instrument.

Result

We found a high correlation between the three methods. Both Lumipulse and Elecsys methods were highly concordant with clinical diagnoses, and the combination of Lumipulse Aβ42 and P‐tau had the highest discriminating power (AUC 0.915, 95% CI 0.822–1.000). The use of Aβ42/Aβ40 ratio instead of Aβ42 alone in AT(N) classification enhanced the diagnostic accuracy (AUC 0.798, 95% CI 0.649–0.947 vs AUC 0.778, 95% CI 0.617–0.939). Finally, the biomarker ratios (P‐tau/Aβ42 and T‐tau/Aβ42) were more consistent with the Aβ42/Aβ40 ratio for both Lumipulse and Elecsys methods, and Elecsys P‐tau/Aβ42 had the highest consistency with amyloid pathology (AUC 0.994, 95% CI 0.986–1.000 and OPA 96.4%).

Conclusion

The Lumipulse and Elecsys CSF AD assays showed high analytical and clinical performances so their use is recommended for the measurement of CSF AD biomarkers compared with unstandardized manual methods.
Influencing factors and strategies to support communication between older adults with dementia and caregivers throughout the care trajectory
Authors: Zwakhalen Sandra , Bormans Kasper
Published: December 2021

Background

Communication is an essential aspect of life and caregiving. However it is often taken for granted although ccommunication between older adults with dementia and their carers is often extremely challenging. Effective communication is essential to provide relationship centered care and tailor care to patients needs.

Objectives

We aimed to determine factors that influence communication in older adults’ with dementia and their caregivers’ and explored strategies to enhance communication that could be supportive throughout the care trajectory.

Design and methods

Factors that impact communication between older adults with dementia and caregivers were determined by using a scoping review and included a thematic analysis of the literature. These determined factors were validated using a large variety of video observations and additional qualitative interviews (n=15). To determine strategies that could be beneficial to improve communication, communication strategies were determined. To determine these strategies existing literature of other expertise areas (including marketing and communication science) was used and think a‐loud sessions with experts were performed.

Results

The scoping review revealed that factors that can affect caregivers' communication with older adults with dementia relate to the older adult, the caregiver and the context of the caregiving situation / environment, and the interactions between these factors. Observations confirmed that most influencing factors were related to the caregivers including for example non‐verbal behaviour. However contextual factors (e.g. organization of care, and care situation) were less observed although these may offer opportunities to enhance the communication. Strategies identified from other fields (f.i. social psychology and consumer behaviour research) were included for example compliance‐without‐pressure‐techniques.

Conclusions

This study gained important insight into influencing factors on communication between older adults with dementia and their caregivers. Strategies as ‘The‐foot‐in‐the‐door’, verbal mimicry and ‘The illusion of choice’ could support communication throughout the care trajectory and are provide useful insights, which are not always taken into consideration in current practice. This information can be used for developing solid interventions to support communication and enhance relationship centred care in accordance to the older adults needs.
Reaching the unengaged: Conversations about dementia risk reduction
Authors: Fair Hannah , Doherty Kathleen , Eccleston Claire , Klekociuk Shannon Z , Farrow Maree
Published: December 2021

Background

The Preventing Dementia Massive Open Online Course (PD‐MOOC) aims to increase public knowledge of dementia risk factors and promote risk‐reducing behaviour. This course attracted 147,000 enrolments from 2016 to 2020. Men and people with low levels of education are under‐represented in the PD‐MOOC. This study investigated whether members of these under‐engaged groups receive dementia risk information “second‐hand” from close contacts who undertake the PD‐MOOC.

Method

In May 2020, first time PD‐MOOC enrolees from Tasmania, Australia, provided qualitative and quantitative data about the people they felt very close or somewhat close to. Participants were retrospectively asked about conversations in which information from the PD‐MOOC was discussed. Two‐proportions z‐tests were used to determine the extent to which “second‐hand” information reached under‐engaged groups.

