bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple sclerosis is associated with lower amyloid but normal tau burden on PET
Authors: Zeydan Burcu , Lowe Val J. , Reichard Ross R. , Przybelski Scott A. , Lesnick Timothy G. , Schwarz Christopher G. , Senjem Matthew L. , Gunter Jeffrey L. , Parisi Joseph E. , Machulda Mary M. , Vemuri Prashanthi , Mielke Michelle M. , Knopman David S. , Petersen Ronald C. , Jack Clifford R. , Kantarci Orhun H. , Kantarci Kejal 
Published: December 2020

AbstractBackgroundWhile β‐amyloid and tau PET imaging are widely studied in cognitive aging and Alzheimer’s disease (AD), little is known about findings in aging multiple sclerosis (MS) patients. As aging is an essential factor in developing neurodegeneration in MS, β‐amyloid and tau biomarkers may be utilized to understand the influence of AD pathophysiology on cognitive aging in MS.MethodWe studied patients with MS (n=16) and controls (n=80) matched for age, sex and APOE ε4 status from the population‐based Mayo Clinic Study of Aging who underwent Pittsburgh compound‐B (PiB) PET imaging. Twelve of the 16 patients with MS and 60 matching controls also underwent flortaucipir (AV1451) tau PET. Cortical PiB and AV1451 standard uptake value ratios (SUVr) from previously determined AD signature regions and from the entire cortex were calculated for group comparisons and testing for associations with age.ResultAD signature PiB SUVr (p=0.044), total cortical PiB SUVr (p=0.048) and the frequency of abnormal PiB SUVrs (p=0.040) were lower in patients with MS than controls. Although AD signature and total cortical AV1451 SUVrs were not different between the groups, the frequency of abnormal AV1451 SUVrs was higher (p=0.041) in patients with MS than controls. The association of AD signature PiB SUVr with age was steeper in the controls compared to patients with MS (p=0.002). Similarly, the association of total cortical PiB SUVr with age was steeper in the controls compared to patients with MS (p=0.002). There was no difference in the association of AV1451 SUVr findings with age between the MS patients and controls (Figure 1). The AD signature PiB SUVr increased more with increasing AD signature AV1451 SUVr in controls than in patients with MS (p=0.03) (Figure 2).ConclusionIn patients with MS, cortical β‐amyloid deposition was lower than age‐matched controls, while cortical tau deposition was not different between the groups. This suggests that some aspect of MS pathobiology retards the accumulation of β‐amyloid, but not the accumulation of tau.
Dementia‐friendly sport and physical activity: A meta‐analysis
Authors: Nguyen Thuy Trang , Vo Tuong Kha , Vo Van Giau 
Published: December 2020

AbstractBackgroundPhysical activity has been suggested as relevant to many health outcomes, including: cardiorespiratory health, musculoskeletal health, cancer, functional health and prevention of falls, depression as well as dementia.MethodMeta‐analyze publicly available PubMed, Science Direct, and Willey data between 2006 and 2019. Keywords such as “dementia,” “sport” and “physical activity” were applied in searching for papers. As a result, 12 studies were selected in the second screening of the study.ResultThe enhancement in the dementia symptom of physical capacity was 1.3 (95% CI: 0.05 to 0.8), ability of activity of daily living was 0.81 (95% CI: 0.13 to 1.6), cognitive function was 0.5 (95% CI: 0.32 to 0.67), and psychological state was 0.40 (95% CI: 0.02 to 0.82).ConclusionThe physical activity for patients with dementia had an effect on the enhancement of physical capacity and combined exercise was the most effective physical activity.
Mild Behaviour Impairment Checklist (MBI‐C): Is there a difference in ratings between patient and close informant?
Authors: Soo See Ann , Ng Kok Pin , Wong Fennie , Yatawara Chathuri , Chiew Hui Jin , Lyn Ng Adeline Su , Ismail Zahinoor , Kandiah Nagaendran 
Published: December 2020

