bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social support factors and cognitive outcomes in mid‐life
Authors: Bruck Margaret , Xia Feng , Dintica Christina S. , Sidney Stephen , Yaffe Kristine 
Published: December 2021

AbstractBackgroundA growing body of evidence suggests that social support is associated with cognitive outcomes including dementia in late‐life. Yet few studies have examined the association between social support and cognition in mid‐life, a critical time of transition to aging. Furthermore, little is known about the effects of other aspects of social function such as emotional support, social strain and loneliness on cognition. Our goal was to investigate the association between several social support factors and cognitive performance in mid‐life.MethodWe studied 2,732 Black and White adults from the Coronary Artery Risk Development in Young Adults (CARDIA) Study who completed a social support questionnaire at baseline (CARDIA Year 20, mean age 45.2 years, 57% female, 45% Black) which assessed aspects of emotional support, social strain, and loneliness. At the 10‐year follow‐up, cognitive performance was evaluated with a battery of five tests: Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), Stroop Test, Verbal Fluency (category and letter fluency), and the Montreal Cognitive Assessment (MOCA) and standardized to z‐scores. We used linear regression to determine the association between emotional support, social strain, and loneliness, categorized as tertiles (comparing high to low), with mid‐life cognition.ResultIn unadjusted models, all three social support factors were associated with cognition 10 years later. After adjusting for age, sex, race, education, marital status, income, and depression, participants reporting higher levels of emotional support performed better on all cognitive tests (DSST High vs. Low (z‐score)=0.13 [95%CI 0.03, 0.23]; RAVLT=0.17 [95%CI 0.07, 0.27]; reverse Stroop=0.15 [95%CI 0.05, 0.26]; Verbal Fluency=0.12 [95%CI 0.01, 0.23]; MOCA=0.19 [95%CI 0.09, 0.28]). Less social strain was associated with higher scores on most tests (DSST Low vs. High=0.16 [95%CI 0.06, 0.26]; RAVLT=0.11 [95%CI 0.01, 0.21]; and MOCA=0.13 [95%CI 0.04, 0.23]). Loneliness was not associated with mid‐life cognition.ConclusionGreater level of social support, particularly emotional support, was associated with better mid‐life cognitive outcomes 10 years later. To better inform risk and prevention efforts, more research should be conducted to investigate the associations between various dimensions of social support and cognitive outcomes across the life course.
Brain age acceleration as biomarker of Alzheimer’s disease progression: Functional network connectivity analysis
Authors: Sendi Mohammad S.E. , Salat David H , Calhoun Vince D 
Published: December 2021

AbstractBackgroundThe brain age gap, the difference between an individual’s brain predicted age and chronological age, is used as a brain disease biomarker and aging. To date, although previous studies utilized mostly structural magnetic resonance imaging (MRI) data to predict brain age, less work has used functional network connectivity (FNC) from resting‐state functional MRI (rs‐fMRI) to indicate brain age and its link with Alzheimer’s disease (AD) progression. This study aims to estimate brain age from FNC and introduce it as a biomarker of AD progression.MethodThis study used 1091 rs‐fMRI data and the chronological age at the time of scanning, ranging from 42‐95, from the Open Access Series of Imaging Studies (OASIS)‐3 cohort. This dataset includes 1021 healthy subjects (HC) and 70 AD patients. We used group independent component analysis to estimate 53 components for the whole‐brain. Then, FNC feature, in total 1378, of each subject was calculated by applying the Pearson correlation. A support vector regression (SVR) was trained on 951 HC subjects in which FNC features and the chronological age was served as predictor and prediction output, respectively. We then tested the trained model on 70 HC (age mean± sd: 73.66± 7.47) and 70 AD (age mean± sd: 73.34± 7.51) subjects to predict their brain age.ResultThe correlation between predicted brain age and the chronological age of HC test data was R=0.73, (p=5.3e‐13, N=70), while the correlation between predicted brain age and AD patients' chronological age was R=0.33 (p=0.004, N=70). This result shows that the model based on HC could better predict the HC age than the AD patients. The brain age gap mean and standard deviation for the test HC and AD group was ‐2.2581± 5.0879 and 2.0814± 7.4520. This result shows that the brain age gap was increased in AD (Cohen’s d=0.68, p<0.001).ConclusionWe proved that FNC, estimated from rs‐fMRI, could predict the brain age in HC. Also, we found an acceleration in the brain predicted age of AD patients. We also found that the AD subjects' brain age gap was significantly higher than the brain age gap of the HC group.
Intracranial stenosis interacts with amyloid positron emission tomography (PET) standard uptake value ratio (SUVR) to predict cognitive decline in a memory clinic cohort
Authors: Lim Mervyn Jun Rui , Gyanwali Bibek , Chen Christopher , Hilal Saima 
Published: December 2021

