bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher levels of the astrocytic marker CSF YKL40 are associated with better memory performance only in amyloid‐positive individuals with subjective cognitive decline
Authors: Sánchez‐Benavides Gonzalo , Milà‐Alomà Marta , Suarez‐Calvet Marc , Brugulat‐Serrat Anna , Grau‐Rivera Oriol , Arenaza‐Urquijo Eider M , González‐de‐Echávarri José Maria , Minguillón Carolina , Fauria Karine , Salvadó Gemma , Shekari Mahnaz , Operto Greg , Cacciaglia Raffaele , Falcon Carles , Kollmorgen Gwendlyn , Suridjan Ivonne , Molinuevo Jose , Zetterberg Henrik , Blennow Kaj , Gispert Juan Domingo ,   ALFA Study
Published: December 2021

Background

It is not clear whether neuroinflammation is a detrimental or a compensatory mechanism in Alzheimer’s disease (AD). Recent evidence suggests that increased levels of YKL40 are related to better memory performance in cognitively unimpaired older individuals with memory complaints. In this study, we aimed i) at replicating these previous findings and ii) extending to other markers by exploring the relationship between cognitive performance and cerebrospinal fluid (CSF) biomarkers of astrocytic (YKL40, GFAP and S100) and microglial (sTREM2) neuroinflammation‐related activation, and to explore whether this association is further modulated by amyloid status and presence of subjective cognitive decline (SCD) in a middle‐aged cohort of cognitively unimpaired individuals.

Method

We included data from 392 individuals from the ALFA+ cohort (mean age 61 years). CSF measures of amyloid pathology (Aβ42/40) pathology and YKL‐40, GFAP, S100 and sTREM2, were analyzed with the exploratory Roche NeuroToolKit assays, a panel of automated robust prototype immunoassays. Individuals were classified as amyloid positive (A+) or negative (A‐) using the Aβ42/40=0.071 cut‐off and as SCD or non‐SCD using the SCD‐Questionnaire. Memory and Executive cognitive composites were used as dependent variables in linear models using CSF biomarkers with covariates (age, sex, education) as predictors. Interaction terms with biomarker*Amyloid status*SCD status were also modeled.

Result

One hundred and thirty‐five individuals (34.4%) were A+ and 107 (27.3%) displayed SCD (Table 1). For Memory composite we found significant interactions for YKL40*Amyloid*SCD (p=0.04) and sTREM2* Amyloid *SCD (p=0.03). In stratified analyses by Aβ and SCD we observed that Memory performance was positively associated with YKL40 in Aβ+ that also display SCD (n=39, p=0.019, Figure 1). No significant associations were found in stratified analysis with sTREM2 (neither by Amyloid nor by SCD status). For GFAP and S100, no associations were observed nor for any analysis with the Executive composite.

Conclusion

Astrocytic (YKL40), but not microglial (sTREM2), activation was associated with better memory performance in those cognitively unimpaired individuals with evidence of Alzheimer’s pathophysiological changes and subjective cognitive decline. Thus, some specific neuroinflammation may be beneficial at the end of the AD preclinical stage, in which subjective SCD arise.
The association between diet in mid‐life and dementia incidence over a 20‐year period
Authors: Glans Isabelle , Sonestedt Emily , Nägga Katarina , Gustavsson Anna‐Märta , Stomrud Erik , Melander Olle , Nilsson Peter , Palmqvist Sebastian , Hansson Oskar
Published: December 2021

Background

Modifiable risk factors account for 40% of worldwide dementias. A potential modifiable risk factor for dementia and cognitive impairment is diet. However, there are conflicting results and methodological weaknesses in previous studies. The aim of this study was to investigate whether midlife diet quality is associated with subsequent risk of developing all‐cause dementia, Alzheimer’s disease (AD) or vascular dementia (VaD). In addition, the association between diet quality and future accumulation of β‐amyloid (Aβ) in cerebrospinal fluid (CSF) was examined.

Method

Baseline examination within the Swedish population‐based Malmö Diet and Cancer Study (MDCS) took place between 1991‐1996 on 30,447 middle‐aged individuals. Participants from the MDCS with complete baseline dietary examination were included in this study (n=28,027) and the follow‐up for incident dementia took place until December 31, 2014. Diagnoses were collected from the Swedish National Patient Register and validated by Memory Clinic physicians. CSF Aβ42 was available in a sub‐population (n=777). Information on dietary habits was gathered through a 7‐day food diary, a detailed food frequency questionnaire and a one‐hour interview. A diet quality index was calculated from adherence to nutrition recommendations of intake of dietary fibre, added sugar, fish and shellfish, fruit and vegetables and red and processed meat (0‐5 points, poor to good). Cox proportional hazard models were used to examine associations between diet and risk of developing dementia adjusted for age, sex, education, total caloric intake and season.

