bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network‐level relationships between cortical neurodegeneration and FDG‐PET hypometabolism across clinical and A/T/N subgroups in AD
Authors: Stocks Jane , Karteek Popuri , Martersteck Adam , Beg Mirza Faisal , Wang Lei 
Published: December 2020

AbstractBackgroundConverging evidence suggests that Alzheimer’s disease (AD) affects multiple large‐scale brain networks. Determining the relationship between network‐level alterations in neuroimaging‐derived metrics of brain structure and function and whether concordance between metrics varies by clinical presentation or pathological status can increase our understanding of the disease process in AD. To this aim, we evaluated the relationship between cortical thinning (neurodegeneration) and cortical glucose hypometabolism within distributed brain networks in individuals across clinical (AD, MCI who later progress to AD, MCI who remain stable, and normal controls) and CSF‐defined A/T/N subgroups.MethodT1‐MPRAGE and FDG‐PET scans were downloaded from the Alzheimer’s Disease Neuroimaging Initiative website (cohorts ADNI‐1&2 at baseline only). Regional W‐score maps were computed for each patient and each imaging modality, to adjust for the effect of normal aging. Using a well‐validated atlas from the Human Connectome Project/Glasser et al. (2016) and the corresponding cortical network solution by Ji et al. (2019), network‐level Pearson correlations were computed between cortical thickness and FDG metabolism, for each participant, reflecting individual consistency in the degree of atrophy and hypometabolism at each network. Multivariate analysis of variance models assessing the effects of clinic diagnostic category and, separately, A/T/N status, on correlations while accounting for age, education and APOE‐4 status were examined.ResultsAmong clinical diagnostic groups, atrophy‐hypometabolism correlations showed significant differences in 11 of 12 networks (Table 1), with correlations increasing by disease severity specifically within networks known to be affected by AD (e.g., frontoparietal, default mode, ventral multimodal; Figures 1 and 2). Among A/T/N subgroups, significant differences in correlation scores were found only within select networks including frontoparietal and default mode networks (Table 2; Figure 3).ConclusionWith increased disease severity, cortical atrophy is increasingly related to cortical FDG hypometabolism across brain networks. In the A/T/N framework, our findings suggest that both amyloid and tau increase this structure‐function relationship. However, considerable heterogeneity was present among all A/T/N subgroups, warranting further exploration. Multimodal neuroimaging analyses can unravel the structure‐function relationships that contribute to clinical outcomes and diagnostic uncertainty in AD.
Evaluation of polygenic risk scores for 17 cancer types in relation to cognitive decline in the UK Biobank
Authors: Graff Rebecca E , Ackley Sarah F , Romero Monica Ospina , Zimmerman Scott C , Elahi Fanny M , Lu Kun Ping , Witte John S , Glymour M Maria 
Published: December 2020

AbstractBackgroundAccumulating evidence suggests that cancer and dementia are inversely associated, wherein cancer survivors have a roughly 40% reduced dementia incidence and vice versa. Survival and diagnostic bias cannot seemingly account for the relationship fully, but causal explanations have not been adequately investigated. We thus considered a possible inverse shared genetic basis in a large population‐based cohort with extensive individual‐level genotypic and phenotypic data.MethodsThe study population included European ancestry individuals from the UK Biobank who 1) were age 60 or over at baseline assessment (incident dementia analyses; n=190,230 individuals, including 1,887 dementia diagnoses after baseline), or 2) had completed at least one test of fluid intelligence – the capacity to solve problems that require logic and reasoning ability, independent of acquired knowledge – at age 60 or over (fluid intelligence analyses; n=127,529 individuals with 163,266 total measures). We selected known independent genetic risk variants to construct polygenic risk scores (PRS) for cancer overall and each of 17 cancer types. We used multivariable logistic regression and random intercept linear mixed models to evaluate per standard deviation increases of each PRS with respect to dementia status and fluid intelligence, respectively. Bonferroni corrected p‐values were used to evaluate statistical significance.ResultsNone of the cancer PRS were significantly associated with dementia (p>0.05/17=0.0029). The directionality of the overall cancer PRS (856 variants) was consistent with improved cognitive outcomes (p
dementia=0.20; p
fluid intelligence=0.052). Among PRS for individual cancers, only that for lung cancer (113 variants) was significantly positively associated with fluid intelligence (p=5.9x10‐4). Among variants comprising the various cancer PRS, four independent variants in the human leukocyte antigen (HLA) complex were significantly positively associated with fluid intelligence (p<0.05/856=5.84x10‐5). All were expression quantitative trait loci for major histocompatibility complex class I genes.ConclusionsA PRS for lung cancer was positively associated with fluid intelligence (i.e., decreasing cognitive decline). The association pattern with HLA‐related variants, which code for proteins involved in antigen presentation to stimulate immune response, suggests potential relevance of immune surveillance for the inverse association between dementia and cancer. Further teasing apart their genetic similarities and differences has the potential to clarify mechanisms of dementia pathogenesis.
Cognition‐related structure in the progression of Alzheimer’s disease
Authors: Mao Chenhui , Li Jie , Huang Xinying , Lei Dan , Liu Caiyan , Dong Liling , Peng Bin , Cui Liying , Gao Jing 
Published: December 2020