Result

Participants (n = 37) provided information about 799 close contacts; networks ranged in size from 8 to 45 people. Participants reported sharing dementia risk information with between 0 and 100% of their close contacts. Overall, information was shared with 437 close contacts. The proportion of men with whom dementia risk information was shared was significantly higher than the proportion of men directly receiving such information via the May 2020 PD‐MOOC (24% vs 15%, p<0.001). The proportion of people with a low level of education (less than high school completion) with whom dementia risk information was shared was significantly higher than the proportion of people with a low level of education directly receiving such information via the May 2020 PD‐MOOC (12% vs 1%, p<0.001). Some participants reported that some of the close contacts with whom they discussed dementia risk were unlikely to engage in dementia risk education themselves: “[my friend] said ‘…well you can tell me about it … after you've done it’ ‐ they weren't prepared to do the course”.

Conclusion

Interpersonal conversations increase the reach of dementia risk information, reaching people and demographic groups that are less likely to engage with interventions like the PD‐MOOC. Interpersonal conversations about dementia risk reduction could potentially be promoted to help reach important target populations for dementia prevention.
Do individuals skimp on health care after spouse’s dementia diagnosis? An analysis of spillover effects of dementia
Authors: Chen Yi
Published: December 2021

Background

Dementia burden imposed on family members are generally recognized as the value of caregiving time. This may understate the full impact of dementia on families if 1) dementia affects family members who are not caregivers, and 2) impacts are beyond loss of time. Considering the shocks in financial resources, time, and emotion ensuing spouse’s dementia diagnosis, individuals may ration needed health care, which in the long run will elevate downstream health care costs. However, evidence for such negative externality is limited and inconclusive. This study aims to examine the impact of spouse’s dementia onset on individual’s health care utilization.

Method

Using Health and Retirement Study linked to Medicare claims, I identified 691 older adults whose spouses had incident dementia during 1992 to 2011, and matched them to 5,073 controls whose spouses were dementia‐free. A fixed effects model was employed to compare their use of flu shot and doctor visit for managing chronic conditions, during one year before and after the index date. Other covariates included time‐varying caregiving roles, health, wealth, spouse’s function, as well as their interaction with spouse’s dementia status.

Result

After adjustment, spouse’s dementia onset was associated with a 3.5‐percentage‐point increase in the likelihood of flu shot uptake. Effects of spouse’s dementia diagnosis did not vary by caregiving or health status. For those with pre‐existing chronic conditions, having a spouse with newly diagnosed dementia predicted more doctor visits. Conditional on transitioning into caregiving (caregiverpre=0 & caregiverpost = 1), spouses of people living with dementia (PLWD) have a marginally higher risk of reducing doctor visits than controls (p=0.053).

Conclusion

There lacks evidence for rationed health care after spouse’s dementia incidence, at least from 1‐year pre‐index to post‐index period. The greater tendency of forgoing regular office visits after the onset of caregiving tasks among spouses of PLWD highlights potential strains in seeking care facing this group. Dementia burden on family are more profound and complex than deprivation of time.
AHEAD 3‐45 study: Preliminary screening and baseline characteristics from a placebo‐controlled, double‐blind study evaluating lecanemab in participants with preclinical Alzheimer’s disease and elevated (A45 trial) and intermediate (A3 trial) amyloid
Authors: Zhou Jin , Irizarry Michael C , Kramer Lynn D , Swanson Chad J , Roberts Claire , Dhadda Shobha , Li David JianJun , Rabe Martin , Krause Stephen , Raman Rema , Donohue Michael C , Sethuraman Gopalan , Johnson Keith A. , Sperling Reisa A. , Aisen Paul S
Published: December 2021

Background

Amyloid beta (Aβ) accumulation begins 10‐20 years before the onset of cortical tauopathy, neurodegeneration, and clinical symptoms in Alzheimer’s disease. Lecanemab (BAN2401), a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ (ie, oligomers, protofibrils), reduced amyloid on PET and slowed cognitive decline in a phase 2 study in early Alzheimer’s disease. AHEAD 3‐45 is evaluating lecanemab treatment in cognitively normal (CN) individuals to determine if very early intervention can prevent pathological progression and cognitive decline prior to significant irreversible neurodegeneration. This study is conducted as a Public‐Private Partnership of the Alzheimer’s Clinical Trial Consortium (ACTC), National Institutes of Health (NIH), and Eisai Inc.

