bluuebunny/crossref_metadata_2025_split huggingface dataset:
Very long term visit‐to‐visit blood pressure variability and the risk of dementia in the Adult Changes in Thought study
Authors: den Brok Melina GHE , van Dalen Jan Willem , Marcum Zachary , van Middelaar Tessa , Hilkens Nina , Klijn Catharina JM , van Gool Willem A , Crane Paul K , Larson Eric B , Richard Edo 
Published: December 2021

AbstractBackgroundHigh visit‐to‐visit blood pressure variability (BPV) is associated with an increased risk of cardiovascular disease. However, for incident dementia, conflicting results are reported. Our objective was to assess the association of very long‐term visit‐to‐visit BPV and the risk of all‐cause dementia in community‐dwelling individuals.MethodCommunity‐dwelling individuals aged 65 years or older and free from dementia were randomly sampled from 1994 onwards from Kaiser Permanente Washington (KPW), Seattle, USA, and included in the Adult Changes in Thought (ACT) study. After enrollment, participants were followed‐up biannually. We retrospectively collected yearly data on blood pressure measurements and medical history from the age of 50 up to recruitment into the ACT study, through KPW electronic databases. Visit‐to‐visit BPV was defined as coefficient of variation (SD/mean*100) calculated with systolic blood pressure measurements. Dementia was diagnosed by an expert panel based on DSM‐IV and NINCDS‐ADRDA criteria. We used Cox regression adjusted for sex, blood pressure trend, antihypertensive medication use and cardiovascular risk factors. Subgroup analyses were performed for midlife (50‐64) and later life (≥65).ResultWe included 1174 individuals with a median age of 78 years [IQR=72‐83] at inclusion in the ACT study. Systolic blood pressure measurements (mean=27.9, SD=8.5, range: 2‐50) were collected over 2 to 54 years (mean=31.8, SD=9.4), and 483 (41.1%) individuals developed dementia. There was no significant association between very long term visit‐to‐visit BPV (mean=12.15; SD=2.67) and incident all‐cause dementia (HR=0.98; 95%CI=0.94‐1.02). Competing risk of death analyses (combined outcome dementia/death) showed a dementia/mortality risk reduction of 4% per point visit‐to‐visit BPV increase (HR=0.96; 95%CI=0.94‐0.99). The associations were similar for visit‐to‐visit BPV in later life (dementia: HR=0.99; 95%CI=0.95‐1.02, dementia/death: HR=0.96; 95%CI=0.93‐0.99). Visit‐to‐visit BPV in midlife was not associated with incident dementia (dementia: HR=0.99; 95%CI=0.96‐1.02, dementia/death: HR=1.01; 95%CI=0.99‐1.02).ConclusionIn our sample, higher very long‐term visit‐to‐visit BPV is associated with lower incident all‐cause dementia risks. This association might be stronger in later life than in midlife.
Orthostatic hypertension is associated with lower plasma Aβ42/Aβ40 ratio: The Multidomain Alzheimer Preventive Trial (MAPT)
Authors: Rouch Laure , Rolland Yves , Hanon Olivier , Vidal Jean‐Sébastien , Andrieu Sandrine , Barreto Philipe de Souto , Vellas Bruno 
Published: December 2021

