bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐reflection is associated with markers of Alzheimer’s disease in cognitively unimpaired older adults
Authors: Demnitz‐King Harriet , Chocat Anne , Collette Fabienne , Dautricourt Sophie , Gonneaud Julie , Jessen Frank , Klimecki Olga M , Salmon Pierre Krolak , Lutz Antoine , Molinuevo Jose Luis , Poisnel Géraldine , Touron Edelweiss , Walker Zuzana , Chetelat Gaël , Marchant Natalie L
Published: December 2021

Background

Self‐reflection is conceptualised as an introspective process that involves active evaluation of one’s thoughts, feelings and behaviours. Engagement in self‐reflection is thought to yield more adaptive stress responses, that in turn result in better short‐term (e.g., reduced inflammatory responses to stressors) and long‐term (e.g., recovery from major depression) outcomes. Despite self‐reflection’s known protective effect against adverse health outcomes, the association between self‐reflection and Alzheimer’s disease (AD) risk is unknown.

Method

Baseline data from 134 healthy older adults (mean age=69.3) enrolled in the Age‐Well clinical trial and 125 older adults with subjective cognitive decline (mean age=72.5) from the SCD‐Well clinical trial were included. All participants completed an assessment of self‐reflection. Modified versions of the Preclinical Alzheimer’s Cognitive Composite 5 were used to measure global cognition in both cohorts. Additionally, in Age‐Well, glucose metabolism and amyloid deposition were assessed with PET scans, and the Lifestyle‐for‐Brain‐Health (LIBRA) AD‐risk index computed to assess health and lifestyle behaviours. Separate linear regressions were run to determine associations between self‐reflection levels and AD markers (i.e., global cognition, glucose metabolism, and amyloid deposition). Analyses adjusted for available prognostic characteristics associated with AD (e.g., age, sex, education and APOE4 status) and levels of psychological distress (i.e., depression and rumination). Furthermore, to explore the potential mechanism linking self‐reflection with AD markers, the relationship between self‐reflection and LIBRA scores was investigated.

Result

Self‐reflection was positively associated with global cognition in both cohorts (Age‐Well: β=0.18, p=0.023; SCD‐Well: β=0.20, p=0.024) and glucose metabolism (Age‐Well: β=0.29, p=0.027; see Figure). No relationship, however, was found with amyloid deposition (Age‐Well: β=0.13, p=0.198). Self‐reflection was associated with LIBRA scores (Age‐Well: β=‐0.31, p=0.002), with lower self‐reflection levels associated with poorer health and lifestyle behaviours.

Conclusion

Self‐reflection was associated with higher glucose metabolism, and with better global cognition in two independent older adult cohorts. For the first time, we introduce preliminary support for self‐reflection as a potential protective factor against AD‐related decline. Furthermore, the results suggest that self‐reflection may affect AD risk by influencing health and lifestyle behaviours. Both Age‐Well and SCD‐Well are clinical trials. Future work will investigate whether modifying self‐reflection via interventions affects AD markers.
Anticholinergic burden and cognitive performance: Cross‐sectional results from the ELSA–Brasil study
Authors: Medeiros dos Santos Adriana Nancy , Brunoni Andre R , Goulart Alessandra C , Viana Maria Carmen , Benseñor Isabela , Lotufo Paulo , Suemoto Claudia Kimie
Published: December 2021

Background

The use of multiple drugs with anticholinergic properties is common in older adults and it may lead to cumulative anticholinergic toxicity and increase the risk of cognitive impairment. We investigated the association between the Anticholinergic Cognitive Burden scale (ACB) and cognitive performance among middle‐aged and older Brazilian adults (35‐74 years).

Method

In this cross‐sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil), 13,065 participants were included (mean age = 51. ± 8.9 years old, 55% female, 53% white). Anticholinergic Cognitive Burden (ACB) was calculated according to the medications in use. We investigated the association of ACB with a global cognitive z‐score and memory, verbal fluency (VF), and Trail Making Test z‐scores, using multiple linear regression models adjusted for sociodemographic and clinical variables.

Result

16% of the sample had an ACB score >0. ACB was associated with worse cognitive performance on the memory (β= ‐0.022, 95% Cl= ‐0.045, 0.001, p=0.056) and in the trail making test (β= ‐0.021, 95% Cl= ‐0.043, 0.000, p=0.054) after adjustment for confounders

Conclusion

Anticholinergic burden was related to worse cognitive performance on the memory and trail making test in Brazilian participants.
Lower motor function prior to the Covid‐19‐imposed lockdown predicts emotional distress in older adults with T2D
Authors: Benari Ori , Ravona‐Springer Ramit , Almog Ganit , Yore Iscka , Zadok Maya , Lin Hung‐Mo , Ouyang Yuxia , Livny Abigail , Beeri Michal Schnaider
Published: December 2021

Background

Type 2 diabetes (T2D) is associated with accelerated cognitive decline and increased dementia risk. Lockdowns imposed due to the Covid‐19 outbreak led to unprecedented changes in the life of older adults. However, little is known about emotional distress consequences. We assessed associations of grey matter (GM) volumes (N=179), cognitive and motor functions (N=403) with emotional distress of older adults with T2D from the Israel Diabetes and Cognitive Decline Study (IDCD).

