bluuebunny/crossref_metadata_2025_split huggingface dataset:
Domains and dimensions of family quality of life among families with a member with neurodegenerative diseases
Authors: Badia Marta , Orgaz‐Baz Begoña , Vicario‐Molina Isabel , Ortega Eva González , Aza Alba ,   NEUROQUALYFAM Group
Published: February 2022

AbstractBackgroundFamily quality of life (FQoL) is a recent construct to be applied in neurodegenerative diseases (NDs). In this context, there is interest in advancing in the measurement of the FQOL as a first step to determine the supports that families need to perceive quality of life. The aim of this study was to test the validity of the Family Quality of Life Survey‐ Dementia (DiZazzo‐Miller & Samuel, 2011) in order to assess FQoL among family members of individuals with NDs who live in the cross‐border area of Spain‐Portugal.MethodThree hundred family members of people with NDs completed the FQoLS‐NDs Survey (Badia et al., 2020). The mean age was 62.4 years (SD = 13.34). Most were males (70%), married (79.7%), not working (64.7%), with low income (66.1%), and had elementary/high studies (73.1%). The majority were the spouse/partner (40.9%) or son/daughter (51.7%) of the care‐recipient and played the role of primary caregiver (93.3%). Sixty percent of care‐recipients were females (M= 79.3 years; SD= 11.7). Sixty two percent presented dementia, 30.4 % Parkinson´s disease, and 7.6% multiple sclerosis. Construct validity was tested by correlation analysis to examine associations between domain level outcomes (i.e., health, financial well‐being, family relationships, support from others, support from services, influence of values, careers, leisure and recreation, and community integration) and global FQoL. Likewise, t‐tests were used to compare the outcome measures (attainment and satisfaction) within each of the nine family domains.ResultGlobal attainment and satisfaction with FQOL‐NDs was found to be significantly correlated with composite attainment and satisfaction from nine domains (r=.489, p<.001 and r=.536, p<.001, respectively). Attainment and satisfaction were positively correlated within the nine domains (ranging from r=.83 to r=‐.69, p<.001). There was a significant difference between domain‐level attainment and satisfaction ratings [t(299)=12.28, p<.001, h2=.34]: the mean level of satisfaction experienced (M=3.71, SD=0.49) was significantly higher than that of attainment (M=3.52, SD=0.49).ConclusionThis study demonstrates that FQOL‐NDs has good validity properties and it is a useful tool to establish FQOL profiles for family caregivers of people with NDs.
Life experiences of people with dementia in Vietnam and among the Vietnamese diaspora: A systematic review of qualitative studies
Authors: Nguyen Tuan Anh , Tran Kham , Hinton Ladson , Roughead Elizabeth E , Esterman Adrian , Dang Thu Ha , Kim Giang Bao , Pham Diep Bich , Nguyen Huong Thi Diem , Crotty Maria , Kurrle Susan , Pham Thang , Le Pham Tuan , Brodaty Henry 
Published: February 2022

AbstractBackgroundAs part of the effort to gather research evidence for the development of Vietnam’s National Dementia Plan, a systematic review was conducted to map dementia research in Vietnam or among the Vietnamese diaspora. This paper aimed to report the qualitative research evidence on the life experiences of people with dementia in Vietnam and among the Vietnamese diaspora.MethodSystematic searches were conducted in June 2019 using Medline, Embase, Emcare, PsycINFO and Cochrane electronic databases, as well as grey literature. Keywords and Medical Subject Headings [MeSH terms] for dementia and associated terms were combined with keywords for Vietnam and its provinces. Qualitative research articles published in English or Vietnamese were included to examine evidence on the life experiences of Vietnamese people with dementia using thematic analysis.ResultOur searches resulted in 3,940 papers, from which 21 qualitative research studies were included for final analysis. The majority of research has not been undertaken in Vietnam but with the Vietnamese diaspora in Western countries and has taken a cultural perspective to analyses. Research in Western countries has focused on the need for culturally adapted and culturally sensitive models of care. Emerging themes about the life experiences of Vietnamese people with dementia identified from the studies included: many people do not have diagnostic terms for dementia but use the descriptive language of symptoms; stigma was a reported problem and on occasions can be observed in the descriptive language used for people with dementia; cultural and traditional values create both an opportunity and a barrier, supporting compassion, family care and relaxation, but creating barriers to accessing health services or long‐term residential care.ConclusionThis is the first systematic review reporting evidence on the life experiences of people with dementia in Vietnam and among the Vietnamese diaspora. Future research is needed on the voice of people with dementia themselves and their caregivers particularly in low and middle‐income countries with regards to living with dementia, pathways to care from diagnosis, treatment, care and support, additional social care and preparedness for end of life care for people with dementia.
