bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma biomarkers in relation to spatial distribution of Alzheimer’s disease neuropathology
Authors: Bilgel Murat , Shah Ishaan , Walker Keenan A. , Moghekar Abhay , Ashton Nicholas J. , Kac Przemyslaw Radoslaw , Karikari Thomas K , Blennow Kaj , Zetterberg Henrik , Thambisetty Madhav , Ferrucci Luigi , Resnick Susan M. 
Published: December 2023

AbstractBackgroundThe clinical utility of plasma biomarkers will in part be based on the information they convey regarding the distribution of neuropathology, especially beyond the information provided by demographics. We examined the associations of plasma biomarkers with cerebral amyloid and tau pathology determined by positron emission tomography (PET).MethodIn the Baltimore Longitudinal Study of Aging, plasma Aβ42/Aβ40, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) concentrations were measured using Quanterix Simoa assays. Plasma concentrations of phosphorylated tau at threonine 181 (p‐tau181) and at 231 (p‐tau231) were measured using in‐house Simoa assays at University of Gothenburg. Using voxelwise linear regression models, we investigated cross‐sectional associations of plasma biomarkers with brain fibrillar amyloid and phosphorylated tau pathology as measured by PET with 11C‐Pittsburgh compound B (PiB) conducted on a GE Advance scanner (N = 189) and 18F‐flortaucipir (FTP) conducted on a Siemens High Resolution Research Tomograph (N = 107), respectively. In addition to unadjusted analyses, we conducted analyses adjusting for age, sex, and race. Results were corrected for multiple comparisons using permutation test‐based threshold‐free cluster enhancement (TFCE).ResultLower plasma Aβ42/Aβ40 was associated with higher PiB distribution volume ratio (DVR) in the unadjusted model, but not in the adjusted model (Figure 1). The remaining plasma biomarkers exhibited statistically significant positive associations with PiB DVR in both unadjusted and adjusted models. The plasma biomarker with the strongest and most widespread association with PiB DVR was p‐tau231 (Figure 2). Both p‐tau biomarkers exhibited statistically significant associations with FTP standardized uptake value ratio (SUVR) in both unadjusted and adjusted models. Aβ42/Aβ40, GFAP, and NfL did not exhibit statistically significant associations with FTP SUVR. Associations of p‐tau biomarkers with PiB DVR were stronger and more widespread than with FTP SUVR. We did not find any statistically significant associations when we repeated the analyses separately by binary PiB group.ConclusionPlasma biomarkers convey information beyond age, sex, and race in relation to the cerebral distribution of amyloid, and to a lesser extent, tau. The smaller sample size of our FTP PET study might in part explain the weaker associations we observed with FTP SUVR compared to PiB DVR.
Racial disparities in epigenetic and cognitive aging
Authors: Yannatos Isabel , Brown Rebecca , Boen Courtney , Stites Shana D. , Xie Sharon X , McMillan Corey T 
Published: December 2023

AbstractBackgroundRacial disparities in cognitive health are persistent and pervasive among older Americans. Black Americans have higher rates of cognitive impairment and dementia than their White counterparts and a significantly higher gap between epigenetic age and chronological age. Epigenetic aging measured by DNA methylation (DNAm) has been linked to cognitive outcomes in previous research, but these studies lacked racial diversity or did not account for important confounders. Rigorous evaluation of DNAm‐age’s contribution to cognitive health disparities is needed. We hypothesize that DNAm‐age gap, measured by two epigenetic clocks GrimAge and Dunedin Pace of Aging methylation (DPoAm), is associated with cognitive performance and decline and mediates significant portions of the Black‐White disparities in these outcomes.MethodWe performed retrospective analyses among 3278 non‐Hispanic participants (80.3% White, 19.7% Black) in the Health and Retirement Study whose 2016 epigenetic age is linked to survey responses and cognitive data. DNAm‐age gap is defined as the residual after regressing epigenetic age on chronological age. Cognitive outcomes are Telephone Interview for Cognitive Status (TICS) score in 2016 and change in TICS score from 2016 to 2018. We include age, gender, and measures of socioeconomic status, health status, and health behaviors as confounders. We implement multiple linear regression models to evaluate associations between DNAm‐age gap and cognitive outcomes and mediation models to evaluate the extent to which DNAm‐age gap mediates the relationship between race and cognitive outcomes.ResultWe found that although both GrimAge and DPoAm age gaps are associated with baseline cognitive performance and longitudinal decline in minimally adjusted models, only GrimAge remained a significant predictor after adjusting for confounders. Similarly, both GrimAge and DPoAm mediate a small but significant portion (∼6‐10%) of the racial disparities in cognitive performance and decline before adjusting for confounding variables. Socioeconomic status (education, wealth, and income) has the greatest attenuating effect.ConclusionAccelerated epigenetic aging for Black compared to White Americans may play a role in racial cognitive aging disparities. Follow‐up work is ongoing to determine the role of chronic psychosocial stressors and other important determinants of cognitive health in DNAm aging and racial disparities.
Efficacy results from the unique long‐term randomised controlled double‐blind LipiDiDiet trial with a multinutrient intervention in prodromal AD/MCI_AD
Authors: Hartmann Tobias , Solomon Alina , Visser Pieter Jelle , van Oudenhoven Floor M , Blennow Kaj , Kivipelto Miia , Soininen Hilkka ,   LipiDiDiet Research Group
Published: December 2023

