bluuebunny/crossref_metadata_2025_split huggingface dataset:
Closer correlations between florbetapir PET measurements of amyloid plaque burden using a cerebral white matter reference region and Alzheimer’s disease‐related hypometabolism
Authors: Wang Michele S , Bi Tingting B , Jing Naomi Y , Ausdemore Jake C , Kramer Harrison L , Chen Yinghua , Luo Ji , Weiner Mike W. , Landau Susan M. , Jagust William J. , Su Yi , Reiman Eric M. , Chen Kewei 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is associated with amyloid‐β (Aß) plaque deposition and a characteristic pattern of cerebral glucose hypometabolism. While a cerebellar reference region is commonly used to characterize cerebral Aβ burden, we demonstrated improvements in the ability of florbetapir PET to track Aβ burden using a cerebral white matter reference region (Chen, et al., 2015). Here, we compare associations between cerebral‐to‐reference region florbetapir PET standard value uptake ratios (SUVRs) using cerebral white matter versus cerebellar reference regions to two FDG PET indices of AD‐related cerebral hypometabolism: “hypometabolic convergence index” (HCI) and “statistical region‐of‐interest” (sROI) (Chen et al, 2010; 2011).MethodWe analyzed 1722 florbetapir and FDG PET scan pairs from the AD Neuroimaging Initiative, including 267 with probable AD dementia (pAD), 592 with MCI and 379 cognitively unimpaired (CU). Florbetapir SUVRs were computed using measures from the cerebral regions‐of‐interest with the cerebral white matter or cerebellar reference regions. HCI and sROI were generated from the FDG PET images. Pearson’s correlations and the Steiger statistical test were used to characterize and compare the extent to which florbetapir SUVRs using cerebellar versus cerebral white matter reference regions were associated with HCI or sROI in the overall group, the pAD, MCI and CU sub‐groups.ResultCorrelations between florbetapir SUVRs using the white matter reference region and HCI (0.59, 0.41, 0.45, and 0.40 in the overall, pAD, MCI and CU groups) were significantly stronger than those using the cerebellar reference region (0.40, 0.23, 0.26, and 0.20, P=1.1e‐16, 3.6e‐06, 1.3e‐09, and 1.0e‐11, respectively). Similarly, inverse correlations between florbetapir SUVR measurements using the white matter reference region and sROI measurements (‐0.51, ‐0.32, ‐0.38, and ‐0.28 in the overall, pAD, MCI and CU groups) were significantly stronger than those using the cerebellar reference region (‐0.34, ‐0.09, ‐0.24, and ‐0.13, P=2.0e‐15, 3.2e‐07, 1.7e‐0, and 4.0e‐07, respectively).ConclusionFlorbetapir PET Aβ plaque measures are more closely associated with the AD‐related pattern of cerebral hypometabolism when SUVRs are generated using a white matter rather than cerebellar reference regions. Additional research is needed to examine if our results are generalizable for other Aβ PET tracers and longitudinal change measures.
Impact on cerebral cortical thickness of lifestyle multidomain intervention: The SUPERBRAIN study
Authors: Moon So Young , Kim Sohui , Choi Seong Hye , Hong Chang Hyung , Park Yoo Kyoung , Na Hae Ri , Song Hong‐sun , Kim Byeong‐Chae , Park Kyung Won , Park Hee Kyung , Choi Muncheong , Lee Sun Min , Chun Buong‐O , Lee Jong‐Min , Jeong Jee Hyang 
Published: December 2021

AbstractBackgroundIn the South Korean study to prevent cognitive impairment and protect brain health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), we explored impact on cortical thickness of 24‐week facility‐based multidomain intervention (FMI) and home‐based MI (HMI).MethodA total of 152 participants, aged 60‐79 years without dementia but with ≥ 1 modifiable dementia risk factor, were randomly assigned to the FMI, HMI, or control groups. Among them, 55 participants (20 FMI, 19 HMI, and 16 control) took brain MRIs at baseline and 24 weeks. We compared between each intervention and control groups in change of global/regional mean cortical thickness at 76 region‐of‐interest (ROI)s of the automated anatomical labelling (AAL); the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); and Serum brain‐derived neurotrophic factor (BDNF) levels. The changes in mean cortical thickness were compared using analysis of covariance with age, sex, education, and scan centers as covariates. ROI‐based analysis was controlled for multiple comparisons with a false discovery rate threshold of P < 0.05.ResultComparing with the control group, the total scale index score of RBANS was more significantly improved in both FMI group (p=0.002) and HMI group (p=0.013), respectively. The serum BDNF more significantly increased only in the FMI group (p=0.029). Mean global cortical thickness more significantly increased only in the FMI group (0.033±0.070 vs ‐0.003±0.040, p=0.035). ROI‐based analysis showed more significantly increased cortical thickness of the orbital, medial, medial orbital parts of right superior frontal gyrus, right olfactory cortex, right rectal gyrus, right anterior cingulate and paracingulate gyri, right middle temporal gyrus, medial orbital and dorsolateral parts of the left superior frontal gyrus, the orbital part of the left middle frontal gyrus, left middle occipital gyrus, and left middle temporal gyrus in the FMI group.ConclusionSignificant differences between the FMI and control groups on changes in cortical thicknesses in at‐risk elderly without substantial impairment in the SUPERBRAIN suggest that group preventive strategies at the facility may be beneficial on cognition through structural neuroplastic changes in the brain areas which play a crucial role in processing social information.
