bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain atrophy and white matter hyperintensities are independently associated with plasma neurofilament light chain in an Asian cohort of patients with mixed pathology
Authors: Chong Joyce R. , Ashton Nicholas J. , Karikari Thomas K. , Hilal Saima , Saridin Francis , Tanaka Tomotaka , Schöll Michael , Blennow Kaj , Zetterberg Henrik , Lai Mitchell Kim Peng , Chen Christopher 
Published: December 2021

AbstractBackgroundRecent studies on subjects with “pure” Alzheimer’s disease (AD) reported significant association between high blood neurofilament light chain (NfL) and AD‐related atrophy and poor cognition, but not with white matter hyperintensities (WMHs). In contrast, studies on non‐demented elderly with cerebral small vessel disease (CSVD) revealed a significant association between blood NfL and magnetic resonance imaging (MRI) markers of SVD including WMHs, lacunes and microbleeds. A major limitation of these studies is the lack of participants with mixed pathology to explore the potential independent and/or combined effects of brain atrophy, CSVD and amyloid burden (Aβ) on blood NfL.MethodThis study included 208 Singaporean participants of an ongoing longitudinal study, including non‐cognitively impaired controls (NCI; n=43), cognitively impaired no dementia (CIND; n=99), AD (n=44) and Vascular dementia (VaD; n=22). The presence of brain atrophy was defined by medial temporal atrophy scores ≥2. CSVD were determined by MRI markers. Brain Aβ was assessed by [11C]‐PiB PET SUVR. Plasma NfL (pNfL) was measured by Single molecule array (Simoa) immunoassay.ResultpNfL concentrations were significantly increased in AD and VaD. In the full cohort, stepwise regression including neuroimaging markers (brain atrophy, WMH, cerebral microbleeds, lacunes and brain Aβ), vascular risk factors (hypertension, hyperlipidemia, diabetes, smoking and APOE ε4 carriership) and demographics (age, gender, education) as independent variables showed that brain atrophy, WMH, age, gender and presence of diabetes to be independently associated with pNfL (all p<0.05). Further univariate general linear models (Fig 1) showed that in the presence of brain atrophy (N+WMH‐) or high WMH (N‐WMH+) alone, pNfL was significantly increased after controlling for age, gender and presence of diabetes (p≤0.007). There was a trend of further increase in pNfL in the presence of both brain atrophy and high WMH burden.ConclusionThe independent associations and potential combined effects of brain atrophy and WMH on pNfL, together with the high prevalence of SVD burden in the elderly, suggests that SVD needs to be considered when interpreting elevated pNfL in elderly patients.
Dissemination of person‐centered community care for mild dementia using local cooperatives in Korea during the COVID‐19 pandemic
Authors: Park Myonghwa , Go Younghye 
Published: December 2021

AbstractBackgroundTo promote aging in place and improve the quality of life for persons with mild dementia during COVID‐19 pandemic, there is a need to support them in their community in‐person approach. Therefore, person‐centered community care for individual service and support in the community is an urgent priority. This study aimed to develop a person‐centered community service for mild dementia patient to collaborate with local cooperatives and test its feasibility.MethodsThis study was done from March to December, 2020. The person centered community service manual was developed based on previous guidelines and studies. The manual guided person‐centered assessment, tailored intervention, and outcome evaluation based on six domains; person‐hood, daily life, cognitive health, physical activity, safety, and community support. The local cooperatives for community care participated to provide comprehensive needs assessment and individualized service to the community residents with mild dementia. The staff visited the patient’s home and provide individual service. The feasibility study was tested with the staff and patients.ResultsThis study found that the service was effective for initial rapport, comprehensive assessment, individualized planning, person‐centered service provision, referral to community service, and outcome evaluation. However, service provider’s increased workloads and the time for home visiting and completing the service were identified as barriers during pandemic period. In addition, service providers still experienced lack of knowledge and skills in enhancing safety such as precaution and social distancing.ConclusionThe person‐centered community service can be useful to enhance the safe and sustainable community services during COVID‐19 pandemics. Collaboration with local cooperatives can be the best practices through the well‐designed manual.
Correlates of subjective cognitive decline (SCD) in a Canadian sample of midlife and older adults
Authors: Hopper Shawna , Hammond Nicole G , Stinchcombe Arne 
Published: December 2021