AbstractBackgroundLifestyle factors such as nutrition and diet are modifiable risk factors for the progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD). A small number of interventions recently showed cognitive and functional benefits. It is unclear however how long these benefits will last, requiring long‐term studies.LipiDiDiet was the first AD double‐blind, placebo‐controlled trial clinical trial to show a significant and sustainable benefit, including a 45% reduction in decline on CDR‐SB performance in a prodromal study population evaluating a multinutrient formulation (Soininen Lancet Neurology 2017; Soininen Alz&Dem 2021). We now extended the analysis from 3 years to up to 6 years of active intervention to investigate long‐term effects.MethodLipiDiDiet is a 6‐year randomised, double‐blind, placebo‐controlled trial, investigating the effects of a nutritional intervention in individuals with prodromal AD/MCIAD. 311 individuals with prodromal AD (IWG‐1) were randomized to active (125ml once‐a‐day drink; Fortasyn Connect [Souvenaid]) or a calorie‐matched control. Following the first 2 years of intervention, participants could opt‐in for annual extensions up to a maximum of 6‐year double‐blind intervention. Individual participants progressing to mild dementia were provided AD medication and/or open‐label active product and could continue in the trial. Main outcomes included Neuropsychological Test Battery (NTB) composites on cognition and memory, and the Clinical Dementia Rating‐Sum of Boxes (CDR‐SB). Modified intention‐to‐treat analyses were performed over 4‐6 years of intervention using a joint model combining longitudinal and survival data.ResultAdding data from all participants who completed the 4‐year visit while still on double‐blind treatment (n = 38) to the previously performed joint model analyses on the 3‐year data showed that the initially observed benefits on cognition, memory, and CDR‐SB appear to have continued beyond 3 years. These and other ongoing analyses are addressing the statistical challenges specific to long‐term AD trials including non‐random patterns of missing data.ConclusionIn addition to the already demonstrated sustainable benefits of Fortasyn Connect in individuals with prodromal AD/MCIAD, combined with feasibility of its long‐term use without indications for health concerns, we now report first results indicating that benefits on cognition, memory, and CDR‐SB are sustained over 4 years.
Cross‐cultural properties of the Cross‐cultural Dementia Screening test and the European Cross‐Cultural Neuropsychological Test Battery
Authors: Delgado‐Álvarez Alfonso , Delgado‐Alonso Cristina , Gil‐Moreno María José , Nielsen T Rune , Goudsmit Miriam , Valles‐Salgado María , Matias‐Guiu Jorge , Díez‐Cirarda María , Matias‐Guiu Jordi A 
Published: December 2023