Individual analysis of reminiscence from nostalgic music videos using text mining
Authors: Urabe Mie , Miyata Chiharu , Fukuda Hiroko , Yoneda Sho , Sakai Katsumi , Kato Yuka , Kitajima Kengo , Kashiwa Yukiko , Sawada Chikao 
Published: December 2021

AbstractBackgroundNostalgic music arouses positive changes in mood and social behavior of persons with dementia.(Barnetta L.,et al.,2006)Our research is an intervention using nostalgic music videos and reminiscence which provides stimulation to the emotions of a person with dementia, and positive emotions occur. In AAIC 2020, we presented this intervention. (Urabe, et al.,2020) The purpose of this study is to clarify the individual changes in narrative of reminiscence of a person with Alzheimer’s disease between the first and the last intervention using text mining.MethodThe participant with Alzheimer’s disease was a female (over 90 years old, MMSE: sixteen points ), and was in a psychiatric hospital in Japan, because of BPSD. We intervened four times using nostalgic music videos she liked, and listened to her memories of youth. We recorded her narrative and analyzed the words of her stories using text mining to see the changes caused by our intervention, and compared the results of the first intervention and the last. The participant’s language was Japanese, so her words were analyzed in Japanese to maintain accuracy. This study was approved by the ethical review board of Kyoto Prefectural University of Medicine and hospital where participant hospitalized.ResultIn the first intervention, the overall number of words were 1271, the number of sentences were 121, and the number of paragraphs were 102. In the last intervention, the total number of words were 2669, the number of sentences were 229, and the number of paragraphs were 150, and was significantly increased more than first intervention. In the co‐occurrence network, there were more connected co‐occurrence words in the last intervention than first intervention. The connections between this co‐occurrence network included three themes, these themes were memory, songs and work.ConclusionWe were able to visualize the narrative of the participant with Alzheimer’s disease, and clarify the individual important keywords in the participant’s memories by using text mining. By reminiscing with nostalgic music videos, it increased the amount of language and revived memories for the patient with Alzheimer’s disease.
Amyloid‐β accumulation is independently related to executive function in cognitively unimpaired adults
Authors: Tideman Pontus , Stomrud Erik , Mattsson Niklas , Palmqvist Sebastian , Hansson Oskar 
Published: December 2021

AbstractBackgroundThe shift from a symptom‐based to a biological definition of Alzheimer’s disease (AD), within the NIA‐AA research framework, has highlighted the importance of biomarkers that are indicative of the neuropathological changes underlying AD. The independent associations of amyloid (Aβ), tau, and neurodegeneration with different cognitive domains in cognitively unimpaired (CU) need to be studied in deeply phenotyped cohorts. In the current study we investigated how the distinctive pathologies and neurodegeneration of AD, according to the AT(N) system, are related to cognition in four cognitive domains in CU adults.MethodWe included 316 CU individuals from the prospective BioFINDER‐2 study. The results were validated in CU participants from the ADNI study (n=376). All cases had CSF biomarkers (Aβ42 and P‐tau181), MRI (cortical thickness of AD‐susceptible regions), Aβ‐PET (neocortical uptake) and tau‐PET (entorhinal cortical uptake) as well as neuropsychological test data (including tests for i) memory, ii) executive function, iii) verbal function, iv) visuospatial function). Multivariable linear regression models, adjusted for age, sex and