bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological treatment of neuropsychiatric symptoms of dementia: A systematic review and network meta‐analysis
Authors: Huang Yu‐Yuan , Dou Kai‐Xin , Zhong Xiao‐Ling , Shen Xue‐Ning , Chen Shi‐Dong , Chen Ke‐Liang , Cui Mei , Dong Yi , Dong Qiang , Yu Jin‐Tai 
Published: December 2020

AbstractBackgroundNeuropsychiatric symptoms (NPS) of dementia are a common issue in dementia patients. It generally presents as three disparate symptom clusters—agitation, psychosis, and mood disorders which have different biological and psychosocial triggers. Therefore, a “one size fits all” solution may not exist. Pharmacological treatments are its treatment of choice, but there is controversy about which agent should be used. We aimed to update and expand our previous work to compare and rank drugs for the treatment of neuropsychiatric symptoms of dementia.MethodsWe included all randomized controlled trials reported as double‐blind and comparing one active drug with another or with placebo. Studies searched Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, from database inception to Jun 28, 2019. Our primary outcome was change in overall neuropsychiatric symptoms measured with standardised rating scales. And the secondary outcomes were change in aggressive behavior, psychosis, apathy, and depressive symptoms. Effect size measures were standardised mean differences (SMD) with 95% credible intervals (CrIs). We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking probabilities. We conducted subgroup analyses to assess the robustness of our findings. Confidence in the evidence was assessed using CINeMA. The study protocol is registered with PROSPERO, number CRD42019132231.ResultsWe identified 8175 citations and of these included 114 trials comprising nearly thirty thousand participants. Effect size estimates suggested galantamine was more effective than placebo for reducing overall neuropsychiatric symptoms. SMD compared with placebo for reduction of aggressive behavior found that aripiprazole and risperidone appeared to be more efficacious, citalopram and methylphenidate for reduction of apathy symptoms, memantine and donepezil for reduction of psychosis. While the certainty of evidence was low to very low.ConclusionThis systematic review synthesized the available evidence on the comparative efficacy of different pharmacological approaches in the management of overall NPS, agitation, psychosis, apathy and depressive symptoms in dementia patients. These results may serve evidence‐based practice and inform patients, physicians, guideline developers. Especially, clinicians should differentiate these disparate symptom clusters since the appreciation of such complexity is vital to determine the appropriate treatment.
Assessments of nutritional status and cognitive function of the elderly in Korea: Cross‐sectional study
Authors: Chang Kyung Ja , Bae Mi‐ae , Lee Go Eun , Kim Sung Hoon 
Published: December 2020

AbstractBackgroundRecently Korea has become an aged society and prevalence of dementia in the elderly is increasing rapidly. The purpose of this study was to investigate the nutritional status and cognitive function of the elderly in Korea.MethodThe subjects were 127 elderly(55 males, 72 females) in Korea. The nutritional status was assessed using the Nutrition Quotient for Elderly(NQ‐E) developed by the Korean Nutrition Society and 24‐hour recall method. The cognitive function was assessed using the Mini‐Mental State Examination for Dementia Screening(MMSE‐DS) and Subjective Memory Complaints Questionnaire(SMCQ). Data were collected through the face‐to‐face survey from June to July, 2019 and they were statistically analyzed using SPSS 20.0. The subjects were compared by dividing them into good group(GG) and poor group(PG) according to the NQ‐E criteria score(62 points).ResultThe total score of the NQ‐E in GG(69.1 points) was significantly higher than that of PG(53.6 points) (p<0.001). The elderly of both groups showed less energy, vitamin A, D, C, niacin, calcium, potassium and magnesium than the Dietary Reference Intakes For Koreans(KDRI). The total score of MMSE‐DS did not show a significant difference between GG(26.4 points) and PG(25.2 points), but scores of ‘Time orientation’ and ‘Place orientation’ in GG were significantly higher than those in PG(p<0.05). The SMCQ means that subjective memory complaints is severe when the score is 6 points or more. Both GG(3.4 point) and PG(5.0 points) showed good status, but the score of PG was significantly higher than that of GG(p<0.01). There was a tendency to have a positive correlation between the total score of NQ‐E and MMSE‐DS of the subjects(p=0.056), and there were negative correlations between the total score, balance, and food behavior in NQ‐E and SMCQ. These results indicated that scores of some cognitive function(MMSE‐DS) in the PG were lower than those in the GG, and it showed a more severe degree of subjective memory complaints. Also, it showed that the better nutritional status in the balance and food behavior, the lower subjective memory complaints of the subjects.ConclusionTherefore, it is necessary to improve nutritional status through sufficient nutrients intake and systematic management to maintain mental health of the elderly.