AbstractBackgroundCross‐cultural neuropsychological tests are essential to avoid potential cultural biases during the performance and score interpretation in diverse populations. We aimed to compare the performance of healthy controls in the Cross‐cultural Dementia Screening test and the European Cross‐Cultural Neuropsychological Test Battery in the majority and minority populations living in Spain.MethodThree hundred cognitively healthy participants were enrolled (58% women, age range 18‐90). One hundred from majority population (Spaniards), one hundred from minority population from Colombia, and one hundred from different minority populations, including participants from Latin America (66%, excluding participants from Colombia), Spaniards of Romani (gipsy) ethnicity (14%), Arab League (10%), and East Europe (10%). We matched the three groups controlling for sex, age, and level of education. All scores on CCD and CNTB were compared and correlated with an acculturation scale, controlling for age and years of education.ResultThere were no differences between groups in most of the items. Only processing speed measures of the CCD (Sun‐Moon test) and verbal fluency tasks of the CNBT showed statistically significant differences between groups. Scores on the acculturation scale were not associated with the neuropsychological test performance of all participants.ConclusionThe absence of differences between groups or acculturation influence on the scores supports the favourable cross‐cultural properties of the CCD and the CNTB. However, some tasks could still be more influenced, especially those associated with processing speed and verbal fluency, which suggests the need to further study and develop new tests and paradigms with better cross‐cultural properties.
Personality and cognition in mild cognitive impairment: predictive role of neuroticism
Authors: De Lucia Natascia , Carraturo Fabio , Belgarbo Alessandra , Maisto Stefano , Merenda Raffaella , Rengo Giuseppe , Maldonato Nelson Mauro , Femminella Grazia Daniela 
Published: December 2023

AbstractBackgroundPersonality traits are usually defined as recurrent and distinctive patterns of thoughts, sensations and actions that present in response to specific requests. In the elderly, personality functioning has been associated with dementia risk. However, the relationship between personality traits and cognitive function in subject at risk of cognitive decline has not been explored yet. The aim of this study is to assess the predictive role of personality traits on cognitive and psychopathological function in subjects with mild cognitive impairment (MCI).Method45 subjects (mean age: 73.6±8.9; mean education: 11.2±4.7) with a diagnosis of MCI e 50 healthy older adults (OA) (mean age: 70.8±6.9; mean education: 9.7±3.7) were enrolled. All participants underwent a neuropsychometric assessment including the evaluation of visuo‐spatial, executive and memory functions, as well as behavioural symptoms with the Neuropsychiatric Inventory questionnaire. Personality traits were evaluated with the Eysenck Personality Questionnaire (EPQ‐R).ResultMCI subjects showed significantly poorer performances on visuo‐spatial, executive and memory tasks compared to OA, as well as more severe depression, apathy, irritability, and sleep disturbances. MCI subjects had higher prevalence of neurotic and introvert traits on the personality test. In MCI subjects, neuroticism was correlated with performance on word repetition test and stroop test, as well as with higher agitation and depression. Introvertion trait was correlated with MMSE and Trail Making test scores. Regression analysis showed a signtificant association between neuroticism, executive function and depression in MCI.ConclusionSpecific personality traits, especially neuroticism, might represent a predictive factor for executive functions decline and for depression in MCI. A deeper understanding of personality functioning in subjects with MCI might help develop more tailored treatments aimed at dementia prevention in these subjects.
The BetterBrains Trial: Baseline characteristics and trial progress of an online multi‐domain lifestyle intervention trial to delay cognitive decline in middle‐aged adults at risk of dementia
Authors: Rosenich Emily , Pirotta Stephanie , Mills Andrea , Norfolk Maya , Da Costa Gabrielle , Barker Anna L , Yassi Nawaf , Churilov Leonid , Sinnott Richard , Buckley Rachel F. , Brodtmann Amy , Rajaratnam Shanthakumar W , Pase Matthew P. , Bush Ashley I , Maruff Paul , Ayton Darshini , Lim Yen Ying ,   BetterBrains Research Group
Published: December 2023

