bluuebunny/crossref_metadata_2025_split huggingface dataset:
A normative study of the Italian version of the CERAD neuropsychological battery in young‐old and old‐old participating in population‐based studies
Authors: Lucca Ugo , Tettamanti Mauro , Riva Emma , Mandelli Sara , Forloni Gianluigi , Galbussera Alessia A. 
Published: June 2023

AbstractBackgroundPrevalence of dementia increases with increasing age. Although cognitive assessment is central to the diagnosis of dementia, normative data on neuropsychological tests in non‐selected elderly populations are limited and those available in the oldest‐old rare. Objectives: To report the distribution of scores and normative data on CERAD neuropsychological test battery in a large elderly population including a sizeable number of very old individuals participating in population‐based studies.MethodSubjects included in the analyses were non‐demented participants in three Italian population‐based studies (Monzino‐80 plus, Varese Province, Lombardy; Heath and Anemia, Biella municipality, Piedmont; and Moltrasio, Como province, Lombardy) and in the first normative study on CERAD battery (Lugli 2002). Participants fulfilling DSM‐IV criteria for dementia were excluded. Tests were administered and scored by specifically trained psychologists following standardized criteria, the same in all four studies. The Italian version of CERAD showed high test‐retest reliability (r = 0.89). Multivariable linear regression models were fitted to investigate the association of age (in years), sex, and education (years of schooling) with performance on CERAD tests.ResultThe total population consisted of 2,501 individuals (mean age: 83 years; women: 64%; average education: 6.8 years; institutionalized: 69 [3%]), 802 of whom were young‐old (65‐79 years of age) and 1,699 old‐old (80+ years: 1,155 octogenarians, 470 nonagenarians, and 74 centenarians). The Table shows the distribution of scores (means, SDs, and 5th percentiles) on each test by the whole population as well as by each age class. Better performance on all tests was significantly associated with lower age and higher education; women scored significantly better than men on Word List Learning and Recall, and men better than women on short‐Boston Naming Test and Constructional Praxis Copy and Recall. Refusal to continue and fatigue were the main reasons put forward by elderly participants for not completing the test battery.ConclusionThe present study provides normative data on a neuropsychological test battery commonly utilized in the diagnosis of dementia in a large, non‐selected population of young‐old and old‐old. Performance on CERAD test battery declines with increasing age and lower years of education; performance on some tests were also influenced by sex.
Polypharmacy as a risk factor for dementia: Scottish population‐based longitudinal record linkage study of 1 225 894 people
Authors: Stirland Lucy E , Russ Tom C , Ritchie Craig W. , Muniz‐Terrera Graciela 
Published: June 2023

AbstractBackgroundPolypharmacy, the concurrent use of multiple medicines, is increasing. Population‐wide studies of its association with dementia are lacking. We examined this relationship longitudinally, at a national level.MethodWe used National Health Service community prescribing data from all adults in Scotland aged ≥50 years who received at least one drug in the first quarter of 2009. These data were linked to death records, including cause of death. We used Cox proportional hazards models to assess associations between the number of unique medicines dispensed in one quarter and mortality with any subtype of dementia over 8.5 years, in the whole sample and stratified by age.ResultThe sample contained 1,225,894 people aged ≥50 years (mean age 67.4 (SD = 10.8) years, 56.1% female, 3.8% care home residents). The mean number of drugs dispensed at baseline was 5.0 (SD = 3.7). Over 8.5 years, there were 336,244 deaths, of which 58,358 had any subtype of dementia on the death certificate.Among the whole sample, the hazard ratio (HR) for dementia mortality with each additional medicine was 1.027 (95% CI 1.024‐1.028). In people aged 50‐64 years, the HR was 1.075 (1.061‐1.089); for 65‐79 year‐olds, HR = 1.043 (1.040‐1.047) and for those aged ≥80 years, HR = 1.009 (1.006‐1.012). All models were adjusted for baseline age, gender, care home residence status and deprivation index based on postcode.ConclusionThere was higher mortality with dementia as the number of dispensed medicines increased. Age‐stratified analyses showed that the association was stronger in younger age groups, perhaps reflecting that younger people taking medication for more comorbidities had an increased risk of dying with dementia. These analyses did not allow adjustment for multimorbidity or the consideration of individual drug classes.
White matter hyperintensities in the corpus callosum are associated with beta‐amyloid, neurodegeneration and cognitive performance
Authors: D'Elia Ylenia , Cassing Vilana , Gaubert Malo , Dell'Orco Andrea , Garnier‐Crussard Antoine , Lange Catharina , Dyrba Martin , Ziegler Gabriel , Duering Marco , Teipel Stefan , Peters Oliver , Priller Josef , Schneider Anja , Wiltfang Jens , Buerger Katharina , Perneczky Robert , Laske Christoph , Heneka Michael T. , Wagner Michael , Spottke Annika , Jessen Frank , Duzel Emrah , Wirth Miranka ,   Delcode Study Group
Published: June 2023

