BACKGROUND: To support clinical trial designs focused on early interventions, our study determined reliable early amyloid-β (Aβ) accumulation based on Centiloids (CL) in pre-dementia populations.
METHODS: A total of 1032 participants from the Amyloid Imaging to Prevent Alzheimer\'s Disease-Prognostic and Natural History Study (AMYPAD-PNHS) and Insight46 who underwent [18F]flutemetamol, [18F]florbetaben or [18F]florbetapir amyloid-PET were included. A normative strategy was used to define reliable accumulation by estimating the 95th percentile of longitudinal measurements in sub-populations (NPNHS = 101/750, NInsight46 = 35/382) expected to remain stable over time. The baseline CL threshold that optimally predicts future accumulation was investigated using precision-recall analyses. Accumulation rates were examined using linear mixed-effect models.
RESULTS: Reliable accumulation in the PNHS was estimated to occur at >3.0 CL/year. Baseline CL of 16 [12,19] best predicted future Aβ-accumulators. Rates of amyloid accumulation were tracer-independent, lower for APOE ε4 non-carriers, and for subjects with higher levels of education.
CONCLUSIONS: Our results support a 12-20 CL window for inclusion into early secondary prevention studies. Reliable accumulation definition warrants further investigations.

OBJECTIVE: The complex aetiology of Alzheimer\'s disease suggests prevention potential. Risk scores have potential as risk stratification tools and surrogate outcomes in multimodal interventions targeting specific at-risk populations. The Australian National University Alzheimer\'s Disease Risk Index (ANU-ADRI) was tested in relation to cognition and its suitability as a surrogate outcome in a multidomain lifestyle randomized controlled trial, in older adults at risk of dementia.
METHODS: In this post hoc analysis of the Finnish Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), ANU-ADRI was calculated at baseline, 12, and 24 months (n = 1174). The association between ANU-ADRI and cognition (at baseline and over time), the intervention effect on changes in ANU-ADRI, and the potential impact of baseline ANU-ADRI on the intervention effect on changes in cognition were assessed using linear mixed models with maximum likelihood estimation.
RESULTS: A higher ANU-ADRI was significantly related to worse cognition, at baseline (e.g., estimate for global cognition [95% confidence interval] was -0.028 [-0.032 to -0.025]) and over the 2-year study (e.g., estimate for 2-year changes in ANU-ADRI and per-year changes in global cognition [95% confidence interval] was -0.068 [-0.026 to -0.108]). No significant beneficial intervention effect was reported for ANU-ADRI, and baseline ANU-ADRI did not significantly affect the response to the intervention on changes in cognition.
CONCLUSIONS: The ANU-ADRI was effective for the risk prediction of cognitive decline. Risk scores may be crucial for the success of novel dementia prevention strategies, but their algorithm, the target population, and the intervention design should be carefully considered when choosing the appropriate tool for each context.

BACKGROUND: We investigated the association between atrial fibrillation (AF) and dementia, and its subtypes (vascular-VaD, Alzheimer, mixed and rare dementia), and identified predictors for dementia in AF patients.
METHODS: The analysis was based on 183,610 patients with new-onset AF and 367,220 non-AF controls in the United Kingdom between 1998 and 2016, identified in three prospectively collected, linked electronic health records sources. Time-to-event (dementia or subtypes) analyses were performed using Cox proportional hazards and weighted Cox. Sub-analyses performed: including & censoring stroke and age (median used as cut-off).
RESULTS: Over a median follow-up of 2.67 years (IQR .65-6.02) for AF patients and 5.84 years for non-AF patients (IQR 2.26-11.80), incidence of dementia in the AF cohort was 2.65 per 100 person-years, compared to 2.02 in the non-AF cohort. After adjustment, a significant association was observed between AF and all-cause dementia (HR = 1.38, 95% CI: 1.31-1.45), driven by a strong association with VaD (HR = 1.55, 95% CI: 1.41-1.70). AF was also associated with mixed dementia (HR = 1.26, 95% CI: 1.01-1.56), but we could not confirm an association with Alzheimer (HR = 1.05, 95% CI: .94-1.16) and rare dementia forms (HR = 1.19, 95% CI: .90-1.56). Ischemic stroke (HR = 1.40, 95% CI: 1.26-1.56), subarachnoid haemorrhage (HR = 2.08, 95% CI: 1.47-2.96), intracerebral haemorrhage (HR = 1.95, 95% CI: 1.54-2.48) and diabetes (HR = 1.32, 95% CI: 1.24-1.41) were identified as the strongest predictors of dementia in AF patients.
CONCLUSIONS: AF patients have an increased risk of dementia, independent of stroke, with highest risk of VaD. Management and prevention of the identified risk factors could be crucial to reduce the increasing burden of dementia.