Methods

During the first Covid‐19‐related lockdown in Israel, we applied a phone questionnaire, which included information about anxiety (“Over the last two weeks, how much have you been bothered by Feeling anxious or nervous?”; Anxiety levels now compared to before Covid‐19), depression (“Over the last two weeks, how much have you been bothered by feeling sad, down, or uninterested in life?”; sad feelings now compared to before Covid‐19), general well‐being (“How are you feeling in general?”), optimism towards the future (“Are you optimistic towards the future?”). Grey matter (GM) volumes (measured by high resolution T1‐weighted MRI), cognitive (a global measure summarizing 14 cognitive tests) and motor function (gait speed and grip strength), are routinely assessed by the IDCD study. Spearman correlation adjusting for age, sex, education, HbA1c and duration of T2D (as well as TICV for the GM analyses) examined associations of GM, cognitive and motor functions with emotional distress measures.

Results

The sample averaged 72 years of age (SD=4.4), and 14 years of education (SD=3.5); 40.9% were female. Lower grip strength prior to lockdown was associated with increased sadness (r=‐0.21, p<0.001) and anxiety (r=‐.011, p=0.020), less optimism (r=0.10, p=0.042) and lower general feeling (r=0.17, p=0.0005). Slower gait speed was associated with increased sadness (r=0.13, p=0.005). Lower GM was associated with greater anxiety during the lockdown (r=‐0.19, p=0.011) and compared to before Covid‐19 (r=‐0.19, p=0.012). Global cognition was not associated with any of the emotional distress measures.

Conclusions

Motor function, but not cognitive function, were associated with lockdown imposed emotional distress in older adults with T2D. These associations point to the importance of good motor function and physical conditioning in emotional well‐being related to acute stress related to stay‐at‐home‐orders.
Associations of fully automated Elecsys CSF and novel plasma biomarkers with Alzheimer's disease neuropathology
Authors: Grothe Michel J. , Moscoso Alexis , Ashton Nicholas J , Zetterberg Henrik , Blennow Kaj , Schöll Michael
Published: December 2021

Background

The development of fully automated analysis platforms for cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and recent advances in blood‐derived biomarkers signify major steps towards a widespread clinical use of fluid‐based biomarkers. We aimed to study AD CSF biomarkers analyzed by fully automated Elecsys immunoassays in comparison to neuropathologic gold standards, and compare their accuracy to plasma phosphorylated tau (p‐tau181) and neurofilament light (NfL) measured using novel Simoa assays.

Method

We compared ante‐mortem Elecsys‐derived CSF biomarkers to standardised post‐mortem assessments of AD and non‐AD neuropathologic changes in 45 participants from the Alzheimer’s Disease Neuroimaging Initiative autopsy cohort. In a subset of 26 participants, we also analyzed ante‐mortem levels of plasma p‐tau181 and NfL. Reference biomarker values were obtained from 146 amyloid‐PET‐negative healthy controls (HC)([18F]Florbetapir‐PET <12 Centiloids).

Result

All CSF biomarkers clearly distinguished pathology‐confirmed AD dementia patients (N=27) from HC (AUCs=0.86‐1.00). CSF total‐tau (t‐tau), p‐tau181, and their ratios with Aβ1‐42, also accurately distinguished pathology‐confirmed AD from non‐AD dementia (N=8; AUCs=0.94‐0.97)(Fig. 1). In pathology‐specific analyses, intermediate‐to‐high Thal amyloid phases were best detected by CSF Aβ1‐42 (AUC[95% CI]=0.91[0.81‐1]), while intermediate‐to‐high CERAD neuritic plaques and Braak tau stages were best detected by CSF p‐tau181 (AUC=0.89[0.79‐0.99] and 0.88[0.77‐0.99], respectively)(Fig. 2). Optimal Elecsys CSF biomarker cut‐offs were derived at 1097/229/19 pg/ml for Aβ1‐42, t‐tau, and p‐tau181. In the plasma subsample, both plasma p‐tau181 (AUC=0.91[0.86‐0.96]) and NfL (AUC=0.93[0.87‐0.99]) accurately distinguished pathology‐confirmed AD (N=14) from HC. However, only p‐tau181 distinguished AD from non‐AD dementia cases (N=4; AUC=0.96[0.88‐1.00])(Fig. 1), and showed a similar, though weaker, pathologic specificity for neuritic plaques (AUC=0.75[0.52‐0.98]) and Braak stage (AUC=0.71[0.44‐0.98]) as CSF p‐tau181. No CSF or plasma biomarker was sensitive to the presence of Lewy body or TDP‐43 pathology, but Elecsys CSF Aβ1‐42 levels detected the presence of cerebral amyloid angiopathy (AUC=0.84[0.73‐0.96]).

Conclusion

We demonstrate for the first time that the fully automated Elecsys CSF biomarkers detect AD neuropathologic changes with very high discriminative accuracy in vivo, and we report corresponding pathology‐based cut‐offs for these standardized biomarker measurements. Preliminary findings in a smaller subsample also support the use of plasma p‐tau181 as an easily accessible and scalable biomarker of AD pathology.
Fighting social isolation of vulnerable people with dementia through remote group meetings: An experience report
Authors: Alves Emily Viega , de Abreu Elisabeth Araujo , Beber Bárbara Costa , Brandao Lenisa
Published: December 2021