AbstractBackgroundSubjective cognitive decline (SCD), a self‐perceived decline in memory among otherwise cognitively healthy older adults, has been linked to increased risk of Alzheimer’s disease (AD). It is believed that SCD may be a first symptomatic expression of preclinical AD. Identification of SCD precursors may allow for early identification and implementation of intervention to prevent cognitive decline.MethodUsing data from the Canadian Longitudinal Study on Aging (CLSA), a national study of over 50,000 participants ages 45‐85 at baseline, we sought to identify potential risk and protective factors for SCD. Participants with diagnosed AD at baseline were excluded. Exposures were measured at baseline and SCD was measured three years later, at first follow‐up, with the question: “Do you feel like your memory is becoming worse?”. A multivariable logistic regression model was used to estimate odds of SCD (analytic sample: n=36,885).ResultResults indicated that 56.1% participants reported SCD. Participants with a post‐secondary education had increased odds of SCD compared to those with less than a secondary school graduation (OR=1.20, 95% CI: 1.09, 1.33). Hearing problems (OR=1.46, 95% CI: 1.36, 1.56) and vision problems (OR=1.14, 95% CI: 1.05, 1.24) were associated with increased odds of SCD. Alcohol consumption also increased the odds of SCD, with infrequent drinkers (OR=1.08, 95% CI: 1.00, 1.16), regular drinkers (OR=1.13, 95% CI: 1.05, 1.22) and frequent drinkers (OR=1.16, 95% CI: 1.07, 1.25) more likely to self‐report SCD than never drinkers. Participants who consumed five or more servings of fruits/ vegetables had reduced odds of SCD (OR=0.95, 95% CI: 0.91, 0.99), when compared to those who consumed <5 servings. Compared to participants who never smoked, former smokers had increased odds of SCD (OR=1.13, 95% CI: 1.08, 1.12), whereas current smokers had reduced odds of SCD (OR=0.91, 95% CI: 0.84, 0.98). Lastly, individuals with diagnosed mood and anxiety disorders had higher odds of SCD compared to those without (OR=1.42, 95% CI: 1.34, 1.50).ConclusionThis study sheds light on prospective correlates of SCD in a large population‐based sample of older Canadians. Many of the factors associated with SCD may be modifiable therefore amenable to early intervention.
Neurodegenerative diseases and lifetime seizure risk: A study of autopsy proven cases
Authors: Vöglein Jonathan , Kostova Irena , Arzberger Thomas , Noachtar Soheyl , Dieterich Marianne , Herms Jochen , Schmitz Peer , Ruf Viktoria , Windl Otto , Roeber Sigrun , Simons Mikael , Höglinger Günter , Danek Adrian , Giese Armin , Levin Johannes 
Published: December 2021

AbstractBackgroundIn the neurodegenerative conditions Alzheimer disease (AD), Lewy body disease (LBD) including the neuropathologically indistinguishable Parkinson disease and dementia with Lewy bodies, frontotemporal lobar degeneration (FTLD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) figures for seizure risk are inconsistent, rare or lacking. This is particular true if neuropathologically confirmed diagnoses are stipulated. Therefore, our goal was to determine the lifetime risk for epileptic seizures and to investigate associated clinical parameters in neuropathologically diagnosed neurodegenerative diseases.MethodCases from the Neurobiobank Munich, Germany, were matched with information from clinical files regarding the occurrence of epileptic seizures. The aforementioned diseases were compared for lifetime seizure risk. The predictive value of the first clinical symptom regarding lifetime risk for seizures was analyzed and associations between the occurrence of seizures and survival was investigated.ResultWe analyzed 454 neuropathologically diagnosed cases with sufficient clinical data available. 144 had AD, 103 LBD, 93 PSP, 53 FTLD, 36 MSA, and 25 CBD. Lifetime risk for epileptic seizures was 31.3% in AD, 20.0% in CBD, 12.6% in LBD, 11.3% in FTLD, 8.3% in MSA and 7.5% in PSP. Patients with AD had a statistically significantly higher lifetime risk for seizures compared to patients with FTLD (p=0.005), LBD (p=0.001), MSA (p=0.005) and PSP (p<0.001). An increased lifetime seizure risk was found in patients with cognitive first symptoms when compared to those with non‐cognitive first symptoms (21.1% vs. 11.0%). A decreases lifetime risk for seizures was observed in cases with motor first symptoms when compared to those with non‐motor first symptoms (10.3% vs. 20.5%). MSA patients with seizures survived longer when compared to those without (12.3 vs. 7.0 years; p = 0.017).ConclusionIn this clinical neuropathological correlation study, nearly every third AD patient and approximately every fifth patient with a neurodegenerative disease experienced epileptic seizures in the disease course. Therefore, epileptic seizures are an important comorbidity in neurodegenerative conditions, in particular in AD. Assessment of the first clinical symptom may improve early estimation of the lifetime seizure risk in the studied neurodegenerative diseases.
The circadian rest‐activity patterns in mild‐moderate Alzheimer’s disease patients
Authors: Targa Adriano , Benitez Ivan David , Dakterzada Faride , Araujo John Fontenele , Minguez Olga , Huerto Raquel , Tahan Nuria , Barbe Ferran , Piñol‐Ripoll Gerard 
Published: December 2021