AbstractBackgroundIntracranial stenosis (ICS) is associated with cognitive impairment and dementia. However, data examining the effect of ICS and beta‐amyloid on cognitive decline are lacking. Thus, we aimed to investigate the effect of ICS on beta‐amyloid and their interaction on cognition in a memory clinic cohort.MethodsParticipants were recruited from the National University Hospital memory clinic in Singapore. Data was collected using a standardized questionnaire, physical examination and 3T MRI. ICS was defined as arterial narrowing that exceeded 50% of the luminal diameter in any of the intracranial vessels. Beta‐amyloid was measured using [11C]‐PiB‐PET global standardized uptake value ratio (SUVR). Cognition was assessed by neuropsychological testing.Results185 participants diagnosed with no cognitive impairment, cognitive impairment no dementia, or dementia were included. The mean age was 75.7 ± 7.3 years and 86 (46.5%) participants were male. A total of 17 (9.2%) participants had ICS and the mean SUVR was 1.4 ± 0.4. In adjusted models, ICS was not significantly associated with elevated SUVR in the overall population (β = ‐0.04; 95%CI = ‐0.24 – 0.16; p‐value = 0.69). In adjusted models, ICS had significant interaction with SUVR in global cognition (p = 0.043), attention (p = 0.024), visual memory (p = 0.019), and visuospatial function (p = 0.047). In patients with no ICS, SUVR was associated with worse cognitive scores, while in patients with ICS, SUVR was associated with better cognitive scores. This interaction remained significant for attention (β [No ICS]: ‐1.57 [95%CI: ‐2.50 to ‐0.63]; β [Yes ICS]: 1.42 [95%CI: ‐1.13 to 3.96]; p = 0.029) and visual memory (β [No ICS]: ‐1.57 [95%CI: ‐2.38 to ‐0.76]; β [Yes ICS]: 1.04 [95%CI: ‐1.17 to 3.24]; p = 0.028) even after further adjustment for ApoE and hippocampal volume.ConclusionIn patients with no ICS, beta‐amyloid was associated with worse cognition, while in patients with ICS, beta‐amyloid was associated with better cognition. This suggests that beta‐amyloid may have a protective effect against cognitive impairment in patients with ICS. Further studies are required to investigate this association and elucidate on the mechanistic pathway of the interaction between ICS and beta‐amyloid on cognition.
Integration of health information technology and promotion of personhood in family‐centered dementia care
Authors: Brown Ellen L , Ruggiano Nicole , Roberts Lisa , Clarke Peter J , Davis Debra J , Hough Monica Strauss , Muñoz Mariateresa (Teri) H , Framil C Victoria , Allala Sai Chaithra 
Published: December 2021