Relationship of APOE, age, amyloid and clinical phenotype in Alzheimer disease
Authors: Whitwell Jennifer L. , Tosakulwong Nirubol , Weigand Stephen D. , Graff‐Radford Jonathan , Ertekin‐Taner Nilufer , Machulda Mary M. , Duffy Joseph R. , Senjem Matthew L. , Jack Clifford R. , Lowe Val J. , Josephs Keith A. ,   ADNI
Published: February 2022

AbstractBackgroundThe apolipoprotein ε4 (APOE4) allele is the most common and well established risk factor for typical late‐onset amnestic Alzheimer’s dementia. Less is known about the role of APOE in patients with atypical clinical presentations of AD, with studies often disagreeing on APOE4 frequencies in these cohorts. We aimed to assess relationships between APOE genotype and age, amyloid‐beta (Aβ) deposition and clinical phenotype in Alzheimer’s disease.Method138 atypical AD patients (57 posterior cortical atrophy and 81 logopenic aphasia) were recruited by the Neurodegenerative Research Group at Mayo Clinic, and underwent APOE testing and Pittsburgh Compound B PET. 318 typical AD patients with APOE genotype and known onset age were identified from ADNI (121 had Aβ‐PET). Aβ‐PET was quantified using the centiloid scale. Logistic regression was used to estimate the proportion of APOE4 carriers by onset age and clinical group. Linear regression was used to estimate mean Aβ centiloid by age, APOE4 status, and clinical group in patients who were Aβ‐positive (centiloid≥19).ResultThe overall frequency of APOE4 carriers was lower in atypical AD (52%) compared to typical AD (66%), particularly for ε4ε4 homozygotes (9% vs 20%). APOE4 frequency increased with age in atypical AD, but showed a bell‐shaped curve in typical AD where highest frequencies were observed between 65‐70 years (Figure). Typical AD showed higher APOE4 frequencies than atypical AD only between the ages of 57 and 69 years. Aβ centiloid was higher in atypical AD compared to typical AD by approximately 16 centiloid units, but did not differ according to APOE4 status (Figure). Aβ centiloid stayed relatively flat with increasing age for both carriers and non‐carriers in atypical AD, but declines with increasing age in typical AD. Relationships between APOE4 and age, as well as centiloid, did not differ between the two atypical AD phenotypes.ConclusionAPOE4 frequency differs between atypical and typical AD but is highly dependent upon age, with higher APOE4 frequency in typical AD only observed between 57 and 69 years. The findings highlight the importance of age and clinical phenotype in understanding the effects of APOE genotype in Alzheimer’s disease.
Factors influencing acceptance of technology across age: Amid the COVID‐19 pandemic
Authors: Whear Sarah A , Wilson Graham , Kourtesis Panagiotis A , Parra Mario A 
Published: February 2022

AbstractBackgroundDigital technologies are creating unprecedented opportunities to improve and increase support to older people with cognitive and mental health problems, and to their family and carers. However, barriers that preclude the implementation of technology driven programs for the assessment and intervention of adults at risk of cognitive decline need to be better understood. This study investigated these outstanding issues, as well as considering the impact that the COVID‐19 Pandemic has had on such barriers.MethodsA sample of 105 participants completed an online survey. Their ages ranged from 18 to 92 years. Of these, 72% were female, 83% had higher education and beyond, 42% were working, 42% were retired, and 14% were unemployed. The questionnaires assessed IT experience alongside awareness, attitudes, and stigmas regarding the use of technologies, particularly those used to support cognitive and mental health. Questionnaires also explored the impact of the COVID‐19 pandemic on these technology‐related factors. We compared these across groups of young (n=45), middle age (n=12) and older adults (n=48).ResultsRelative to younger participants, older participants were less aware of, and held stronger stigmas against healthcare technologies, even though they reported more IT experience. IT awareness was associated to more positive (r=0.619, p<0.001) and less negative IT Attitudes (r=‐0.271, p=0.015), more acceptability (r=‐0.374, p=0.001) and receptiveness towards technologies (r=‐0.610, p<0.001). Male participants appeared to be more aware of such technologies than female participants. However, relative to men, women had increased the number of ways and frequency with which they used technologies since the COVID‐19 pandemic started, and older people in general felt more inclined to endorse the need to learn more about healthcare technologies.ConclusionsHaving more accumulated IT experience throughout our lives may not necessarily lead to better acceptance of healthcare technologies. More awareness about such specific technologies will help overcome stigmas, and challenging environments such as those imposed by the COVID‐19 pandemic may lead to positive changes in perception and acceptance of such technologies. These are necessary steps towards the personalisation of healthcare technologies to support vulnerable adults at risk of dementia.