Result

During a median of 19.8 years of follow‐up, 1,943 (6.9%) participants were diagnosed with dementia. Individuals adhering to diet recommendations did not lower the risk of developing all cause dementia (HR 0.98, 95% CI 0.95‐1.02), AD (HR 0.99, 95% CI 0.95‐1.04) or VaD (HR 0.98, 95% CI 0.91‐1.06). No significant association was found between diet score and abnormal Aβ accumulation measured with CSF Aβ42 (OR 1.10, 95% CI 0.66‐1.84),

Conclusion

: In this long‐term prospective cohort study, adherence to dietary recommendations for fibre, sugar, fish, fruit and vegetables and red and processed meat was not significantly associated with subsequent reduced risk for developing all‐cause dementia, AD or VaD.
Age‐dependency of total tau in the cerebrospinal fluid is corrected by amyloid‐beta 1‐40: A correlational study in healthy adults
Authors: Zebhauser Paul Theo , Berthele Achim , Franz Marie‐Sophie , Goldhardt Oliver , Diehl‐Schmid Janine , Priller Josef , Ortner Marion , Grimmer Timo
Published: December 2021

Background

Tau‐proteins are established biomarkers of neuroaxonal damage in a wide range of neurodegenerative conditions. Although measurement of total‐Tau (t‐Tau) in the cerebrospinal fluid (CSF) is widely used in research and clinical settings, the relationship of age and t‐Tau in the CSF is not yet fully understood. While a small number of studies reported a correlation between age and t‐Tau in the CSF of healthy adults, in clinical practice the same cut‐off‐value is used independently of patient’s age.

Method

To further explore the relationship between age and t‐Tau in the CSF and to disentangle neurodegenerative from drainage‐dependent effects in normal aging, we analyzed CSF‐samples of 83 carefully selected cognitively healthy adults and included amyloid‐beta 1‐40 (Aβ40) as a putative marker of drainage from the brain’s interstitial system in our analyses.

Result

We found a significant correlation of t‐Tau and age, which was no longer present when correcting t‐Tau‐ for Aβ40‐concentrations.

Conclusion

These findings were replicated under varied inclusion criteria and call into question the reported association of age and t‐Tau in the CSF. Furthermore, they suggest diagnostic utility of Aβ40 as a possible proxy for drainage‐mechanisms of peptides into the CSF when interpreting biomarker concentrations in the context of neurodegenerative disease.
Presence of endogenous Aβ in plasma of patient with Alzheimer’s disease differentiates Aβ oligomerization tendencies caused by synthetic Aβ
Authors: Choi Youngki , Yu Ji Sun , Joh Yechan , Kang Sungmin , Youn Young Chul , An Seong Soo , Kim Sangyun
Published: December 2021

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. A number of studies have presented accumulating evidence that oligomeric amyloid‐β (Aβ) is the major factor in the AD pathogenesis. To detect oligomeric Aβ, Multimer Detection System‐Oligomeric Amyloid‐β (MDS‐OAβ), a technique for measuring Aβ oligomerization in plasma to diagnose AD was previously developed. In this study, In this study, we aim to evaluate the role of the seeding effect in plasma in differentiating between AD and individuals without AD pathology.

Method

Plasma was spiked with synthetic Aβ peptides and incubated to confirm the tendency of Aβ oligomerization in AD samples and samples without AD pathology. AlphaLISA assay was performed in comparison with MDS‐OAβ to confirm the relationship between endogenous Aβ and spiked synthetic Aβ peptides in plasma. In addition, Aβ immuno‐depletion in plasma confirmed the effect of synthetic Aβ peptides on the Multimer Detection System (MDS) signals.

Result

The difference in the seeding effect between AD plasma and normal control plasma was confirmed. AlphaLISA assay presented that synthetic Aβ peptide recruits endogenous Aβ in plasma and the seeding effect is significantly increased in AD plasma than normal control plasma. In addition, the absence of the MDS signals in Aβ‐depleted plasma supported that the increased oligomerization tendency in AD plasma is dependent on the presence of endogenous Aβ in plasma. MDS‐OAβ can differentiate between AD patients and non‐AD controls by measuring the degree of Aβ oligomerization after spiking synthetic Aβ into plasma samples with incubation.

Conclusion

Spiking of synthetic Aβ peptides had a greater seeding effect in AD plasma than in normal control plasma. Therefore, the measurement of Aβ oligomerization in plasma using MDS‐OAβ has high utility in AD diagnosis.
Why don’t Alzheimer’s disease patients know that they forget?
Authors: Razafimahatratra Solofo , Guieysse Thomas , Medani Takfarinas , Lejeune François‐Xavier , Houot Marion , George Nathalie , La Corte Valentina , Klarsfeld André , Dreyfus Gérard , Pantazis Dimitrios , Dubois Bruno , Andrade Katia
Published: December 2021

Background

Alzheimer’s disease (AD) patients are often unaware of their memory deficits even at early stage of disease. Anosognosia has been related to frontal dysfunction although its underlying neural mechanism is still unknown. We hypothesized that it may result from an inability to monitor ongoing behavior due to a failure in the error‐monitoring system. Our main objective was to study this system in individuals at risk for AD.

Method

The study involved the 318 cognitively normal individuals of the INSIGHT cohort. All were age 70 and over at entry with a known brain amyloid status assessed by PET. We recorded the error negativity (ERN) and error positivity (Pe) of event‐related potentials (ERPs) in each of these individuals annually over 5 years. The cognitive task was the recognition of words, which had been memorized one hour before. ERPs were obtained by averages that were time‐locked to the erroneous response. All differences were tested through linear mixed‐effects models with group (Prog A+, NotProg A+; i.e., amyloid positive individuals who progressed or not to AD) and time (M0, M60, or Mdiag; i.e., months from study admission or month of AD diagnosis), as well as interaction between both as fixed effects, the subject identifier as a random effect to account for the paired measurements at M0 and M60 or Mdiag, and inclusion of age at M0 for covariate adjustment. Post hoc tests were performed on the interaction.