7β‐hydroxycholesterol increases amyloidogenic pathway and may serve as a peripheral biomarker of Alzheimer’s disease
Authors: Ha Junghee , Cho So Yeon , Lee Jimin , Kim Hyunjeong , Choi Man Ho , Kim Eosu 
Published: December 2020

AbstractBackgroundOxidized cholesterols have been related to Alzheimer’s disease (AD). However, the role of 7β‐hydroxycholesterol (7β‐OHC) in AD pathogenesis is largely unexplored: There is a lack of understanding of whether the increase in 7β‐OHC levels in AD is a consequence of neurodegeneration process or 7β‐OHC plays a direct role in AD pathogenesis. Thus, we aimed to explore the potential of 7β‐OHC as a biomarker of AD and to observe the direct effect of 7β‐OHC on AD pathologies.Method7β‐OHC levels in scalp hairs were assessed by gas chromatography‐mass spectrometry (GC‐MS) methods in persons with normal cognition (NC, n = 82), mild cognitive impairment (MCI, n = 39) and AD (n = 81). Also, we examined the relationship between hair 7β‐OHC levels and various clinical features representing cognitive status. Upon stereotaxic injection of 7β‐OHC into the hippocampus of mice, we investigated AD pathologies such as β‐amyloid, tau, and neuroinflammation. We also assessed the behavioral effects of intracerebroventricular injection of 7β‐OHC using the touchscreen‐based 5‐choice serial reaction time task (5‐CSRTT).Result7β‐OHC levels were increased in hairs of persons with AD compared to those with NC (p = 0.001). There was also a significant correlation between hair 7β‐OHC levels and the scores of Mini‐Mental State Examination (MMSE) and Global Deterioration Scale (GDS) after controlling age, gender, education ,and statin use. In the animal experiment, we found that hippocampal 7β‐OHC injection induces microglial and astrocytic activation and increases levels of interleukin (IL)‐1β and IL‐6, suggesting neuroinflammation. It also promoted the amyloidogenic pathway by upregulating BACE 1 while downregulating alpha‐secretase, TACE. In the behavioral assessment, we found that 7β‐OHC treatment increases perseveration, compatible with frontal lobe dysfunction.ConclusionOur results suggest that 7β‐OHC in scalp hair could serve as a convenient peripheral biomarker of AD. Given that accumulative levels of steroid molecules in hairs indicate its plasma exposure levels in the past several months, our study also suggests that increased plasma 7β‐OHC may be a preceding factor that can increase AD pathology.