AbstractBackgroundWMH in the corpus callosum (CC), as previously related to AD pathology(1) and lower cognition in AD patients(2), are suggested to play an important role in AD. The Aim of this study was to substantiate the associations between WMH location, biomarkers of AD pathophysiology, and cognitive performance in the DELCODE study.Method429 participants were included (HC: 126, SCD: 165, MCI: 87, AD: 51). WMH volumes were segmented from FLAIR images. WMH volumes were adjusted for total intracranial volume and log‐transformed. Beta‐Amyloid and total Tau (Aß42 and tTau, measured in CSF) and neurodegeneration (ND, measured by hippocampal volume) were log‐transformed and used as surrogate markers for AD pathophysiology. Cognitive performance was assessed by a global cognitive composite.Path modelling, adjusted for age, sex and education, was performed to estimate direct and indirect associations between regional WMH volumes (in the CC splenium, body, genu and the frontal lobe as possible control region), AD biomarkers and cognition.ResultsThe correlation matrix (Figure 1) showed the highest correlation of Aß42 and tTau with WMH volume the splenium CC.Greater WMH volume in the splenium CC was directly associated with lower global cognition (Figure 2a, ß = ‐0.10, p = 0.01) and indirectly through Aß42 (ß = ‐0.10, p = 0.001) and ND (Figure 2b, ß = ‐0.05, p = 0.001). The same indirect association was statistically significant regarding tTau (ß = ‐0.03, p < 0.001). Model outcomes were similar for the body and genu of the CC.For frontal WMH volume, the direct association with global cognition was not statistically significant (ß = ‐0.002, p = 0.96), only through indirect associations with Aß42 (ß = ‐0.05, p = 0.003) and ND (ß = ‐0.02, p = 0.05).ConclusionWMH in the CC are associated with lower cognitive performance through direct and indirect associations with Aß42 and neurodegeneration. Similar associations were seen for frontal WMH. However, a direct association between frontal WMH volume and cognition was not noticed, when considering AD biomarkers. Our study substantiates the clinical relevance and impact of WMH in the CC, in particular the splenium, in AD.
1)Gaubert et al.,2021
2)Garnier‐Crussard et al.,2021
Five year dementia registry in Thailand: Regional distribution, etiologies, and outcome of dementia
Authors: Senanarong Vorapun , Rattanabannakit Chatchawan , Hunnangkul Saowalak , Wongkom Natthamon , Likitjaroen Yuttachai , Witoonpanich Pirada , Phanthumchinda Kammant 
Published: June 2023

AbstractBackgroundThere is a lack of epidemiological knowledge about whether individuals with dementia receive the same quality of diagnostics and treatment.MethodWe explored the ICD10 National Health Security Office (NHSO) in‐patient record of dementia in Thailand. We analyzed the prevalence, etiologies, regional distribution, and outcome of dementia in Thailand during 2015‐2019.We reviewed a cross‐sectional cohort study based on data from the NHSO.ResultStudied in‐patients diagnosed with dementia between 2015 and 2019 (n = 29,895; 40,981 visits) 17,058(57.1%) were female. 3,665(12.3%); 11,638(38.9%); 8,845(29.6%); 1,814(6.1%); 1,418(4.7%); and 2,515(8.4%) were in the northern, central, northeast, eastern, western, and southern part of Thailand respectively. Among 29,895 dementia cases, 15.4%, 18.7%, 20.2%, 24.1%, and 21.6% were prevalence cases in 2015, 2016, 2017, 2018, and 2019 (registered up to 30th September where was the end of fiscal year) respectively. 16.1% were single, 68.5% were married, 6.6% were divorced, and 8.9% had other marital status. 85% aged 65 and over. Mean age of these cohort was 75.42(sd = 11.97) years old. The etiologies registered as dementia were as followed: 9.3% had AD, 0.2% had bvFTD, 9.3% ha VaD, 2.1% had other degenerative dementia, 77.4% ha unspecified dementia, and 1.8% had cognitive impairment due to metabolic and physiological condition. During these 5 years, 59.3% were dead. Mean duration of admission were 9.84(sd = 19.84) days. Mean cost of expense during admission were 31,521.79(sd = 80,647.68) Baht.ConclusionThe dementia registry offers the surrogate clinical best practice and patient outcomes. The importance and significance in having dementia data cannot be undervalued.
Effect of social isolation and loneliness on functional abilities mediated by cognition (E‐cog) in Mexican older adults during the first wave of COVID‐19 pandemic
Authors: Durón Dafne Estefania , Aguilar‐Navarro Sara Gloria , Gutiérrez Lidia Antonia , Quiroz Yakeel T. , Mimenza Alberto , Avila Jose Alberto 
Published: June 2023