AbstractBackgroundMild Behavioural Impairment‐Checklist (MBI‐C) is a validated questionnaire that measures sustained later‐life emergent neuropsychiatric symptoms among people with prodromal dementia. Using this checklist as a MBI case ascertainment instrument, the prevalence of MBI was found to be 5.8% in subjective cognitive decline (SCD) and 14.2% in mild cognitive impairment (MCI). While the MBI‐C can be self‐administered or administered through a close informant via face‐to‐face or phone interviews, it is unknown whether patients and close‐informants differentially report on the MBI‐C. Here, we aim to examine the differences in self‐administered and close‐informant administered MBI‐C scores in a specialty clinic population.Method87 (25 SCD and 62 MCI) patients from the Singapore National Neuroscience Institute memory clinic completed the MBI‐C and Geriatric Depression Scale (GDS)4. Close‐informants completed the MBI‐C and Zarit caregiver burden scale (Zarit)5. The MBI‐C is a 34‐item questionnaire organized into five domains; 1) motivation, 2) emotional regulation, 3) impulse control, 4) social cognition, and 5) abnormal thoughts. MBI is defined by an MBI‐C total score of >6.5 in MCI 3 and a >8.5 total score in SCI2. Paired sample T‐test evaluated the difference in MBI‐C scores between patients and close‐informants. Pearson correlation test evaluated the associations between MBI‐C with GDS and Zarit scores.ResultOut of 87 participants (Mage= 67.62, SD=9.08), 29 participants were diagnosed with MBI. The frequency of MBI did not differ between SCI and MCI (40% in SCI and 30% in MCI). We found that MBI‐C domain scores did not differ significantly between patients and close‐informants (p>0.05). GDS scores positively correlated with MBI total score (p<0.01), motivation (p<0.01), emotional regulation (p<0.01), impulse control (p<0.01), social cognition (p=0.001) and abnormal thoughts (p=0.018). Zarit scores positively correlated with MBI total score (p=0.017) and impulse control (p=0.009).ConclusionMBI is common in our Asian clinic population with preclinical prodromal dementia diagnosed using the MBI‐C and was associated with greater caregiver burden and depressive symptoms. Importantly, we found that patients and their close‐informants do not report differently on the MBI‐C. Our findings suggest that both patients and close‐informants may provide reliable measures of the patient’s neuropsychiatric symptoms using the MBI‐C.
Masupirdine in combination with donepezil and memantine in patients with moderate Alzheimer's disease: Subgroup analyses of memantine regimen, plasma concentrations and duration of treatment
Authors: Nirogi Ramakrishna , Goyal Vinod Kumar , Bhyrapuneni Gopinadh , Palacharla Veera Raghava Chowdary , Ravulu Jyothsna , Jetta Satish , Jasti Venkat 
Published: December 2020

AbstractBackgroundMasupirdine (SUVN‐502), a selective 5‐hydroxytryptamine‐6 (5‐HT6) receptor antagonist has demonstrated efficacy in animal models of cognitive impairment. To assess its clinical utility, a randomized, double blind, placebo controlled 26 week phase 2 study was conducted in moderate Alzheimer’s disease (AD) patients who were on stable treatments with donepezil and memantine.MethodIn the phase 2 study, a total of 564 moderate AD patients with MMSE scores between 12 and 20 were randomized to receive either 50 mg or 100 mg of masupirdine or placebo once daily for 26 weeks. All patients were treated with donepezil 10 mg + memantine 10 mg BID or Namenda XR 28 mg QD; or Namzaric (donepezil 10 mg + 28 mg Namenda XR). The primary efficacy endpoint was change from baseline in the Alzheimer's Disease Assessment Scale ‐ Cognitive Subscale (ADAS‐Cog11). In subgroup analyses, impact of memantine regimen, memantine plasma concentrations and memantine treatment duration on the efficacy of masupirdine in moderate AD patients was analysed.ResultIn participants whose memantine plasma concentrations were ≤100 ng/mL at Week 26, there was lesser decline in ADAS‐Cog 11 scores in participants taking masupirdine than in those on placebo. In participants taking the higher masupirdine study dose of 100 mg daily, there were also congruent signals for less decline on MMSE and CDR‐SB. Additionally, in participants whose memantine plasma concentrations were ≤100 ng/mL at Week 26, masurpirdine treatment was associated with Week 26 response rates on the ADAS‐Cog 11, for improved or stable scores compared to baseline, that were twice that of placebo. In participants on background memantine treatment for > 4 years, masupirdine treatment (versus placebo) was associated with lesser decline in ADAS‐Cog 11 scores.ConclusionSubgroup analyses of the masupirdine Phase 2 POC study to assess potential effects of memantine regimen, memantine plasma concentrations and duration of treatment on primary and secondary study outcomes revealed several potential signals for differential effects favoring masupirdine treatment. These observations merit better understanding and further possible investigations of masupirdine as a potential treatment for AD dementia.
Effects of serum homocysteine, depression and instrumental daily living ability on cognitive function in elderly people at high altitudes
Authors: Zhu Aiqin , Hou Yonglan , Li Guofeng 
Published: December 2020