Visit‐to‐visit blood pressure variability is associated with functional decline in older adults: The S.AGES cohort
Authors: Rouch Laure , Vidal Jean‐Sébastien , Hanon Olivier ,   S.AGES Investigators
Published: December 2020

AbstractBackgroundVisit‐to‐visit blood pressure variability (BPV) has been increasingly recognized as a predictor of cardiovascular events, all‐cause mortality and more recently of cognitive decline and dementia. All these associations may be mediated by vascular damage which is a determinant of functional decline in older adults. We aimed to investigate the impact of visit‐to‐visit systolic, diastolic, mean arterial pressure and pulse pressure variability on functional decline in non‐institutionalized patients aged ≥ 65 years.Method3042 subjects from the S.AGES (elderly subjects) cohort underwent clinical examinations every 6 months during 3 years. Systolic, diastolic, mean arterial pressure and pulse pressure variability were evaluated using standard deviation, coefficient of variation, average real variability, successive variation, variation independent of mean and residual standard deviation. Functional decline was assessed using the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales and defined over time as any help required to perform at least one task. Cox proportional hazards models were used for the analyses.ResultAmong the 3042 subjects, 527 (17.3%) had functional decline (ADL) over time. After adjustment for demographics, systolic blood pressure, antihypertensive drugs, coronary artery disease, diabetes mellitus, chronic heart failure, atrial fibrillation, transient ischemic attack or stroke, smoking, dyslipidemia and Mini Mental State Examination at baseline, higher systolic blood pressure variability was associated with greater risk of functional decline (ADL) (adjusted HR per 1‐SD increase of coefficient of variation = 1.12, 95% CI [1.03‐1.22], p<0.01). Similar results were observed for diastolic blood pressure variability (adjusted HR = 1.11, 95% CI [1.01‐1.22], p=0.03) and mean arterial pressure variability (adjusted HR = 1.15, 95% CI 1.05‐1.25, p<0.01). Higher pulse pressure variability was no longer significantly associated with functional decline after adjustment for age (p=0.6). Similar patterns were found with all indicators of variability and loss of autonomy defined using IADL.ConclusionHigher blood pressure variability could be a novel risk factor for functional decline and controlling blood pressure instability a promising interventional target in preserving autonomy in older adults.
The effect of child‐centered play therapy and person‐centered therapy consultation on behavioral and psychological symptoms of dementia in people with dementia of Alzheimer's type
Authors: Kuo Ching‐Yi 
Published: December 2020

AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) is highly correlated with early nursing home placement, caregiver burden, and cognitive and functional decline. Non‐pharmacological interventions should be first‐line used given the side‐effect of medication. Child‐centered play therapy (CCPT) is a proven scientifically and culturally responsive psychotherapy modality that is widely used with children and a variety of problematic behaviors, including individual with brain injury. Person‐centered therapy consultation (PCTC) is a recognized form of psychotherapy with an emphasis on self‐actualization and therapeutic relationships that facilitate psychological changes. This pilot study of people with dementia of Alzheimer's type who exhibit BPSD in Taiwan examines a combination of CCPT and PCTC an effective non‐pharmacological intervention for people with dementia and their caregivers.MethodA single‐case research design will be employed. Three PWD receive 40‐minute weekly CCPT sessions for 8 weeks. Three family caregivers receive 50‐minute weekly person‐centered therapy consultations over 8 weeks. PWD will enter a follow‐up phase for 2 weeks after the last CCPT session. Measures: Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory Distress Scale (NPI‐D), Geriatric Depression Scale (GDS), Clinical Dementia Rating (CDR), and Alzheimer’s Disease Assessment Scale‐cognitive subscale (ADAS‐cog) are used to measure the effectiveness of CCPT on alleviating BPSD.ResultThe research process is on‐going.ConclusionThe research process is on‐going.
Increased functional connectivity of anterior insula to anterior cingulate cortex in amnestic mild cognitive impairment: A longitudinal resting‐state fMRI study
Authors: Fan Xiang , Li Hui , Li Kuncheng 
Published: December 2020

AbstractBackgroundThe insula has been reported as a crucial role in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). However, the mechanism and functional connectivity (FC) changes of insula in follow‐up remain unclear. Exploring specific insula network interaction can contribute to a better understanding of integration and segregation patterns of aMCI.MethodTwenty aMCI and twenty healthy controls (HC) participants were recruited and underwent resting‐state functional magnetic resonance imaging (rs‐fMRI) and neuropsychological assessment at baseline and 15 months afterward. Rs‐fMRI data were preprocessed using SPM 12 and CONN software. FC of two insular subregions in each hemisphere were defined as anterior insula connectivity (AIC) and posterior insula connectivity (PIC). Using data driven clustering technique, the insular lobe was subdivided based on whole brain functional connectivity. Two‐way analysis of covariance was used with covariates of gender, age, education, follow‐up interval, volume of gray matter and global correlation (GCOR).ResultWithin group FC maps of HC and aMCI exhibited similar patterns both at baseline and follow‐up. For the left anterior insula, significant connectivity with bilateral anterior cingulate gyrus (ACC), paracingulate gyrus, putamen, frontal orbital cortex, inferior frontal gyrus, and temporal pole were identified. The right anterior insula was positively associated with bilateral insula, ACC, central opercular cortex, frontal orbital cortex, and right junction region of temporal, frontal and parietal lobe. The posterior zone of the insula (both the right and the left) exhibited significant connectivity with the bilateral Insular, ACC, central opercular cortex, precentral gyrus, postcentral gyrus, supramarginal gyrus, parietal operculum cortex, as well as the junction region of temporal, frontal and parietal lobe. For interactive main effects, the right AIC showed significantly increased FC with the left ACC, while the left PIC showed decreased FC with the right precuneous, in aMCI as compared to HC.ConclusionInsula rsFC changes could be potential biomarkers of aMCI and reveal some definite neuropathological mechanism due to pathologic processes in AD. We considered the rsFC increase of AIC with ACC as compensatory and decrease of the PIC with the precuneus as deterioration of follow‐up due to the course of disease.
