bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between use of assistive technologies and activities of daily living in Alzheimer’s disease: Does cognitive score matter?
Authors: Brigola Allan Gustavo , Trucco Ana Paula , Camino Julieta , Mioshi Eneida 
Published: December 2020

AbstractBackgroundAssistive technologies (AT) can be useful to support the day‐to‐day care of people with dementia, especially those with Alzheimer’s disease (PwDA). This study investigated the frequency of use of AT in PwDA. We also explored the association of using AT and functional ability, considering age, sex and cognition as covariates.MethodCross sectional analyses including 70 PwDA (assessed 2016‐2019). Global cognition was assessed with the Addenbrooke’s Cognitive Examination (ACE‐III). Disability Assessment for Dementia (DAD) assessed performance of basic (BADL) and instrumental (IADL) activities of daily living. Information on use of AT in regards to a) Prompts/Reminders, b) Leisure, c) Communication devices, was collected. Linear regression models were used to explore the association between use of AT and Basic ADLs and Instrumental ADLs. Covariates included global cognition, age and sex of participants.ResultsOverall, sample mean age was 78.8±6.6 years; 60% of participants were male. Average Basic ADL score was 70.5±27.5; Instrumental ADL average score was 34.7±26.8, reflecting greater disability in instrumental ADLs. In terms of AT, 32.9% used Prompts/Reminders; 34.3% reported use of technologies for Leisure; 12.9% reported use of technologies for Communication devices. When controlling by age and sex (model A), the use of Communication technologies was inversely associated with Basic ADLs (β=‐22.81;95%CI:‐43.9;‐1.6;p=0.035), explaining 17% of the variance. When controlling by age, sex and global cognition (model B), the association between use of communication technologies and Basic ADLs was not significant. In regards to instrumental ADLs, use of technologies for Communication, Prompts/Reminders and Leisure were not associated with Instrumental ADL scores in models A and B.ConclusionUse of AT for Communication appears to be driven by the greater level of disability of the user in basic ADLs, which seems to fulfil their need for this AT. However, if PwDA's cognitive scores are also low, the use of AT does not influence performance in Basic ADLs any longer. Use of AT for Prompts/Reminders and Leisure was not associated with performance in Basic and Instrumental ADLs, reflecting the need for better understanding the importance of cognitive ability in using AT for maintaining function.
Examining risk of dementia in lifestyle engagement subgroups of community‐dwelling older adults: A latent class approach
Authors: Moored Kyle D , Parisi Jeanine M , Snitz Beth E , DeKosky Steven T , Williamson Jeff D , Fitzpatrick Annette L , Carlson Michelle C 
Published: December 2020

AbstractBackgroundEngagement in lifestyle activities may be neuroprotective, but it remains unclear what aspects of engagement are most beneficial. For self‐reported activity inventories, examining response patterns may better characterize both quantitative (e.g., number) and qualitative (e.g., characteristic/motivational) differences in engagement.MethodParticipants were 3069 individuals from the Gingko Evaluation of Memory (GEM) Study who were evaluated for dementia and completed neuropsychiatric testing over 8 years. We used a subset of 18 physical, intellectual, or social activities from the Lifestyle Activity Questionnaire. We performed latent class analysis to characterize subgroups with distinct activity response patterns and examined whether they have differential risk of incident dementia and domain‐specific cognitive impairments over time. Cox proportional hazards models were used to examine subgroup differences in risk of cognitive impairments.ResultA three‐class model was chosen based on fit statistics and interpretability. Class 1 (Highly intellectually/socially active) participated in more social leisure activities (e.g., movies) than Classes 2 (Socially/less intellectually active) and 3 (Less intellectually/socially active). Class 2 participated in more institutional social activities (e.g., church) than Class 3. In an unadjusted Cox proportional hazard model, Class 1 had a reduced risk of dementia compared to Classes 2 (HR=1.32, 95% CI: [1.1,1.6], p=.013) and 3 (HR=1.53, 95% CI: [1.2,1.9], p<.001). After adjusting for potential demographic and health confounders, Class 1 had a statistically significant reduced risk of dementia compared to Class 3 (HR=1.40, 95% CI: [1.1,1.8], p=.003), but the reduction in risk compared to Class 2 was only trending (HR=1.26,95% CI: [1.0,1.6], p=.051).ConclusionThese results suggest that subgroups characterized by less engagement in leisure social and intellectual activities have increased risk for dementia. Our findings also highlight subgroup differences in activity types (e.g., participation in social institutions in Class 2) that may be leveraged by further behavioral interventions to reduce risk of dementia with age.