AbstractBackgroundOrthostatic hypertension (OHYPER), an emerging hemodynamic cardiovascular risk factor, is associated with cardiovascular events and mortality. Recent findings indicated that it could be an important risk factor for cognitive decline and dementia, including Alzheimer’s disease (AD). We aimed to assess the association between OHYPER and low plasma Aβ42/Aβ40 ratio, a surrogate biomarker for brain amyloidosis, associated with greater risk of mild cognitive impairment (MCI) and AD.MethodWe included 483 non‐demented community‐dwelling participants aged ≥ 70 years from the Multidomain Alzheimer Preventive Trial (MAPT). OHYPER was assessed at baseline and defined as an increase of at least 20 mmHg in systolic blood pressure (BP) and/or 10 mmHg in diastolic BP after standing. Plasma Aβ42 and Aβ40 were measured at 12 months, using an immunoprecipitation and liquid chromatography‐mass spectrometry assay. Low plasma Aβ42/Aβ40 ratio was defined as ≤ 0.107. Logistic regression models were used to assess the association between OHYPER and low plasma Aβ42/Aβ40 ratio.ResultOf 483 participants (mean age 76 years, 59% female), 113 (23.6%) had OHYPER and 161 (33.3%) low plasma Aβ42/Aβ40 ratio. OHYPER was associated with low plasma Aβ42/Aβ40 ratio (OR = 1.58, 95% CI [1.02‐2.44]) in unadjusted models. Adjustment for age, sex, education, MAPT randomization group, lying BP, antihypertensive drug use, MCI, and presence of 1 or 2 ApoE ε4 alleles did not change the results (OR = 1.67, 95% CI [1.02‐2.72]). Sensitivity analyses using the 25th percentile of plasma Aβ42/Aβ40 ratio (≤ 0.103) as an alternative cutoff and long‐term OHYPER (at least two‐thirds of visits over 12 months) reported consistent findings.ConclusionOHYPER was associated with lower plasma Aβ42/Aβ40 ratio in community‐dwelling older adults, even after accounting for potential confounders. Monitoring OHYPER may have clinical utility for identifying patients who are at risk for cognitive decline, AD or in the preclinical stages of the disease.
Early detection of frontotemporal dementia (EDoF): A digital biomarker study
Authors: Convery Rhian S , Russell Lucy L , Bocchetta Martina , Rohrer Jonathan D 
Published: December 2021

AbstractBackgroundWith the commencement of clinical trials in frontotemporal dementia (FTD), robust biomarkers that can detect the earliest signs of the disease and also measure treatment effect, are essential. Pen and paper assessments are laborious, administered infrequently, and can rely on subjective reporting. Using digital devices allows for more frequent, often continuous, assessment from home, whilst producing a wealth of objective data. The Early Detection of Frontotemporal dementia (EDoF) study aims to develop a series of digital measures that may be useful for the diagnosis of FTD and for outcome measures in trials.MethodThe EDoF study includes: a computerised cognitive battery, a mobile eye tracking device, a novel app that passively measures cognitive function by monitoring smartphone metadata, speech and language analysis using machine learning algorithms, actigraphy, and gait analysis. These measures are being validated in a large control population before being tested in symptomatic and presymptomatic genetic FTD within the Genetic FTD Initiative (GENFI) study.ResultWe are currently recruiting participants to the initial arms of the study, with over 1,300 healthy controls having already completed the computerized cognitive battery. The mobile eye tracking device measures eye movement abnormalities but also uses instructionless eye movement tasks to measure executive function and social cognition. Pilot eye tracking data shows abnormalities of these tasks in symptomatic FTD, and also for antisaccadic eye movements in presymptomatic FTD. Normative data for all of the measures will be generated helping to assess construct validity and retest reliability.ConclusionEDoF is the first study aiming to use a comprehensive set of digital measures to detect early FTD. It may also prove useful for home monitoring within future therapeutic trials of FTD.
TNF inhibitors for the prevention of Alzheimer’s disease: Preliminary findings from the rheumatoid arthritis medication and memory study (RESIST)
Authors: McDowell Bethany , Holmes Clive , Edwards Christopher J , Cardwell Christopher , McHenry Michelle , Meenagh Gary , McGuinness Bernadette 
Published: December 2021