Performances of the plasma Aβ biomarker in longitudinal data
Authors: Nakamura Akinori , Kato Takashi , Okada Yusuke , Ishii Kenji , Ishii Kazunari , Ito Kengo , Arahata Yutaka , Kaneko Naoki , Iwamoto Shinichi , Tanaka Koichi , Ikeuchi Takeshi , Yanagisawa Katsuhiko , Iwatsubo Takeshi , Toba Kenji ,   the J‐ADNI and ORANGE registry study groups
Published: December 2020

AbstractBackgroundWe recently developed a high‐performance plasma biomarker that reliably predicts individual brain status of amyloid‐β (Aβ) burden using immunoprecipitation‐mass spectrometry (IP‐MS). This study aimed to analyze performances of the plasma Aβ biomarker in a longitudinal dataset using J‐ADNI data.MethodThere were 165 subjects, including 38 cognitively normal (CN), 61 MCI and 46 AD individuals who participated in the J‐ADNI study, and 132 of them had two times of follow‐up data within 36 months. The plasma composite biomarker was generated by combining plasma ratios of APP669‐711/Aβ1‐42 and Aβ1‐40/Aβ1‐42, which were measured by the IP‐MS assay. Using PiB‐PET as the standard of truth (Aβ+ or Aβ‐), plasma biomarker performances were analyzed using the ROC analysis. Relationships of plasma composite biomarker values and longitudinal changes in Aβ deposition (assessed by PiB‐SUVR), degree of medial temporal atrophy (assessed by VSRAD® z‐scores of structural MRI), and cognitive decline (assessed by cognitive test scores) were analyzed.ResultThe ROC analyses showed that the composite biomarker performs good both in base line data and follow up data with AUC greater than 90%. There were no significant changes in plasma composite biomarker values across longitudinal observations. The baseline composite biomarker values were significantly correlated with annual rate of Aβ deposition, especially within subjects whose baseline PiB‐SUVR was relatively small (less than 2.0). The baseline composite biomarker values were also significantly correlated with the rate of medial temporal atrophy and the rate of cognitive decline.ConclusionClinical utility of the plasma Aβ biomarker was validated in J‐ADNI longitudinal data, and it provided information for future disease progression.