Brain microstructure mediates effects of tau on cognitive decline in early Alzheimer’s disease
Authors: Reas Emilie T. , Smirnov Denis S. , Banks Sarah J. , Galasko Doug R. , Brewer James B. 
Published: February 2022

AbstractBackgroundTau propagation from medial temporal regions to neocortex correlates with cognitive decline and neurodegeneration. Microstructural damage to medial temporal gray matter and associated white matter predicts Alzheimer’s disease (AD)‐related cognitive impairment. However, whether brain cytoarchitectural injury mediates effects of tau on cognitive dysfunction, or promotes cognitive decline via convergent pathways, remains unresolved.MethodWe used restriction spectrum imaging (RSI) to identify microstructural brain abnormalities associated with total tau, and to determine whether they mediate tau‐related cognitive decline. RSI, cerebrospinal fluid total tau, global cognitive function and verbal episodic memory data were acquired on 34 participants ranging from cognitively normal to mild AD (21 normal controls, 13 cognitively impaired (mild cognitive impairment or early AD)). Longitudinal RSI and cognitive data were collected two and four years post‐baseline, respectively. Restricted isotropic diffusion (RI), neurite density (ND), and isotropic free water (IF) were computed in hippocampus, entorhinal cortex, and six white matter tracts. Partial correlations examined associations among tau, microstructure, and cognition and mediation analyses assessed whether microstructure mediates tau‐related cognitive decline. Linear regressions compared the sensitivity of tau, amyloid and microstructure to cognitive outcomes. Partial correlations tested whether tau predicts subsequent microstructural change.ResultTau most strongly correlated with reduced RI, a measure of intracellular integrity, in the hippocampus and fornix. Tau and microstructure in all examined regions correlated with baseline and longitudinal cognitive performance. Hippocampal and fornix RI mediated effects of tau on cross‐sectional memory and global cognitive function, but direct effects of tau on cognition were not significant. White matter and entorhinal microstructure better predicted baseline memory and global cognition, and hippocampal IF better predicted global cognitive decline, than did tau or amyloid. Tau predicted more rapid decline in white matter RI and ND.ConclusionMarkers of tau‐related neurodegeneration may reflect hippocampal and fornix injury that promotes memory impairment and dementia progression. However, medial temporal and white matter microstructure better predicts cognitive outcomes than tau and amyloid, implicating additional factors contributing to neural injury underlying cognitive decline. RSI may be useful for identifying microstructural brain abnormalities consequent to AD pathology or other risk factors, that signal early cognitive dysfunction.
Cardiovascular risk factors, white matter hyperintensities and executive function: Difference among Mexican Americans and non‐Hispanic whites
Authors: Vintimilla Raul , Hall James R. , Johnson Leigh Ann , Yaffe Kristine , Toga Arthur W. , O'Bryant Sid ,   The Health and Aging Brain Study (HABS‐HD) Study Team
Published: February 2022

AbstractBackgroundCardiovascular risk factors (CVRF) differ between ethnicities but is not clear if the relationship with white matter hyperintensities (WMH) and executive function is also different. The purpose of this study was to examine the prevalence of cardiovascular risk factors and their effect on WMH and executive function in a sample of Non‐Hispanic Whites (NHW) and Mexican American (MA) elders.MethodWe studied 1100 (585 NHW, 515 MA) cognitively normal subjects from the Health and Aging Brain Study (HABS‐HD) with signed consent, 3T MRI (Siemens Skyra), clinical evaluation, and cognitive testing. WMH volume was measured from FLAIR using the Statistical Parametric Mapping (SPM) Lesion Segmentation Tool. Linear regression was used to predict the effect of CVRF on WMH. Log transformed WMH adjusted for intracranial volume (derived from Freesurferv6.0 analysis of T1 MPRAGE) were used to predict Trails B (executive function). Age, sex, and education were entered as covariates in the models.ResultSixty‐three percent of the sample were female. MA were significantly younger (mean age 62.6 vs 68.8), less educated (mean education years 9.84 vs 15.64), and had smaller WMH volumes (‐0.13 vs 0.02) than NHW. There was no difference on Trails B scores. MA had a higher prevalence of diabetes and obesity (p=<0.0001), but the prevalence of hypertension and dyslipidemia did not differ among the groups. WMH volume was associated with hypertension in both groups (p=<0.001), while the association with diabetes was only present on MA (p=<0.001). Dyslipidemia and obesity were not associated with WMH volume in any group. WMH predicted Trails B scores in NHW (B = ‐0.13, t =‐4.29, p = <0.001), and MA (B = ‐0.17, t = ‐3.25, p = 0.001). Results remained significant after adjusting for age, sex, education, and CVRF.ConclusionOur findings suggest that the association of CVRF with WMH differs among MA and NHW. Executive function was related to WMH volume in both groups, but it is likely that for MA a metabolic component is more important. Ethnicity should be considered when assessing the association of CVRF, small vessel disease, and cognition.