AbstractBackgroundTypical Alzheimer’s disease (AD) presented with memory loss, followed by global involvement of cognitive domains in the progression of the disease. Bilateral medial temporal lobe and posterior atrophy was most common structure imaging changes.Method111 patients diagnosed probable AD based on 2011 NIA‐AA guideline were enrolled. All of them had systemic cognitive evaluation including MMSE, MOCA, CDR, ADL and domain specific batteries. The severity of the disease was defined by MMSE score: 1‐10 severe, 11‐20 moderate, 21‐30 mild. 3D‐T1 MRI data were analyzed using voxel based morphometry supported by DR. BRAIN platform. The volumes of bilateral hippocampus, superior temporal gyrus, superior parietal lobe, posterior cingulate gyrus as well as total grey matter and white matter were calculated.ResultThe male: female ratio was 38:73. The average age was 70.8. The mild: moderate: severe ratio was 48:38:25. The volume of left hippocampus was 2127.8, 1973.2, 1757.6mm3 in mild, moderate and severe group respectively. The volume of right hippocampus was 2426.8, 2275.9, 2101.3mm3. The volume of left superior temporal gyrus was 5354.9, 4888.8, 4358.1mm3. The volume of right superior temporal gyrus was 5690.6, 5139.5, 4872.8mm3. The volume of left superior parietal lobe was 8663.0, 7873.0, 7065.6mm3. The volume of right superior parietal lobe was 8533.1, 7858.9, 7227.1mm3. The volume of left posterior cingulate gyrus was 3364.7, 3028.5, 2816.3mm3. The volume of right posterior cingulate gyrus was 3071.3, 2779.2, 2612.0mm3. Atrophy of all the above area was significantly associated with progression of AD, while posterior area more prominent. The volume of total grey matter was 549373.9, 514908.9, 488812.2mm3. The volume of total white matter was 435153.6, 422331.1, 423894.8mm3. Grey matter volume was significant related to cognition while white matter not, which was in consistent with previous knowledge.ConclusionCognition deterioration was associated with structure atrophy in the progression of AD. Bilateral hippocampus, superior temporal gyrus, superior parietal lobe, posterior cingulate gyrus were all closely related. Besides hippocampus, we reported diffuse cortex including lateral temporal lobe and posterior areas structure change was important.
Corticobasal syndrome in a 23‐year‐old female
Authors: Castro‐Suarez Sheila , Lopez Lucia , Lanata Serggio 
Published: December 2020

