bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of a mindfulness‐based versus health self‐management intervention on cognitive performance in older adults with subjective cognitive decline (SCD): The SCD‐Well randomized controlled trial
Authors: Whitfield Tim , Demnitz‐King Harriet , Schlosser Marco , Barnhofer Thorsten , Collette Fabienne , Dautricourt Sophie , Delarue Marion , Frison Eric , Gonneaud Julie , Klimecki Olga M , Lutz Antoine , Paly Léo , Poisnel Géraldine , Salmon Eric , Schild Ann‐Katrin , Walker Zuzana , Wirth Miranka , Chetelat Gaël , Jessen Frank , Marchant Natalie L ,   The Medit‐Ageing Research Group
Published: December 2021

AbstractBackgroundSubjective cognitive decline (SCD) denotes self‐reported cognitive concerns in the absence of objective cognitive impairment. Individuals with SCD convert to dementia at twice the annual rate of healthy controls, with relatively poorer cognition in SCD conferring additional risk. Non‐pharmacological interventions are currently undergoing intensive evaluation for promoting cognitive function in SCD.MethodThis study utilized data from the SCD‐Well randomized controlled trial. One hundred forty‐seven older adults with SCD, recruited from clinics in four European countries, were randomized to one of two 8‐week non‐pharmacological interventions: the Caring Mindfulness‐Based Approach for Seniors (CMBAS), or a Health Self‐Management Program (HSMP). Participants’ objective cognitive performance was assessed at baseline, post‐intervention, and 24‐weeks follow‐up using a battery of tests. Four of these (RAVLT, WAIS‐IV Coding, Mattis DRS‐2 and Category Fluency) were combined to yield an abridged version of the Preclinical Alzheimer’s Cognitive Composite 5 (PACC5Abridged). Linear mixed models estimated the change in outcome measures (the PACC5Abridged and its constituents) within and between arms. All models were adjusted for country and participant demographics (sex, age, and education), as well as the time‐varying effect of participants’ repeated practice with the outcome measures.ResultThere was a statistically significant improvement in the PACC5Abridged in both arms of the trial (p<.001), which did not differ between groups. The mean change in PACC5Abridged from baseline to 24‐weeks was 0.28 for CMBAS, and 0.22 for HSMP (pooled baseline SD 0.72). The effect of participants’ repeated practice on the PACC5Abridged was non‐significant, ruling out retest effects as a substantive explanation for results. Amongst the PACC5Abridged constituent tests, significant improvement was observed in the RAVLT and WAIS‐IV Coding.ConclusionThis clinical trial evaluated the effect of two 8‐week non‐pharmacological interventions on objective cognitive performance in SCD. Scores on a composite measure of early Alzheimer’s disease related cognitive dysfunction improved in both arms, even after accounting for practice effects. These results paralleled those of the primary outcome measure (trait anxiety), for which scores also improved in both arms. This work adds to the growing body of evidence that non‐pharmacological interventions can impact cognition in individuals at increased risk of dementia.