UNASSIGNED: Refugees experience higher rates of mental illness such as depression and post-traumatic stress disorder (PTSD) which are documented risk factors for dementia. Faith and spiritual practices have been shown to play a significant role in patients\' understanding and coping with illness, however, this field of study among refugee populations remains lacking. This study aims to address this literature gap by examining the role of faith on mental health and cognitive health among Arab refugees resettled in Arab and Western countries.
UNASSIGNED: A total of 61 Arab refugees were recruited through ethnic community-based organizations in San Diego, California, United States (N = 29) and Amman, Jordan (N = 32). Participants were interviewed through in-depth, semi-structured interviews or focus groups. Interviews and focus groups were transcribed, translated, and coded using inductive thematic analysis and organized based on Leventhal\'s Self-Regulation Model.
UNASSIGNED: Faith and spiritual practices significantly impact participants\' illness perceptions and coping procedures regardless of resettlement country or gender. Several themes emerged: (1) participants believe in the interdependent relationship between mental and cognitive health. (2) There is a self-awareness of the impact of the refugee experience and trauma on participants\' mental health problems, leading to a belief of increased personal risk for developing dementia. (3) Spiritual fatalism (belief that events are predetermined by God, fate, or destiny) greatly informs these perceptions of mental and cognitive health. (4) Participants acknowledge that practicing faith improves their mental and cognitive health, and many read scripture to prevent dementia. (5) Finally, spiritual gratitude and trust are important coping procedures that build resilience among participants.
UNASSIGNED: Faith and spirituality play an important role in shaping Arab refugees\' illness representations and coping procedures of mental and cognitive health. Holistic public health and clinical interventions tailored to the spiritual needs of aging refugees and incorporating religion in prevention strategies are increasingly needed to improve the brain health and wellbeing of refugees.

BACKGROUND: Informal care for people with dementia not only affects the well-being of the primary caregiver but also changes their roles and interactions with the social environment. New online interventions might facilitate access to social support. Recently, an online social support platform, Inlife, was developed in the Netherlands and aims to enhance social support and positive interactions in informal support networks.
OBJECTIVE: This study aimed to evaluate the effectiveness of Inlife for caregivers of people with dementia.
METHODS: A randomized controlled trial with 96 caregivers of people with dementia was performed. Participants were randomly assigned to the Inlife intervention or the waiting list control group. After 16 weeks of Inlife use, the waiting list control group could start using Inlife. Effects were evaluated at baseline (T0), 8 weeks (T1), and 16 weeks (T2). The 16-week follow-up assessment (T2) served as the primary endpoint to evaluate the results for the primary and secondary outcome variables evaluated with online self-report questionnaires. The primary outcomes included feelings of caregiver competence and perceived social support. The secondary outcomes included received support, feelings of loneliness, psychological complaints (eg, anxiety, stress), and quality of life.
RESULTS: No significant improvements were demonstrated for the intervention group (n=48) relative to the control group (n=48) for the primary outcomes (feeling of carer competence: b=-0.057, 95% CI -0.715 to 0.602, P=.87; perceived social support: b=-15.877, 95% CI -78.284 to 46.530, P=.62) or any secondary outcome. This contrasts with our qualitative findings showing the potential of Inlife to facilitate the care process in daily life. Adherence was not optimal for all Inlife users. Additional per-protocol and sensitivity analyses also revealed no beneficial results for high active Inlife users or specific subgroups. Inlife users were more active when part of a larger network.
CONCLUSIONS: Researchers should be modest regarding the effectiveness of online caregiver interventions in terms of quantitative measures of well-being and quality of life. Nevertheless, online tools have the potential to facilitate the caregiver process in daily life. Lessons learned include the importance of harnessing the power of human interaction in eHealth, making use of the user\'s social capital, and the need to develop research methods that can identify benefits in daily life that are ecologically valid for caregivers.
BACKGROUND: Netherlands Trial Register NTR6131; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6131.
UNASSIGNED: RR2-10.1186/s13063-017-2097-y.