Result

Our study focused on two subgroups identified after 5 years of follow‐up: 1) amyloid positive (A+) individuals who progressed to AD (Prog A+, n=15); and 2) A+ individuals who did not progress to AD (NotProg A+, n=35). When compared to M0 for intragroup analysis or to M60 for intergroup analysis, the Prog A+ group at Mdiag displayed significantly slower reactions and higher error rates, and its Pe amplitude was also significantly lower.

Conclusion

Our results indicate the existence of a monitoring system failure in early stages of AD, which may be the substrate of anosognosia.
Age‐dependent functional connectivity changes across large‐scale brain networks disrupt memory consolidation processes
Authors: Fassbender Ronja V. , Risius Okka , Dronse Julian , Nellessen Nils , Richter Nils , Fink Gereon R. , Kukolja Juraj , Onur Oezguer A.
Published: December 2021

Background

Episodic memory decline characterizes “normal” aging but is also a core symptom of Alzheimer’s disease. Therefore, considerable efforts have been undertaken to study this memory domain and its neural substrates. Recent studies have mainly focused on encoding‐ and retrieval‐ related processes. However, some findings suggest that episodic memory deficits are at least in part due to impaired consolidation processes.

Methods

We investigated age effects on consolidation‐related functional network changes and their vulnerability to cognitive interference, using fMRI data of 13 young (20–30 years) and 16 senior (49–75 years) participants. FMRI scanning was performed prior to and during a spatial memory paradigm, consisting of encoding, consolidation, and retrieval phases. To ensure that the observed connectivity changes were due to consolidation processes, the consolidation phase was manipulated over two sessions: (1) no manipulation and (2) repeated stimulus‐presentation with interfering spatial context information.

Results

We compared the fractional amplitude of low‐frequency fluctuations (fALFF) to analyze spontaneous brain activity changes from pre‐ to post‐encoding rest. In the control condition, fALFF decreased within left supramarginal gyrus (SMG), right middle temporal gyrus (MTL), and left precuneus (Pc), whereas, fALFF increased within parts of the occipital and inferior temporal cortex. To evaluate the integration in large‐scale brain networks, connectivity analyses between the fALFF‐derived seeds and network ROIs were performed. We observed significant coupling between consolidation‐related brain regions and large‐scale brain networks during consolidation, with connectivity between the SMG and large parts of the memory network modulated by aging. There was also a disruptive effect of interference on connectivity between the Pc and parts of the salience network. Of particular importance for successful consolidation, however, is the connectivity between parts of the occipital lobe, the inferior and middle temporal gyrus. Connectivity within this network, which corresponds to the ventral visual stream, may predict subsequent memory performance. The predictive value appears to be higher in young than in seniors.

Conclusion

Our results support the assumption that age‐related memory decline is at least partly caused by impaired consolidation processes. We showed that consolidation requires a complex interplay between large‐scale brain networks, which is partially disrupted by aging and thus becomes insufficient.
Association of body mass index with brain structure and biomarkers of inflammation in cognitively unimpaired middle‐aged adults with and without evidence of β‐amyloid pathology
Authors: Grau‐Rivera Oriol , Sala‐Vila Aleix , Operto Greg , Garcia Marina , Arenaza‐Urquijo Eider M , Suarez‐Calvet Marc , Sánchez‐Benavides Gonzalo , Milà‐Alomà Marta , González‐de‐Echávarri José Maria , Minguillón Carolina , Suridjan Ivonne , Kollmorgen Gwendlyn , Molinuevo Jose , Zetterberg Henrik , Blennow Kaj , Gispert Juan Domingo ,   ALFA Study
Published: December 2021

Background

Obesity has been linked to brain atrophy and peripheral inflammation. However, the association between body mass index (BMI) and brain structure can be confounded by Alzheimer’s disease (AD) pathology‐related weight loss, and its association with neuroinflammation remains unknown. We explored associations of BMI with brain structure and biomarkers of peripheral and central nervous system inflammation in cognitively unimpaired middle‐aged adults with and without evidence of β‐amyloid (Aβ) pathology.

Method

We analyzed data from 385 ALFA+ study participants. We measured plasma C‐reactive protein (CRP), CSF p‐tau and t‐tau with the Elecsys® immunoassays and CSF Aβ42, Aβ40 and neuroinflammation biomarkers (sTREM2, GFAP, YKL40, S100 and IL6) with the exploratory Roche NeuroToolKit robust prototype assays. We used separated linear regression models to analyze associations of BMI with plasma CRP, CSF AD and neuroinflammation biomarkers, and mean cortical thickness (CTh) in a composite AD signature region. We explored voxelwise associations (p<0.001, k=100) between BMI and gray matter volume (GMv) with SPM12. We stratified all analyses by Aβ status (defining positivity as Aβ42/40<0.071) and adjusted by age, sex, systolic blood pressure, triglyceride, glycated hemoglobin and physical exercise levels.