AbstractBackgroundAlterations in the circadian rhythms are present in the presymptomatic phase of Alzheimer’s disease (AD), possibly contributing to its pathogenesis. However, it is unknown whether such alterations could be associated with worse outcomes once the individuals are diagnosed with the disease. We aimed to evaluate the association between the rest‐activity rhythm and AD‐related outcomes in patients with mild‐moderate AD.MethodThe cohort included 100 individuals with mild‐moderate AD. The rest‐activity rhythm was assessed through the use of actigraphy for 14 days. Cerebrospinal fluid was obtained to determine the levels of distinct pathological markers of the disease and neuropsychological evaluation was carried out at the beginning of the study and after 12 months of follow‐up.ResultWe observed that older age was associated with increased fragmentation of the rest‐activity rhythm (per 1 SD increase, change [SD] of 0.311 [0.096]; p = 0.002) whist female sex was related to higher synchronization between the endogenous rhythm and the zeitgebers (per 1 SD increase, change [SD] of 0.780 [0.193]; p < 0.001). The rest‐activity rhythm was also associated with disease‐related outcomes. Accordingly, there was an association between higher NF‐L levels an increased relative amplitude (per 1 SD increase, change [95% CI] of 240.480 [59.176 to 421.784]; p = 0.010). In addition, increased fragmentation of the rhythm at the baseline was associated with enhanced cognitive decline after one year of follow‐up independently of age, sex, ApoE4 status, educational level, and pharmacological treatment (per 1 SD increase, change [95% CI] of ‐0.576 [‐1.148 to ‐0.005]; p = 0.048).ConclusionOur results suggest a potential role for the rest‐activity rhythm in predicting both molecular and clinical outcomes in patients with mild‐moderate AD. Further studies are warranted to confirm these findings and to elucidate whether there is causality among the observed associations. In case of a positive response, the circadian rest‐activity rhythm could be a promising target to prevent the cognitive decline.
HIV‐associated neurocognitive disorder: An investigation using structural neuroimaging in a c‐ART treated Tanzanian cohort
Authors: McDonald Lucy , Koipapi Sengua , Howlett William , Dekker Marieke , Urasa Sarah , Kalaria Rajesh , Walker Richard , Firbank Michael J , Paddick Stella‐Maria 
Published: December 2021

