bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of structured cognitive stimulation therapy program for older adults with dementia
Authors: Sanchez Cintia P 
Published: December 2020

AbstractBackgroundCognitive stimulation therapy (CST) is an evidence‐based psychosocial intervention for people with mild‐to‐moderate dementia due to various etiological factors.ObjectiveThe aim of the present study was to assess the efficacy of a structured group CST program, in individuals who have vascular or Alzheimer dementia.MethodsOlder adults with mild vascular or Alzheimer dementia (N = 20) were assigned to one of two programs: one group (N = 10) attended during one year, two sessions per week program of the group structured CST program, while the other, active control group (N = 10) took part in alternative activities. The following domains were examined: cognitive functioning, quality of life, mood, behavior, functional activities of daily living.ResultsCompared with the active controls, the structured group CST program showed a greater improvement in general cognitive functioning after the intervention (i.e. score increase on the Mini‐Mental State Examination and clock test score). A trend towards improvement was also identified in short term/working memory and perceived quality of life (Quality of life (QoL) of elderly with dementia). No significant differences emerged between the two groups for the other domains considered.ConclusionThe present results support the efficacy of structured group CST program in people with dementia. Key Words: Cognitive stimulation therapy (CST), Minimental State Examination (MMSE), Quality of life of elderly with dementia (QoL).
Experimental design for evaluating the effect of lighting interventions on patients with Alzheimer's: A review
Authors: Mathur Pegah , Rider Traci Rose , Place Wayne 
Published: December 2020

AbstractBackgroundAlzheimer’s disease is expected to become a major public health problem in the U.S. for the aging population. It is projected that in 2050, 65% of the aging population will die of Alzheimer’s. This raises the questions of whether and how we are prepared to provide care for this growing population. In this regard, the built environment can have a crucial role in supporting care and cure processes for the disease. Among the environmental variables that impact the provision of care for Alzheimer patients, lighting is especially consequential as it is known as a non‐invasive cure method that can stimulate the circadian rhythm and mitigate the issues of sleeping disturbance and agitation. Nevertheless, previous experimental research on this topic is inconclusive since many studies failed to present important variables and strategies used in their experimental designs (e.g. characteristics of the lighting device, exposing light intensity and spectral quantity, time‐series design and frequency of the interventions, the amount of light entered into the subject’s eyes).MethodThis paper reviews the existing research on lighting and Alzheimer’s to develop a framework that gives structure to the design of experimental research on the effect of lighting interventions on Alzheimer’s patients (e.g. variables, contextual factors, control strategies).ResultThis framework can facilitate future research on this topic as it enables the researchers to improve the internal validity of their results by improving their research design. Furthermore, this proposed framework can lead to a consistency in defining and using variables, control factors, and applicable findings across different studies to facilitate replication of experimental studies and inform the researcher on the generalizability of the findings.ConclusionFurthermore, this proposed framework can lead to a consistency in defining and using variables, control factors, and applicable findings across different studies to facilitate replication of experimental studies and inform the researcher on the generalizability of the findings.
U.S. POINTER (USA)
Authors: Baker Laura D. , Espeland Mark A. , Kivipelto Miia , Whitmer Rachel A. , Snyder Heather M. , Carrillo Maria C. , Antkowiak Susan , Chavin Melanie , Cleveland Maryjo , Day Claire E. , Desai Pankaja , Elbein Richard , Farias Sarah Tomaszewski , Gitelman Darren , Katula Jeffrey A. , Lambert Katherine , Leng Xiaoyan Iris , Lovato Laura , Morris Martha Clare , Ngandu Tiia , Papp Kathryn V. , Pavlik Valory N , Raman Rema , Robertson Julie , Rushing Scott , Salloway Stephen , Solomon Alina , Su Jing , Ventrelle Jennifer , Williams Benjamin J. , Williamson Jeff D. , Woolard Nancy , Yu Melissa 
Published: December 2020