Project Description

With the COVID‐19 pandemic (WHO, 2020), social distancing became a crucial means to prevent further spread of the disease (Wendy et al, 2020). This raises concerns for dementia care (Wang et al, 2020), as social distancing leads to reduced cognitive stimulation, exercise, social networking and leisure activities (Brown et al, 2020). Active participation in art has shown positive impacts on the psychosocial wellbeing of stroke survivors (Morris et al, 2019). Additionally, engaging with humor potentially improves the memory, communication and self‐esteem of people with dementia (PWD) (Stevens, 2012). This study aims at reporting an innovative, interdisciplinary remote intervention targeted at groups of PWD and stroke survivors during the COVID‐19 pandemic. These were part of the university community outreach program Playful Living, which aims at promoting digital inclusion, quality of life and equity through artistic group activities. The project began in 2020 and consists of weekly group meetings through online platforms, with different creative practices happening each week. These include dance, gastronomy, storytelling and clowning. There are 32 participants: 13 PWD, 14 stroke survivors and 5 older adults with no diagnosis of neurological conditions. All participants were selected considering social vulnerability determinants: income, race, gender and educational background. Participants were divided into four groups, each with a fixed team (students of Speech Therapy, Psychology, Dance and Dramatic Arts) and moving members. So far, seven meetings took place. The activities have provided different opportunities for sharing memories, experiencing and expressing emotions through art. Participants reported looking forward to the meetings, with increasing participation and bonding. A major concern has been digital inclusion: stable internet access, camera and microphone management. Those aspects directly affect participants' ability to engage in group dynamics and potentially impact their self‐esteem and well‐being. However, improvements are observed on a daily basis, thanks to the combined efforts of team members and caregivers. The project has provided participants with means for self‐expression and social interaction in a safe environment. Perceived difficulties thus far point toward the need for continued efforts in terms of social and digital inclusion for this population currently and beyond the pandemic setting.
The development of a national evaluation framework for the First Link® program across Canada
Authors: Whate Alexandra , Kernoghan Alison , Elliott Jacobi , Stolee Paul , Sivananthan Saskia
Published: December 2021

In Canada, the Alzheimer Society’s First Link® program connects people living with dementia and their caregivers to the information, supports and services they need as early as possible and throughout the progression of the disease. Since its launch in 2002, First Link® has been implemented in all provincial societies across Canada. We have developed a national evaluation framework to guide the Alzheimer Society to gather data to assess First Link’s® impact on the health system. This work has been conducted with active engagement and consultation with the Alzheimer Society, persons living with dementia and their caregivers and other health system stakeholders. We have also received guidance from a national project advisory committee of stakeholders. A contribution analysis lens was used to understand how the First Link® program may contribute to health system outcomes. First, we assessed the current state of the First Link® program across Canada and developed a theory of change. Key informant interviews with First Link® staff, clients and community referral partners, as well as those without direct experience with the First Link® program, were used to gather evidence to build upon and test the theory of change. We then mapped all available and potential data sources to the theory of change to develop a draft evaluation framework with indicators that show program impact. The draft evaluation framework will be presented to stakeholders for feedback and tested and revised in a rapid cycle evaluation at a representative group of Alzheimer Society pilot sites. The outcomes of this initiative will provide data to support the Alzheimer Societies’ efforts to build a national case for ongoing, sustainable funding for First Link®.
Dementia‐inclusive radio series ‘Talkin’ About Neurodegeneration'—A look under the dementia umbrella and a follow‐on series to award‐winning ‘Voyage Around My Brain’ on NearFM
Authors: Meenan Karen Patricia
Published: December 2021

Background

‘Talkin’ About Neurodegeneration’ a ground‐breaking radio series sharing voices of Brain Health Experts, with people living with different neurodegenerative diseases, their caregivers and other experts working in the arts – a four‐way conversation about living with dementia. The aim is to spotlight lesser‐known diseases in particular LBD which is the most common dementia that nobody knows about and educate listeners that Alzheimer’s Disease is not the only one associated with dementia. Radio producer, researcher, broadcaster and GBHI Fellow, Karen Meenan was awarded CRAOL National Gold Award for ‘Voyage Around My Brain’ which introduced listeners to people living with dementia, their caregivers and Brain Health Experts from GBHI over 17 weeks with 50+ guests, half of whom were living with dementia. CRAOL stated ‘congratulations for sharing the voices of people living with dementia, we need to hear these stories, great twist to have experts on the same programme’. Listenership on NearFM on Monday 7‐8pm has almost doubled v same period last year with regular emails saying how listeners enjoy learning new aspects about dementia. ‘Thank you for this programme, I look forward to it eagerly each week’ ‘My Dad has Parkinson’s disease, I didn’t realise that dancing was an important part of his care, thanks for letting me know’ ‘Thanks for the spotlight on insomnia, I have had trouble sleeping for years, I’m going to put into practice some of the suggestions by your guests last week’ … as samples of the correspondence. ‘Talkin’ About Neurodegeneration’ will tell the story of these diseases in an engaging, educational and entertaining way – how did Lewy Body Dementia get its name, how is Huntington’s disease in South Africa traced back to one individual, why is dancing good for people living with Parkinson’s disease and how can reminiscence theatre spark memories for people living with Alzheimer’s Disease. Karen Meenan is designing and building a new website for people in Ireland living with Lewy Body Disease – there is nothing in place for these estimated 6,000 people at present. ‘Talkin’ About Neurodegeneration’ is a component of this new website. This is her GBHI Pilot Project.
Establishment of updated biomarker cut‐off values for the second‐generation Elecsys β‐amyloid(1–42), pTau and tTau CSF immunoassays
Authors: Hansson Oskar , Rutz Sandra , Corradini Veronika , Manuilova Ekaterina , Logan Chad , Blennow Kaj
Published: December 2021