Alzheimer’s disease mortality high in rural areas in South: 1999‐2019
Authors: Kulshreshtha Ambar , Ramer Stephanie , Cato Sarah , Hajjar Ihab 
Published: December 2021

AbstractBackgroundUrban‐rural differentials exist in the United States for both socio‐economic and cultural reasons. Geographic variation in Alzheimer’s mortality exist, but how it applies to specific urbanization levels has not been examined previously. We sought to describe the pattern and magnitude of urban‐rural variations in Alzheimer’s mortality in the United States.MethodsWe used data from the National Center for Health Statistics to examine trends in Alzheimer’s death rates (ICD‐10 codes G30) between 1999 and 2019 by urbanization levels. Alzheimer’s mortality was defined as death from Alzheimer’s in over the age of 65 years using data from death certificates. Urbanization classification is per 2013 NCHS definitions. Crude and age‐adjusted changes in Alzheimer’s mortality rates were calculated in the overall population and in specific urbanization groups: in large and medium metros (urban); and non‐metros (rural). We also examined differences by race and sex. Poisson regression was used to model data.ResultsFrom 1999‐2019, the age‐adjusted mortality rate from Alzheimer’s has increased significantly from 16 to 30 deaths per 100,000, an 88% increase. Significant disparities by urbanization and census region exist. Mortality rates are highest in the rural areas in the East South‐Central region, where the death rate from Alzheimer’s is 274 per 100,000 in those over 65. Mortality rates are lowest in urban areas in the Mid‐Atlantic region, where the death rate is 86 per 100,000. Trends over time show a widening disparity across region and urbanization. Women had higher age‐adjusted AD mortality rates than men, regardless of metro area or race.ConclusionsRural areas particularly in South are experiencing a disproportionate burden of Alzheimer’s disease mortality. The reason for this trend might be manifold and related to access to primary care, timely diagnosis, and the rising proportion of older Americans living in these areas. Identifying and understanding the underlying causes of disparities in AD mortality among communities is key in designing targeted public health policies and interventions to curb the epidemic.
A cognitive composite for genetic frontotemporal dementia: GENFI‐cog
Authors: Poos Jackie M. , Nicholas Jennifer M , Moore Katrina M , Russell Lucy L , Peakman Georgia , Jiskoot Lize C. , van den Berg Esther , Papma Janne M. , Seelaar Harro , Pijnenburg Yolande A.L. , Moreno Fermin , Sanchez‐Valle Raquel , Borroni Barbara , Laforce Robert , Masellis Mario , Tartaglia Maria Carmela , Graff Caroline , Galimberti Daniela , Rowe James B , Finger Elizabeth , Synofzik Matthis , Vandenberghe Rik , Mendonca Alexandre , Tagliavini Fabrizio , Santana Isabel , Ducharme Simon , Butler Christopher , Gerhard Alexander , Levin Johannes , Danek Adrian , Otto Markus , van Swieten John C , Rohrer Jonathan D 
Published: December 2021

AbstractBackgroundDevelopment of endpoints for clinical trials in frontotemporal dementia (FTD) is increasingly urgent. In other neurodegenerative diseases composite scores are often used as outcome measures but are, as of yet, lacking in FTD. The aim of this study was to create gene‐specific cognitive composite scores for MAPT, GRN and C9orf72 mutation carriers and provide recommendations on recruitment and trial duration.Method69 C9orf72, 41 GRN, 28 MAPT mutation carriers with a CDR® plus NACC‐FTLD global score ≥0.5 and 275 controls completed a neuropsychological battery covering five cognitive domains. Logistic regression was used to identify the combination of tests that discriminated best between mutation carrier groups and controls. Weighted averages of the test scores in the models were calculated based on the regression coefficients (GENFI‐cog). Sample size estimates were calculated for individual tests and composite. The treatment effect was estimated as the mean difference between CDR® plus NACC‐FTLD 0.5 and 1 groups. Time‐to‐event analysis was used to determine the fraction of patients within GENFI that converted from CDR® plus NACC‐FTLD 0.5 to ≥1.ResultThe most sensitive model in C9orf72 mutation carriers included a combination of executive, social cognitive and visuoconstructive tests (Table 1). A combination of executive, social cognitive, semantic and memory tests was most sensitive in GRN mutation carriers, and a combination of social cognitive, attention, semantic and memory tests in MAPT mutation carriers, resulted in the most sensitive model. The estimated sample size to detect a treatment effect was lower for the composite than for most individual tests (Table 2). A Kaplan‐Meier curve (Figure 1) showed that after three years 50% of individuals convert from CDR® plus NACC‐FTLD global score 0.5 to 1 or more.ConclusionWe created gene‐specific cognitive composite scores for C9orf72, GRN and MAPT mutation carriers (GENFI‐cog) which resulted in substantially lower estimated sample sizes to detect a treatment effect than most individual cognitive tests. Only 50% of patients with a CDR® plus NACC‐FTLD of 0.5 convert to ≥1 in a three‐year period. GENFI‐cog has potential as a cognitive endpoint for upcoming trials and the results from this study provide important information concerning trial duration and sample sizes.