AbstractBackgroundU.S. POINTER aims to test whether a multidomain lifestyle intervention focused on physical and cognitive activity, nutrition, and risk factor management reduces risk of cognitive decline in a heterogeneous population of older adults in the U.S. The study adapts the FINGER (Finnish Intervention Geriatric Study to Prevent Cognitive Impairment and Disability) interventions to fit American culture and works with community partners at 5 sites across the country to develop sustainable community‐based intervention programs.MethodsU.S. POINTER is a 2‐year RCT that is enrolling 2000 cognitively normal older adults (60‐79 years) who are at risk for decline due sedentary lifestyle, poor diet and other factors such as family history of memory impairment and suboptimum cardiovascular health. Recruitment utilizes electronic health records, as well as grassroots approaches to engage traditionally underrepresented groups. Participants are randomized to one of two lifestyle intervention groups – Self‐Guided or Structured Lifestyle Intervention – that differ in format, intensity and accountability. U.S. POINTER includes partnerships with local chapters of the Alzheimer's Association and lifestyle specialists to assist with intervention delivery. The primary outcome is 2‐year change in cognitive function measured with a composite score that permits harmonization with FINGER.ResultsRecruitment began in 2019 at the vanguard site in North Carolina. Study progress at all 5 participating sites will be presented. Progress toward harmonization with FINGER and other international study teams in the WW‐FINGERS network will also be discussed.ConclusionAs a member of the WW‐FINGERS network of trials, U.S. POINTER provides an unprecedented opportunity to leverage lessons learned in FINGER and expand this work to test the generalizability of the findings to a heterogeneous American cohort with different cultural needs and practices. The results, in combination with those from other WW‐FINGERS studies, have the potential to identify a strategy to slow cognitive decline on a global scale.
Contrasting alterations between cortical and subcortical myelin across age, AD diagnosis, and amyloid and tau pathology as assessed by quantitative R1 mapping
Authors: Kohli Akshay , Kecskemeti Steven , Adluru Nagesh , Jonaitis Erin M , Asthana Sanjay , Blennow Kaj , Zetterberg Henrik , Carlsson Cynthia M , Alexander Andrew L , Johnson Sterling C , Bendlin Barbara B 
Published: December 2020

AbstractBackgroundAccumulation of pathology in cortical tissue are early pathological hallmarks of Alzheimer’s disease. High resolution T1w/T2w ratio maps from structural MRI may reflect tissue microstructure with sensitivity to myelin, iron, and dendritic density. Few studies have investigated this in AD with conflicting reports of directionality of T1w/T2w ratios in individuals with AD diagnosis and pathology. However, these ratios will be sensitive to pulse sequences, protocols and bias field inhomogeneities, limiting their utility in clinical and research contexts. Here we employ R1 (=1/T1) relaxometry mapping, a quantitative imaging measure that is sensitive to myelin, to investigate relationships between cortical and subcortical tissue microstructure, age, AD diagnosis, and amyloid and tau pathology.MethodParticipants from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention underwent 3T MRI with whole‐brain, 1mm isotropic MPnRAGE T1 relaxometry with motion correction (Kecskemeti et al., 2016) (N=605/CN, 39/AD; age = 65.49 +/‐ 7.89 yrs) with a subset undergoing lumbar puncture for CSF Aß42/Tau biomarker classification (N = 141/A‐T‐, 26/A+T‐, 22/A‐T+, 18/A+T+). T1‐weighted images were processed using ANTS and CAT12, and transformation warps were applied to produce subcortical R1 maps in MNI space (6mm smoothing) and cortical R1 surface meshes (164k mesh, 5mm smoothing). Vertex‐wise (GM) and voxel‐wise (WM) ANCOVA were performed (p<0.05 FWE corrected). Covariates included age, sex, study protocol, and AD diagnosis in model 1, and age, sex, years between CSF collection and MRI, study protocol, and A/T biomarker group in model 2.ResultSignificant associations between R1 and age, clinical AD diagnosis, and A/T pathology were found (Figure 1A‐C). Post‐hoc tests revealed increased R1 due to A/T pathology driven by A+T+ individuals. In contrast, significant widespread decreases in subcortical R1 were found with age and AD diagnosis (Figure 1D&E), with no significant alterations in subcortical R1 due to biomarker status.ConclusionCortical and subcortical tissue exhibit differential tissue microstructural changes in response to aging, AD diagnosis and pathology. Importantly, increases in cortical R1 in unimpaired A+T+ individuals may reflect increased remyelination prior to the development of cognitive impairment. Future research will assess longitudinal relationships of R1 with age, cognition and markers of neurodegeneration.
Imaging ketone metabolism in the brain in Alzheimer's disease using hyperpolarized 13C spectroscopy
Authors: Page Lydia M Le , Shin Soo Hyun , Qiao Kai , Chaumeil Myriam M 
Published: December 2020