AbstractBackgroundThe Corticobasal Syndrome (CBS) is characterized by unilateral parkinsonism and higher cortical dysfunction including apraxia, cortical sensory loss, agnosia, and alien limb phenomena. The underlying neurodegenerative causes of CBS include tauopathies (Corticobasal degeneration [CBD], progressive supranuclear palsy), Alzheimer disease, Lewy body disease, and prion disease, with CBD being most common (CBS‐CBD). Disease onset is typically in the fifth to sixth decade of life. Here we present a case of a woman with sporadic CBS due to underlying tauopathy with first signs and symptoms of disease noted at the age 23 yearsMethodThe patient is a participant of the University of California, San Francisco (UCSF) Memory and Aging Center (MAC) observational, longitudinal research program. The patient underwent structured neurological history and examination, neuropsychological testing, brain MRI, and neurodegenerative disease biomarker studiesResultThe patient is 28‐year‐old, right‐handed, bilingual (Spanish and English) woman with 12 years education. She presented with a 5 year history of slowly progressive left upper and lower extremity sensorimotor deficits, involuntary movements of the left upper extremity, and imbalance. There was no family history of progressive neurological or psychiatric illness. Her neurological examination was notable for left upper and lower extremity rigidity, myoclonic jerks, and dystonic posturing of the left hand. She demonstrated ideomotor apraxia, agraphesthesia, astereognosis, and finger agnosia of the left hand. Neuropsychological examination revealed mild deficits in frontal‐executive functions. Serological and cerebrospinal fluid analyses were unrevealing. Brain MRI with and without gadolinium enhancement showed severe right‐sided peri‐rolandic atrophy. Tau PET imaging showed asymmetric moderate tracer uptake over the dorsal fronto‐parietal cortices. Genetic testing was negative for MAPT, C9orf72, GRN, TARDBP, FUS, PSEN1, PSEN2, and APP mutations/expansions.ConclusionCBS is rare before the age of 50 years. We present a case of a 28‐year‐old woman who meets research criteria for CBS, with brain MRI and tau PET imaging findings suggestive of underlying tauopathy, most likely CBD (CBS – CBD). To our knowledge, this is the youngest case of CBS – CBD ever reported.
The effects of Orengedokuto for decreasing behavioral deviation and the rejection of care by patients with dementia
Authors: Urabe Shinji , Tsuchida Hideto , Tamura Junichi , Nabika Toumei , Shirakikawa Shinsuke , Yoshikawa Yoshimi , Moritoki Yukihiro , Matsuo Koji , Tsunemi Teppei , Wada Takatosi , Shiomoto Takayuki , Urabe Mie 
Published: December 2020

AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) increase the distress of patients with dementia and the burden for care givers and they are the symptoms that need to be solved immediately. In particular, behavioral deviation and rejection cause a high possibility of harming others, they are important problems to be solved to increase the quality of life for patients and caregivers. But effective treatment for BPSD has not been established yet. Antipsychotics are not recommended for the treatment of agitation and aggression in BPSD, because they increase the risk of death of the elderly according to the Food and Drug Administration.(FDA, 2005) So, as a medicine with fewer side effects and gives the expected effect, herbal medicine is used often for BPSD in Japan. Based on the clinical effects on these symptoms in our clinical practices, we focused on Orengedokuto within Japanese herbal medicine. In previous research of Orengedokuto, we reported that Orengedokuto decreased the aggression in the patients with dementia. (Urabe et al.,AAIC2019) The purpose of this research is to clarify the effect of Orengedokuto on deviation and rejection behavior of patients with dementia.MethodThe subjects were 33 patients with dementia admitted to a psychiatric hospital in Japan. The groups were a group of patients with dementia who were administered with Orengedokuto (ODG;23 patients, average age ; 84 years old) and a control group of patients with dementia who did not take Orengedokuto (NODG; 10 patients, average age ; 82 years old). We evaluated the patients with Behavioral Pathology in Alzheimer’s disease (Behave‐AD), Mini Mental State Examination, the reduction of effects of deviation and rejection were compared with the changes before and after administration between ODG and NODG.ResultThe average score of deviation, was 5.9 before administration but decreased to 1.2 at the time of discharge in ODG (p<0.05). In NODG, the average score of deviation, was 5.8 before administration, was 3.6 t at the time of discharge.ConclusionIn ODG, deviation and rejection behavior was improved and the burden for caregivers was reduced.
A cost‐efficient model for predicting cerebral Aβ burden using MRI and neuropsychological markers in the ADNI‐2 cohort
Authors: Ko Hyunwoong , Ihm Jungjoon 
Published: December 2020