Method

AHEAD 3‐45 consists of two trials (A3 and A45) with distinct dosing regimens tailored to baseline brain amyloid levels. Both individual trials are conducted under a single protocol, screening process, and common schedule of assessments. In the A3 Trial, approximately 400 CN participants with intermediate amyloid (approximately 20‐40 centiloids) who are at risk for further amyloid accumulation will be randomized 1:1 to placebo or lecanemab, with infusion every 4‐weeks . In the A45 Trial, approximately 1000 CN participants with elevated amyloid (>40 centiloids) who are at risk for cognitive decline will be randomized 1:1 to placebo or lecanemab, with infusions initially biweekly then every 4‐weeks. The primary outcome measures are brain amyloid accumulation by amyloid PET (A3) and the Preclinical Alzheimer’s Disease Cognitive Composite 5 (PACC5) scale (A45), both at 216 weeks.

Result

As of January 19, 2021, 194 participants were screened, and 20 participants were randomized into A3 (2) and A45 (18). Overall, 37% of participants (n=109) who completed amyloid PET are eligible for A3 (n=10) and A45 (n=30) based on amyloid level. Initial screening and baseline characteristics data will be presented. Preliminary results of PET eligibility across the two trials appear consistent with projections based on existing observational data (ADNI and HABS).

Conclusion

The initial experience with screening and randomization from the AHEAD 3‐45 Study suggests it is feasible to identify participants across the continuum of preclinical Alzheimer’s disease, who are at‐risk for amyloid accumulation and cognitive decline, for disease modifying treatment trials.
The impact of age, sex, and genetics on the relationship between objectively measured habitual physical activity and brain volume: A cross‐sectional UK Biobank study
Authors: Brown Belinda M , de Frutos Jaisalmer , Porter Tenielle , Vacher Michael , Laws Simon M
Published: December 2021

Background

Grey matter atrophy occurs as a function of ageing and is accelerated in neurodegenerative conditions, such as dementia. Previous research suggests higher physical activity is associated with larger grey matter volumes; however, there appears to be individual variability in this association. Understanding factors that can affect the relationship between physical activity and brain volume will enable identification of individuals that gain the greatest neural benefits from physical activity.

Method

Data from 10,084 men and women (aged 50+ years) of the UK Biobank were used to examine: 1) the relationship between actigraphy‐measured habitual physical activity and brain volume; and 2) whether the relationship between objectively‐measured physical activity and brain volume is moderated by age, sex, BDNF Val66Met, or APOE ε4 allele carriage. All participants underwent a magnetic resonance imaging scan to quantify grey matter volumes, activity monitoring, and genotyping.

Result

Physical activity was associated with larger total grey matter volume (B = 0.14, p = 0.001) and right hippocampal volume (B = 1.45, p = 0.008). The physical activity*sex interaction was significant for cortical grey matter (B = 0.22, p = 0.003), total grey matter (B = 0.30, p < 0.001), and right hippocampal volume (B = 3.62, p = 0.001). A relationship between physical activity and brain volume was observed in males only (cortical grey matter volume, B= 0.13, p = 0.01; total grey matter volume, B=0.23, p < 0.001; and right hippocampal volume, B = 2.29, p = 0.008). No other moderating factors of the physical activity and brain volume relationship were identified.

Conclusion

Our results indicate that in males, but not females, an association exists between habitual physical activity and brain volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of sex‐effects on the relationship between physical activity and brain volume.
Recruitment and retention of culturally diverse older adults into aging research: Investigation planning to explore intergenerational influence
Authors: Gaillard Trudy , Neff Donna Felber , Webb Fern J
Published: December 2021

Background

African American [AA], Latino/Hispanic [LH], and Caribbean [CN]) older adults remain underrepresented in aging clinical research, leading to a knowledge gap regarding best treatments for these populations. Studies have found that culturally diverse older adults often consult family members when making healthcare treatment decisions. However, family members’ involvement when recruiting AA, LH and CN populations into health research studies is relatively unexplored as a potential recruitment strategy. The overall purpose of this research is to understand how intergenerational influence (IGI) – defined as the influence of one generation on another in terms of the transfer of skills, attitudes, preferences, values, and behaviors – can be leveraged to recruit and retain culturally diverse older adults into aging research.