Feasibility of treating hearing loss to prevent dementia in MCI: Results of the face to face and remote interventions in the Treating Auditory impairment and Cognition Trial (TACT)
Authors: Gonzalez Sergi Costafreda , Bamiou Doris‐Eva , Lewis Glyn , Livingston Gill , Omar Rumana , Pavlou Menelaos , Proctor Danielle , Schilder Anne 
Published: December 2021

AbstractBackgroundAge‐related hearing loss is an independent and potent risk factor for dementia. There is observational evidence that hearing aid use may mitigate deterioration in cognitive performance and could prevent dementia, but experimental evidence is lacking. A trial on whether treating hearing loss reduces the risk of dementia may not be feasible because people often do not access or use hearing aids even when prescribed. We designed the Treating Auditory impairment and Cognition Trial (TACT) as a manual‐based preventative intervention, promoting and supporting hearing aid use in those with Mild Cognitive Impairment. We studied the feasibility of a full‐scale randomized controlled trial.MethodWe conducted a pilot trial of a new intervention designed to increase uptake and adherence to hearing aid treatment. Pre COVID‐19, we randomized MCI participants to face‐to‐face interventions: the active arm is a home‐based hearing assessment and hearing aid fitting, with study audiologist and research assistant delivering motivational and practical support in 4 visits over 3 months. Participants in the control arm were referred to standard audiological care through their general practitioner without additional hearing support, and given a healthy ageing educational intervention on dementia risk factors, matched in contact with the study team. Follow‐up for both interventions was at 6 months. After the onset of COVID‐19, additional MCI participants, who had not received hearing aids, were allocated to active remote hearing support. This did not involve any face‐to‐face contact with the study team but provided hearing support remotely, with outcomes collected after 1 month.ResultPre COVID‐19, N=36 MCI participants were randomized to the original face‐to‐face study interventions, with follow‐up measures collected at 6 months, also in a face‐to‐face session. After the onset of COVID‐19, a further N=11 received the remote hearing intervention. We will present results from these samples. The pre‐specified outcomes of the pilot include recruitment, randomization, retention, and acceptability of the interventions, with secondary outcomes including difference in usage of hearing aids between active and control arms, and cognition, mood, and social function.ConclusionThe results of this study may influence hearing care in all settings as well as dementia prevention.
Association between APOE‐ε4 allele and CSF amyloid in memory performance differ by sex
Authors: Brugulat‐Serrat Anna , Tsoy Elena , Milà‐Alomà Marta , Sánchez‐Benavides Gonzalo , Buckley Rachel F. , Gispert Juan Domingo , Molinuevo Jose , Possin Kate L , Kramer Joel H ,   EPAD Consortium
Published: December 2021

AbstractBackgroundThere is growing evidence of sex differences in the association between Alzheimer’s disease (AD) biomarkers and cognition. However, few studies have examined the effect of sex on the associations between established AD risk factors and cognitive performance in clinically normal older adults. This study aimed to elucidate potential sex differences in the relationship between APOE‐ε4 status, AD biomarkers, and cognitive performance in a large multinational cohort of clinically normal older adults.MethodParticipants were 952 cognitively unimpaired older adults from the multicenter European Prevention of Alzheimer’s Disease (EPAD) study (age range 50‐88 years, mean age 65.0(7.0), mean education 14.6(3.6) years, 58% females). All participants underwent a lumbar puncture and CSF Aβ42, p‐tau and t‐tau biomarkers (Roche Elecsys®) were measured, APOE genotyping, and a battery of digital cognitive tests (UCSF TabCAT; Favorites (associative memory), Dot Counting (executive function), and Flanker (processing speed)). APOE genotype was dichotomized (ε4 carrier vs. ε4 non‐carrier). We performed multiple linear regression models to examine the effect of sex, CSF biomarkers, APOE‐ε4, and their interactions on cognitive performance covarying for age, education, and testing language.ResultThere were no differences in age (p=.07), frequency of APOE‐ε4 carriers (33.1%, p=.55) or CSF biomarkers (all p>0.1) between males and females. Females had lower educational attainment (p=.01). Females outperformed males on an associative memory task (p=.002), whereas males performed better on tasks of working memory (p=.01) and inhibitory control (p=.01). A sex*Aβ*APOE‐ε4 status interaction (p=.01) revealed APOE‐ε4 carriership and abnormal levels of CSF Aβ were associated with poorer associative memory performance only in males (Fig 1).ConclusionSex seems to moderate the association between CSF Aβ and APOE‐ε4 allele and memory performance in cognitively unimpaired older adults. Our results suggest a cross‐sectional association of APOE‐ε4 and CSF Aβ with cognitive performance in males that complement previous literature on the relationship between APOE‐ε4 and longitudinal cognitive decline in females. Taken together, these findings highlight the importance of understanding the complexity of sex differences in individuals at higher risk of AD.