UNASSIGNED: Due to their low cost, less invasive nature, and ready availability, plasma biomarkers of Alzheimer\'s disease have been proposed as one-time screening tools for clinical trials and research. The impact of ethnoracial factors on these biomarkers has received little attention. The current cross-sectional study investigated the levels of Aβ40, Aβ42, total tau (t tau), and neurofilament light (NfL) across diagnoses for each of the three major ethnoracial groups in the United States in a community-based cohort of older adults.
UNASSIGNED: A total of 1,862 participants (852 Mexican Americans (MAs); 775 non-Hispanic Whites (NHWs), and 235 African Americans (AAs)) drawn from The Health & Aging Brain Study-Health Disparities (HABS-HD) study were included. Diagnoses were assigned using an algorithm (decision tree) verified by consensus review. Plasma samples were assayed using Simoa technology. Levels of each biomarker were compared for the three ethnoracial groups across cognitive diagnoses using ANOVA covarying sex and age.
UNASSIGNED: Significant differences were found across the groups at each level of cognitive impairment. Cognitively unimpaired (CU) AA had significantly lower levels of each of the biomarkers than cognitively unimpaired MA or NHW and NHW had higher levels of Aβ40, and NfL than the other two groups. MA had higher t tau than AA or NHW. Mild cognitive impairment (MCI) group NHW had the highest levels on all the biomarkers and AA had the lowest. NHW and MA have higher levels of Aβ40, Aβ42, and t tau there was no difference between the groups for Aβ42. NHW had significantly higher levels of Aβ40, t tau, and NfL than AA. AA had a higher Aβ42/Aβ40 ratio than either NHW or MA for CU MCI.
UNASSIGNED: The use of plasma biomarkers of cognitive decline is promising given their advantages over other biomarkers such as CSF and imaging but as the current research shows, ethnoracial differences must be considered to enhance accuracy and utility. Developing ethnoracial-specific cut points and establishing normative ranges by assay platform for each of the biomarkers are needed. Longitudinal research to assess changes in biomarkers during a cognitive decline is ongoing.

BACKGROUND: AMYPAD Diagnostic and Patient Management Study (DPMS) aims to investigate the clinical utility and cost-effectiveness of amyloid-PET in Europe. Here we present participants\' baseline features and discuss the representativeness of the cohort.
METHODS: Participants with subjective cognitive decline plus (SCD+), mild cognitive impairment (MCI), or dementia were recruited in eight European memory clinics from April 16, 2018, to October 30, 2020, and randomized into three arms: ARM1, early amyloid-PET; ARM2, late amyloid-PET; and ARM3, free-choice.
RESULTS: A total of 840 participants (244 SCD+, 341 MCI, and 255 dementia) were enrolled. Sociodemographic/clinical features did not differ significantly among recruiting memory clinics or with previously reported cohorts. The randomization assigned 35% of participants to ARM1, 32% to ARM2, and 33% to ARM3; cognitive stages were distributed equally across the arms.
CONCLUSIONS: The features of AMYPAD-DPMS participants are as expected for a memory clinic population. This ensures the generalizability of future study results.