AbstractBackgroundTo explore the level Homocysteine (Hcy), depressive state and daily living ability on the decline of cognition ability in elderly under hypoxic environment.MethodBetween June 2017 and June 2019, 288 participants of elderly (mean aged 67.13 years) Han subjects living in Xining City (altitude 2,260 meters) of Qinghai Province were divided into three groups: 125 Mild cognitive impairment (MCI), 20 Alzheimer’s disease (AD), 83 control. Serum HCY level was determined by BECKMAN COULTER biochemical analyzer. The cognition ability were used by Mini‐mental State Examination (MMSE), Geriatric Depression Scale (GDS), Auditory Verbal Learning Test (AVLT),Digit Span Test)DST),Activities Daily Living (BADL), Instrumental Activities of Daily Living (IADL). Fund project: National Key R&D Program of China (No : 2018YFC1315201).Result1. There was no significant difference in age, gender, educational level among the three groups. 2. Compared with controland MCI groups, Hcy of AD group was significantly increased (p<0.05). GDS and IADL scores of AD group was significantly higher than MCI and control groups (p<0.05,p<0.01). 3. Compared with control group, BADL score of AD group was significantly increased (p<0.01), while there was no significant difference the BADL score between control and MCI group (p> 0.05). 4. The scores of DST, AVLT and MMSE in the forward and reverse direction, delayed memory, attention, calculation and working memory and visuospatial ability of HHcy group were significantly lower than those of normal Hcy group (p<0.01, p<0.05, p<0.05). 5. MMSE score was negatively correlated with Hcy, IADL and GDS (r=‐0.324, ‐0.228,‐0.191;p<0.01,p<0.05). Logistic analysis showed that HCY was the risk factor of cognitive dysfunction (OR=1.005, 95% CI: 1.005‐1.109, p<0.05).ConclusionThe decline of cognition ability in the elderly at high altitude is correlated with Hcy, IADL and GDS. HHcy is the major risk factor for cognitive dysfunction. Combined MMSE, GDS and IADL scale scores provide objective basis for the warning, prevention and control of early cognitive dysfunction in the elderly under hypoxic environment.
Association between mean corpuscular volume and cognitive impairment in an 8‐year cohort study in the community‐dwelling elderly
Authors: Li Yi‐Ming , Chen Yen‐Ching , Chen Jen‐Han , Chiou Jeng‐Min , Chen Ta‐Fu , Lai Liang‐Chuan 
Published: December 2020

AbstractBackgroundMean corpuscular volume (MCV) is the average volume of red blood cells (RBC). Larger MCV reduces the amount of RBC reaching the brain, while smaller MCV was associated with iron‐deficiency anemia and the subsequent cognitive impairment. Few studies have relating MCV levels to cognitive impairment and their findings were inconsistent. This study aimed to explore this association in community‐dwelling older adults.MethodThis study is part of an ongoing cohort study Taiwan Initiatives for Geriatric Epidemiological Research (TIGER, 2011‐ present). A total of 605 non‐demented older adults (age 65+) were recruited at baseline (2011‐2013). After exclusion of participants with dementia at baseline, history of stroke, brain tumor, loss of consciousness, missing data of MCV, 319 elderly were included for analysis. Global and domain‐specific cognition (logical memory, attention, verbal fluency, and executive function) were assessed for each participant at baseline, 2‐year, 4‐year, and 6‐year follow‐ups. MCV was assessed at baseline and then tertitled; high MCV indicates the highest tertile (≥92.7 fL); low MCV indicates the lower tertiles (<92.6 fL). The generalized linear mixed models (GLMM) were used to estimate the association between MCV and cognitive impairment adjusted for important covariates.ResultAt baseline, the mean age of the study participants was 71.6 years old and the mean MCV at baseline was 90.7 fL. For the multivariable analyses, the effect of baseline MCV on global cognition (assessed by Montreal Cognitive Assessment–Taiwanese version, MoCA‐T) increased as age increased [MCV×age interaction: β= ‐0.07, 90% confidence interval (CI)= ‐0.14 to ‐0.004, p‐value= 0.04], which became more evident in women (β= ‐0.15, 95% CI= ‐0.23 to ‐0.06). After stratification by age groups, the increase of baseline MCV was associated with poor global cognition in the older group (age ≥75: β= ‐0.90, 95% CI= ‐1.65 to ‐0.15). No significant findings were observed in cognitive domains or other strata.ConclusionHigh baseline MCV was associated with an increased risk of cognitive impairment as age increased. MCV may be used an early marker for dementia in the community‐dwelling older adults.
Effect of multidomain interventions on estimated dementia and cardiovascular risk reduction: An individual‐participant data meta‐analysis from FINGER, MAPT, and pre‐DIVA
Authors: Barbera Mariagnese , Ngandu Tiia , Levälahti Esko , Coley Nicola , Mangialasche Francesca , Hoevenaar Marieke P , Peltonen Markku , Andrieu Sandrine , Richard Edo , Soininen Hilkka , Meiller Yannick , Kivipelto Miia , Solomon Alina 
Published: December 2020