AbstractBackgroundA raised level of serum TNFα observed in patients with Alzheimer’s disease has been associated with an increased rate of neurodegeneration and risk of conversion from mild cognitive impairment (MCI) to AD dementia. This led to the hypothesis that reduction in peripheral TNFα via TNF inhibitors (TNFi) may reduce the rate of neurodegeneration and may protect against development of AD.MethodThe rheumatoid arthritis medication and memory study (RESIST) is an 18‐month observational study which aims to compare the rate of cognitive decline between TNFi and conventional synthetic disease modifying anti‐rheumatic drugs (csDMARDs) in patients with both rheumatoid arthritis (RA) and MCI. Participants ≥ 55 years of age were recruited from rheumatology clinics in both Northern Ireland and Southampton and were cognitively assessed using the Free and Cued Selective Reminding Test (FCSRT) and Montreal Cognitive Assessment (MoCA). At the time of analysis n=130 participants had completed a 6‐month assessment and n=69 had completed a 12‐month assessment. ANCOVA analysis was conducted to calculate the difference in mean (and 95% CI) FCSRT and MoCA scores at both 6‐ and 12‐month timepoints between TNFi and csDMARD treatment groups, adjusting for baseline cognitive scores. Further adjustments were made for age, gender, RA disease activity and other confounding variables.ResultThere was no evidence of a difference between TNFi and csDMARD treatment in cognitive outcomes measured by FCSRT (6‐month cohort (mean difference 0.58, 95% CI ‐ 1.40, 2.56, p = 0.565); 12‐month cohort (mean difference ‐1.09, 95% CI ‐3.57, 1.38, p = 0.381)) or MoCA (6‐month cohort (mean difference ‐1.09, 95% CI ‐3.57, 1.38, p = 0.381); 12‐month cohort (mean difference ‐0.04, 95% CI ‐1.06, 0.98, p = 0.940)) after adjustment for baseline cognitive scores nor was there a difference in cognitive outcomes between treatment groups after adjustment for additional confounders.ConclusionThis preliminary analysis found little evidence of a relationship between TNFi and better cognitive performance however analysis was limited by lack of power and short follow‐up periods. This analysis will be repeated once RESIST has ended to determine if there is any statistically significant cognitive benefit of TNFi treatment after 18‐months.
Simultaneous assessment of posture and saccadic eye movement with visual stimuli using head‐mounted display virtual reality technology in healthy older adults
Authors: Imaoka Yu , Flury Andri , de Bruin Eling Douwe 
Published: December 2021

AbstractBackgroundPostural sway and saccadic eye movement could be potential biomarkers to diagnose Alzheimer’s disease (AD) [1, 2]. We developed a new assessment system to evaluate posture and saccadic eye movement simultaneously in healthy older adults (OA) with visual stimuli of distractors, lower contrast, and stereopsis, which are also considered to be another deficit in people with AD [3‐5]. We hypothesised that more latency and errors in saccade would be observed in the condition with visual stimuli.Method14 healthy older adults (71.9±4.8 years, 7 men / 7 women) joined the experiment after taking Montreal Cognitive Assessment (MoCA). The system consisted of stabilometer (GP‐5000, ANIMA Corporation, Japan) and a head‐mounted display virtual reality technology (VIVE Pro Eye, HTC Corporation, Taiwan). We measured both posture and eye movement simultaneously in the following test conditions: #1‐2) eyes‐open and closed without VR, #3‐4) pro‐ and anti‐saccade tests in 2D environment, and #5‐6) pro‐ and anti‐saccade tests in 3D environment. We developed the 2D environment for the baseline saccade measurement and 3D environment with more visual stimuli [6]. Each test took 60 seconds with 30 saccade trials.ResultThe participants achieved MoCA score of 27.5±1.6. We found significant difference in saccade latency between saccade types (mean: P < 0.001, SD: P < 0.001) but less significant difference between VR scenery (mean: P = 0.01, SD: P = 0.42). Moreover, we observed less significant difference in saccade error rate between saccade types (P = 0.07) and between VR scenery (P > 0.77). We did not see significant difference in postural sway (P > 0.05).ConclusionThe results may imply that the healthy OA had sufficient attentional resources to both conduct the saccade tasks and maintain their posture in the designed VR environment with visual stimuli. Further research is required to evaluate the difference between OA with and without cognitive impairment. References: 1. Bahureksa, L., et al. (2017) 2. Wilcockson, T.D.W., et al. (2019) 3. Rizzo, M., et al. (2000) 4. Lee, C.N., et al. (2015) 5. Cunha, J.P., et al. (2016) 6. Imaoka, Y., et al. (2020)
Trial readiness amongst EPAD longitudinal cohort study participants: Insights from the SPEAR study
Authors: Brenman Natassia F. , Milne Richard , Brayne Carol 
Published: December 2021