Background

Compared with the first‐generation (Gen1), second‐generation (Gen2) Elecsys® cerebrospinal fluid (CSF) immunoassays (currently under development, Roche Diagnostics International Ltd) for detection of β‐amyloid(1–42) (Abeta42), phospho‐tau(181P) (pTau) and total‐tau (tTau) have higher thresholds for biotin interference. Abeta42 Gen2 is re‐standardized to Abeta42 certified reference materials ERM‐DA480/IFCC, ERM‐DA481/IFCC and ERM‐DA482/IFCC and has an extended measurement range. Additionally, the newly developed pre‐analytical ‘Routine‐Use’ protocol provides more reliable analyte recovery for Abeta42 against comparators (Hansson et al., Alzheimers Dement. 2020;16(S3):e047394). Here, we establish adjusted cut‐off values for concordance of Abeta42, pTau/Abeta42 and tTau/Abeta42 Gen2 results with amyloid‐PET based on those previously established for Gen1, accounting for different pre‐analytical protocols.

Method

CSF samples from 26 patients with normal pressure hydrocephalus were collected per the Routine‐Use protocol for fresh CSF (n=3 aliquots/patient) and two clinical trial protocols (BioFINDER and Roche‐Trial) for frozen CSF (<–60°C; n=4 aliquots/patient). Abeta42, pTau and tTau were quantified using Elecsys Gen1/Gen2 immunoassays (cobas e 601 analyzer; Roche Diagnostics International Ltd). Bias at medical decision point was estimated for comparison of Gen1 and Gen2 immunoassays (Roche‐Trial protocol) by weighted‐Deming regression. Original cut‐off values were determined in the BioFINDER cohort using Gen1 immunoassays (Hansson et al.). Adjusted cut‐off values for Gen2 immunoassays with both Routine‐Use and Roche‐Trial protocols were determined. Concentration bias between Routine‐Use and Roche‐Trial protocols was also investigated, measured using Gen2 immunoassays. Mean percentage differences provided estimates of overall bias between protocols and protocol‐assay combinations.

Result

No clinically meaningful differences between assay generations and pre‐analytical protocols were obtained for pTau or tTau. Bias at medical decision point for Abeta42 Gen2 immunoassay versus Gen1 was –20% (95% confidence interval [CI]: –22%, –18%). Bias between concentrations of Abeta42 measured using BioFINDER/Gen1 versus Routine‐Use/Gen2 was –6.3% (95% CI: –8.7%, –3.9%). Cut‐off values for Routine‐Use/Gen2 were adjusted based on this result (). Bias between Routine‐Use versus Roche‐Trial protocols for Abeta42 Gen2 was –22% (95% CI: –24%, –19%). Cut‐off values for Roche‐Trial/Gen2 were adjusted based on this result.

Conclusion

Elecsys CSF Abeta42 results were independently affected by immunoassay generation and pre‐analytical protocol, while tau results were unaffected. Appropriate adjusted cut‐off values have been established.
The impact of the COVID‐19 pandemic on cognitive health
Authors: Brooker Helen , Hayman Vincent , Aarsland Dag , Creese Byron , Ballard Clive , Corbett Anne
Published: December 2021

Background

The COVID‐19 pandemic has presented an extraordinary and unprecedented challenge to individuals, society and governments. Aside from the direct clinical impacts of COVID‐19, the social restrictions are likely to have had considerable impacts on cognitive and mental health. Understanding these trends will be critical to improve future responses to outbreaks and to improve the treatment and care provided to individuals affected.

Method

PROTECT is an innovative online study (www.protect.org.uk) in adults aged 50 and over in the UK, Participants complete annual cognitive assessment and health measures including the PHQ‐9 and GAD‐7. Participants were divided into three cohorts (Normal Cognition, Stage 2 Early AD and Stage 3 Early AD, based on the FDA framework) using baseline data from the cognitive assessment battery. This analysis utilised data from a total of 5301 participants followed annually over the last 5 years, including the year of the COVID‐19 pandemic. It also utilises the newly published FLAME composite cognitive measure that has shown sensitivity to cognitive decline.

Result

In the participants with worsening PHQ‐9 and GAD‐7 scores between 2019 and 2020 (63%), composite measures of Speed [Stage 2: p=0.008, d=0.27; Stage 3: p=0.0006, d=0.17], and accuracy of Attention [Stage 2: p=0.004, d=0.11; Stage 3: p=0.0016, d=0.21], Memory [Stage 2: p=0.0011, d=0.3; Stage 3: p=0.0009, d=0.22] and Executive Function [p=0.08], as well as the composite FLAME measure [p=0.0014, d=0.28], showed a larger decline over the last 12 months compared to the prior assessment period. Whilst no significant increase in the rate of decline was seen in people without worsening of depression or anxiety.

Conclusion

The pandemic has had a detectable and significant detrimental impact on key aspects of cognitive health in adults over 50, including adults with early cognitive impairment (stage 2 and 3 pre‐clinical AD in the FDA framework) mediated predominantly through worsening of mental health.
Piloting an innovative knowledge translation and exchange (KTE) approach on educational resources for caregivers
Authors: Malvern Riley , Sivananthan Saskia , Christie Nathan
Published: December 2021

Background

Knowledge translation and exchange (KTE) is about moving knowledge into practice, involving stakeholders in an ongoing iterative process. The Alzheimer Society of Canada (ASC) approaches KTE by emphasizing ongoing collaborations with our primary audiences: people with lived experience of dementia, healthcare providers, and researchers. Knowing that people have diverse learning styles and preferences for accessing information, ASC is diversifying the range of educational resources that are currently provided through a traditional medium (i.e., printed information sheets) to a multimedia range of KTE tools that can better meet the needs of our audiences. Beginning with a pilot project that explored the practical application of KTE to a key education resource, ASC has developed an operational process with the involvement of stakeholders to help our audiences access and benefit from the information they need in a manner that accommodates them.