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) are leading causes of disability and often result in communication deficits that can complicate ADRD caregiving and clinical care. Augmentative and Alternative Communication (AAC) devices have been shown to provide assistance in communication for persons with ADRD, although many of these devices have been criticized for limited ability to customize content or design, and not addressing the impact of communication deficits on the larger family unit. This program of research has been informed by related theoretical frameworks: person‐centered (PCT) and family‐centered theories (FCT).MethodAn interdisciplinary team working with stakeholders are designing a novel information technology prototype with a touchscreen to promote communication and personhood for persons with ADRD. This improved ACC device is best described as an AAC Plus. The AAC Plus goes beyond traditional AAC in that it can be integrated into an existing healthcare delivery system and provide real‐time clinical data and health trends to the healthcare provider for early detection, intervention, and monitoring of clinical symptoms. In addition, the AAC Plus: (1) is designed to promote engagement and communication for interactions between the caregiver and person with ADRD using ubiquitous touchscreen technology; (2) facilitates tracking of behavioral and other clinical information about the person with ADRD, such as sleep and appetite; (3) has easily customizable interfaces for the caregiver and person with ADRD.ResultUsability and feasibility will be tested using common use case scenarios, user experience testing, alpha testing, and beta testing methodologies to evaluate ease‐of‐use and cognitive ergonomics for both caregivers and persons with ADRD. This will include evaluating the design layout, user flow, and integrated content for the device’s interfaces. Once usability and feasibility is established, the team will conduct a randomized trial of the AAC Plus, in collaboration with Memory Centers in the United States (R01 AG068572‐01).ConclusionThis presentation will provide content on the process of development and human‐computer interaction methodologies used to develop an evidence‐based, innovative technology for people with ADRD and their caregivers. Attention will also be given for developing technologies for ADRD care that integrate person and family‐centered design.
The association between isolated hypertension and brain volumes in UK Biobank
Authors: Newby Danielle , Winchester Laura M , Sproviero William , Fernandes Marco , Ghose Upamanyu , Li Qingqin S , Launer Lenore J , Nevado‐Holgado Alejo J 
Published: December 2021

AbstractBackgroundHypertension is a well‐established risk factor for cognitive impairment, brain atrophy and dementia. Isolated hypertension is where either systolic or diastolic blood pressure is high and the other measure is normal. It is unknown the impact of isolated hypertension on brain atrophy and how it compares to non isolated hypertension (NIH). Therefore it is important to investigate the impact of isolated hypertension to help understand its impact on future dementia risk and cognitive decline. We investigated relationships between isolated hypertension on brain volumes using the largest cohort of healthy individuals from the United Kingdom.MethodUsing the UK Biobank cohort, we carried out a cross‐sectional study using 31,513 participants [mean age 63 years, 53% female] with BP measurements and brain MRI data. We used linear regression models to determine the associations between isolated systolic (ISH) and isolated diastolic hypertension (IDH) split by BP medication use with brain volumes (total volume, total grey matter, hippocampal and white matter hyperintensities (WMH)).ResultIndividuals with ISH and taking BP medications (n = 3137) had smaller grey matter volumes (β = ‐0.04 [95%CI ‐0.07 to ‐0.03]), and greater WMH (β = 0.25 [95%CI 0.21 to 0.28]) compared to normotensive individuals (n = 14677). Interestingly, individuals with IDH and taking BP medications (n =140) also had smaller total grey matter (β = ‐0.11 [95%CI ‐0.19 to ‐0.04]) and larger WMH (β = 0.26 [95%CI 0.12 to 0.41]). Individuals with ISH have comparable total grey matter atrophy to individuals with NIH not taking medications (ISH β = ‐0.044 vs NIH β = ‐0.027) and have comparable WMHs (ISH β = 0.25 vs NIH β = 0.022).ConclusionOur results indicate that individuals with isolated hypertension have greater total grey matter atrophy and vascular pathology and this atrophy is similar to certain subsets of individuals with non isolated hypertension. These results provide a further emphasis of preventative strategies particularly focusing on isolated systolic hypertension as well as non isolated hypertension in maintaining brain health to reduce dementia risk earlier in life.
Association of psychological stress with risk of dementia: A systematic review and meta‐analysis
Authors: Franks Katherine H , Bransby Lisa , Saling Michael M , Pase Matthew P 
Published: December 2021