AbstractBackgroundMultidomain interventions based on management of vascular and lifestyle risk factors could potentially reduce the risk of dementia and cardiovascular disease. Given the slow progressive nature of these conditions, dementia in particular, clinical endpoints may not be achievable within trials’ time‐frame. Well‐established risk scores could be useful surrogate outcomes. In this individual‐participant data meta‐analysis, we assessed the effect of three multidomain dementia prevention interventions on the CAIDE and FINRISK risk scores for dementia and cardiovascular disease, and the impact of baseline characteristics on the response to such interventions.MethodBaseline and 24‐month data from the FINGER, MAPT, and preDIVA dementia/cognitive decline prevention trials carried out in three European cohorts of older adults, were pooled at individual‐participant level (N=6465). Linear mixed‐model with maximum likelihood estimation and random effect by trial and study‐site was used to estimate changes in CAIDE and FINRISK risk scores in the intervention group vs control. Subgroup‐treatment effect interactions were tested to assess the influence of sex, baseline age, education, MMSE, and dementia or cardiovascular disease risk on the response to the interventions. The effect of the interventions on individual modifiable risk factors relevant for both risk scores was also investigated.ResultThe interventions led to a significant reduction of both CAIDE (estimated effect: ‐0.173; 95% CI: ‐0.268 to ‐0.077; P<0.001) and FINRISK (estimated effect: ‐0.108; 95% CI: ‐0.181 to ‐0.035; P=0.001) scores. A significantly larger reduction of CAIDE score was reported in women compared to men (P value for interaction=0.007) and a similar, but not significant, pattern was reported for FINRISK score. Interactions by other baseline characteristics were also not significant. Significant reduction of blood pressure (P≤0.001), and waist circumference (P=0.027), but not of BMI nor serum cholesterol, was observed. No baseline characteristic affected the response on these outcomes.ConclusionMultidomain interventions had beneficial effects on the estimated risk of dementia and cardiovascular disease, measured by the CAIDE and FINRISK scores. Women benefited more than men in terms of dementia risk, whereas effects of baseline age, education, cognitive status, and risk of dementia or cardiovascular disease on the response to the interventions could not be demonstrated.
SUVN‐I6107: A novel muscarinic M1 receptor‐positive allosteric modulator (M1‐PAM) for the treatment of cognitive deficits
Authors: Abraham Renny , Goura Venkatesh , Grandhi Venkata Ramalingayya , Tadiparthi Jayaprakash , Ganuga Narender , Medapati Rajesh Babu , Muddana Nageswara Rao , Palacharla Veera Raghava Chowdary , Bhyrapuneni Gopinadh , Bojja Kumar , Mekala Venkat Reddy , Srirangavaram Maheswari , Badange Rajesh Kumar , Reballi Veena , Goyal Vinod Kumar , Pandey Santosh Kumar , Jayarajan Pradeep , Nirogi Ramakrishna 
Published: December 2020