Amyloid‐β and tau pathologies relate to distinctive brain dysconnectomics in autosomal‐dominant Alzheimer’s disease
Authors: Guzman‐Velez Edmarie , Diez Ibai Palacio , Schoemaker Dorothee , Pardilla‐Delgado Enmanuelle , Fox‐Fuller Joshua T. , Vila‐Castelar Clara , Baena Ana Y. , Sperling Reisa A. , Johnson Keith A. , Lopera Francisco , Sepulcre Jorge , Quiroz Yakeel T. 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD)‐related pathology (i.e., amyloid‐β and neurofibrillary tangles) disrupts functional networks that support higher‐order cognitive functions. Yet, it is not well known how the brain’s functional architecture is differentially associated with in vivo pathology in preclinical AD, which is critical for predicting disease risk and progression. We intersected functional connectivity and PET images to examine how in vivo amyloid‐β and tau pathologies are associated with weighted‐degree centrality patterns, known to be important for understanding network organization and information transmission hubs, in cognitively‐unimpaired individuals with autosomal‐dominant AD due to the Presenilin‐1 (PSEN‐1) E280A mutation.Method21 cognitively‐unimpaired PSEN1 E280A carriers and 31 non‐carriers underwent resting‐state fMRI, 11C Pittsburgh compound B‐PET and 18F Flortaucipir‐PET. We used graph‐based network analyses to examine weighted‐degree centrality, the sum of weights from edges connecting to a node. A general linear model was used to compare connectivity maps between groups, and partial correlations were used to examine the relationship between individual‐subject maps with whole‐brain amyloid‐β and tau PET. A significance threshold of p<0.05 was used. Analyses were covaried for age and corrected for multiple comparisons.ResultCompared to non‐carriers, mutation carriers exhibited reduced weighted‐degree in the medial occipitoparietal and posterior cingulate cortices. Greater amyloid‐β was associated with reduced weighted‐degree in the lateral temporal lobe and fusiform gyrus, and greater weighted‐degree in the lateral and medial prefrontal cortices. In turn, greater tau burden was associated with greater weighted‐degree in the lateral and medial temporal regions, anterior and posterior cingulate cortices, lateral parietal cortex and precuneus, and decreased weighted‐degree in dorsomedial prefrontal cortex.ConclusionOur findings show that cognitively‐unimpaired individuals who are genetically‐determined to develop AD dementia in their forties have abnormal patterns of functional connectivity that resemble spatial patterns of amyloid‐β and tau propagation. Regions that had weaker connections with nearby and distant regions showed greater amyloid‐β burden, while regions that were highly functionally connected exhibited greater tau burden, which has been suggested to increase the probability of tau seeding and propagation. These findings contribute to our understanding of how functional connectivity patterns can help predict risk and monitor AD progression from preclinical to clinical stages.