Untangling the roles of amyloid and tau in synaptic and axonal loss in the course of Alzheimer’s disease
Authors: Pereira Joana B. , Janelidze Shorena , Ossenkoppele Rik , Brinkmalm Ann , Mattsson Niklas , Stomrud Erik , Smith Ruben , Zetterberg Henrik , Blennow Kaj , Hansson Oskar 
Published: December 2020

AbstractBackgroundIt is currently unclear how rising amyloid‐β (Aβ) and tau tangles are linked to changes in synaptic function and axonal structure over the course of Alzheimer’s disease (AD).MethodHere we assess how presynaptic (synaptosomal‐associated protein 25, SNAP‐25), postsynaptic (neurogranin, Ng) and axonal (neurofilament light chain, NfL) biomarkers change in early and late AD, in individuals with or without Aβ and tau pathology based on Aβ‐PET (18F‐flutemetamol) and tau‐PET (18F‐flortaucipir). In addition, we explore the relationship between these biomarkers with memory and global cognition as well as functional and anatomical brain connectivity.ResultOur findings show that the synaptic markers SNAP‐25 and Ng are increased in early AD, i.e. in Aβ‐positive individuals without evidence of tau pathology. In this group, higher synaptic levels were associated with more Aβ pathology, worse memory and functional changes in the default‐mode network, but not global cognition or anatomical connectivity. In contrast, NfL levels became abnormal in later disease stages, i.e. in individuals with both Aβ and tau pathology. In this group, higher NfL was associated with more tau and worse global cognition, but not Aβ pathology or default mode network connectivity. Finally, reduced anatomical connectivity was only associated with tau pathology in late AD.ConclusionAltogether, these findings support the hypothesis that Aβ and tau have downstream effects on synaptic and axonal function in a stage‐dependent manner. Increases in Aβ are related to presynaptic and postsynaptic markers, which affect functional connectivity in early disease stages. This is followed by an increase of tau, which affects both axonal markers and anatomical connectivity in later disease stages.
Dementia diagnosis disparities by race and ethnicity
Authors: Lin Pei‐Jung , Daly Allan , Olchanski Natalia , Cohen Joshua T , Neumann Peter J , Faul Jessica D , Fillit Howard M , Freund Karen M 
Published: December 2020

AbstractBackgroundDementia is often underdiagnosed, and self‐reported data suggest that this problem may be more common among racial and ethnic minority groups. This study examined racial and ethnic disparities in the timeliness in which individuals receive a formal dementia diagnosis.MethodThis analysis used eight waves of US national surveys from 2000‐2014 Health and Retirement Study, linked with Medicare and Medicaid claims. We identified study participants age ≥70 with dementia using a well‐validated statistical model based on individual’s age, gender, education, cognition, and functional limitations. We assessed the proportion of patients not receiving a coded diagnosis of dementia in their claims by the time the prediction model classified them as having dementia. We used logistic regression models to compare the likelihood of missed or delayed dementia diagnoses in claims by race and ethnicity, adjusting for patient characteristics. We analyzed dementia severity, measured by cognition (TICS scores for self‐respondents; IQCODE scores for proxy‐respondents) and functional limitations, at the time of a dementia diagnosis documented in claims, by race/ethnicity. All analyses adjusted for sampling weights.ResultOur sample included 3,966 older adults with dementia. Forty‐two percent had a missed or delayed dementia diagnosis in their claims. This proportion was higher among non‐Hispanic blacks and Hispanics than among non‐Hispanic whites (46% and 54% vs. 41%, p<0.001). Logistic regression model indicated more frequent missed/delayed dementia diagnoses among non‐Hispanic blacks (OR=1.27; 95% CI: 1.05‐1.53) and Hispanics (OR=1.83; 95% CI: 1.43‐2.35), compared to non‐Hispanic whites. Over the study period, 76% had a dementia diagnosis documented in their claims. At the time of diagnosis, non‐Hispanic blacks and Hispanics had poorer cognitive function and more functional impairments, compared to non‐Hispanic whites.ConclusionNon‐Hispanic blacks and Hispanics may experience missed or delayed diagnoses of dementia more often than non‐Hispanic whites. When they are diagnosed, non‐Hispanic blacks and Hispanics may have more advanced dementia compared to non‐Hispanic whites. Public health efforts such as the Brain Health Initiative should tailor campaigns to different ethnoracial groups when promoting early diagnosis of dementia. The medical community should implement provider training on culturally competent dementia care and improve documentation of dementia diagnostic findings in health insurance claims.