Result

BMI was positively associated with CRP levels in Aβ‐ and Aβ+ groups (p<0.001). We found no significant associations between BMI and CSF AD or neuroinflammation biomarkers. BMI was negatively associated with mean CTh in the AD signature region in the Aβ‐ (p<0.001), but not in the Aβ+ group (p=0.543). Voxel‐based morphometry analyses showed widespread negative associations between BMI and GMv in Aβ‐ participants involving bilateral prefrontal, medial temporal, parietal, occipital, thalamic and cerebellar regions (Figure 1), without positive associations. Among Aβ+ participants, we found positive associations with BMI in small clusters in the cerebellum, middle frontal and anterior cingulate gyri (Figure 2), without negative associations.

Conclusion

In the absence of Aβ pathology, higher BMI is associated with brain atrophy involving AD‐related areas, suggesting that midlife obesity may increase dementia risk by mechanisms unrelated to AD pathology. Conversely, among individuals on the AD continuum, higher BMI appears to be associated with more preserved brain structure. We found no evidence of an association between higher BMI and neuroinflammation.
Eye‐tracking task detects early executive function deficits in presymptomatic frontotemporal dementia
Authors: Russell Lucy L , Convery Rhian S , Greaves Caroline V , Kaski Diego , Rohrer Jonathan D
Published: December 2021

Background

As research moves from understanding the natural history of frontotemporal dementia (FTD) to therapeutic trials, reliable and valid psychological measures are required to assess the efficacy of treatments. Current psychometric tests have only been able to identify subtle changes in genetic FTD around 5 years before the onset of symptoms suggesting more sensitive tasks are required.

Method

The aim of this study was to investigate whether an anti‐saccade eye‐tracking task could detect impaired executive function in a cohort of individuals that are at‐risk of developing genetic FTD. A total of 18 mutation carriers (MCs) and 20 mutation negative control participants completed the task, being instructed to look in the opposite direction to the red dot when it appeared on the screen. There were eight trials in the horizontal direction at 5 and 8 degrees of visual angle (°VA) and four trials in the vertical condition at 5°VA. The number of correct and self‐corrected anti‐saccades was calculated and a linear regression, covarying for sex, was used to assess performance between mutation carriers and controls.

Result

Of the 18 mutation carriers, 8 had expansions in chromosome 9 open reading frame 72, 6 had progranulin mutations and 5 had mutations in microtubule‐associated protein tau. The mean age for the mutation carriers group overall was 33.2 years, and 34.3 for the control group. The mutation carriers had significantly fewer correct anti‐saccades than the control group when the stimuli was presented in the vertical direction (MCs: mean = 1.44, SD = 1.29; controls: 2.32, 0.95; p = 0.016). There were no significant differences observed in the number of correct anti‐saccades in the horizontal direction, nor in the number of self‐corrected anti‐saccades made in either direction.

Conclusion

This preliminary study suggests that early executive function deficits can be detected presymptomatically in FTD using an anti‐saccade eye‐tracking task. It is possible that tasks like this, using eye‐tracking with very simple instructions, may be able to help assess the efficacy of therapeutic trials in the near future.
Independent effects of white matter hyperintensities on frailty among individuals with Alzheimer's disease
Authors: Yang Hyun‐ju , Park Joon Hyuk
Published: December 2021

Background

With an aging global population, recent years have seen rapid expansion in the attention of the frailty. Thus, understanding, and determinant the potentially modifiable risk factor for frailty is a major concern for health care policy and provision.

Method

Subjects were recruited for the study from the dementia clinic of Jeju National University Hospital between January 2018 and January 2020. All of the subjects were evaluated by using CERAD‐K and diagnosed probable AD and possible AD by a panel of two experienced dementia research neuropsychiatrists. WMH volume was calculated using automated segmentation analysis and further partitioned into three categories (Kim, BIOL PSYCHIATRY 2008). Frailty evaluated by Korean Frailty Index (KFI) and classified into three categories according to the cutpoints. Other physical performances such as BMI, muscle mass index, grip strength, and gait speed measures were performed by experienced researchers specialized in geriatric assessment. comorbidity status using the Charlson comorbidity index, and depressive symptoms using GDS was examined.

Result

In total, 34 subjects (23.6 %) were classified as frail 47 subjects (32.6 %) were classified as prefrail, and 63 subjects (43.8 %) were classified as a non‐frail group. The frail group had higher WMH volume compared to the non‐frail group (p=0.002), and these trends remained significant after linear regression analyses. According to the new subclassification of WMH, using the non‐frail group as a reference, total WMH volume (OR=6.297, p=0.013), JVWMH volume (OR=12.955, p=0.014), and PVWMH (OR=3.382, p=0.025) were associated with frail. Furthermore, according to the path model, only the gait speed mediated the association between WMH and frailty.

Conclusion

In our study provides evidence of a cross‐sectional relationship between WMH and frailty, and there is a difference in the association between the subclassification of WMH volume and frailty. Furthermore, we suggest that gait speed could be a useful biomarker for assessment of the frailty.
What elements are important in current treatment and care guidelines to provide culturally sensitive care for people with a migration background with dementia? A systematic analysis
Authors: Schmachtenberg Tim , Monsees Jessica , Thyrian Jochen René
Published: December 2021

Background

Among people with a migration background, problems such as underdiagnosis of dementia and underprovision are more widespread than in people without a migration background. The development of guidelines for culturally sensitive care of this population can be the first important action to address these inequalities. This article aims to provide a systematic overview of the key elements and measures regarding culturally sensitive care referred to in papers, reports, and guidelines.