AbstractBackgroundBetterBrains is a prospective, blinded endpoint, 24‐month randomised controlled trial (RCT). It aims to test the effectiveness of an online, person‐centred, modifiable risk factor (RF) management program in delaying cognitive decline in middle‐aged adults (aged 40‐70) with a family history of dementia. This study aims to describe blinded baseline characteristics of the randomised sample and provide trial engagement statistics.MethodParticipants enrolled in BetterBrains (betterbrains.org.au) complete all assessments on an online platform. RF assessment related to vascular health, sleep, mood, and social/cognitive engagement was conducted and participants with ≥1 RF were eligible. Participants complete assessments of cognition, general health, medical history, and lifestyle habits at baseline, 12, and 24‐months post‐randomisation. Primary outcome is absence of decline on at‐least one out of four cognitive tests at 24‐months. Participants randomised to the intervention arm receive a minimum of 6 person‐centred telehealth consultations over 12‐months with an allied health clinician trained in motivational interviewing. All participants receive monthly educational blogposts.ResultSince August 2021, 1518 participants have enrolled and 856 (56%) were randomised (Figure 1). Blinded baseline analyses reveal that randomised participants are mostly female (84%), white (93%), live in metropolitan areas (73%), and all report a first‐degree dementia family history. Mean age is 60 years (±6.7) and participants have 15.4 years of education (±3.9) on average. Mean number of reported RFs is 5 out of a possible 19. Readiness to change lifestyle behaviours to reduce dementia risk was high, with 71% of participants indicating implementation of at‐least some lifestyle changes prior to trial entry. Only 3% of randomised participants have withdrawn. Of participants who have reached 12‐months post‐randomisation (N = 349), 74% have completed follow‐up cognitive testing.ConclusionLow attrition and high follow‐up rates suggest high acceptability and feasibility of the online BetterBrains methodology. The sample is likely at increased risk of dementia, due to high prevalence of first‐degree dementia family history, female gender, and co‐occurrence of multi‐domain modifiable dementia RFs. Presentation of findings will include a detailed breakdown of study methodology, baseline demographic/risk characteristics, and trial progress.
Diversity of sociodemographic backgrounds and healthcare utilization in cognitively impaired older adults
Authors: Rahemi Zahra , Malatyali Ayse , Adams Swann Arp 
Published: December 2023

AbstractBackgroundWith increasing life expectancy, cognitive impairments have become an important public health issue worldwide and in the U.S. Socioeconomically‐disadvantaged populations, including racial/ethnic minorities, are more vulnerable as they have higher rates of underlying conditions and cognitive impairments, such as Alzheimer’s disease and related dementia. With progressive impairments in cognition, behavior, and functionality, patients, families, and healthcare systems face challenges associated with healthcare, including increased costs of care for emergency department visits, hospitalizations, and revisit rates. Our purpose was to examine the relationships between sociodemographic variables and healthcare utilization in older adults with cognitive impairment.MethodThe Health and Retirement Study (HRS), Rand data (2014), were used to understand sociodemographic predictors of healthcare utilization (hospital stay days, nursing home days, home care days, and numbers of doctor’s visits). Due to the skewness of the data, we grouped each category for the length of healthcare utilization into never, short, medium, and long. Only those persons with dementia or impaired cognition were included.ResultOf the 3,924 older adults from the HRS sample, 22% had a diagnosis of dementia and 78% had impaired cognition. Ethnicity, education, and age were significantly associated with the length of hospital stay. Hispanics and those with lower education and younger were less likely to use long hospital stays than others. Ethnicity, marital status, gender, and age were predictors of nursing home length of stay. Blacks, Hispanics, men, and married and younger respondents were less likely to stay long in nursing homes. Blacks and younger respondents were less likely to have long home care utilization. Race, ethnicity, rurality, gender, education, and age were predictors of doctor’s visits. Blacks, Hispanics, rural residents, men, those with lower education, and younger had fewer doctor’s visits. Race, ethnicity, and education were consistent predictors across utilization types.ConclusionThis study provides evidence of the need to understand how older adults with cognitive impairments and multiple marginalized identities (i.e., age, gender, race, ethnicity) can access and use healthcare. This study is important to provide the groundwork for further studies to explore the intersectionality of healthcare utilization and socioeconomic status in patients with cognitive impairments.
Measurement Invariance of the NIH Toolbox‐Cognition Battery Across Demographic Characteristics
Authors: Pal Subhamoy , Reader Jonathan M , Gregoire Allyson , Bhaumik Arijit K , Fisher Jordan , Goldstein Felicia C , Gershon Richard C. , Weintraub Sandra , Giordani Bruno 
Published: December 2023