Methods

Specific aims are to 1) explore IGI among 360 AA, CN and LH adults 2) test messages in key markets and 3) enroll 3,000 AA, CN and LH adults > 65 into a statewide health registry. To start, we established the infrastructure to conduct this research: organize a tri‐institutional team developing materials to conduct mixed methods (focus group guides; surveys) to answer specific aim 1; establish a statewide governing council; recruit a qualitative team; and obtain approval from the lead Institution’s Ethics Review Board.

Result

Our tri‐institutional team comprises researchers from various disciplines who created focus group guides, survey materials, and online tools for use with focus group participants (Specific Aim 1). We have also established the Florida Statewide Governance Aging (FL‐SAGE) Council consisting of 25‐members throughout Florida, who will inform all aspects of this research. We have also recruited 12 facilitators who have conducted qualitative work with our populations of focus, AA, CN and LH older adults. Another aspect of this tri‐institutional collaboration is the ability to achieve ethics approval from one institution, allowing for more concise monitoring.

Conclusion

We hope to demonstrate that our IGI model can be leveraged as an additional strategy to recruit and retain culturally diverse older adults into aging research. Before that, we recognize the significance of establishing a sound infrastructure to conduct this work. We hope our findings will assist other researchers working with diverse populations.
The Engaging Communities of Hispanics for Aging Research (ECHAR) Network
Authors: Medina Luis D
Published: December 2021

Background

Hispanics/Latinos (H/Ls) comprise 18% of the U.S. population but only about 5% of NIH‐funded Alzheimer’s disease research participant samples. Exclusion of this ethnic group – the largest in the U.S. – limits our interpretation or research findings and understanding of the causes of disparities. The Engaging Communities of Hispanics for Aging Research (ECHAR) Network is a collaborative, transdisciplinary network aimed at engaging, educating, and motivating H/Ls for participation in AD/ADRD research by addressing several barriers to inclusion, including health literacy and AD/ADRD‐related communication. In addition to improving H/L recruitment that will allow us to better examine AD/ADRD health disparities, ECHAR contributes to the development of inclusion science.

Method

Relying on a community‐engaged approach, ECHAR employs a novel method – Boot Camp Translation (BCT) – to translate medical jargon into action‐based, community relevant messages. Over the course of several months, community stakeholders work closely with the research team to develop AD/ADRD communication that is more effectively consumed by local communities. An additional objective of ECHAR is to invite BCT participants to form local community advisory boards (CABs). By joining the research infrastructure, CAB members help develop and guide effective strategies to further improve community relations and inclusion.

Result

We have three established research teams in metropolitan areas with large H/L populations (Houston, TX; Denver, CO; Las Vegas, NV) carrying out BCTs in each of these cities throughout this year. Building off prior work from our group, the BCTs will help answer two questions: (1) What are key messages about AD/ADRD that are locally relevant to these communities? (2) How do we best disseminate these messages to local communities? Our work thus far has demonstrated a need for locally tailored messaging and strategies for dissemination (i.e., precision recruitment).

Conclusion

The ECHAR Network aims to (1) establish CABs and train them on AD/ADRD in three cities; (2) develop key, culturally‐informed, AD/ADRD‐related materials as well as dissemination and evaluation strategies for H/L recruitment; and (3) develop sustainable research infrastructure to enhance outreach by supporting health disparities investigators and pilot grants. This approach is a first of its kind in the context of H/Ls and AD/ADRD recruitment.
A pilot study of social and structural determinants of health (SSDOH) measures in an Alzheimer’s Disease Research Center (ADRC) cohort
Authors: Midgett Sharnita , Mechanic‐Hamilton Dawn , Karlawish Jason , Wolk David A , Stites Shana Dh
Published: December 2021

Background

Research shows that people have different experiences, opportunities, and challenges depending on their background and life circumstances. These circumstances can be important social and structural determinants of health (SSDoH) that may help explain heterogeneity in cognitive, functional, and interventional outcomes in Alzheimer’s disease and related dementias (ADRDs). The National Institute on Aging has set as a priority understanding the effects of SSDoH. This information may help elucidate disease mechanisms and modifiers as well as aid discovery of disease modifying treatments that are effective across diverse populations.