AbstractBackgroundLoneliness and social isolation are known risk factors for cognitive decline; their effect in older adults (OA) after COVID‐19 lockdown is emerging.ObjectiveTo establish an association between loneliness with functional abilities mediated by cognition in Mexican OA during the first wave of the COVID‐19 pandemic.MethodCross‐sectional study derived from the cohort “The impact of COVID 19 on well‐being, cognition, and discrimination among older adults in the United States and Latin America”, which included 308 older adults recruited between March‐August 2020 whose cognition‐mediated functional abilities were determined with the Everyday Cognition Scale (E‐Cog) questionnaire. The presence of loneliness (The De Jong Gierveld Loneliness Scale) was a binomial variable. Univariate linear regression models were constructed to determine the association between loneliness, and E‐Cog (Ln) scores, which were later adjusted for potentially confounding variables like age and education. In addition, participants were categorized into tertiles of the global E‐Cog score with the following ranges: Tertile 1 (T1): 37.46 ‐46; Tertile 2 (T2): 46.01‐58 and Tertile 3 (T3): 58.01 or more and were compared using ANCOVA. Satistical analyses were conducted using SPSS version 25.0 for MAC (Chicago, IL, USA), figures were made with RStudio (R version 4.1.0, RStudio, Inc., Boston, MA)ResultThe mean age was 65.4 ± 7.9 years and 75.7% were women. The mean E‐Cog was 57.4 (SD: ± 19.1). 84% of participants (n:259) had loneliness. Those with less perception of loneliness had a better performance on E‐Cog by tertiles. The univariate linear model showed a positive and statistically significant association between loneliness and E‐Cog, adjusted by age, sex and education level (β 0.41, 95% CI: 0.22‐0.38, p: <0.01). This model explained 16.1% of the variability of the E‐Cog score.ConclusionOA with self‐reported loneliness had the worst performance in functional abilities mediated by cognition. These data suggest the need for increased vigilance of those who have loneliness due to its potential deleterious effect on cognitive function.
Neutrophil count, serum cytokines, and cognitive function among dementia‐free older adults: a population‐based cohort study
Authors: Fa Wenxin , Liang Xiaoyan , Liu Keke , Wang Nan , Liu Cuicui , Tian Na , Zhu Min , Cong Lin , Wang Yongxiang , Hou Tingting , Qiu Chengxuan , Du Yifeng 
Published: June 2023