AbstractBackgroundThe tablet‐based NIH Toolbox‐Cognition Battery (NIHTB‐CB) was compared against the established NACC Uniform Data Set 3.0 (UDS 3.0) neuropsychological battery (used across Alzheimer’s Disease Research Centers). NIHTB‐CB factor invariance is critical for drawing appropriate cross‐demographic conclusions. Invariance was assessed across both batteries for consensus‐driven clinical diagnosis, sex, and age in a large sample of participants from the Advancing Reliable Measurement in Alzheimer’s Disease and Cognitive Aging (ARMADA) study. Goals of this project were to establish the factor relationship of these two batteries and examine their invariance across the aforementioned demographic characteristics.MethodNIHTB‐CB tasks measure Crystalized and Fluid ability. Tests were administered to 571 participants aged 65 to 99 years (mean age 77.2±7.8, 41% female) with normal cognition or amnestic mild cognitive impairment. Groups were classified for age (< = 85 and > 85), gender, and diagnosis. Exploratory Factor Analysis (EFA) was tested for each group with confirmatory factor analysis. If the model fit sufficiently between groups for the configural model, then metric, scalar, and strict invariance models were also examined. Uncorrected standard scores were used for analyses.ResultA four‐factor model emerged as the best fitting model and was invariant across all demographic groups through adjustments. Factor 1: Language (MINT Total, Oral Reading, Picture Vocabulary); Factor 2: Auditory retention (Digits Forward Total and Digits Backward Total); Factor 3: Learning/Memory (List Sorting Working Memory, Picture Sequence Memory, Craft Story 21 Immediate Recall, Craft Story 21 Delayed Recall, Benson Delayed Recall, Animals Category, Vegetables Category, and MoCA Total Score); Factor 4: Attention/Executive Functioning (Dimensional Card Sort, Flanker, Trails A, Trails B, Pattern Comparison Processing Speed, and Benson Recall). We found strong support for strict invariance across the assessed demographic characteristics.ConclusionA four‐factor structure comprised of NIHTB‐CB and UDS 3.0 tests supports the validity of the NIHTB‐CB by matching both UDS 3.0 and NIHTB‐CB measures as expected. Strong support for strict invariance reflects the psychometric equivalence of the NIHTB‐CB construct across the groups. The psychometric properties of the NIHTB‐CB subtests therefore are generalizable across samples. By satisfying the assumption of measurement invariance, inferences made using the NIHTB‐CB about between‐group differences are presumed valid.
Cardiovascular Disease Risk Scores and Risk of Cognitive Decline and Dementia in Older Men and Women
Authors: Vishwanath Swarna , Hopper Ingrid , Chowdhary Enayet , Wolfe Rory , Freak‐Poli Rosanne , Reid Christopher , Tonkin Andrew M , Murray Anne , Shah Raj C , Chong Trevor T.‐J. , Woods Robyn , McNeil John J , Orchard Suzanne , Nelson Mark , Steves Claire J , Ryan Joanne 
Published: December 2023

AbstractBackgroundRisk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia in older adults who do not have a history of CVD remains unclear. The aim of this study was to determine whether CVD risk scores are associated with subsequent cognitive decline and dementia in initially healthy older men and women.MethodParticipants were from a prospective cohort of 19,114 individuals aged 65+ years without prior CVD event or major cognitive impairment. The Atherosclerotic Cardiovascular Disease risk score (ASCVDRS) and the Framingham risk score (FRS) were calculated at baseline, with women and men analysed separately due to large differences in overall level of CVD risk. Dementia was adjudicated by clinical experts according to DSM‐IV criteria. Cognitive decline was defined as a >1.5 SD decline in cognitive score from their own baseline value on any of the four cognitive tests looking at global cognition, episodic memory, psychomotor speed or verbal fluency.ResultOver a median follow‐up of 6.4 years, 4,325 individuals had cognitive decline and 850 individuals developed dementia. ASCVDRS, was associated with dementia and cognitive decline, in men and women, whether considered as a continuous measure and as tertiles. For example, men and women in the highest ASCVDRS tertile had a 41% and 45% increased risk of dementia compared to the lowest tertile respectively (HR [95%CI] men: 1.41 [1.08,1.85], women: 1.45 [1.11,1.89]). However, higher FRS was not associated with incident dementia and only associated with an increased risk of cognitive decline among women (FRS continuous: 1.08 [1.01,1.26]; highest vs. lowest tertiles: 1.13 [1.01‐1.26]).ConclusionThese results provide some evidence for ASCVDRS as a measure of shared CVD risk factors for identifying/predicting risk of dementia and cognitive decline in healthy older adults regardless of sex. Further research is needed to confirm the findings and to validate these results in more heterogeneous populations.