Method

Using a triangulation of the models from a systematic literature analysis by Becker (2018), discourse analysis by Keller (2011), and qualitative content analysis by Mayring (2014), written statements from n=64 documents and oral statements from n=4 events were collected, paraphrased, and coded.

Result

Guidelines for the care of people with a migration background and dementia should focus on these topics: raising awareness in migrant communities about dementia and available healthcare services; building structures that promote the intercultural opening of healthcare systems; ensuring early and valid dementia diagnosis among people with a migration background; supporting, informing, and training care providers; overcoming communication barriers between care providers and people with a migration background with dementia; ensuring unrestricted access to healthcare for people with a migration background; providing culturally and linguistically sensitive support, care and treatment of people with a migration background with dementia; and conducting research on the care situation of this population.

Conclusion

Due to the specific needs and the particular challenges regarding the care of people with a migration background with dementia, which require a specific healthcare strategy with a comprehensive set of measures, the development of separate guidelines for the care of people with a migration background with dementia at the national level is recommended. In addition, the development of European guidelines for culturally sensitive care of people with a migration background with dementia can be an instrument for reducing dementia‐specific care inequalities. As a first step, a consensus on the definition of the term "migrant" should be sought at the European level.
Maintain Your Brain trial: Early findings and lessons learned from adherence and compliance data
Authors: Brodaty Henry , Heffernan Megan , Anstey Kaarin J , Fiatarone Singh Maria A , Jorm Louisa , Lautenschlager Nicola T , Maeder Anthony , McNeil John , Sachdev Perminder S , Valenzuela Michael , Chau Tiffany ,   Maintain Your Brain Collaborative Team
Published: December 2021

Background

Technology and web‐based approaches potentially provide scalable population‐based interventions to reduce modifiable risk factors for dementia. Key issues in online interventions are recruitment and retention. To devise strategies to improve population reach We investigated which factors influence recruiting and maintaining participants in such an intervention, the in‐progress Maintain Your Brain trial.

Method

Invitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). For MYB, participants were required to be eligible for at least one of four modules to be enrolled (physical activity, nutrition, brain training and mental wellbeing). All participants received modules based on their risks and were randomly allocated to either personalised coaching (intervention) or static information (control). Associations between participant characteristics (listed Table 1) and likelihood of completing set assessment tasks was assessed at two key stages – end of baseline and end of 12‐month follow‐up using stepwise (forward) regression.

Results

Of 96,418 people invited, 12,281 (13%) participants started baseline and completed a mean of 6.2 (SD 4.3) of ten assessments. Of these, 6,236 (6%) were enrolled in the trial. At 12‐months participants completed a mean of 5.0 of 8 assessments (SD = 3.8). Completion rate of the primary outcome (two tasks) was 62% (3,869). In the final regression model for baseline (Table1), overall associations were weak even though statistically significant, with only years of education not entered in the final model. The follow‐up model included retirement status, gender, baseline dementia risk and baseline wellbeing. However, this model (df1 = 1, df2 =6231; R2 = .01) accounted for even less variation than baseline model (R2 = .04).

Conclusion

Overall, regression models of participant characteristics accounted for a low amount of variation in task completion rates at both baseline and follow‐up. Participants were less likely to complete baseline tasks if they were older, male, not living with a spouse or alone and not retired or had lower dementia risk score and more psychological distress.
Prevalence of dementia in people with migration background in Europe
Authors: Monsees Jessica , Schmachtenberg Tim , Thyrian Jochen René
Published: December 2021

Background

The proportion of elderly people with migration background increases, therefore it can be assumed that the proportion of people with migration background and dementia will increase as well. So far, prevalence data for dementia and migration on an European level is only scarcely available. This study is part of a project to create an EU‐atlas on dementia and migration and depicts the prevalence data on dementia and migration in the 27 EU and 4 EFTA member states as well as the UK.

Method

Prevalence data will be estimated based on dementia prevalences of the country the people are living in and the number of people with a migration background from different ethnicities in that country.

Result

An extensive collection of information about dementia and migration depicting prevalence of dementia in people with a migration background on a European level will be provided.

Conclusion

Obtaining this information can help to uncover gaps in the health care systems and communities on an European level by highlighting a vulnerable population that is not receiving the attention and support that it needs. This can serve as a starting point to see where action must be taken and may therefore lead to better health care for people with migration background and dementia.
Exploring discordant data in dementia clinical trials
Authors: Kott Alan , Miller David S.
Published: December 2021

Background

We have observed numerous apparent inconsistencies in direction of scale (eg – MMSE, ADAS‐Cog and CDR) change between visits across multiple dementia clinical trials. While all instruments are not expected to move in the same direction, clinically meaningful changes in opposite directions may signal scoring and/or administration errors in one or more scales. In this analysis, we explore a) the extent to which such discordances between the MMSE, ADAS‐Cog and CDR occur in dementia clinical trials, and b) whether any associations between the presence of such discordances and scoring and/or administration errors exist.