PERK inhibition promotes the rescue of protein translation and Nrf2‐related antioxidant response
Authors: Lanzillotta Chiara , Zuliani Ilaria , Tramutola Antonella , Abisambra Jose F. , Barone Eugenio , Perluigi Marzia , Domenico Fabio Di 
Published: December 2020

AbstractBackgroundMany neurodegenerative disorders in which aberrant protein conformers aggregate into pathological inclusions, such as tauopathies, also present endoplasmic reticulum stress and chronic activation of the PERK branch of the unfolded protein response (UPR). The adaptive effects of the PERK pathway include reduction of translation by transient inhibition of eIF2α and antioxidant response via induction of the transcription factor Nrf2. In contrast, prolonged activation of the UPR leads to sustained reduction in protein synthesis and induction of cell death pathways. To further investigate the role of the PERK pathway in neurodegenerative disorders, we focused on Down syndrome (DS), a secondary tauopathy, in which aging confers a high risk of Alzheimer‐like dementia (AD), Aβ plaques formation and tau tangle deposition. We recently determined that the UPR is dysregulated in a murine DS model. Therefore, our project aims to investigate if restoring PERK pathway, by using a well‐established PERK inhibitor (GSK2606414), could mitigate the early UPR activation and result in reduced brain pathology.MethodTs2Cje (mouse model of DS) at 6 months of age were treated with GSK2606414 a well‐known PERK inhibitor. To target directly the brain, we use the intranasal route. The analysis of the proteins of interest has been carried out by confocal microscopy, Western Blot and real time PCR. Furthermore, we use SUnSET, a non‐radioactive puromycin based approach adapted in vivo, to measure protein synthesis.ResultOur data report that the pharmacological inhibition of PERK, by GSK2606414, ameliorate chronic PERK induction observed in DS mice restoring its downstream signalling aberrantly regulated during pathology. In particular, we demonstrate, in Ts2Cje treated mice the rescue from eIF2a‐mediated disruption of protein synthesis. In addition, we show that the compound was able to promote the Nrf2‐related antioxidant response reducing protein oxidative damage. Such effect was obtained by the increase of PI3K interaction with Nrf2 and by the restrain of Bach1 binding to ARE sequences.ConclusionOur study provides further insights about the role of PERK in DS pathology and in the development of AD, proposing PERK inhibitors as novel therapeutic agents able to rescue trisomic‐related defects of proteostasis and antioxidant response.
Subjective cognitive decline, APOE genotype, and incident Alzheimer’s disease: The AGES‐Reykjavik Study
Authors: Geerlings Mirjam I. , Gerritsen Lotte , Vonk Jet M.J. , Gudnason Vilmundur , Launer Lenore J. 
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) may be a marker of preclinical Alzheimer’s disease (AD) in some individuals and is related to biomarkers of AD. We investigated the longitudinal associations of SCD and APOE genotype with incidence of dementia and AD.MethodData are from 4,349 older adults (76±5 years, 59% women) without dementia who participated in the population‐based AGES‐Reykjavik Study. SCD was assessed with the question ‘Has your memory gotten worse in the past 12 months’. A 1.5T brain MRI was performed in all participants. Five mutually exclusive groups were defined: 1) normal (i.e. no SCD, no MCI, no dementia)/APOE e4 negative (n=2039); 2) normal/APOE e4 positive (n=711); 3) SCD/APOE e4 negative (n=806); 4) SCD/APOE e4 positive (n=355); 5) MCI (regardless of APOE) (n=438). MCI and dementia, including AD, were assessed according to international criteria. We used Cox regression analyses adjusted for age, sex, and education to estimate the Hazard Ratios of each group with incident dementia, including AD and non‐AD dementia.ResultDuring on average 9 years of follow‐up, 843 persons developed dementia, including 397 with AD. Within the normal/APOE e4 negative group conversion rate to dementia was 13%; these rates were 20%, 20%, 30%, and 38% for groups 2 through 5, respectively. For AD, the conversion rates for groups 1 through 5 were 6%, 12%, 10%, 21%, and 23%. Cox regression analyses showed that compared to the normal/APOE e4 negative group, the normal/APOE e4 positive group had 2.48 times higher risk of AD (95% CI 1.84‐3.34), the SCD/APOE e4 negative group 1.78 times higher (1.31‐2.42), the SCD/APOE e4 positive group 5.23 times higher (3.83‐7.16), and the MCI group 4.43 times higher (3.24‐6.06) (Figure 1).ConclusionSubjective cognitive decline and APOE e4 positivity each increased the risk of AD development, but the combination of a subjective cognitive symptom and a biomarker posed the strongest risk for AD, comparable to that of MCI. These findings may help to identify high‐risk groups in the population to target for preventive or therapeutic interventions.