Method

A resource for the KTE pilot project was chosen based on a data driven approach to assess need and impact (i.e., number of website views, downloads, printed resource orders and feedback from stakeholders). Using ASC’s KTE framework and the results of an environmental scan that identified KTE approaches used by other organizations, the team operationalized the KTE framework through a focus on four dimensions: 1) audiences, 2) information channels, 3) feasibility and 4) accessibility of the resource. Key stakeholders, including Alzheimer Society support staff and family caregivers, collaborated with ASC on the development of the tools through focus groups.

Result

An infographic and a small video series on practical communication tips for caregivers were created. These KTE tools will support caregivers in staying connected to the person living with dementia at all stages of the disease; as the information is broad and digestible, it can be used by other audiences, such as healthcare providers.

Conclusion

The KTE pilot project is a stepping‐stone to establish a more integrative KTE approach to ASC’s educational resources. The process established through this project will ensure that those who turn to ASC for information can find reliable, up‐to‐date and evidence‐based content through a variety of tools that are engaging, easy to understand and accessible.
Neuroanatomical substrates of attention processing speed in early dementia with Lewy bodies (DLB): A white‐matter voxel‐based morphometry and diffusion tensor imaging study
Authors: Botzung Anne , Mondino Mary , Noblet Vincent , Philippi Nathalie , Blanc Frédéric
Published: December 2021

Background

Based on a previous study (Botzung et al., 2019) that revealed the importance of grey matter (GM) integrity in the striatum for attention processing speed, the purpose of this study was now to examine, in early DLB patients, the relationship between impaired attentional speed performances and white matter changes.

Method

We administered the Trail Making Test A (TMTA) to 73 prodromal to moderate DLB patients (mean MMSE = 26.4) and 30 control subjects (mean MMSE = 28.9) to assess attention processing speed. Three‐dimensional (3D) MRI and Diffusion‐weighted images (DTI) were acquired for all participants and correlational analyses were performed in the patient group using WM‐VBM, fractional anisotropy (FA) and mean diffusivity (MD).

Result

Behavioral results showed significantly impaired performances in patients in comparison to control subjects (p = .004). In addition, correlational analyses using WM‐VBM revealed negative WM correlations in the anterior corpus callosum and in the anterior cingulum (p < .05 FDR). Using DTI (p < .05 FDR), correlated with TMTA scores, we found reduced FA in bilateral frontal and posterior regions, and increased MD in bilateral anterior and posterior networks.

Conclusion

WM‐VBM analysis revealed the involvement of anterior corpus callosum and cingulum, which could indicate a disruption of the loops connecting striatal regions and the prefrontal cortex. Changes in both FA and MD also correlate with impaired attentional speed: further DTI analyses are still ongoing to question the degree of which white matter tracts are disrupted between the striatum and cortical anterior and posterior networks, respectively.
Multidomain interventions for dementia risk reduction: Can we detect a change in the signal?
Authors: Lussier Isabelle , Guillemont Juliette , Bacon Simon L , Boivin Michel , Ferland Guylaine , Lavoie Kim , Paré Guy , Belleville Sylvie
Published: December 2021

Background

There is increasing evidence that modifiable lifestyle factors account for around 40% of worldwide dementia cases. Given the multifactorial etiology of dementia, multidomain lifestyle interventions have generated major interest. Results from randomized controlled trials (RCTs) suggest that implementing multidomain interventions in at‐risk individuals is an effective strategy to delay disease onset. As per the Obesity‐Related Behavioral Intervention Trials (ORBIT) model, to ensure successful interventions, pre‐efficacy trials are needed to ascertain that each intervention component can yield a predefined clinically significant change (CSC). Therefore, the main objective of this Proof‐of‐Concept was to determine if each individual part of an online multidomain dementia risk reduction program can achieve a CSC in the targeted behavioural risk outcome.

Method

This was a 12‐week, within‐subject, treatment‐only study with three single‐domain groups (Diet, Physical Activity [PA] or Cognitive Engagement [CE]) and one multidomain group. The study enrolled cognitively healthy individuals aged 50‐70 with at least one risk factor among the targeted domains. The personalized intervention was delivered via a digital, coach‐supported application. Primary outcomes were the percentage of participants showing a CSC at study end in each domain. CSCs were defined as a change ≥ 1 point on the Canadian Mediterranean Diet Score, ≥ 300 METs‐min/week on the short version of the International Physical Activity Questionnaire, and ≥ 6 points on the Cognitive Activity Questionnaire, respectively. Additional outcomes comprised feasibility indicators.

Result

Thirty‐nine participants (mean age=63.1 [51‐68]; 82.1% female) were recruited, with 31 participants enrolled in the single‐domain groups (Diet, N=11; PA, N=7; CE, N=13). Within the single‐domain groups, participants received 7.9 (6‐9) coaching sessions. The number of participants achieving a CSC was 5 (45.5%) in the Diet group, 3 (42.9%) in the PA group and 6 (50.0%) in the CE group. Overall compliance and retention were 93.5% (89.6‐98.0) and 97.4% (92.3‐100), respectively.