Method

Blinded data were obtained from multi‐national dementia clinical trials in early AD. Visit‐to‐visit point change was calculated for the MMSE, ADAS‐Cog and CDR‐sb. Clinically meaningful changes were defined as ≥ 4 points for the ADAS‐Cog, 3 points for the MMSE and 1 point for the CDR‐sb. We defined discordance occurring when at least 2 of 3 instruments showed clinically meaningful change, but in opposite directions. We also evaluated data from the corresponding Endpoint Quality reviews of both the worksheet and audio recordings of these assessments. These were performed by calibrated, independent Clinicians and assessed whether there were any administration and/or scoring errors. Descriptive statistics and logistic regression analyses were used to address our questions.

Result

Data were collected from 4,892 randomized subjects. Visit‐to‐visit discordances were identified in 1,732 out of 15,321(11.30%) collected visits. Discordances were significantly less likely at baseline than after randomization (OR=0.54; CI=0.49‐0.61). The presence of baseline discordances significantly increased the odds of post‐baseline discordances (OR = 1.7; CI=1.4‐2.1). No association between the presence of discordances and administration or scoring errors was identified.

Conclusion

We have identified over 11% of study visits affected by clinically meaningful discordances between the visit‐to‐visit changes between the MMSE, ADAS‐cog and CDR‐SB. Despite the expected lower presence of baseline than post‐baseline discordances, discordances at baseline affected over 8% of randomized subjects. The lack of association between the discordances and administration or scoring errors is surprising and we plan further analyses to understand this phenomenon better.
An app to measure functional decline in managing finances in Alzheimer’s disease: Preliminary results of the RADAR‐AD study
Authors: Stavropoulos Thanos G. , Mpaltadoros Lampros , Lazarou Ioulietta , Grammatikopoulou Margarita , Muurling Marijn , de Boer Casper , Curcic Jelena , Kouzak Rouba , Verheij Herman , Nies Vera J.M. , Durudas Andre , Hannesdottir Kristin , Hinds Chris , Daskalova Yoanna , Owens Andrew P. , Wu Yuhao , Erdemli Gul , Stolk Pieter , Lucivero Federica , Narayan Vaibhav A. , Aarsland Dag , Nikolopoulos Spiros , Tsolaki Magda , Visser Pieter Jelle , Kompatsiaris Ioannis
Published: December 2021

Background

The on‐going ‘Remote Assessment of Disease and Relapse – Alzheimer’s Disease’ (RADAR‐AD, https://www.radar‐ad.org/) international study uses remote monitoring technologies (RMT’s) to continuously and objectively monitor functional decline in Alzheimer’s Disease (AD). Managing finances is an Instrumental Activity of Daily Living (IADL), usually measured via traditional pen‐paper methods and interviews. To simulate this IADL, we present the ‘Banking App’ and preliminary results from the RADAR‐AD study.

Method

In the app, users enter a PIN, an amount to withdraw and confirm all inputs, using a numpad on a tablet’s touchscreen that resembles an ATM (Figure 1) provided in eight translations. Metrics collected include the duration and correctness of each step (i.e. PIN, Amount and confirmation) and attempt as a whole. The 36 participants to date (Figure 2), from four European sites, performed neuropsychological tests (e.g., MMSE, Rey) and include 20 amyloid negative cognitively normal healthy controls (HC) and 16 amyloid positive, of which 6 cognitively normal preclinical AD (PreAD), 6 cognitively impaired prodromal AD (ProAD) and 4 Mild to Moderate AD (MildAD). Clinicians provided a PIN and an amount to enter from a bill in a controlled lab setting. Statistical analysis included One Way ANOVA, t‐test and Mann‐Whitney between groups in pairs and Pearson correlation.

Result

ANOVA showed significance between groups mainly in amount and confirmation durations (p=0.010, p=0.002), leading to t‐test in group pairs (Figures 3 in numbers, visualized in Figure 4), showing increasing durations for more cognitively impaired groups and significant difference between amount and confirmation durations between HC and MildAD (p=0.011, p=0.002). Pearson correlations and heat map (Figure 5) relate app metrics and neuropsychological tests (e.g., MMSE, ADCS with correct amount, p=0.005, and confirmation duration, p=0.001).

Conclusion

Preliminary findings highlight that managing finances via an app relates to cognitive assessment, further supporting the potential of this IADL in early AD using technology. This promising early data including near‐significant trends (e.g., duration of tasks between PreAD and ProAD) will be investigated deeper as the study and data collection are on‐going. This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking RADAR‐AD (grant No 806999) and their associated partners.
Synergistic effects of CSF Aβ42 and p‐Tau on functional resting‐state connectivity in cognitively unimpaired individuals
Authors: Cacciaglia Raffaele , González‐de‐Echávarri José Maria , Milà‐Alomà Marta , Operto Greg , Falcon Carles , Minguillón Carolina , Fauria Karine , Suridjan Ivonne , Kollmorgen Gwendlyn , Molinuevo Jose , Zetterberg Henrik , Blennow Kaj , Suarez‐Calvet Marc , Gispert Juan Domingo ,   ALFA Study
Published: December 2021

Background

Cerebral beta‐amyloid (Aβ) deposition disrupts functional resting‐state connectivity in cognitively unimpaired (CU) individuals. However, only a few studies have investigated these associations using Aβ cerebrospinal fluid (CSF) markers. Moreover, the reorganization of functional brain networks across the progressive stages of preclinical Alzheimer’s disease (AD) remains poorly understood. Here, we aim to identify functional connectivity (FC) differences in middle‐aged CU individuals, grouped as a function of both CSF Aβ (A) and pathological tau (T).