AbstractBackgroundThere is a newly emergent ageing population of people living with HIV (PLWH) in Africa. However, there is little research into HIV‐associated neurocognitive disorder (HAND) in this population. Existing research suggests HAND is prevalent however the aetiology remains unclear. This study aims to determine whether HAND is truly prevalent and explore potential causes in PLWH on c‐ART using objective structural measures.MethodA systematic sample of PLWH aged ≥ 50 receiving combination antiretroviral treatment (cART) according to local guidelines were recruited from a HIV clinic in Kilimanjaro, Tanzania. Demographic data and comorbidities were self‐reported. HIV‐disease management data were obtained from detailed clinic data sheets. HIV viral load and CD4 count were measured. A detailed low‐literacy neurocognitive battery, informant history for functional impairment and neurological examination were conducted and HAND diagnosis made by consensus panel using AAN criteria. Cerebral atrophy (brain and ventricle volume) and WMH were measured using quantitative analysis of 1.5T MRI.ResultThis cohort (n=91, 100% on cART, 64.8% female) had well‐managed HIV (75.9% suppressed viral load, median CD4 507 cells/ul). However, 66.7% had gross atrophy on their MRI scan, and HAND had a prevalence of 63.7%. The significant independent predictor (IP) of decreased brain volume was older age at HIV diagnosis (p=.001), and of increased ventricle volume was increased age (p<.0001), male gender (p<.0001) and increased frailty (p<.0001). The significant IPs of increased WMH volume were increased age (p<.0001) and smoking (p=.021). Only memory impairment independently predicted all structural measures.ConclusionThis is the first MRI study of older c‐ART treated PLWH in Africa. Despite c‐ART and good disease management, HAND was objectively prevalent and unrelated to measures of HIV disease severity. Cerebral atrophy and WMH were associated with factors of neurodegeneration. Cerebral atrophy was associated with male gender and older age at diagnosis. Association with older age at diagnosis may be 'legacy effect' of early CNS effect of the HIV virus rather than current management.
Distinctive effect of biological sex in AD‐related CSF and plasma biomarkers
Authors: Milà‐Alomà Marta , Brinkmalm Ann , Rodriguez Juan Lantero , Karikari Thomas K. , Ashton Nicholas J. , Kvartsberg Hlin , Grau‐Rivera Oriol , Sala‐Vila Aleix , Sánchez‐Benavides Gonzalo , Arenaza‐Urquijo Eider M. , Brugulat‐Serrat Anna , Akinci Muge , González‐de‐Echávarri José Maria , Minguillón Carolina , Fauria Karine , Suridjan Ivonne , Kollmorgen Gwendlyn , Stoops Erik , Vanmechelen Eugeen , Zetterberg Henrik , Blennow Kaj , Molinuevo Jose , Suarez‐Calvet Marc ,   for the ALFA study
Published: December 2021

AbstractBackgroundClinical studies indicate that Alzheimer's disease (AD) disproportionately affects women. Although previous studies reported sex differences in fluid biomarkers, there is a need for a comprehensive analysis across the disease continuum. The aim of this study was to compare AD‐related biomarkers in cerebrospinal fluid (CSF) and plasma between women and men in middle‐aged cognitively‐unimpaired individuals at risk for AD.MethodWe measured Aβ42, Aβ40, Mid (M)‐p‐tau 181, N‐terminal (N)‐p‐tau 181, N‐p‐tau 217, M‐p‐tau 231, t‐tau, NfL, neurogranin, SNAP25, GAP43, synaptotagmin1, sTREM2, YKL40, GFAp, S100B, IL6, sVCAM1, sICAM1, MCP1 and α‐synuclein in CSF; and N‐p‐tau181, NfL, GFAp, MCP1, sICAM1 and sVCAM1 in plasma. Biomarker measurements were performed using immunoassays (colorimetric, MSD, Elecsys®, Simoa and the exploratory Roche NeuroToolKit robust prototype assays) and mass spectrometry. We tested sex differences in demographic variables (using t‐test or Chi‐squared) and in cardiovascular factors (using ANCOVA adjusted for age and APOE‐ε4 status). Sex differences in biomarkers were assessed with 3 different ANCOVA models, adjusted for (i) age, (ii) age and CSF Aβ42/40 and (iii) age and cardiovascular factors that showed sexual divergence.ResultWe studied 384 participants of the ALFA+ cohort. Men had higher education, APOE‐ε4 prevalence, physical activity, diastolic blood pressure, BMI, glucose and triglycerides than women. In contrast, women had higher vitamin B12, LDL, HDL and total cholesterol as compared to men. In CSF (Table 1), men had higher NfL, GFAp, MCP1, sICAM1 and sVCAM1, while women had higher neurogranin, synaptotagmin‐1 and N‐p‐tau 217, after adjusting for age (Model I). These differences remained significant after adjusting for CSF Aβ42/40 (Model II). In plasma (Table 2), we observed an opposite pattern compared to results in CSF: women showed higher NfL, GFAp and sICAM1 after adjusting for age (Model I) and for CSF Aβ42/40 (Model II). Sex differences in CSF NfL, sICAM1, sVCAM1, and plasma sICAM1 remained significant after adjustingg for cardiovascular factors (Model III).ConclusionAD‐related fluid biomarkers of neurodegeneration and neuroinflammation/endothelial dysfunction differ between women and men, but these differences have an opposite direction for some biomarkers in CSF and plasma. These results highlight the importance of considering sex differences in AD‐related fluid biomarkers.
Association between telomere length and cognitive function among cognitively unimpaired individuals at risk of Alzheimer’s disease
Authors: Rodríguez‐Fernández Blanca , Vilor‐Tejedor Natalia , Sánchez‐Benavides Gonzalo , Arenaza‐Urquijo Eider M , Minguillón Carolina , Fauria Karine , DeVivo Immaculata , Navarro Arcadi , Gispert Juan Domingo , Molinuevo Jose , Sala‐Vila Aleix , Crous‐Bou Marta ,   for the ALFA study
Published: December 2021