Brain network functional connectivity changes following psychosocial stress in subjective cognitive decline
Authors: Albert Kimberly , Boyd Brian , Newhouse Paul A. , Taylor Warren D. 
Published: December 2020

AbstractBackgroundNeurodegenerative processes in early AD may disrupt the coordinated activity of brain networks important for the regulation of endocrine and emotional stress response. Stress reactivity and the effect of psychosocial stress on brain network function may thus be useful markers of neural changes related to early AD processes. The goal of this study was to examine the effect of psychosocial stress on brain network function in older adults with Subjective Cognitive Decline (SCD), a population at increased risk for Alzheimer’s disease.MethodParticipants (n=25) were evaluated to exclude cognitive impairment and significant psychiatric disorders. SCD was operationalized using the Cognitive Complaints Index (CCI) with a required minimum score of 20%.The Montreal Imaging Stress Task (MIST) was used to induce moderate psychosocial stress. Subjective measures included the stress subscale of the Stress‐Arousal Checklist (SACL) and the Profile of Mood States (POMS).Resting‐state fMRI scans were completed before and after the MIST. Seed‐based analyses were used to examine changes in functional connectivity (FC) in the default mode (DMN‐posterior cingulate), cognitive control (CCN‐dorsolateral prefrontal cortex), and salience (SN‐anterior insula) networks (p uncorrected <0.005, FDR corrected p <0.05).ResultParticipants had an average CCI of 45% (SD = 10.5%). There was an increase in subjective stress (stress‐SACL; t=6.12, p < 0.0001) and worsening mood symptoms (POMS total score; t=3.23, p=0.004) during the MIST. In the DMN, stress exposure with the MIST resulted in decreased FC between the posterior cingulate cortex and regions of the CCN, (middle and superior frontal gyri). In the SN, stress exposure increased FC between the right anterior insula and the right middle/inferior temporal gyri and DMN regions including the precuneus and posterior cingulate cortex. We did not observe changes in FC in the CCN.ConclusionThese findings suggest that in SCD stress reduces coordinated activity of the CCN and DMN and increases connectivity between SN and DMN which may reflect impaired regulation of DMN activity and enhanced vigilance for emotional information. Further work is needed to determine how these changes may differ from normal aging and whether network changes may indicate early AD‐related cognitive and emotional disruption.