Conclusion

The results of this study support moving forward to the next ORBIT framework step, which includes refinement of the Luci intervention components and the design of a pilot feasibility trial to test the program in a larger sample of participants.
Analysis of recruitment planning for under‐represented participants in NIA‐funded Alzheimer’s disease and Alzheimer’s disease related dementias clinical trials
Authors: Han Sae H , Massett Holly A , Shakur Mujaahida , Lockett Jaron , Mitchell Alexandra K
Published: December 2021

Background

Inclusion of underserved participants is mandated by the National Institutes of Health (NIH), yet they remain under‐represented in NIH research, including Alzheimer’s and Related Dementias (AD/ADRD) clinical trials. Diverse representation is critical in AD/ADRD trials as African Americans (AA) and Hispanics/Latinos (H/L) are disproportionately affected by the disease. Research indicates that a priori recruitment planning is critical to successful recruitment into trials. This abstract analyzes the planned inclusion enrollment reports (IERs) and recruitment strategies described in grant applications for active National Institute on Aging (NIA)‐funded AD/ADRD clinical trials (N=271)

Method

This analysis used two methods: 1) documented the planned IERs for each NIA‐funded AD/ADRD clinical trial (active as of 10/16/2020); 2) conducted content analysis documenting: a) justification for IER, b) presence of a plan (yes/no), c) key enrollment strategies proposed (overall and for under‐represented populations), and d) quality of proposed recruitment planning (intercoder reliabilities: 80‐90%).

Result

Across the trials, median percent of total enrollment goal by IER categories were: Non‐Hispanic (91%) vs. Hispanic (9%); White (74%), AA (16%), Asian (4%), Other Races (2%). The top reason (62%) justifying trials’ IERs was “proportions represents trial site demographics.” Only 5% reported “proportions represent disease studied.” Most trials (91%) provided recruitment plans; however, 55% included no strategies specific to recruiting under‐represented populations. The majority (52%) of plans were rated medium quality (2‐3 strategies); the remaining were equally split between low and high quality (24% each). A median of 2 recruitment strategies were listed per trial; top strategies were: 1) traditional advertisements, 2) underserved‐focused community outreach, and 3) provider referrals. Additional analyses will be reported by intervention type, trial phase, and site type.

Conclusion

Our findings show inclusion planning for active NIA AD/ADRD clinical trials is heavily weighted towards non‐Hispanic Whites. Even if trials meet their IER goals, they will be under‐enrolling H/L, Asians, and Other Races as compared to the US Census data (2019). Most trials have recruitment plans, though not focusing on strategies targeted at recruiting those under‐represented. NIA should consider developing more robust guidelines to ensure grant applications have targeted, achievable, evidence‐based minority recruitment goals and plans set a priori.
Tau‐load in the lingual gyrus impacts anxiety levels during the COVID‐19 pandemic in participants of longitudinal observational studies in aging
Authors: Servaes Stijn , Lussier Firoza Z , Bezgin Gleb , Wang Yi‐Ting , Stevenson Jenna , Tissot Cécile , Elgbeili Guillaume , Arias Jaime Fernandez , Therriault Joseph , Benedet Andréa Lessa , Chamoun Mira , Pascoal Tharick A. , Bzdok Danilo , King Suzanne , Gauthier Serge , Rosa‐Neto Pedro
Published: December 2021

Background

By obtaining a better grasp on the impact of the COVID‐19 pandemic on individuals with cognitive impairment, this knowledge could be used to improve the delivery of information to this particular group. We aimed to assess the relationship between tau deposition and the change in anxiety levels, before and during the pandemic. We hypothesized that since the pandemic, higher tau loads would lower the change in anxiety. Furthermore, we expected these anxiety levels not to be associated with COVID‐19 related stress in participants with cognitive decline.

Methods

63 participants of the Translational Biomarker of Aging and Dementia (TRIAD) cohort (cognitively healthy, N=38; cognitively impaired, N=25, of which 7 had dementia due to Alzheimer’s disease), were assessed to evaluate their individual change in anxiety levels (GAD‐7). This was done at three different timepoints, of which the latest fell during the COVID‐19 lockdown period. Two rates of change, one before and one during the pandemic, were determined using the following definition: (next timepoint – current timepoint)/time difference. In addition, at the latest timepoint, subjective stress due to COVID‐19 was measured using the Montreal Assessment of Stress related to COVID‐19 (MASC). To assess the levels of tau, standard uptake value ratios (SUVR) from previously obtained [18F]MK‐6240 PET‐scans were used.

Results

[18F]MK‐6240 tracer binding in the lingual gyrus was negatively associated with the rate of change in GAD‐7 scores after correcting for age, sex, years of education and the presence of APOE ε4, but only in cognitively impaired individuals during the pandemic (fig 1A). In addition, the GAD‐7 score at the latest timepoint was associated with stress related to COVID‐19, but only in cognitively healthy individuals (fig 1B and 1C).

Conclusions

The presence of tau in the lingual gyrus negatively affected the rate of change in GAD‐7 scores during the COVID‐19 pandemic in individuals with cognitive impairment. This could indicate that information pertaining to the pandemic does not reach these individuals in an efficient manner. The missing association between COVID‐19 induced stress and the latest GAD‐7 scores in these individuals is a further indication of this.
The use of cognitive measures in older adults with concurrent hearing and vision impairment: A scoping review
Authors: Dumassais Shirley , Aubin Gabrielle , Jaiswal Atul , Gupta Shikha , Santhakumaran Sangeetha , Wittich Walter
Published: December 2021

Background

Older adults with dual sensory impairment (DSI/combined hearing and visual impairment), are more likely to obtain poorer scores on cognitive tests. Whether these results are due to poor cognitive function or inappropriate or absent adaptation of test administration for sensory impaired older adults is unclear. Given that this population is at higher risk of developing dementia, e.g., due to Alzheimer’s disease, ensuring optimal test administration is imperative to provide adequate cognitive care. Therefore, we mapped the existing scientific literature on various cognitive measures/tools that have been used to screen or assess cognitive impairment in older adults with DSI.