UNASSIGNED: Most evidence about dementia risk comes from relatively affluent people of White European ancestry. We aimed to determine the association between ethnicity, area level socioeconomic deprivation and dementia risk, and the extent to which variation in risk might be attributable to known modifiable clinical risk factors and health behaviours.
UNASSIGNED: In this nested case-control study, we analysed data from primary care medical records of a population of 1,016,277 from four inner East London boroughs, United Kingdom, collected between 2009 and 2018. The outcome measures were odds ratios for dementia according to ethnicity and deprivation, before and after the addition of major modifiable risk factors for dementia; and weighted population attributable risk for comparison between individual risk factors.
UNASSIGNED: We identified 4137 dementia cases and 15,754 matched controls (mean age for cases and controls were 80·7 years, (SD 8·7); 81·3 years, (SD 8·9) respectively, range 27-103). Black and South Asian ethnicity were both associated with increased risk of dementia relative to White (odds ratios [95% CI]: Black 1·43 [1·31-1·56]; South Asian 1.17 [1·06-1·29]). Area-level deprivation was independently associated with an increased risk of dementia in a dose-dependent manner. Black and South Asian ethnicity were both associated with a younger age at dementia diagnosis (odds ratios [95%CI]: 0·70 [0·61-0·80] and 0·55 [0·47-0·65], respectively). Population attributable risk was higher for ethnicity (9·7%) and deprivation (11·7%) than for any established modifiable risk factor in this population.
UNASSIGNED: Ethnicity and area-level deprivation are independently associated with dementia risk in East London. This effect may not be attributable to the effect of known risk factors.
UNASSIGNED: Barts Charity (MGU0366).

Studies of self-reported coffee consumption and smoking on risk of dementia have shown results conflicting with two-sample Mendelian randomization studies. We tested the hypotheses that coffee consumption and smoking influence risk of dementia using observational and one-sample Mendelian randomization designs with individual level data.
We included 114,551 individuals from two Danish general population cohorts (median age 58 years). First, we tested whether high self-reported coffee consumption/smoking were associated with risk of dementia. Second, whether genetically predicted high coffee consumption/smoking due to variation near CYP1A1/AHR/CHRNA3 genes were associated with risk of dementia.
We observed 3,784 dementia events. Moderate self-reported coffee consumption was associated with low risk of all dementia and non-Alzheimer\'s dementia, with a similar trend for Alzheimer\'s disease. Genetically predicted high coffee consumption was associated with high risk of all dementia (hazard ratio [95% confidence interval] per +1 cup/day: 1.20 [1.01-1.42]), with a similar trend for non-Alzheimer\'s dementia (1.23 [0.95-1.53]). High self-reported smoking was associated with high risk of non-Alzheimer\'s dementia. High genetically predicted smoking was associated with a trend towards high risk of all dementia and Alzheimer\'s disease (hazard ratios per +1 pack-year: 1.04 [0.96-1.11]) and 1.06 [0.97-1.16]).
Moderate self-reported coffee consumption was associated with low risk of all and non-Alzheimer\'s dementia, while high genetically predicted coffee consumption was associated with a trend towards the opposite. High self-reported smoking was associated with high risk of non-Alzheimer\'s dementia, with a similar trend for genetically predicted smoking on all dementia and Alzheimer\'s disease.

In reports of randomized controlled trials, thorough description of the attention control condition has been recommended, yet is frequently lacking. The Tele-Savvy Caregiver program for informal caregivers of persons living with dementia was tested in a randomized controlled trial with an attention control condition. The purpose of this trial was to test Tele-Savvy\'s efficacy in reducing the negative effects of caregiving on caregivers, promoting quality of life for persons living with dementia, and improving caregiver mastery. We describe the design and implementation of and examine the outcomes associated with the attention control condition. Caregivers were randomized to the immediate Tele-Savvy (active condition), Healthy Living (attention control), or waitlist. The attention control content was focused on healthy lifestyle and was not intended to affect the outcomes that Tele-Savvy targeted. The attention control group was similar to Tele-Savvy in the intervention structure and duration: it consisted of seven weekly group videoconferences and 36 video lessons. Data on outcomes of caregivers and persons living with dementia were collected at baseline and 3 and 6 months postbaseline. Multilevel mixed effects models were used to determine changes in the outcomes. One hundred and eleven caregivers were randomized to the attention control condition (attrition 21.6%). Eighteen formative assessment interviews focusing on caregivers\' experience in the attention control condition were conducted. The attention control condition completers had no statistically significant changes in the variables that Tele-Savvy targeted. These results may be used in the design and implementation of attention control conditions in behavioral intervention research.