Complementary analyses of the AMBAR trial: Impact of discontinuations, consistency of results across outcomes and additional adjustments
Authors: Hendrix Suzanne B. , Núñez Laura , Boada Mercè , Lopez Oscar L. , Grifols Carlota , Barceló Miquel , Páez Antonio 
Published: December 2020

AbstractBackgroundThe AMBAR study enrolled 496 mild‐to‐moderate Alzheimer’s disease (AD) patients from Spain and US centers, 347 of which were randomized [1:1:1:1] to three treatment arms of plasma exchange (PE) with different doses of albumin with or without intravenous immunoglobulin (IVIG) or placebo (sham PE) arm. PE treatment showed slow cognitive and functional decline in AD patients, with variable significance in outcome (primary: ADCS‐ADL, ADAS‐Cog; secondary: CDR‐Sb, ADCS‐CGIC), baseline disease severity, and treatment arm (low‐albumin; low‐albumin+IVIG, high‐albumin+IVIG, and all three combined). The percentage of patient dropouts ranged from 20% in the placebo to 34.9% in the low‐albumin+IVIG group. In this analysis we investigated the effect of possible biases due to discontinuations and baseline imbalances, and assessed the consistency across outcomes.MethodThe impact of discontinuations was determined by least squares mean estimates from the Mixed Model for Repeated Measures (MMRM) analysis using the z‐score carried forward analysis (zLOCF). The overall impact of the treatment on the disease was determined by a global statistical test which combined with equal weighting three outcomes (ADCS‐ADL, ADAS‐Cog, CDR‐Sb) into a single outcome. An analysis of relevant outcomes was performed adjusting for key baseline characteristics.ResultAnalysis of discontinuations suggested that the treatment differences and effect sizes estimated using the primary model MMRM are likely to be conservative and that lowering dropouts is likely to increase effect sizes. Effect sizes were consistent across outcomes (between 51% and 76%). The GST score showed slowing of progression at month 14 with statistically significant differences between all active treatments and placebo from month 9 onward. When the model was adjusted for key baseline characteristics, the analysis showed statistically significant differences against placebo of all treatment groups in most of the relevant outcomes.ConclusionResults of this analysis disprove the possible bias of dropout effect in the AMBAR trial. Effect sizes were consistent across outcomes and the Global Statistical Test showed an overall impact of the treatment on the disease. The analysis corrected for baseline factors supports and reinforces the findings that the PE‐treated arms were superior to the placebo group.
Alzheimer’s disease worries, fears, and stigma and their relationship to genetic and interventional research engagement
Authors: Bardach Shoshana H , Kent Saida , Jicha Gregory A 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) research increasingly focuses on risk factors, including attention to genetics, and clinical trials in the area of prevention, necessitating the engagement of healthy participants willing to undergo genetic testing and potentially take experimental medications. Objective: This study seeks to: 1) describe older adults’ beliefs about AD genetic testing, worry about AD, and fear of AD stigma, and 2) explore how these constructs relate to various forms of AD research participation.MethodSurveys were sent via mail both to participants active in AD‐observational research and those that were not. Surveys included questions on benefits and limitations of AD genetic testing, AD worry, and fear of AD stigma. Three measures of research participation were explored: 1) Being a current research participant, 2) Self‐report of clinical trial participation, and 3) Expressing interest in a genetic registry.ResultSurveys were returned from 502 individuals. The majority of respondents perceived greater benefit than risk associated with AD genetic testing. Overall AD worry and perceptions of AD stigma were low. Higher levels of AD worry and lower perceptions of AD stigma were both associated with being a current AD research volunteer. AD worry and stigma were unrelated to reports of clinical trial participation or genetic registry interest; however, both of these research participation measures were associated with higher ratings of AD genetic testing benefit.ConclusionThese results demonstrate that beliefs about AD genetic testing, as well as AD worry and stigma, are related to research participation, but these relationships vary based on the form of research participation investigated. Further work needs to be done to identify how best to use these findings to direct outreach and recruitment efforts.