education, were performed, first using CSF Aβ42, P‐tau181 and cortical thickness and secondly using Aβ‐PET, tau‐PET and cortical thickness.ResultIn BioFINDER‐2, abnormal Aβ‐status was independently associated with executive function, regardless of biomarker (CSF Aβ42 β=0.128, p=0.024; Aβ‐PET β=0.124, p=0.049), but not memory or any other cognitive domains. Tau, on the other hand, was independently related to memory (CSF P‐tau181 β=0.132, p=0.018; tau‐PET β=0.189, p=0.002). Cortical thickness was independently associated with executive function (CSF‐based model, β= ‐0.161, p=0.013; PET‐based model, β= ‐0.186, p=0.005) and verbal function (CSF‐based model, β= 0.163, p=0.011; PET‐based model, β= 0.156, p=0.018). In a second step, only participants without evidence of tau pathology or neurodegeneration were included, again resulting in an association between Aβ and executive function (CSF Aβ42, β=0.189, p=0.005; Aβ‐PET, β=0.146, p=0.023), but not with other cognitive domains. Results were overall replicated in the ADNI cohort.ConclusionThese findings suggest an independent relationship between early Aβ accumulation and worse executive function in CU individuals while tau is associated with memory. This finding contributes to our understanding of how cognitive deficits are manifested in early AD, especially in regard to Aβ accumulation.
Epidemiological impact of Alzheimer´s disease and other dementias in the Spanish‐Portuguese border region
Authors: Alonso‐Sardón Montserrat , Martín‐Delgado María Antonia , Pérez‐Martín Raixa Noemí , Ortega Eva González ,   NEUROQUALYFAM group
Published: December 2021

AbstractBackgroundDementia has reached epidemic proportions and become a huge Public Health problem. Alzheimer’s disease (AD) is the most common type of dementia. In Spain, more than 800,000 people suffer from AD (Spanish Society of Neurology‐SEN). Age is the main risk marker for developing this disease. Its prevalence is three times higher in women than in men due to females’ higher life expectancy. The aim is to know the epidemiological profile and quantify the current scope of the AD and other dementias in the rural Spanish‐Portuguese border area, one of the most depopulated and aging regions in Europe.MethodA cross‐sectional descriptive study was designed to estimate the prevalence of persons diagnosed with an ICD‐9‐CM or ICD‐10 code diagnosis of dementia in ten Basic Health Areas of the cross‐border rural area of province of Salamanca, Spain, during June‐July 2020 (39,354 inhabitants). The cases were recorded from the Electronic Clinical Record of Primary Care (MEDORA) by the Regional Health Management of Castilla y León.ResultA total of 579 individuals suffer some type of dementia in the Spanish‐Portuguese border region, with a predominance of females (70%) vs. males (30%), and an age range of 38 to 109 years (Figure_1). AD was diagnosed in 307(53%) persons and other dementias in 272(47%). Gender distribution of the diagnoses is different in women and men (p<0.001) (Table_1). The mean(±SD) age was 85.2±7.6 years for women and 82.5±8.7 years for men (p<0.001). The mean(±SD) age of Alzheimer´s patients was lower, 83.7±7.1 vs. 85.2±8.9 (p=0.031) (Figure_2). The global prevalence of dementia was 1.47 per 100 inhabitants (0.78% in AD vs. 0.69% in other dementias). The prevalence of dementia was 2.12% in females and 0.85% in males. Prevalence range in the ten Basic Health Areas: from 2.98 (La‐Alberca) to 0.77 (Tamames) per 100 inhabitants. 26.4% of people with AD and other dementias in this region were institutionalized.ConclusionThe prevalence data obtained confirm that AD and other dementias must be considered a public health problem in the rural Spanish‐Portuguese border region that represents a significant deterioration in the quality of life (QoL) in patients and their families.