AbstractBackgroundTelomere length (TL) is an objective biomarker of biological aging and it has been proposed to play a crucial role in Alzheimer's disease (AD) progression by impairing cognitive resilience. However, published studies show inconsistent results and a very limited number of studies have evaluated the role of TL in aging and midlife individuals. The main objective of this study was to evaluate the association between TL and cognitive performance in middle‐aged cognitively unimpaired individuals at increased risk of AD.MethodsThe study included 1,079 participants from the ALFA (ALzheimer and FAmilies) cohort. Relative TL was determined by qPCR from DNA extracted from peripheral blood leukocytes. TL values were normalized by computing z‐scores. A cognitive battery was administered to assess verbal memory, psychomotor speed, visual processing and executive function. Further, episodic memory, executive function and global cognitive composites were calculated by averaging normalized raw scores of all subtests in each domain. Generalized linear models with Poisson/quasi‐binomial distributions and linear regression models were implemented to assess the cross‐sectional association between TL and cognitive subtests as well as TL and cognitive composites, respectively. All models were adjusted by sex and age. Additionally, stratified analyses by APOE‐ɛ4 status were conducted. Statistical significance was set at P≤0.05.ResultsLonger TL at baseline was associated with better performance on executive function subtests related to visual processing, attention/working memory and reasoning only in APOE‐ɛ4 non‐carriers [Table 1]. Similarly, APOE‐ɛ4 non‐carriers showed a significant association between longer TL and better scores on executive function composites [Table 2]. In contrast, no associations between TL and memory‐related tests were observed.ConclusionsOur results suggest a potential role for telomeres on maintaining cognition in aging, specifically in individuals at low genetic risk of AD. Further longitudinal analyses are warranted to better understand the role of the APOE‐ɛ4 genotype on these associations and their potential impact on cognitive resilience in the context of the AD continuum.
Cerebral amyloid angiopathy and visuospatial functioning: Analysis of the clock drawing test
Authors: MacLean Davis , Zwiers Angela , Cox Emily , Ismail Zahinoor , Camicioli Richard , Smith Eric E. 
Published: December 2021

AbstractBackgroundCerebral amyloid angiopathy (CAA) contributes to cognitive impairment as well as dementia in the elderly. In clinical cohorts, symptomatic CAA is associated with impairments in executive function and processing speed. Because CAA severity tends to be highest in the occipital and posterior temporal and parietal lobes, it may also affect visuospatial function. We hypothesized that participants with a clinical diagnosis of CAA will have impaired performance on tests of visuospatial function when compared to control, mild cognitive impairment (MCI) and Alzheimer’s disease (AD) participants.MethodParticipants with CAA presented with lobar intracerebral hemorrhage, transient focal neurological episodes, or mild cognitive impairment; met Boston criteria for probable CAA; and did not have dementia. Clocks were scored based on a published 20‐point system (Mendez, JAGS 1992). Clock items were subcategorized by general contours, number items, and hand items (Mendez, JAGS 1992); and by a subset of 9 items correlated in prior literature with visuospatial function and temporal‐parietal hypoperfusion (visuospatial items).ResultData from 53 CAA without dementia, 43 MCI, 30 AD with mild dementia (MMSE ≥20), and 40 control participants were analyzed (mean age 71.6 [SD 7.5]; 47% women). Compared to controls, CAA participants performed significantly worse on total score, hand items, and visuospatial items (Table 1). AD participants performed worse than controls on all components except general contour, and MCI participants did not differ from controls. Among CAA participants, total and visuospatial scores did not correlate with history of stroke, number of microbleeds, or white matter hyperintensity volume (p>0.10).ConclusionMean performance on the clock drawing test is lower in CAA patients without dementia than controls, suggesting visuospatial impairment. This impairment may be related to vascular amyloid deposition in posterior brain regions; however, it was not correlated with typical markers of CAA severity suggesting it may be an early but not necessarily progressive feature. Future research should investigate the mechanisms of visuospatial impairment in CAA—including whether it is related to posterior white matter damage or parieto‐occipital atrophy—and its association with daily function and risk for cognitive decline.