Memory training in older adults with mild cognitive impairment: Positive effects are found five years after MEMO training compared to control intervention
Authors: Belleville Sylvie , Cuesta Marc , Bier Nathalie , Brodeur Catherine , Gauthier Serge , Gilbert Brigitte , Grenier Sébastien , Ouellet Marie‐Christine , Viscogliosi Chantal , Hudon Carol 
Published: December 2021

AbstractBackgroundCognitive training was found to have a positive effect on the memory of healthy older adults, including long‐term benefits (Rebok et al, 2014). This finding offers hope that cognitive training could contribute to prevention approaches. However, little is known regarding the long‐term benefits of cognitive training in older adults with mild cognitive impairment (MCI), many of whom are in the early phase of Alzheimer’s disease. In a prior randomized controlled trial (Belleville et al, 2018), we reported a short‐term benefit of cognitive training on the delayed recall of older adults with MCI. The objective of this study was to assess the impact five years later.MethodThis is the five‐year follow‐up of a single‐blind randomized controlled trial (MEMO+). Participants with amnestic MCI were randomized to memory training or an active (psychosocial intervention) or passive (no‐contact) control condition. Interventions were provided in small groups over eight two‐hour sessions with a single booster session offered three months following training. In the initial study, participants were assessed post‐training, as well as three and six months after the intervention. The 127 participants with MCI, who completed the 6‐month post‐training assessment, were contacted five years post‐training. Primary outcomes included a 12‐word free recall task, a self‐reported strategy used in everyday life, and the Montreal Cognitive Assessment screening test (MoCA). Participants randomized to cognitive training were compared to those randomized to the control conditions.ResultParticipants with MCI, who were randomized to the cognitive training condition, showed a reduced 5‐year decline on the delayed recall task when compared to participants in the control conditions. Participants randomized to the cognitive training condition also demonstrated superior delayed recall and MoCA performance than those in the control condition, five years post‐training. There were no differences on self‐reported strategy use.ConclusionThe positive effect of cognitive training was found five years later on measures of delayed memory and global cognitive status in individuals with MCI. This indicates that the use of cognitive training is a valid preventive approach and has potential to delay the onset of dementia in at‐risk individuals.