Incident cognitive impairment in a longitudinal cohort of older adults in rural South Africa, 2014‐19
Authors: Kobayashi Lindsay , Farrell Meagan T , Langa Kenneth M , Mahlalehla Nomsa , Wagner Ryan , Berkman Lisa 
Published: December 2020

AbstractBackgroundWe aimed to determine the incidence of cognitive impairment and its key sociodemographic, social, and health‐related predictors at the first longitudinal follow‐up of the population‐representative “Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa” (HAALSI) cohort in South Africa.MethodData were from 3,861 adults aged ≥40 in rural Agincourt sub‐district, South Africa from 2014‐19, who were free from cognitive impairment at baseline. Cognitive impairment was defined as scoring ≥1.5 SD below the baseline mean composite time orientation and episodic memory score, or requiring a proxy interview with “fair” or “poor” proxy‐reported memory. Limitations to activities of daily living (ADLs) were compared according to incident cognitive impairment status. Incidence rates (IRs), incidence rate ratios (IRRs), and 95% confidence intervals (CIs) for cognitive impairment were estimated according to sociodemographic, social, and health‐related characteristics using modified Poisson regression. IRs and IRRs were weighted to account for mortality over the follow‐up. IRRs were adjusted for age, sex/gender, and country of birth.ResultOver a mean follow‐up of 3.7 years, 309/3,861 at‐risk participants newly developed cognitive impairment (IR=24.0 per 1000 person‐years (PY); 95% CI: 21.6‐26.8). Incidence increased steadily with age, from IR=9.1 per 1000 PY (95% CI: 5.5‐16.1) among those aged 40‐44 years at baseline to IR=76.5 per 1000 PY (95% CI: 63.2‐93.4) among those aged 80+. At least one ADL limitation was prevalent at follow‐up in 39% of those with an incident cognitive impairment, compared to 7% of non‐cognitively impaired participants. The incidence of cognitive impairment did not vary by sex/gender, HIV infection status, or cardiovascular risk factors, but was strongly graded according to education, literacy, household assets, employment, marital status, and frequency of alcohol consumption. For example, IRR=1.13 (95% CI: 0.91‐1.40) for female vs. male, IRR=1.05 (95% CI: 0.77‐1.43) for HIV‐positive vs. HIV‐negative, IRR=2.40 (95% CI: 1.81‐3.17) for illiterate vs. literate.ConclusionThis study presents one of the first incidence rate estimates for cognitive impairment in sub‐Saharan Africa, where populations are beginning to rapidly age. Social and socioeconomic disparities in incident cognitive impairment rates were apparent in a similar pattern as in many high‐income countries.
Understanding resistance, resilience and repair: An analysis of electronic medical records to identify ‘successful aging’ free of Alzheimer’s disease and related dementias
Authors: Miller Amber H. , Marra David E. , Anton Stephen , Maraganore Demetrius M. 
Published: December 2020

AbstractBackgroundAs the number of individuals living with Alzheimer’s disease and related dementias (ADRDs) increases in the United States, it is important to discover ways to preserve and improve brain health across the lifespan through prevention. This is especially important for the rapidly growing over age 90 segment of the population (“oldest old”). This project defined ‘Successful Aging’ and utilized Electronic Medical Records (EMR) to understand the characteristics of successfully aged individuals over 90 throughout the State of Florida. This epidemiological investigation will also discover common lifestyle factors that contribute to the risk management of ADRDs.MethodA panel of distinguished researches, in the fields of dementia, aging, and biomedical informatics and health outcomes at the University of Florida, convened to develop a computable phenotype of “Successful Aging”, derived from the EMR. Utilizing the OneFlorida Data Trust, a repository of healthcare data for 75% of Floridians (∼15 million patients), researchers computed a successful aging phenotype, using discretely coded demographics, ICD‐9/ICD‐10 diagnostic codes.ResultThe research investigators identified 19 parameters of ‘Successful Aging’ and universally agreed to three primary criteria: over the age of 90, not residing in a nursing home, and free of ADRD. From the OneFlorida Data Trust, 281,927 individuals were identified as residing in Florida, alive and over the age of 90, a 2.01% prevalence. In this over 90s population, 187,514 (66.5%) did not have a diagnosis of ADRD and 94,413 (33.5%) had ADRD diagnosis. Of the 187,514 non‐ADRD individuals, 65,008 (23.1%) did not reside in a nursing home zip code and exhibited the three primary criteria for successful aging. There were 45,710 (16.2%) individuals who demonstrated all 19 parameter criteria (Figure 1).ConclusionFlorida is the third‐most populous state, with the highest percentage of elders, and the most ADRD per capita. Studies in this special population are crucial to understanding ‘Successful Aging’. Future research will validate the EMR computed phenotype by contacting the ‘Successful Agers’ in Florida to further investigate demographic, medical, and social characteristics that promote resistance, resilience, and repair. This validation will lead to the development of preventive interventions that can reduce the lifestyle risk of developing ADRDs.