AbstractBackgroundDetecting cerebral Aβ is still expensive, invasive, and have limited accessibility. In this respect, the current study aims to identify and compare predictability of MRI markers with neuropsychological markers for accurate prediction of cerebral Aβ status in AD cohort through machine learning (ML) approaches.MethodsPredictability of the candidate markers for cerebral Aβ status was examined by analyzing 724 participants from the ADNI‐2 cohort at baseline visit (170 control subjects, 95 with SMC, 324 with MCI and 135 with AD; mean age 73.2 years, range 55–90). Demographic variables (age, gender, education, and APOE status), structural MRI markers (cortical thickness and volume), and neuropsychological test scores were used as input in several ML algorithms. Cerebral Aβ burden was measured using florbetapir PET images. We first calculated the predictability of each ML model, and the adaptive LASSO algorithm with 10‐fold cross validation was implemented to identify the relative predictability of predictors in the selected model.ResultsML models with MRI markers predicted cerebral Aβ status with the 85% predictability. Out of five combination of candidate markers, neuropsychological markers with demographics showed the most cost‐efficient result compared to MRI methods. The adaptive LASSO model with out‐of‐sample classification was able to distinguish abnormal levels of Aβ based on significantly predictable features. The AUC was 0.85 in the ADNI‐2 cohort, indicating the same performance with MRI‐based models.ConclusionsOur results are twofold: the result has first identified the predictability in MRI markers using ML approaches, and secondly demonstrated the neuropsychological model with demographics could predict Aβ positivity, suggesting a more cost‐efficient method for detecting cerebral Aβ status compared to MRI markers. More specifically, with advantages in cost and its non‐invasive procedure, the method could be utilized as a brief screening tool in AD risk population for clinical trials or AD therapy. To this end, This research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ITRC(Information Technology Research Center) support program(IITP‐2020‐2017‐0‐01630) supervised by the IITP(Institute for Information & communications Technology Promotion).
Role of vitamin D mediated signaling in iron‐induced neurodegeneration: Implications in the pathogenesis of Alzheimer's disease
Authors: Banerjee Anindita , Ganguly Upasana , Chakrabarti Sasanka 
Published: December 2020

AbstractBackgroundThe neurodegeneration of sporadic Alzheimer's disease (AD) has several environmental, metabolic and endocrine components. Results of post‐mortem analysis of increased iron accumulation in AD brain and various epidemiological studies indicating association of AD with vitamin D insufficiency, prompted us to examine the role of vitamin D signaling in an experimental model of neurodegeneration induced by iron on undifferentiated SHSY5Y cells.MethodSHSY5Y cells were exposed to ferric ammonium citrate (FAC, 25‐ 400 μM) with or without 1,25 dihydroxyvitamin D for 24 ‐ 48 h followed by the measurements of oxidative damage markers, mitochondrial functional status, APP, BACE expressions and cell death parameters. Separately similar parameters were assessed in SHHSY5Y cells where vitamin D receptor VDR expression was knocked down by specific siRNA.ResultWe observed that vitamin D ameliorated various features of FAC induced cytotoxicity such as oxidative damage, mitochondrial membrane depolarization, impaired ATP synthesis and loss of cell viability. Exposure of SHSY5Y cells to FAC resulted in elevated APP and BACE mRNA levels which could be prevented by 1,25 dihydroxyvitamin D. Iron caused differential effects on VDR mRNA and protein expression levels in SHSY5Y cells; an increase in mRNA but a decrease in protein expressions. The iron effects were significantly prevented by co‐treatment with 1,25 dihydroxyvitamin D. The effects of VDR knock‐down on both control and FAC‐ treated cells showed augmented cell death with significant mitochondrial dysfunction, lipid peroxidation and oxidative damage.ConclusionOur experimental data suggest that vitamin D and VDR mediated signaling is integral in cell survival under basal condition as well as during iron‐induced cytotoxicity. The results have implications in the context of NBIA in aging and the pathogenesis of AD.
Sitting time, physical activity, and cognitive impairment in mid‐life adults: Findings from the Cooper Center Longitudinal Study
Authors: Gafni Tal , Weinstein Galit , Shuval Kerem , Carolyn Barlow E , Gabriel Kelley Pettee , Willis Benjamin L , David Leonard , Haskell William L , DeFina Laura F 
Published: December 2020