Method

A scoping review was conducted using the Arksey and O’Malley framework (2005). Scientific articles were searched across eleven databases (CINAHL, Embase, Global Health, Mednar, OAIster, OpenGrey, PsycEXTRA, PsycINFO, PubMed, Web of Science, and WorldWideScience). The inclusion criteria were: the articles considered and/or measured cognitive function, in individuals with DSI, aged 65 and older. Extracted data included sample cognitive status, cognitive measure type (objective or subjective), reported cognitive domains evaluated by the measure, psychometric properties as well as reported, if any, sensibility measures during administration.

Result

Of 11,595 articles retrieved, fifty‐six (n = 56) met the inclusion criteria. All but five (n=5) studies employed an objective measure of cognitive function. The most commonly used cognitive test in studies with older adults with DSI is the Mini‐Mental State Examination (1975) with almost 1/3 of the studies reporting its use (n=17). More importantly, none of the studies in this scoping review used cognitive tests that were adapted for vision and hearing impairment, highlighting that optimal cognitive assessment in DSI is neglected.

Conclusion

Most objective cognitive tests include vision‐ and hearing‐dependent items and require functional vision and/or hearing for both the administration and the execution of these tests. Our study confirmed the use of commonly used standardized tests, initially validated in a healthy population, to measure the cognitive function of older adults with DSI. Identifying these generally utilized tools is the first step to developing optimal adaptations in their administration for this vulnerable population.
Platform extension for second‐generation Elecsys β‐amyloid(1−42), pTau, and tTau cerebrospinal fluid (CSF) immunoassays on cobas e analyzers
Authors: Rutz Sandra , Wittig Martina , Geiselmann Gudrun , Müller‐Hübner Laura
Published: December 2021

Background

The Elecsys® β‐Amyloid(1−42) CSF Gen2 (Abeta42 Gen2), Phospho‐Tau (181P) CSF Gen2 (pTau Gen2), and Total‐Tau CSF Gen2 (tTau Gen2) immunoassays currently in development for the detection of Alzheimer’s disease will become available on cobas e 801 and e 402 platforms (Roche Diagnostics International Ltd). This study evaluated the analytical performance of second‐generation Elecsys CSF immunoassays on extended cobas e platforms.

Method

CSF samples were analyzed using the Elecsys Abeta42 Gen2, pTau Gen2, and tTau Gen2 CSF immunoassays on cobas e 801 and e 402 analyzers at the Roche Penzberg site. Repeatability and intermediate precision were evaluated per the CLSI EP05‐A3 protocol using two assay‐specific PreciControl samples and a panel of native CSF samples covering the assay measuring range (two runs per day with two aliquots over 21 days; n=84). Coefficients of variation (CVs [%]) and standard deviations were calculated. Method comparisons (lot‐to‐lot and between platform) were conducted according to the CLSI EP09 protocol. For the lot‐to‐lot comparison, native CSF samples were analyzed for Lot A and B with all three Elecsys immunoassays on cobas e 801. For the platform comparison, native CSF samples were analyzed with all three Elecsys immunoassays on cobas e 801 and e 402. Passing‐Bablok regression and Pearson’s correlation were calculated.

Result

Good precision was observed for all three Elecsys CSF immunoassays on cobas e 801. CVs for repeatability were ˂5% for Elecsys Abeta42 Gen2 and ˂2% for Elecsys pTau Gen2 and tTau Gen2, and for intermediate precision were ˂6%, ˂3%, and ˂2% for Elecsys Abeta42 Gen2, pTau Gen2, and tTau Gen2, respectively (Tables 1‐3). Method comparison experiments demonstrated good lot‐to‐lot agreement on cobas e 801 (Pearson’s r: 0.999−1.000) and good platform agreement between cobas e 801 and e 402 (Pearson’s r: 0.999−1.000) (Table 4). Broader on‐board and calibration stability were observed for the Elecsys CSF immunoassays on cobas e 801 and e 402 compared with cobas e 601 (data not shown).

Conclusion

Second‐generation Elecsys CSF immunoassays demonstrated good analytical performance on extended cobas e platforms, including good precision, lot‐to‐lot and platform agreement, supporting their use and the implementation of CSF biomarkers in clinical routine.
Patient preferences for prognostic counseling in idiopathic/isolated REM sleep behavior disorder
Authors: Gossard Thomas R , Teigen Luke N , Timm Paul C , Feemster John C , McCarter Stuart J , St. Louis Erik K
Published: December 2021

Background

To examine patient preferences regarding prognostic counseling for idiopathic/isolated REM sleep behavior disorder (iRBD). Idiopathic/isolated REM sleep behavior disorder (iRBD) carries an approximate 73‐91% long term risk for phenoconversion to dementia with Lewy bodies (DLB) and Parkinson disease (PD). Previous research has shown that most providers counsel their patients concerning this risk, yet patients’ values and preferences regarding counseling are unknown.

Methods

122 participants with iRBD in the Mayo Clinic iRBD Patient Registry enrolled. Participants were sent a survey concerning prognostic counseling and their experience in being diagnosed with iRBD.