Modifiable factors associated with cognitive resistance in the Framingham Heart Study
Authors: Hwang Phillip H , Mez Jesse , Farrer Lindsay A , Devine Sherral , Auerbach Sandford H , Qiu Wendy , Liu Chunyu , Au Rhoda 
Published: December 2021

AbstractBackgroundCognitive resistance to Alzheimer’s disease (AD) refers to an individual’s capacity to avoid the appearance of Alzheimer’s dementia syndrome in the context of risk factors on pathologic processes. We sought to identify associations between potential modifiable risk factors for AD and cognitive resistance.Method2,318 participants from the Offspring and Omni cohorts in Framingham Heart Study without prevalent dementia and at high risk for AD were selected. High risk for AD was defined as having ≥2 of the following risk factors measured at baseline: (1) age >80 years; (2) diagnosis of cardiovascular disease or coronary heart failure; (3) carrier of ≥1 APOE ε4 allele; (4) plasma Aβ42/40 ≤0.1049 (Perez‐Grijalba et al.; 2019); (5) C‐reactive protein level ≥10 mg/L (Morley and Kushner; 1982); and (6) female sex. Cognitively resistant individuals were defined as those at high risk for AD that did not progress to a clinical diagnosis of dementia/AD. Standardized research criteria were used to ascertain all‐cause dementia and AD. Potential modifiable risk factors for AD measured at baseline included diabetes, hypertension, obesity, depression, smoking, and education. Logistic regression was used to examine associations between these factors and cognitive resistance to AD.ResultOver an average period of 36 years, absence of diabetes (OR = 3.63; 95% CI = 2.37 – 5.55; p <0.001) and absence of hypertension (OR = 1.60; 95% CI = 1.02 – 2.51; p = 0.038), as well as not smoking (OR = 2.10; 95% CI = 1.41 – 3.13; p <0.001), at baseline were significantly associated with cognitive resistance. Absence of depression, absence of obesity, or high education were not associated with cognitive resistance.ConclusionIndividuals at high risk for AD who do not have diabetes or hypertension, or do not smoke may be cognitively resistant to AD. These findings support the heart‐brain connection for dementia prevention and healthy cognitive aging.
Does discrimination mediate the association between education and later‐life cognitive outcomes in a cohort of Black Americans? An example of parametric g‐estimation with latent variables in the STAR study
Authors: Cintron Dakota W , Glymour M Maria , Whitmer Rachel A , Mungas Dan M , Gilsanz Paola , Barnes Lisa L , Calmasini Camilla , Eng Chloe W , George Kristen M , Peterson Rachel L 
Published: December 2021

AbstractBackgroundIdentifying mediators between education and later‐life cognition is an important step in developing prevention measures. We evaluate everyday and major lifetime discrimination as potential mediators of the impact of education on later‐life cognition. To address bias that might occur due to either time‐varying confounding or unreliable measurement of discrimination, we use a novel parametric g‐estimation approach.MethodParticipants in the Study of Healthy Aging in African Americans (STAR, n = 764, ages 52‐90) self‐reported education (high school [HS] degree, general educational development [GED], or less [ref]; bachelor’s degree; or graduate degree). Validated measures of everyday discrimination (9‐items assessing frequency with 6‐point Likert responses) and major lifetime discrimination (9‐items, dichotomous yes‐no), were conceptualized as latent variables (Table 1). The observed cognitive outcome was the average of the verbal episodic memory, semantic memory, and executive function Spanish and English Neuropsychological Assessment Scales (SENAS). We used linear regression to estimate the total effect of education on later‐life cognition and parametric g‐estimation with latent discrimination measures to estimate the controlled direct effect (CDE) of education on cognition if the discrimination measures were set to their sample averages. Models were adjusted for measurement error in the discrimination measures using Fuller’s Method. Standard errors were bootstrapped.ResultMost participants were female (68.32%) and the average age was 69.0 (Table 2). Both bachelor’s (b=0.41[0.21,0.60]) and graduate (b=0.43[0.22,0.64]) degrees were associated with better cognition compared to HS/GED or less (Table 3). More education was associated with higher levels of major lifetime discrimination. The CDEs of a bachelor’s and graduate degree, if everyone had the average level of everyday and major life discrimination, were 0.32[0.06,0.61] and 0.55[0.24,0.82], respectively (Table 3 and as a function of different fixed averages in Figure 2).ConclusionThis study provides a novel demonstration of parametric g‐estimation methods that correct for measurement error with latent variables and allow for possible feedback between education and early and late‐life confounders. Accounting for exposure to discrimination slightly increased the magnitude of the association between graduate education and cognition in this older sample of Black American adults, because education was associated with greater exposure to major life discrimination.