AbstractBackgroundEvidence suggests that prolonged sedentary time (i.e., daily sitting or reclining during waking hours) is independently related to metabolic syndrome and type 2 diabetes, which are risk factors for cognitive impairment. In the current study, we examined the independent and joint association of sedentary time and physical activity (PA) on the odds for cognitive impairment among community dwelling mid‐to‐later life adults.MethodThis cross‐sectional study included 3,780 individuals aged ≥55y, who came to the Cooper Clinic (Dallas, Texas) for preventive medicine visits (2010‐2019), and enrolled in the Cooper Center Longitudinal Study. Participants provided detailed information on their sitting habits and PA levels. Cognitive function was assessed through the Montreal Cognitive Assessment (MoCA). The independent and joint relations of reported sitting time (≤25%, 50% and ≥75% of the time) and PA levels (not meeting, meeting and exceeding guidelines) with cognitive impairment (MoCA score<26) was examined using multivariable logistic regression, while adjusting for potential confounders.ResultOf the total analytic sample (mean age 61±6y; 71% men), 22.5% were classified as cognitively impaired. Participants sitting ≥75% of the time had significantly higher odds (OR=1.60; 95% CI 1.19‐2.17) for cognitive impairment compared to those sitting almost none of the time, irrespective of PA levels. Joint association analysis with sedentary time ≤25% and exceeding physical activity guidelines (>1000 MET min/week) as referent, showed that the highest odds for cognitive impairment were in those sitting ≥75% of the time while meeting or not meeting PA guidelines (OR=1.71 [1.14‐2.56] and 1.70 [1.22‐2.37], respectively). However, those who reported sitting 75% of the time or more had lower odds of cognitive impairment when in the exceeding physical activity strata (OR=1.48; 95%CI 1.10‐2.00; see figure).ConclusionProlonged sitting time and insufficient physical activity might each independently increase the likelihood of cognitive impairment. Yet, engaging in extensive PA might attenuate the risk associated with prolonged sitting.
Chitotriosidase attenuates microglia‐associated inflammation via HDAC3/NF‐κB pathway in D‐galactose and aluminum‐induced rat model with cognitive impairments
Authors: Yu Xingyan , Yu Weihua , Wu Lihua , Yang Wenkai , Lü Yang 
Published: December 2020

AbstractBackgroundChitotriosidase (CHIT1, chitinase 1) is elevated in the cerebrospinal fluid and peripheral blood of Alzheimer’s disease (AD) patients. Our previous study has shown that CHIT1 provides potential protection through microglial polarization and reduction of β‐amyloid (Aβ) oligomers on rats models of AD. Histone deacetylase 3 (HDAC3) plays an important regulatory role in the expression and regulation of proteins associated with AD pathophysiology. In addition, nuclear factor‐kappa B (NF‐κB) signaling pathway activation in neurons is involved in the development and progression of AD. NF‐κB activation is regulated by HDAC3 deacetylation. In this study, we investigated the role of CHIT1 in HDAC3/NF‐κB signaling in D‐galactose and aluminum‐induced rat model with cognitive impairments.MethodRats in each group were euthanized and transcardial perfusion was performed with 0.9% saline. Brain tissues (cortex and hippocampus) from these rats were quickly removed. The prepared samples were used for western blotting (WB), and real‐time polymerase chain reaction (RT‐PCR). For paraffin sections, rats were anesthetized and perfused with 4% paraformaldehyde following normal saline infusion. Once the limbs became stiff, the brains were removed for dehydration, embedding and sectioning.ResultWe found that the protein and mRNA levels of HDAC3 and NF‐κB were reduced after CHIT1 treatment, and the expression level of IκBα increased after CHIT1 treatment. Anti‐inflammatory factors (Arg‐1, IL‐10, and CD206) were increased while pro‐inflammatory factors (TNF‐a, IL‐1β, and iNOS) were decreased in D‐galactose/aluminum‐induced AD rats with CHIT1 treatment.ConclusionThese results indicate that CHIT1 can regulate microglial polarization via HDAC3/NF‐κB p65 pathway in D‐galactose and aluminum‐induced rat model with cognitive impairments.