Method

We analyzed CSF and resting‐state functional magnetic resonance imaging (fMRI) data from 349 CU participants of the ALFA study (mean age=60.21 years). CSF Aβ42 and Aβ40 were assessed with the exploratory Roche NeuroToolKit robust prototype immunoassays, while p‐Tau181 was measured with the Elecsys® Phospho‐Tau (181P) CSF immunoassay (Roche Diagnostics International Ltd). Participants were grouped into three categories according to their biomarker status, resulting in three groups: A‐T‐, A+T‐, and A+T+. fMRI volumes were parceled into 218 regions, and correlations in the filtered fMRI signal among parcels were computed. We first assessed the impact of continuous CSFAβ42/40 concentration in the entire sample and subsequently assessed AT biomarker group differences in FC. A threshold of uncorrected p<0.005 using non‐parametric pair‐wise clustering was implemented.

Result

A higher cerebral Aβ deposition, reflected by lower CSFAβ42/40, was associated with reduced FC within the default mode network (DMN), but increased FC between the visual network and the DMN, as well as the salience networks. Compared with A‐T‐, A+T‐ showed decreased within‐DMN connectivity (Fig. 1). Finally, compared with A+T‐, A+T+ individuals showed reduced FC within the temporo‐hippocampal (THN) and the executive control networks (ECN) (Fig. 2).

Conclusion

This is the first study assessing FC in CU individuals adopting a staging of preclinical AD relying on multiple CSF biomarker classification. We report that CSFAβ42/40 disrupts the DMN but the co‐occurrence of Aβ and tau yields reduced connectivity in the THN and ECN, suggesting that Aβ and tau may interact in promoting a network reconfiguration extending beyond the DMN. Future studies shall clarify whether these differences reflect a correlate of pathology or rather a compensatory strategy to support cognitive performance in the face of AD pathology.
Interests of nursing homes residents with dementia for virtual reality‐based leisure activities: A cross‐sectional pilot study
Authors: Schüssler Sandra , Häussl Alfred , Paletta Lucas , Binder Thomas , Fürli Hermine , Koch Beatrix , Reidl Sybille , Beranek Sarah , Hartmann Robert , Sighart Martin , Schneeberger Michael , Andreu Jean‐Philippe
Published: December 2021

Background

A lack of resources in nursing homes can lead to standardized (leisure) activities for residents because of insufficient tailoring of individual interests. Virtual reality (VR) has the potential to provide enjoyable leisure activities for positive outcomes like well‐being. This study explores past and possible future interests of nursing home residents with dementia for the development of VR‐based (leisure) activities.

Method

This cross‐sectional pilot study, a first step in a mixed‐methods project, used a standardized questionnaire based on the Modified Interest Checklist – Diverse Learners. In total, seven residents with mild dementia from one rural Austrian nursing home participated in the study in February 2020.

Result

The residents were mainly female (57%), on average 82 years old and partially care dependent. The most‐mentioned past interests were playing cards (85.7%) as well as swimming, cycling, singing, practicing arts and crafts, cooking and baking, gardening, and listening to music/the radio (71,4% each) followed by (family) visits, watching television, washing and ironing clothes with 57,1% each. Further reported interests were hiking, taking walks, dancing, and travelling/going on holidays with 42.9%. There was no interest (0%) in rowing, philosophy, playing computer games, Yoga, Zumba, American football, or baseball. Residents most‐mentioned possible future interests were singing, decorating rooms, listening to music/ the radio, and driving a car with 85.7%, followed by getting a massage, ninepin bowling, gardening, cooking and baking, watching TV, taking day trips, and reading with 71.4% each. Furthermore, 57.1% of the residents would enjoy doing some laundry and ironing, repair works, barbecues, and going walking or shopping. There was no interest (0%) in sports activities such as soccer, baseball, golf, or American football.

Conclusion

Surveying past and possible future interests of nursing home residents with dementia shows that especially the (leisure) activities gardening, listening to music/the radio, cooking and baking, washing and ironing clothes and taking walks are of high interest. This is the basis for the next step in the project, using qualitative interviews to obtain more detailed descriptions of residents’ explored interests to then develop VR‐scenarios for residents’ individual (leisure) activities needs.
Impact on ALFF and ReHO mapping of lifestyle multidomain intervention: The SUPERBRAIN study
Authors: Choi Seong Hye , Moon So Young , Shin Seong A. , Jeong Jee Hyang , Hong Chang Hyung , Park Yoo Kyoung , Na Hae Ri , Song Hong‐sun , Park Hee Kyung , Choi Muncheong , Lee Sun Min , Chun Buong‐O , Lee Jong‐Min
Published: December 2021

Background

In the South Korean study to prevent cognitive impairment and protect brain health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), we explored impact on amplitude of low‐frequency fluctuation (ALFF) and regional homogeneity (ReHo) mapping of 24‐week facility‐based multidomain intervention (FMI) and home‐based MI (HMI).