AbstractBackgroundWith no effective disease‐modifying treatments, there is a need to identify lifestyle risk factors that may prevent or delay the onset of dementia. One proposed risk factor is psychological stress. Although many studies have investigated the association between stress and dementia, to our knowledge, no meta‐analysis has examined this. The current study investigated the association between different aspects of psychological stress (including neuroticism, stressful life events and perceived stress) and the risk of incident dementia in adults without cognitive impairment.MethodThe study was prospectively registered and conducted in accordance with PRISMA guidelines. PsycINFO, Embase and MEDLINE were searched for eligible observational, prospective studies from database inception to October 2020. Pooled hazard ratios (HRs) were generated using random‐effects models to separately examine each aspect of stress in relation to the incidence of all‐cause dementia and Alzheimer’s disease (AD) dementia.ResultOf the 1607 studies screened, 15 (18 cohorts) were included in meta‐analyses. Across studies, higher perceived stress was significantly associated with an increased risk of all‐cause dementia (Cases/Total N = 203/1,882: hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.07‐1.95). Exposure to two or more stressful life events (versus none) was also significantly associated with an increased risk of all‐cause dementia (Cases/Total N = 3,352/11,597: HR = 1.72, 95% CI = 1.14‐2.60), while one or more stressful life events was not. Higher neuroticism was significantly associated with an increased risk of AD dementia (Cases/Total N = 497/4,771: HR = 1.07, 95% CI = 1.01‐1.12), but not all‐cause dementia.ConclusionPsychological stress in adulthood is associated with an increased risk of dementia. Further research is needed to clarify the mechanisms underlying these associations.
Are we targeting the right population? Application of eligibility criteria of 10 dementia prevention trials to the general population
Authors: Licher Silvan , Wolters Frank J , Pavlović Jelena , Kavousi Maryam , Leening Maarten JG , Ikram M Kamran , Ikram M Arfan 
Published: December 2021

AbstractBackgroundVarious trials have investigated the effects of multidomain lifestyle interventions on cognitive decline, but with limited clinical benefit. This could be due to these trials targeting older individuals with elevated cardiovascular risk factors, who often already qualify for preventive intervention. We aimed to determine clinical implications of trials by application of trial eligibility criteria and prognosis to the general population.MethodWe conducted a literature review and sought to identify large (≥500 participants), phase‐3 multidomain lifestyle trials for the prevention of cognitive decline or dementia. We extracted eligibility criteria, and applied these to participants from the population‐based Rotterdam Study (40≥years). We determined what proportion of trial‐eligible individuals qualified for preventive intervention according to American (ACC/AHA) and European (ESC/EAS) cardiovascular prevention guidelines. To evaluate whether trial inclusion criteria optimally captured individuals at high risk of dementia that could benefit most, we compared remaining lifetime dementia risk, with 10‐year predicted risks for cardiovascular events.ResultOut of 1448 abstracts, we five identified published dementia prevention trials (DR’s EXTRA, FINGER, preDIVA, MAPT and HATICE). Through trial registries, we identified another five (US‐POINTER, MIND‐CHINA, MYB‐Trial, J‐Mint and AgeWell.de) that were ongoing at time of the search. Among 5381 Rotterdam Study participants (mean age 72 years, 58% women), eligibility across published trials ranged from 48% for MAPT to 87% for PREDIVA, largely mimicking estimates from original trial reports. Variability in eligibility was wider for ongoing trials, and ranged from 0.9% for US‐POINTER, to 21% for Age‐Well.de up to 94% for J‐Mint. The vast majority of individuals already qualified for both lifestyle and pharmaceutical interventions (e.g. statins or antihypertensives) based on their cardiovascular risk (ACC/AHA: from 65% for DRs EXTRA to 93% for AgeWell.de, for ESC/EAS: from 60% for DR’s EXTRA to 83% for HATICE). Remaining lifetime dementia risk was higher when individuals were at lower 10‐year cardiovascular risk.ConclusionMultidomain dementia prevention trials target a segment of the population that already qualifies for preventive interventions based on their cardiovascular risk according to cardiology guidelines. These findings call for adapted recruitment strategies in dementia trials, to adequately capture the population at risk in whom maximum benefit can be achieved.
Heterogeneity in imaging‐based spread of tau and atrophy in atypical AD
Authors: Whitwell Jennifer L. 
Published: December 2021