AbstractBackgroundSPEAR (Study of Participant Experience of Alzheimer’s disease Research) was a sub‐study of work on the Ethical, Legal and Social Implications of the European Prevention of Alzheimer’s Dementia (EPAD) project. The EPAD Longitudinal Cohort Study (LCS) aimed to generate a detailed picture of biological and cognitive change over time, and to build a ‘readiness cohort’ to recruit eligible and willing participants into clinical trials. This poster presents findings about the willingness of cohort participants to participate in a future clinical trial.MethodA mixed‐method study was conducted with members of the EPAD Longitudinal Cohort Study (LCS) to explore motivations to participate, study experience and likely future participation in an Alzheimer’s prevention trial. A questionnaire was completed by 101 participants and 7 study partners from 4 EPAD sites across the UK. In‐depth qualitative interviews were conducted with 25 EPAD participants and study visits observed from the same 4 sites.ResultOver half of participants would consider participating in a clinical trial at the time of data collection. Almost none reported that they would “never” participate. The timing, location and duration of trials were important in how likely they would be to participate. The qualitative findings revealed a range of tentative attitudes towards the prospect of being recruited to a clinical trial, including feeling “morally obliged to continue” or indicating “I don’t want a drug,” should they agree to participate. Some said changes in their memory or cognition may also influence future decisions.ConclusionWhilst we saw high levels of willingness to participate in a clinical trial, these data highlight the importance of understanding how motivations, willingness, and expectations for trial participation may change over time. This supports the use of a staged consent model such as that adopted by EPAD. Qualitative research is needed to understand underlying reasons for participants’ trial readiness to identify any ethical issues in the recruitment of future trial participants.
The effects of age and hypertension on cerebral small‐vessel disease differ between men and women at midlife: The PREVENT Dementia study
Authors: Low Audrey , Prats‐Sedano Maria , Stefaniak James D , Dounavi Maria‐Eleni , McKiernan Elizabeth , Carter Stephen F , Mak Elijah , Su Li , Muñiz‐Terrera Graciela , Ritchie Karen , Ritchie Craig W , Markus Hugh S , O'Brien John T 
Published: December 2021