AbstractBackgroundMuscarinic acetylcholine receptors (mAChRs) belong to family of G protein coupled receptors (GPCRs) which are widely expressed throughout the body. Muscarinic receptors have been implicated in the pathophysiology of various central nervous system disorders. M1 muscarinic receptor subtype plays a vital role in cognition, attention mechanisms and sensory processing. Discovery and development of selective M1 muscarinic ligands have been largely unsuccessful mainly due to high conservation of the orthosteric binding site among this receptor family. Thus, ligands that positively modulate the less conserved M1 muscarinic allosteric site may be advantageous over the orthosteric agonistsMethodSUVN‐I6107 is a lead compound from the M1 positive allosteric modulator (PAM) program. The effects of SUVN‐I6107 on the allosteric site of the M1 receptor was evaluated using the reporter gene assay. In addition, binding potential towards the orthosteric site across the muscarinic receptor subtypes was also studied. The pharmacokinetic properties of SUVN‐I6107 were studied both in rodent and non‐rodent species. The pro‐cognitive potential of SUVN‐I6107 was studied in diverse models of learning and memory. The safety of SUVN‐I6107 was assessed using in‐vitro and in‐vivo systems.ResultSUVN‐I6107is a selective M1‐PAM with no agonistic activity across the muscarinic receptor subtypes. SUVN‐I6107 has good oral bioavailability in animal models. It also has excellent brain penetration with adequate protein free fraction. SUVN‐I6107 reversed the time induced memory deficit in the object recognition task. It also attenuated the scopolamine induced memory deficits in the object recognition as well as the contextual fear conditioning task. SUVN‐I6107 enhanced the cerebral blood flow in rats, potentiated the effects of donepezil, and promoted non‐amyloidogenic APP processing in rats. SUVN‐I6107 did not have the side effects associated with the stimulation of the cholinergic system. SUVN‐I6107was found to be safe in the cardiovascular safety assays and early stage animal toxicity studies.ConclusionSUVN‐I6107is a novel, selective and potent M1‐PAM,demonstrating efficacy in animal models and devoid of cholinergic side effects.
Blood‐brain barrier dysfunction and perioperative neurocognitive disorders: Cognitive Recovery after Elective Surgery (CREATES) study design and methods
Authors: Daiello Lori A , Wang Danny JJ , Jones Richard N , Boxerman Jerrold , Tremont Geoffrey , O'Bryant Sid , Kendall Mark , Cioffi William G , De Oliveira Gildasio S. , Ott Brian R , Inouye Sharon K 
Published: December 2020

AbstractBackgroundImpaired blood‐brain barrier (BBB) function is observed in preclinical models of postoperative cognitive dysfunction and has been identified as an early indicator of neurodegeneration in those at risk for Alzheimer’s disease. Using a novel brain imaging technique, water exchange index mapping MRI (WEI‐MRI), the CREATES study will investigate the extent to which BBB dysfunction predicts the incidence of perioperative neurocognitive disorders (postoperative delirium and postoperative cognitive dysfunction).MethodCREATES is an 18‐month cohort study that will enroll older adults without dementia (N=230) scheduled for major elective non‐cardiac surgeries under general anesthesia. The preoperative baseline evaluation includes WEI‐MRI brain imaging, neuropsychological tests, and blood sample collection for analysis of selected biomarkers associated with inflammation and microvascular dysfunction (soluble vascular adhesion molecule 1, soluble intercellular adhesion molecule 1, thrombopoietin, interleukin‐18, fatty acid binding protein, pancreatic polypeptide Y, chemokine I309, serum amyloid A, C‐reactive protein, alpha‐2‐macroglobulin, beta‐2 microglobulin, factor VII, adiponectin, apolipoprotein J, and neurofilament light). Delirium will be assessed daily during hospitalization using the Confusion Assessment Method diagnostic algorithm. Baseline assessments, including WEI‐MRI brain imaging will be repeated at postoperative month 3. Subsequently, neuropsychological testing and blood sample collection will be performed during follow‐up (months 6, 12, & 18). Incidence of mild cognitive impairment and Alzheimer’s disease will be evaluated by an expert panel using NIA‐AA diagnostic criteria at postoperative months 12 and 18.ResultPrimary analyses will investigate associations between 1) preoperative BBB permeability and incident postoperative delirium; and 2) postoperative BBB permeability and incident postoperative cognitive dysfunction during follow‐up. Relationships between serum biomarkers, BBB permeability, and incidence of neurocognitive disorders will be modeled in exploratory analyses.ConclusionBBB dysfunction is an indicator of brain vulnerability and neurodegeneration that may also be an important risk factor for postoperative delirium and delayed or incomplete cognitive recovery. CREATES is the first study of perioperative cognitive outcomes to utilize WEI‐MRI brain imaging, an innovative technique to evaluate BBB integrity which does not require administration of intravenous gadolinium‐based contrast agent. The results will provide important insights into the underlying mechanism(s) of perioperative neurocognitive disorders and potential biomarkers of prognostic significance.