AbstractBackgroundAfter a ketogenic diet (KD), some cognitive improvements have been seen in Alzheimer’s disease (AD) patients. In vivo measurement of cerebral BHB metabolism is critically needed to properly assess patient response, as blood ketone level (especially beta‐hydroxybutyrate (BHB)) is not always coupled to brain ketone metabolism. Here, we evaluate a new imaging method, 13C magnetic resonance spectroscopy (MRS) of hyperpolarized (HP) [1‐13C]BHB, for in vivo assessment of ketone metabolism.Method[1‐13C]BHB was hyperpolarized and injected with BDH at 11.7T or in a C57BL/6J mouse at 3T, and dynamic 13C MRS acquired. Non‐HP [1‐13C]BHB was injected in a C57BL/6J mouse, brain metabolites extracted using chloroform/methanol, and 13C data acquired (11.7T). C57BL/6J (n=6‐8) or AD hAPP‐J20 mice (n=3) received either a KD (TD.160153, Envigo) or control diet (TD.150345, Envigo). Serum BHB levels (Precision Xtra) and brain BDH activity (BMR) were measured. Ex vivo data were analyzed using Mestrenova; in vivo data in jMRUI.ResultT1 was 41s (1.5T); 37s (3T); 28s (11.7T) (Fig.1A). Metabolism of HP [1‐13C]BHB (181ppm) to HP 13C AcAc (175ppm) by BDH was detected (Fig.1B‐C). [1‐13C]BHB and 13C AcAc were seen in brain extracts after [1‐13C]BHB injection (Fig.1D). Serum BHB and BDH activity were significantly elevated, but not correlated, in both healthy KD mice (Fig.2A‐C), and hAPP‐J20 KD mice (Fig.2D‐F). Following intravenous injection, HP [1‐13C]BHB and product HP 13C AcAc were observed in the live mouse brain (Fig.3). We believe this is the first observation of HP [1‐13C]BHB metabolism in the mouse brain.ConclusionKD increased BHB serum levels and brain BDH activity in healthy and AD mice. These two values were not correlated, confirming the necessity of an in vivo marker of ketone metabolism. Detection of conversion of HP [1‐13C]BHB to AcAc is feasible both ex vivo and in vivo. Future studies will image KD‐fed hAPP‐J20 mice. References: 1) Taylor, M.K., et al. Alzheimer’s Dement. Transl. Res. Clin. Interv. 4, 28–36 (2018). 2) Laffel, L. Diabetes. Metab. Res. Rev. 15, 412–426 (1999). 3) Grabacka, M., et al. Int. J. Mol. Sci. 17, 2093 (2016). 4) Najac, C. et al. Sci. Rep. 9, 3402 (2019).
Sovateltide (IRL‐1620) promotes neural regeneration and protects mitochondrial function in APP/PS1 transgenic mouse model of Alzheimer’s disease
Authors: Briyal Seema , Voshtina Ralf , Gulati Anil 
Published: December 2020

AbstractBackgroundMitochondrial dysfunction plays a central role in a common pathophysiology causing neuronal cell death in Alzheimer’s disease (AD). Endothelin B (ETB) receptor agonist, sovateltide, is being investigated as a potential therapeutic agent for AD, however, its mechanism of action of sovateltide is not yet established. The present study was undertaken to investigate whether sovateltide enhances neural regeneration by regulating mitochondrial function.MethodAPP/PS1 transgenic mice and C57BL/6 control mice were divided into two groups (vehicle and sovateltide). Sovateltide (5 μg/kg) was intravenously injected, three times at 2 hour intervals on days 1, 3 and 6 of every month until study end points (3, 6 and 12 months age). Control mice received equal volume of saline. Memory deficit was conducted using morris water maze test. Separate sets of mice were sacrificed at the end of 3, 6 and 12 months and brain harvested to determine the expression of markers for mitochondrial dysfunction, neuro‐ and synapto‐genesis using both western blot and immunofluorescence techniques.ResultAPP/PS1 transgenic mice showed significant (p<0.001) impairment in spatial memory. Sovateltide treatment significantly reduced learning and memory deficit in 6 months (40%) and 12 months (46%) aged transgenic mice. We found that sovateltide enhanced the expression of neuronal differentiation marker, NeuroD1 (p<0.0001) and DoubleCortin (p<0.0001) compared to vehicle group at 6 and 12 months. Expression of neural marker for mature neurons, NeuN (p<0.0001), was enhanced along with an upregulation of synaptic proteins (synapsin‐1, synaptophysin, and postsynaptic density‐95) compared to vehicle at 6 and 12 months of APP/PS1 transgenic mice. Furthermore, we found a shift in dynamics from fission to fusion proteins in sovateltide treated mice. An upregulation (p<0.0001) of mitochondrial fusion‐related proteins, Mfn1, Mfn2, Opa1, and downregulation of fission proteins, Drp1 and Fis1, in sovateltide group compared to vehicle at 6 and 12 months was observed. There were no changes in the expression of any markers at 3 months.ConclusionSovateltide has shown neural protective and regenerative effect by attenuating mitochondrial dysfunction impaired memory deficits, and supports the use of sovateltide as a possible pharmaceutical intervention for the treatment of Alzheimer’s disease.
Newest and successful therapy approach for Alzheimer's, dementia care: Rediscover recovery practical reference training
Authors: Mayer Gabriele 
Published: December 2020