AbstractBackgroundSex differences exist in the prevalence, prognosis, and clinical manifestation of cerebral small vessel disease (SVD) and dementia. Given the role of SVD in cognitive impairment – both directly and through accelerating neurodegenerative pathology – understanding sex differences in SVD risk factors could inform targeted intervention strategies. In this longitudinal study, we examined sex differences in the effects of age and hypertension on SVD at midlife.Method185 cognitively‐healthy midlife adults underwent 3T MRI at baseline and two‐year follow‐up. SVD markers were white matter hyperintensities (WMH) volume, enlarged perivascular spaces, microbleeds, lacunes, and global SVD burden (composite score of all four SVD markers). Piecewise linear regression analysis estimated change‐points in age, beyond which WMH accelerates. To examine sex as a moderator of age and hypertension on SVD cross‐sectionally, interaction analysis was conducted in general linear models, adjusting for age and education. To assess interactions on longitudinal SVD progression, linear mixed effects models were fitted, adjusting for the same covariates and random intercept of subjects.ResultMales were twice as likely to have hypertension compared to females (males:53.8%, females:26.4%, X
2=7.97, p=.005). Interaction analysis demonstrated that the effect of hypertension on SVD was amplified in females, compared to males, both cross‐sectionally (WMH: t=2.42, p=.017) and longitudinally (WMH progression: t=3.37, p<.001; new microbleeds: t=2.57, p=.011) (Fig 1). Findings remained consistent when additionally controlling for antihypertensive medication. In terms of age, piecewise linear regression estimated a WMH change‐point at age 50.2 (SE=3.2) in the whole sample, 50.6 years (SE=3.8) in males, but was undetectable in females (Fig 2). Sex*age interaction demonstrated that the effect of age on global SVD burden was amplified in males compared to females (t=‐2.43, p=.016) (Fig 3). Sex*age*hypertension interaction showed that hypertension intensified the effect of age on global SVD burden in males but not females (t=‐2.67, p=.008), for whom hypertension was a stronger predictor than age.ConclusionOlder men (especially those with hypertension) and women with hypertension (regardless of age) were at greatest risk of SVD. Our findings highlight the importance of hypertension management as early as midlife in relation to SVD, but suggest that this may be especially effective for women.
Divergent brain connectivity patterns in relation to cognition in Alzheimer’s disease and frontotemporal dementia
Authors: Pini Lorenzo , de Lange Siemon , Pizzini Francesca B , Galazzo Ilaria Boscolo , Manenti Rosa , van den Heuvel Martijn , Pievani Michela 
Published: December 2021

AbstractBackgroundDivergent functional connectivity (FC) abnormalities between networks linked with core cognitive deficits have been reported in Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD), the default mode (DMN) and ventral‐attention (VAN), respectively. As cognition relies on the balance between brain networks, we investigated the coupling patterns between different cognitive domains and networks.MethodTwenty‐one bvFTD (age: 71±10), 22 AD (age: 72±6) and 20 healthy controls (HC, age: 72±6) underwent cognitive evaluation and 3T resting‐state functional MRI (rsfMRI). We investigated the relationship between memory, language, executive, visuospatial and emotion recognition with FC of cognitive networks: DMN, VAN, frontoparietal (FPN), and dorsal‐attention (DAN). The visual network (VIS) was included as a control network. FC was assessed with a connectome analysis. Cortical parcels were defined using a high‐resolution structural MRI parcellation. Connectivity matrices were created assessing correlations between parcels within each functional network (Yeo 2011 parcellation). Correlation values were thresholded to retain positive values. FC and cognitive differences between groups were assessed with Kruskal‐Wallis test, Spearman’s correlation was used to assess relationships between FC and cognition.ResultCompared to HC, AD and bvFTD showed impairment in all cognitive domains (p<0.001), and bvFTD scored worse than AD in emotion recognition (p=0.013). At the network level, AD showed reduced FC in the DMN, FPN and DAN (p<0.05) and bvFTD in the VAN (p<0.05) compared to HC. In bvFTD, reduced VAN connectivity was associated with executive deficits (r=0.444; p=0.038). In AD, reduced FPN connectivity was associated with language deficits (r=0.441; p=0.04), while the opposite pattern was observed in bvFTD (r=‐0.468; p=0.028). Moreover, in AD patients DMN connectivity was negatively associated with executive deficits (r=‐0.56; p=0.007). A significant interaction was detected between AD and bvFTD for the following cognitive‐network associations: VAN‐executive: p=0.027; FPN‐language: p=0.015. No significant association was detected between DMN‐memory in AD or VAN‐emotion recognition in bvFTD (p>0.06), nor between cognition and VIS (p>0.09 for all associations).ConclusionThese results suggest a divergent FC‐cognitive pattern between AD and bvFTD in attention/executive networks/functions. We speculate that, as pathology spreads, disease‐specific symptom‐network coupling might weaken, and aberrant patterns may emerge in other domains.
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

AbstractBackgroundSelf‐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.MethodBaseline 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.ResultSelf‐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.ConclusionSelf‐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.