Results

Of 81 respondents (67.2% response rate), 74% were men with an average age of 65.7 ± 9.7 years. Responses indicated a strong preference toward receiving prognostic information; 92.5% felt knowledge concerning neurodegenerative disease risk was important, while 87.6% felt prognostic discussion was important to maintain trust in their physician. Additionally, 95.7% indicated they desired more information, while only 4.3% would have desired less information regarding prognostic risk following iRBD diagnosis. Most respondents agreed strongly that prognostic information was important for discussions with their family and friends and future life planning, and expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia.

Conclusions

iRBD patients indicated a strong preference for disclosure of neurodegenerative prognostic risk information, preferred more rather than less information, and felt prognostic information was important for family discussions and life planning. This data informs prognostic counseling practices regarding iRBD and other neurodegenerative diseases.
Clinical and analytical comparison of three assays for plasma p‐tau isoforms on an ultrasensitive platform
Authors: Bayoumy Sherif , Dulk Ben Den , Hussainali Zulaiga , Verberk Inge M.W. , van der Flier Wiesje M , Zwan Marissa D. , Dage Jeffrey L. , Teunissen Charlotte E.
Published: December 2021

Background

Plasma phosphorylated Tau (P‐tau) protein is a promising biomarker for early detection of Alzheimer’s Disease (AD), reflecting abnormal tau metabolism in CSF and brain. Different Tau isoforms have been shown as specific biomarkers to detect AD including plasma tau phosphorylated at threonine 181 (P‐tau181) and at threonine 217 (P‐tau217). Novel plasma tests have been developed on various platforms for different isoforms and using various reagents, but these have not been compared directly for their analytical and clinical performance. In this study, we directly compared three novel P‐tau blood assays to investigate the clinical and technical differences between each assay.

Method

We included the following assays: plasma P‐tau181 from Quanterix, P‐tau181 Lilly and P‐tau217 Lilly assays, all run on the Simoa HD‐X (Quanterix). We analytically compared the novel assays for the parameters: precision, linearity, parallelism, limit of detection, recovery and sensitivity. The clinical performance of each assay was evaluated using plasma samples from 40 non‐demented healthy individuals of www.hersenonderzoek.nl (median age 66 years, 68 % females) and 40 AD‐dementia cases of the Amsterdam dementia cohort (median age 66, 60 % females). Using a receiver operating characteristics (ROC) curve analysis, we compared the discriminatory ability of each assay. Here, we present the clinical performance results.

Result

Plasma P‐tau217 and both plasma P‐tau181 assays were highly correlated, with correlation coefficients over 0.82 (all p< 0.001). Patients with AD‐dementia showed elevated levels of P‐tau181 and P‐tau217 in comparison to healthy controls (P‐tau 217 AUC = 0.995 (0.986‐1.00), P‐tau181 Quanterix AUC=0.936 (0.885‐987), P‐tau 181 Lilly AUC= 0.938 (0.87‐1.00)). The P‐tau217 Lilly assay numerically outperformed both the P‐tau 181 assays in discriminating between AD‐dementia and control cases with a sensitivity of 97.5% at a specificity of 95%. The P‐tau181 Quanterix and Lilly showed a sensitivity of 100% at 89.5%, 79% specificity, respectively.

Conclusion

Our findings suggest that the novel plasma P‐tau isoform tests are useful for the diagnostic work up of AD‐dementia.
AlzPED: Optimizing the predictive power of drug efficacy studies in Alzheimer’s disease animal models
Authors: Chakroborty Shreaya , Sharma Ali , Martin Zane , Yuan Jean , Petanceska Suzana S , Refolo Lorenzo M
Published: December 2021

Background

Poor translation of preclinical efficacy from animal models to the clinic is a major challenge to successful therapy development for Alzheimer’s disease (AD). Assessments of preclinical animal studies highlight the need for an emphasis on rigor in study design and methodology and a consensus towards a uniform set of study design elements and best practices. The Alzheimer’s Disease Preclinical Efficacy Database (AlzPED), a searchable and publicly available knowledgebase developed by the National Institute on Aging, has identified and compiled a standardized set of best practices and experimental design guidelines to effectively promote the translation of preclinical therapeutic studies in AD animal models to the clinic.

Method

Using key word‐driven literature searches published studies are acquired and curated by two experts for data on authors, funding source, AD animal models, therapeutic targets and therapeutic agents, study design, and outcome measures, prior to publication in the database. Rigor in study design and methodology is evaluated with a Rigor Report Card consisting of a standardized set of expert‐recommended study design elements.

Result

AlzPED hosts curated summaries from more than 1100 published preclinical therapeutic studies in AD animal models, and data related to 223 therapeutic targets, 1020 therapeutic agents, 200 animal models, more than 1500 AD‐related outcome measures, and thousands of principal findings. Evaluation of Rigor Report Cards from each study demonstrates significant under‐reporting of critical elements of methodology such as power/sample size calculation, blinding for treatment, blinding for outcomes, randomization, balancing for sex, animal genetic background, and inclusion/exclusion criteria, these being reported by fewer than 30% of the more than 1100 curated studies.

Conclusion

Analysis of curated studies demonstrates serious deficiencies in reporting critical elements of methodology. These deficiencies diminish the scientific rigor, reproducibility, and translational value of the preclinical studies. Adopting a standardized set of best practices like those proposed by AlzPED can improve the predictive power of preclinical studies in AD animal models and promote the effective translation of preclinical drug testing data to the clinic.