Anger in family caregivers of people with behavioral variant frontotemporal dementia versus Alzheimer’s disease
Authors: Chen Kuan‐Hua 
Published: February 2022

AbstractBackgroundAmple evidence exists that family caregivers of a person with dementia (PWD) suffer a disproportionate level of burden, stress, and strain compared to non‐caregiving individuals. Less is known about the specific negative emotions experienced by dementia caregivers, such as anger. Anger is experienced by 40‐60% of dementia family caregivers and is associated with feelings of resentment towards the PWD. Anger may mediate aspects of caregiver well‐being and the quality of care of the PWD. Caregivers may experience increased anger due to behavioral symptoms of the PWD, but this has not been well‐characterized. Frontotemporal dementia (FTD), particularly the behavioral variant (bvFTD), is characterized primarily by behavioral symptoms. In contrast, cognitive symptoms may be more prominent in Alzheimer’s Disease (AD). We examined anger ratings of family caregivers for PWDs diagnosed with bvFTD, the two other FTD subtypes (i.e., semantic variant primary progressive aphasia [svPPA], and non‐fluent variant primary progressive aphasia [nfvPPA]), and AD.MethodWe studied 48 familial PWD‐caregiver dyads (19 bvFTD, 9 svPPA, 8 nfvPPA, 12 AD). PWD behavioral symptoms were assessed using the Neuropsychiatric Inventory (NPI). PWD cognitive symptoms were assessed using the Mini‐Mental State Examination (MMSE). Caregivers self‐reported their anger on the State Anger Scale.ResultAn ANOVA revealed that caregivers of people with bvFTD, svPPA, nfvPPA, and AD differed in anger (F=3.22; p=.03). Posthoc analyses revealed that bvFTD caregivers reported greater anger (M=1.50, SD=.46) than AD caregivers (M=1.18, SD=.21, p=.02). No other group difference was found. Follow‐up analyses revealed that within bvFTD and AD caregivers, higher caregiver anger was associated with higher scores on the NPI reflecting greater PWD behavioral symptoms (r =.63, p<.001), but not cognitive functioning on the MMSE (r=‐.03, p=.85). Importantly, PWD behavioral symptoms fully mediated the association between disease diagnosis (i.e., bvFTD vs. AD) and caregiver anger. We did not find a similar mediation effect for PWD cognitive functioning.ConclusionAnger among family caregivers is higher among those caring for persons with bvFTD compared to AD. Our findings reveal the important role that behavioral symptoms in PWDs play in explaining caregiver anger.
Neuronal networks are differentially affected in mutation carriers versus non‐carriers in autosomal dominant Alzheimer’s disease
Authors: Yang Kao Lee , Adluru Nagesh , McKay Nicole S. , Gordon Brian A. , Benzinger Tammie L.S. , Nair Veena A. , Prabhakaran Vivek , Alexander Andrew L. , Singh Vikas , Bendlin Barbara B. ,   Dominantly Inherited Alzheimer Network
Published: February 2022

AbstractBackgroundAutosomal dominant Alzheimer’s disease (AD) is caused by known genetic mutations which results in the biochemical consequences that underlie the pathological basis of the disease, and a disease process driven by amyloid accumulation. Mutation carriage is characterized by substantial amyloid accumulation, and dementia onset at or around the age of parental dementia onset. Dementia onset is likely due to neurodegeneration, including loss of neuronal networks, although changes to structural connectivity remain incompletely characterized. Here, we report preliminary connection‐wise analysis of neuronal networks based on mutation and cognitive status, as well as estimated years to symptom onset (EYO), in autosomal dominant AD.MethodCross‐sectional diffusion tensor imaging (DTI) data from participants in the Dominantly Inherited Alzheimer Network were analyzed. DTI pre‐processing was performed using FSL and MRtrix3. Network node regions were identified based on the IIT‐Desikan gray matter atlas. Threshold‐free network‐based statistics (TFNBS) method was applied to test the effect of group as well as the linear interaction effects of the EYO and group on neuronal networks. The groups examined were mutation carrying AD (AD:MC), cognitively unimpaired mutation carriers (CU:MC), and cognitively unimpaired non‐carriers (CU:NC). Age and sex were used as nuisance variables in the linear models.ResultSample characteristics are shown in Table 1. Group level effects are shown in Figure 1. EYO by group interaction effects are shown in Figure 2. The names of the corresponding gray matter regions are shown in Table 2. Threshold‐free network‐based ‐statistic matrices for the interaction effects are shown in Figure 3.ConclusionAD:MC and CU:MC groups had higher weighted totals (a proxy of intra‐axonal cross‐sectional area of fiber bundles) in most of the neuronal connections. In addition, a similar increase in the weighted totals was observed as CU:MC group approached EYO. Increased cross‐sectional area may reflect loosening and shortening of fiber bundles with disease progression. Characterizing these regions among cognitively unimpaired individuals may inform the specific disease pathophysiology that act upon brain structures and lead to dementia. Future studies will examine these patterns among individuals with late onset AD and assess longitudinal relationships.