AbstractBackgroundDifferent clinical phenotypes of atypical AD are each associated with characteristic patterns of neurodegeneration and tau deposition on PET. However, longitudinal patterns of tau accumulation and atrophy dissociate and there is significant subject‐level heterogeneity in patterns of progression. We investigate the degree to which heterogeneity in tau progression and atrophy is related to age, apolipoprotein (APOE) genotype and clinical progression.MethodThe Neurodegenerative Research Group (NRG) recruited 138 atypical AD patients (posterior cortical atrophy [PCA] = 57, logopenic progressive aphasia [LPA] = 81), of which 57 underwent longitudinal 3T head MRI and [18F]flortaucipir PET. Region‐of‐interest and voxel‐level analyses were utilized to assess relationships between rates of both atrophy and flortaucipir accumulation with age and APOE ε4 genotype. Principle component analysis using 12 different cognitive tests was used to assess patterns of clinical decline, with the principle components correlated to neuroimaging.ResultFastest rates of tau accumulation were observed in the frontal lobes in PCA and LPA, while fastest rates of atrophy were observed in occipital lobe in PCA and left temporoparietal lobe in LPA. Cortical rates of tau accumulation, particularly in the frontal lobe, were faster in younger patients and in APOE ε4 non‐carriers within LPA and PCA. Spatial patterns of tau accumulation were similar in both carriers and non‐carriers. Cortical rates of atrophy, particularly in parietal regions, were faster in younger patients in PCA and LPA, and in APOE ε4 non‐carriers. Conversely, rates of medial temporal atrophy were faster in older patients and APOE ε4 carriers. Increased rates of tau accumulation across the cortex, but particularly in frontal regions, corresponded to greater severity of clinical decline across tests over time.ConclusionRates of tau accumulation and atrophy are both influenced by age and APOE genotype in atypical AD, but with different regional associations observed for each modality. These findings highlight heterogeneity present in neuroimaging signatures of atypical AD beyond clinical phenotype.
Intellectual curiosity and action initiation are subtypes of apathy affected in Huntington’s disease gene expansion carriers
Authors: Hendel Rebecca Kjærgaard , Hellem Marie Nathalie Nickelsen , Hjermind Lena Elisabeth , Nielsen Jørgen Erik , Vogel Asmus 
Published: December 2021

AbstractBackgroundApathy is a prevalent behavioral symptom in neurodegenerative diseases. In Huntington’s Disease, apathy can result in severe loss of function for the patient and substantial caregiver distress. The research‐based evidence of apathy is characterized by a lack of generalizability due to methodological differences. In this study we wished to characterize apathy in premanifest and motor‐manifest Huntington’s Disease gene expansion carriers and controls.Method82 Huntington’s Disease gene expansion carriers (premanifest and motor‐manifest) and 32 controls were included in the study (Mini‐Mental State Examination score ≥ 24 and Montreal Cognitive Assessment score ≥ 19). Apathy was quantified using the Lille Apathy Rating Scale and the Short Problem Behaviors Assessment for Huntington’s Disease. Analyses of association were performed between apathy on the Lille Apathy Rating Scale and motor function, cytosine‐adenine‐guanine repeat length, cytosine‐adenine‐guanine age product score, neuropsychiatric and cognitive screening tests.ResultCompared to premanifest and control participants, the motor‐manifest Huntington’s Disease gene expansion carriers scored significantly higher on the global score on the Lille Apathy Rating Scale and on two subscales (Intellectual Curiosity and Action Initiation – see table 1). Likewise, motor‐manifest HD gene expansion carriers scored significantly higher on the Short Problem Behaviors Assessment for Huntington’s Disease. Significant correlations were found between apathy on the Lille Apathy Rating Scale and the motor score, the neuropsychiatric measures and the cognitive screening tests. Apathy was present in 22 % of the Huntington’s Disease gene expansion carriers (including four premanifest participants) when examined with the Lille Apathy Rating Scale. The apathetic participants had significantly higher motor score and were significantly affected on the neuropsychiatric measures and the cognitive screening tests. When entered a multiple stepwise regression model, apathy was predicted by the motor score and the depression score. No other variables could significantly predict apathy on the Lille Apathy Rating Scale.ConclusionApathy is a frequent and early symptom of disease in Huntington’s Disease gene expansion carriers, and it has a specific expression that might be related to the underlying neuropathology. Apathy is related to disease progression, cognitive decline and neuropsychiatric symptoms.