Method

A total of 152 participants, aged 60‐79 years without dementia but with ≥ 1 modifiable dementia risk factor, were randomly assigned to the FMI, HMI, or control groups. Among them, 56 participants (20 FMI, 20 HMI, and 16 control) took brain MRIs at baseline and 24 weeks. We compared between each intervention and control groups in change of ALFF and ReHo mapping. The changes in ALFF and ReHo mapping were compared using analysis of covariance with age, sex, education, and scan centers as covariates. ROI‐based analysis was controlled for multiple comparisons with a false discovery rate threshold of P < 0.05.

Result

Only in the FMI group, a significant increase of ALFF in left medial orbitofrontal gyrus was observed after intervention. When 24‐week ALFF change in the left medial orbitofrontal gyrus was compared between each intervention and control groups, there was no difference. In HMI, increased ReHo was evident in right cuneus at follow‐up, whereas increased ReHo in left medial orbitofrontal gyrus and left anterior cingulate and decreased ReHo in right superior parietal lobule and right precuneus were observed in FMI group. The ReHo change in right cuneus was significantly higher in HMI group compared to the control group. The ReHo change in left medial orbitofrontal gyrus was notably higher in FMI compared to the control group. The correlation analysis revealed a positive correlation between the ReHo change in left medial orbitofrontal gyrus and change of serum brain‐derived neurotrophic factor (BDNF) levels in FMI group.

Conclusion

Significant differences between the FMI and control groups on changes in ReHo in at‐risk elderly without substantial impairment in the SUPERBRAIN suggest that group preventive strategies at the facility may be beneficial on cognition through neuroplastic changes of functional processing circuits in the brain areas which play a crucial role in processing social information.
The heterogeneity of subjective cognitive decline: A data‐driven approach on a population‐based sample
Authors: Rolandi Elena , Ribaldi Federica , Vaccaro Roberta , Colombo Mauro , Frisoni Giovanni B , Guaita Antonio
Published: December 2021

Background

Subjective Cognitive Decline (SCD) has been largely studied as a risk condition for cognitive decline, mainly in memory clinics or research settings. SCD samples are highly heterogeneous, including both individuals with early Alzheimer’s disease and others with psychological vulnerabilities and/or physical comorbidity. Aims: identify distinct SCD subgroups in a population‐based sample of cognitively normal (CN) older adults; explore cross‐sectional differences among SCD subgroups and controls (noSCD); investigate the effect of SCD status on 8‐year cognitive changes.

Method

The InveCe.Ab population‐based study (NCT01345110) enrolled people aged 70‐74 years residing in Abbiategrasso (Milan). Participants underwent multidimensional assessment (blood sampling, lifestyle interview, medical and neuropsychological assessment) at baseline (Nov 2009‐Jan 2011) and after 2, 4 and 8 years. CN participants at baseline completing at least 60% of neuropsychological assessment were included in the present investigation. Those reporting any cognitive complaints to the geriatrician were classified as SCD. Hierarchical cluster analysis was conducted in SCD including 9 relevant variables: education, depressive symptoms, cardiovascular risk, comorbidity, subjective cognitive complaints (numbers) and 4 neuropsychological scores measuring memory, executive functions, visuospatial abilities and language respectively. Cross‐sectional differences among the SCD subgroups identified and noSCD were performed using Kruskal‐Wallis test. Longitudinal cognitive changes according to baseline SCD status (noSCD, SCD subgroups) were estimated using linear mixed models, adjusted for age and education.

Result

Two clusters were identified in SCD. Table 1 shows cross‐sectional results. SCD1 (N=141), compared to SCD2 and CN, were less educated, have higher comorbidities, depressive symptoms and SCD complaints. SCD1 showed lower performances on executive and visuospatial functions, while SCD2, despite being healthier and more educated, showed reduced episodic memory. At longitudinal analysis, all cognitive functions declined due to aging (Time; p<.001). SCD2 displayed a steeper worsening on executive function (Group*Time; p<.001).

Conclusion

The presence of SCD at the population level could be informative of future cognitive decline when reported by individuals with higher education. Future studies are needed to clarify the meaning of this condition in the aged population, in order to identify early those at increased risk of actual cognitive decline.
Early stages of tau pathology and its associations with functional connectivity, atrophy and memory
Authors: Berron David , Vogel Jacob W. , Insel Philip , Pereira Joana B. , Xie Long , Wisse Laura , Yushkevich Paul A. , Palmqvist Sebastian , Mattsson‐Carlgren Niklas , Stomrud Erik , Smith Ruben , Strandberg Olof , Hansson Oskar
Published: December 2021

Background

In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau‐PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior‐medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance.

Method

We included 215 β‐amyloid negative cognitively unimpaired, 81 β‐amyloid positive cognitively unimpaired and 87 β‐amyloid positive individuals with mild cognitive impairment, who each underwent [18]F‐RO948 tau and [18]F‐flutemetamol amyloid PET imaging, structural T1‐MRI and memory assessments as part of the Swedish BioFINDER‐2 study.

Result

First, event‐based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions (see Figure 1). Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau‐related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior‐medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy.

Conclusion

In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease‐stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe‐cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.