AbstractBackgroundPrevious research has suggested that neutrophils could release cytokines to be involved in low‐grade chronic inflammation, which might contribute to cognitive dysfunction. However, population‐based studies have not explored the relationship between neutrophils and cognitive function in older adults. Here, we examined the associations of absolute neutrophil count (ANC) with cognitive performance and cognitive decline among rural Chinese older adults and further explored the potential mediation role of serum cytokines in their associations.MethodThis population‐based longitudinal study included 1666 dementia‐free participants (age ≥60 years; 976, 58.58% women) in the substudy of MIND‐China who undertook the baseline examination in March‐September 2018; of these, 1087 were followed in November‐December 2019. At baseline, ANC was measured using a Mindray BC 6800 automated hematology analyzer. We used the neuropsychological test battery to assess global cognitive function, memory, attention, verbal fluency, and executive function. Serum IL‐6 and eotaxin3 concentrations were measured using Meso Scale Discovery (MSD). Data were analyzed using multivariable general linear models and mediation models.ResultThe cross‐sectional analysis of data at baseline (n = 1666) showed that ANC (range, 0.3 ‐ 24, 109/L) was significantly associated with a lower memory z‐score (multi‐adjusted β coefficient: ‐0.131; 95% CI: ‐0.254 ‐ ‐0.008), but not with attention, verbal fluency, and executive function. Mediating modeling analysis suggested that 22.35% and 10.33% of the association between ANC and memory function were mediated by serum IL‐6 and eotaxin3, respectively. The analysis of longitudinal data (n = 1087) suggested a nonlinear relationship between ANC and memory z‐score decline, with the fourth quartile of ANC (vs. the third quartile) being significantly associated with a multi‐adjusted β coefficient of 0.146 (95% CI: 0.009 ‐ 0.283) for decline in memory z‐score.ConclusionHigher ANC is associated with worse memory performance and faster cognitive decline in rural‐dwelling Chinese older adults, in which their association may be mediated partly by serum cytokines.
Association of kidney function with dementia and brain pathologies: A community‐based cohort study
Authors: Wang Jiao , Wang Shuqi , Dove Abigail , Guo Jie , Qi Xiuying , Bennett David A , Xu Weili 
Published: June 2023

AbstractBackgroundKidney function has been linked to cognitive function, but its relation to dementia and mechanisms underlying this relation remains unclear. We aimed to examine the association of impaired kidney function with dementia and brain pathologies.MethodWithin Rush Memory and Aging Project, 1380 dementia‐free subjects (75.22% female; mean age: 79.42±7.61 years) at baseline were followed for up to 22 years. Blood samples were taken at baseline and serum creatinine was measured to calculate estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. Kidney function dichotomized as normal (eGFR ≥ 60 mL/min/1.73 m2) or impaired (eGFR <60 mL/min/1.73 m2). Dementia, including Alzheimer’s dementia, was diagnosed following international criteria. During the follow‐up, 469 participants died and underwent autopsies for neuropathological assessment (including Alzheimer’s disease [AD], vascular, and other brain pathologies). Data were analyzed using Cox regression, Laplace regression, and logistic regression.ResultAt baseline, 895 (64.86%) participants with normal kidney function and 485 (35.14%) with impaired. Over follow‐up (median [interquartile range]: 5 [2–9] years), 300 (21.74%) participants developed dementia, including 273 (19.78%) with Alzheimer’s dementia. In multi‐adjusted Cox regression, lower eGFR was does‐dependently associated with higher dementia risk (hazard ratio [HR] = 1.01, 95% confidence interval [CI]: 1.01–1.02, P = 0.003) and Alzheimer’s dementia risk (HR = 1.01, 95% CI: 1.00‐1.02, P = 0.002). Compared to normal kidney function, impaired kidney function was associated with a greater risk of dementia (HR = 1.49, 95% CI: 1.16–1.91) and Alzheimer’s dementia (HR = 1.45, 95% CI: 1.12–1.89). The median time to the development of dementia or Alzheimer’s dementia was 2.48 (95% CI: 0.36–3.03) or 2.56 (95% CI: 0.37–2.79) years shorter in people with impaired vs. normal kidney function, respectively. In brain pathology analysis, impaired kidney function was significantly related to higher burdens of cerebral amyloid angiopathy (odds ratio = 2.03, 95% CI: 1.23–3.35).ConclusionImpaired kidney function is associated with an increased risk of dementia and Alzheimer’s dementia. Vascular mechanisms may underlie this association.
Particularities of Cerebrovascular Changes in Patients with Dementia during Alzheimer’s Disease in Comparison with Distal Cerebral Atherosclerosis
Authors: Maksimovich Ivan V 
Published: June 2023