Evaluation of the Elecsys NeuroToolKit panel in early Alzheimer's disease populations across six clinical trials
Authors: Rabe Christina , Thorne Nick , Voyle Nicola , Mertes Michaela , Mellino Gaspare , Quan Marian , Bittner Tobias 
Published: December 2021

AbstractBackgroundWe evaluated the Roche Elecsys® NeuroToolKit (NTK) assay panel of 12 cerebrospinal fluid (CSF) biomarkers in patients from a total of six clinical trials of crenezumab and gantenerumab in sporadic Alzheimer’s disease (AD), with respect to the correlations between individual biomarkers, and their associations with patient characteristics and disease severity. Additionally, we assessed their ability to measure and predict disease progression.MethodCSF samples were collected at baseline and follow‐up (Phase II, 1.5 years; Phase III, 1 and 2 years) from a subset of patients enrolled in the Phase II ABBY (NCT01343966)/BLAZE (NCT01397578) studies of crenezumab in mild‐to‐moderate AD, the Phase III CREAD (NCT02670083)/CREAD 2 (NCT03114657) studies of crenezumab in prodromal‐to‐mild AD, the Phase III SCarlet RoAD (NCT01224106) study of gantenerumab in prodromal AD, and the Phase III Marguerite RoAD (NCT02051608) study of gantenerumab in mild AD. NTK assays included beta‐amyloid (1‐42), beta‐amyloid (1‐40), alpha‐synuclein, GFAP, IL‐6, neurogranin, neurofilament light chain (NfL), phospho‐Tau (181P), S100B, sTREM2, total Tau, and YKL‐40. Correlations between biomarkers, longitudinal changes in biomarkers, and correlation between baseline biomarker levels and cognitive progression were evaluated across all six studies.ResultAll biomarkers except IL‐6 positively correlated with each other; the highest correlations were between total Tau, phospho‐Tau (181P), and neurogranin (Spearman’s rho >0.9). NfL, GFAP, YKL‐40, and sTREM2 biomarkers positively correlated with patient age. Analyses of ABBY, BLAZE, CREAD, and CREAD2 showed consistent findings across all studies. Levels of NfL, GFAP, and α‐synuclein biomarkers increased at the 1 year and 1.5‐year timepoints. NfL correlated with disease severity and progression in the prodromal‐to‐mild population. Additionally, results from NTK measurements in SCarlet RoAD and Marguerite RoAD CSF samples will also be presented.ConclusionThe NTK provided robust data and sufficient measuring range for the biomarkers tested. Further evaluation of these biomarkers is needed to understand their potential utility for clinical trials as pharmacodynamic biomarkers or for selecting patient populations. Elecsys is a trademark of Roche.
Association between tooth loss and cognitive performance: 11‐year follow‐up cohort study
Authors: Asher Sam , Stephen Ruth , Ngandu Tiia , Koskinen Seppo , Suominen Anna Liisa , Solomon Alina 
Published: December 2021

AbstractBackgroundEmerging evidence suggests tooth loss to adversely affect cognition. This study assessed association between tooth count and cognitive performance over 11 years.MethodThis study included 6537 participants (2933 males, 3604 females), aged 30‐99 years old (mean 53.4 years) from Finnish Health 2000 and 2011 Surveys. Tooth count was assessed clinically in 2000. Cognitive status was assessed either in 2000, 2011 or both, through battery of cognitive tests including Mini‐Mental Scale Examination (MMSE, short version, max 16‐points), Immediate word recall, Delayed word recall and Verbal Fluency (number of animals correctly listed). Cognitive tests were dichotomized according to median. Number of remaining teeth were categorized into 0, 1‐9, 10‐19 and ≥20. Logistic regression analyses were adjusted for age, gender, years of education, cardiovascular risk factors (FINRISK score), homocysteine, vitamin D and alcohol consumption.ResultIn cross‐sectional analyses at baseline, lower tooth count was associated with lower cognitive tests scores. 10‐19 versus ≥20 teeth was associated with lower MMSE, and immediate and delayed recall scores. 1‐9 teeth was associated with lower MMSE score. Having 0 teeth was associated with lower MMSE and immediate recall scores.In longitudinal analysis significant associations were observed between 10‐19 teeth in 2000 and lower MMSE and immediate recall scores in 2011. No association was observed between tooth count and verbal fluency in either cross‐sectional or longitudinal analyses (Table 1). Similarly, no association was observed for tooth count and decline in any cognitive test score over 11 years.ConclusionPreliminary results indicate that tooth loss may be linked to lower cognitive performance. Having 10‐19 versus ≥20 teeth appears to be particularly important. Individuals with 10‐19 teeth might have active or current periodontitis which could explain the observed associations. In contrast, individuals with low number of remaining teeth (0 or 1‐9) might not have periodontitis or lower burden of periodontal inflammation. The impact of periodontitis on cognition needs to be assessed in future studies. Acknowledgements: The authors wish to acknowledge Juho Vainio Foundation (Finland), Finnish Brain Foundation (Finland) & Päivikki and Sakari Sohlberg Foundation (Finland), Finnish Dental Society Apollonia and Finnish Dental Association.