Method

A battery of SSDoH measures was constructed based on instrument content relevance and psychometric properties. The battery is being pilot tested in a diverse cohort of older adults. We will report the results of that pilot testing.

The battery consists of self‐report measures in 6 categories: (1) Education: highest grade or academic level completed, (2) Occupation: occupational cognitive requirements score (OCRS) and occupation description, (3) Economic Status and Strain: financial strain (2‐item mean index), total economic problems (7‐item inventory, range: 0–7) and Agency for Healthcare Research and Quality (AHRQ) socioeconomic status index, (4) Subjective Stress: Everyday Discrimination Scale (EDS), Perceived Stress Scale (PSS), self‐report primary caretaker well‐being, and the Social Deprivation Index (SDI), (5) Early Life Stressors: parental stressors (3‐item mean index), parental educational involvement (2‐item mean index), hunger (1 item), and parental/caregiver education, occupation and health status during participant’s childhood (3 items), (6) Subjective Social Support and Status: Social Network Index (SNI) and the MacArthur Scale of Subjective Social Status. Sociodemographic data collected includes self‐report of age, race, and sex, orientation, gender and identity (SOGI) questions. Collection of race data is based on National Institutes of Health (NIH) standards.

Result

We describe the results of pilot testing of SSDoH measures in the Penn ADRC UDS cohort, including return rates, participant experience, and other measures of feasibility and usefulness.

Conclusion

We discuss the feasibility of routinely collecting SSDoH data in an ADRC research cohort. We describe factors to consider when selecting modules to implement in standing cohorts and options for adapting the SSDoH module‐based battery to a range of research cohorts.
Older adults with Alzheimer’s disease exhibit an altered relationship between plasma sTREM2 and inflammatory markers
Authors: Weber Grace E. , Khrestian Maria , Tuason Elizabeth D. , Shao Yvonne , Pillai Jagan A. , Rao Stephen M. , Feng Hao , DeSilva Tara M. , Stauffer Shaun , Leverenz James B. , Bekris Lynn M.
Published: December 2021

Background

Alzheimer’s disease (AD) is the 6th leading cause of death in the US, and currently lacks a blood‐based biomarker for early detection. Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune regulator shown to be protective against AD; a soluble form (sTREM2) circulates in peripheral blood and is a potential indicator of disease progression. Genetic variants of TREM2 are risk factors for AD and other neurodegenerative diseases. Multiple studies also have reported an altered peripheral immune response in AD. However, little is known about the relationship between plasma sTREM2 and the altered peripheral immune response in AD. Our objective was to examine the relationship between sTREM2 and inflammatory markers in a spectrum of older adults including cognitively normal (CN) controls, amnestic mild cognitive impairment (MCI) and AD. The hypothesis of this exploratory study was that TREM2‐related inflammatory activity is a stage specific (MCI or AD dementia) biomarker of AD.

Method

Stages of AD progression were characterized based on symptoms, designated in our study as CN controls, MCI, and AD. Alternatively, CSF amyloid beta, phosphorylated tau and total tau were measured, as described by the NIA‐AA Research Framework “ATN continuum”. Our study aims were to (1) define the relationship between sTREM2‐related inflammatory activity and AD clinical diagnosis, and (2) characterize sTREM2‐related inflammatory activity within the ATN continuum. Plasma sTREM2 and 38 cytokines were measured using the Luminex platform.

Result

We investigated this hypothesis in an exploratory cohort of CN, MCI, and AD subjects. We observed differential plasma sTREM2 and cytokines levels, correlations, and patterns across both AD groups defined by symptoms and the ATN continuum. This suggests the existence of alteration in normal peripheral sTREM2‐related inflammatory activity along AD and ATN stages.

Conclusion

These data provide important support to the hypothesis that TREM2‐related inflammatory activity is a stage specific biomarker of AD progression. Our results provides the groundwork for future functional investigation and therapeutic strategy research.