AbstractBackgroundWhen studying the causes of dementia, there are certain difficulties in differentiating existing cerebrovascular changes. We present the features of cerebrovascular changes in Alzheimer’s disease (AD) and in distal forms of cerebral atherosclerosis.MethodsThe research included 935 patients, of whom: 93 people aged 34‐80 (mean age 67.5), 32 men (34.40%), 61 women (65.59%), suffered from AD. According to their dementia severity, the patients were subdivided: (TDR‐0) ‐ 10, (TDR‐1) ‐ 29, (TDR‐2) ‐ 36, (TDR‐3) ‐ 18;• 842 people aged 29‐81 (mean age 74.5), 622 men (73.87%), 220 women (26.13%), with distal cerebral atherosclerosis and chronic cerebrovascular insufficiency. According to their dementia severity, the patients were subdivided: (CDR‐1) ‐ 284, (CDR‐2) ‐ 18.• The examination plan included cerebral MRI, CT, scitrigraphy (SG), rheoencephalography (REG), cerebral multi‐gated angiography (MUGA).ResultsIn patients with AD, changes in angioarchitectonics and microcirculation are manifested in:• Absence of calcium salts deposits and atherosclerotic changes in intracerebral arteries;• Increased tortuosity of the distal parts of the intracerebral arteries;• Reduction of the capillary bed in the temporal and frontoparietal regions;• Development of multiple large arteriovenous shunts with early venous discharge of arterialblood in the same regions;• Development of abnormal venous trunks in the same regions;• Development of intracerebral stagnation of venous blood;These changes are called “Dyscirculatory angiopathy of Alzheimer’s type” (DAAT).In patients with distal cerebral atherosclerosis, changes in angioarchitectonics and microcirculation are manifested in:• Multiple calcium salts deposition and atherosclerotic changes in the intracerebral arteries;• Multiple disseminated contraction of the intracerebral capillary bed;• Development of multiple small disseminated intracerebral arteriovenous shunts;• Lack of pronounced intracerebral venous congestion.ConclusionsDyscirculatory angiopathy of Alzheimer’s type (DAAT), regardless of the severity of dementia, is an AD‐specific cerebrovascular and microcirculatory lesion of the brain not associated with atherosclerotic processes.In patients with distal cerebral atherosclerosis, regardless of the severity of dementia, vascular disorders are of disseminated atherosclerotic character. Anatomically, the lesion of the capillary bed and the presence of arteriovenous shunts are of disseminated character, and there is no pronounced venous stasis. Timely detection of these changes is very important for diagnosis.
Novel residual neural network approach for analyzing amyloid PET scans: Associations with cerebrospinal fluid beta amyloid and episodic memory
Authors: Tagmazian Arina , Schwarz Claudia , Pitkänen Esa , Vuoksimaa Eero 
Published: June 2023

AbstractBackgroundDiagnosing Alzheimer’s disease (AD) based on the biological definition depends on accurately determining amyloid‐β (Aβ) status. In this research, we aimed to create a deep learning model for predicting Aβ cerebral spinal fluid (CSF) measures directly from amyloid PET scans, and compare the result with AD clinical hallmarks.MethodWe developed a novel residual neural network (ResNet) model to predict CSF Aβ from amyloid PET scans and trained the model using 1,870 scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Episodic memory (EM) was measured with immediate and delayed recall in the Rey Auditory Verbal Learning Test (AVLTim/AVLTdel) and in Logical Memory (LMim/LMdel) subtest from the Wechsler Memory Scale. We investigated associations of predicted CSF values with EM measures and compared our model against the traditional approach of determining cortical amyloid with a standardized uptake value ratio (SUVR) measure. We used Pearson correlations to investigate the associations of cortical amyloid with CSF and AD clinical markers. Further, we looked at these correlations separately in different clinically defined groups (cognitively normal, mild cognitive impairment (MCI), and AD).ResultResNet accurately predicted Aβ CSF measures (r = 0.93, p<1e‐10). SUVR significantly correlated with clinical CSF (r←0.65, p<1e‐10) and with ResNet model predicted CSF (r←0.67, p<1e‐10). The predicted CSF is also significantly associated with EM (LMim and LMdel, r = 0.46; AVLTim, r = 0.40; AVLTdel, r = 0.34; p<1e‐10). Correlations in those with AD were generally weaker (SUVR, r←0.37; EM, 0.02<r<0.29) than in those with MCI (SUVR, r←0.70; EM, 0.27<r<0.43) or in cognitively healthy (SUVR, r←0.56; EM, 0.16<r<0.28).ConclusionWe developed to our knowledge the first ResNet model, which predicts Aβ CSF measures with high accuracy. Predicted CSF values strongly correlate with clinical AD hallmarks. However, there are many questions that warrant further study, and we aim to investigate our model in relation to early prediction and diagnosis of AD, and in studying the discordance between biological and clinical AD classifications.