Cerebrospinal fluid levels of 8‐isoprostane, a marker of oxidative stress, are elevated in patients with Alzheimer’s disease compared to healthy subjects: Does the malfunction in the cell’s powerhouse lead to Alzheimer’s disease?
Authors: Jensen Camilla Steen , Kellberg Amanda Oliva , Hasselbalch Steen Gregers , Simonsen Anja Hviid 
Published: December 2021

AbstractBackgroundOxidative stress may play an important role in the pathology of Alzheimer’s disease (AD). 8‐Isoprostane is a prostaglandin (PG)‐F2‐like compound belonging to the F2 Isoprostane class that is produced in vivo by the free radical‐catalyzed peroxidation of cells membrane arachidonic acid. 8‐Isoprostane is a biomarker of oxidative stress, and could possibly be a surrogate marker of the mitochondrial health in AD.MethodWe measured concentrations of cerebrospinal fluid (CSF) 8‐isoprostane from 113 subjects ranging from healthy subjects (HS, n=25) , to Mild Cognitive Impairment with positive AD biomarkers (MCI+, n=16), AD( n=40), and non‐AD dementia (non‐AD, n=32). Analysis was done using 8‐isoprostane Enzyme‐linked immunosorbent assay from Cayman Chemicals (Cayman Chemicals, MI, USA).ResultPatient characteristics can be seen in Table 1. Analyzing the CSF levels of 8‐isoprostane, a significant difference between 8‐isoprostane concentrations among the groups (ANOVA) was found. Post‐hoc test (t‐test) revealed a difference between the HS and AD groups (Figure 1).ConclusionIn conclusion 8‐isoprostane may be a good surrogate marker of cellular oxidative stress and may be used to evaluate mitochondria’s role in AD pathology in vivo.
Slowing as a multidomain and vascular geriatric syndrome: Apathy symptoms, gait speed and information processing speed in a geriatric memory clinic population
Authors: de Schraaf Sara AJ Van , Meester Hanneke FM Rhodius‐ , Aben Laurien , Sizoo Eefje M , Peters Mike JL , Trappenburg Marijke C , Hertogh Cees MPM , Klein Martin , Muller Majon 
Published: December 2021

AbstractBackgroundThe occurrence of slowing in mood, thinking and walking increases with age. It is, however, unclear if and how slowing in mood, thinking and walking, are interrelated and whether slowing is associated with the presence of cerebral small vessel disease (CSVD).MethodFor this study, we included 566 geriatric outpatients (49% female; age 79 ±6 years) from the Amsterdam Aging Cohort. Patients underwent brain imaging, a comprehensive geriatric assessment and a neuropsychological assessment. Three slowing aspects were investigated: apathy symptoms, processing speed and gait speed. CSVD measures included white matter hyperintensities (WMH), lacunes, and microbleeds. Associations between the slowing aspects and of cerebral small vessel disease with the slowing aspects were analyzed using multiple linear regressions and Poisson regressions for count data. To test the occurrence of CSVD in the population increased with accumulation of slowing aspects, using predefined cut‐offs, logistic regressions were used.ResultOf the total population, 18% had two or more impaired slowing aspects below predefined cut‐offs. Cross‐sectional regression analyses showed that lower gait speed was associated with lower information processing speed (B = ‐.36, 95% CI = ‐.48 to ‐.23) and more apathy symptoms (B = ‐.18, 95% CI = ‐.27 to ‐.09), independent of age, sex, education level, depressive symptoms and sedative medication. Increased WMH volume was associated with worse slowing outcomes: gait speed (B = ‐0.49, 95% CI = ‐0.71 to ‐0.28), processing speed (B = ‐0.36, 95% CI = ‐0.55 to ‐0.18) and apathy (Incident Rate Ratio = 1.29, 95% CI = 1.05 to 1.57, p <.05). Moreover, patients with a higher number of impaired slowing aspects had a higher odds of having a larger volume of WMH (Fazekas ≥ 2; ORs 1.69 to 3.47) or having more than three microbleeds (ORs 2.73 to 3.79).ConclusionThis study provides further evidence that slowing in mood, thinking and walking are closely related and more present in patients with cerebral small vessel disease. Longitudinal data is needed to unravel the direction of the complex relationship between cerebral small vessel disease and mental, cognitive and physical slowing.