AbstractBackgroundThrough minimized information all sensory organs activities/abilities real‐world/daily life, brain cells less “input”, pathological biochemical reactions/milieu, more slow down :perceptions, psycho‐social, brain functions, etc. Disorders: all perceptions, relationship disturbances. Social too fast, withdrawn activities, negative navigation, modern words. Persons lost relationship structures real‐world/daily life. Reactions: doing nothing, panic, aggressively, going down, abuse medications, internet, alcohol and needs help. Caregivers do best but in their structures. Thus withdraw activating “input” brain; “individually subjective selective‐ processing”, no consciousness/concentration in real‐world/daily life. Persons out of structures, fall backwards own development, status like babies. Perceptions less. Caregivers give structures, pathological circle.MethodPractical working, with intermittent accompanied families, caregivers.ResultNewest, successful “Rediscover Recovery Practical Reference Training” special knowledge, developed: Gabriele Mayer,‐ only in daily life/real‐world,‐ rebuilding person’s status. Training: orientation, ‐relationship to real‐world/daily life objects/subjects, doing little activities himself he can do, comment: ”well done”.‐Body scheme; consciousness/concentration.‐Relationship to himself (“I”). Do not with him tasks/duties only wants, can do in way he knows. Take older words he used. Brain works with older, covered up association fields, repeats call up older patterns. Person in daily life: verbally this in his words: activates brain cells, more perceptions “input”, relationship to real‐world/daily life doing. Family, caregivers: take over therapy by avoiding frustration, give place person, that he can do, if it’s right way daily life. The long‐term care: repeat therapy daily life/real‐world time/time, develop from child to own development stages. Higher perceptions all sensory organs, more “input” brain.ConclusionPsycho social Factors, Environment: After individual training person trains himself with social daily life/real‐world, more “input” brain, social environment takes contact. The technology: does not exist to deal with volume of connections information in real‐world quality full ranges “Input” for brain, brain cells connections. Abstract pictures are not be used to test Alzheimer’s, Dementia, etc. Illness in real‐world brain, test only with real‐world subjects/objects pictures with real‐world words. It needs therapy: “Rediscovery Recovery Practical Reference Training”, than can live life intermittent accompanied by someone else. Topics of interesting: See above, causes research publish: ”Rediscover Recovery Practical Reference Training” ISBN 978‐0‐9904836‐0‐1, in German: “Die Kombinationstherapie fuer Muskeln, Sehnen und Gelenke” ISBN 078‐3‐00‐018641‐7.
Exploring molecular biomarkers with potential prognostic value in longitudinal observational studies on Alzheimer’s disease
Authors: Vanmechelen Eugeen , Goossens Julie , Dewit Nele , Smirnov Denis S , Jacobs Dirk , Belbin Olivia , Alcolea Daniel , Lleó Alberto , Galasko Doug R 
Published: December 2020

AbstractBackgroundIncorporation of biomarkers into the diagnosis of AD has shifted its disease definition from clinical dementia (on average 7 years) into a biological change that may span two decades of a human life. Synaptic biomarkers and neurofilament light (NfL) have shown some potential to predict stage and disease course, however few studies have combined these markers in larger sample sets.MethodNegative controls, preclinical subjects (n=90), and subjects with MCI (n=57) and mild AD (n=46) from the longitudinal observational study at the UCSD Shirley‐Marcos ADRC (UCSD cohort) were tested for their biomarker levels. One molecular/synaptic marker, neuronal pentraxin 2 (NPTX2), is quantified in CSF with an ELISA containing two monoclonal antibodies (mAbs). We describe a newly developed NfL assay based on two mAbs that specifically targets the C‐terminus of coil 2a from human NfL. A third marker is synaptobrevin 2 (VAMP2), an essential component of the synaptic vesicle. Classical biomarkers such as t‐tau, β‐amyloid42 and synaptic markers SNAP25 and neurogranin were available for this sample set.ResultAs expected, CSF NfL levels increase gradually over the course of the disease, while VAMP2, as well as SNAP25 and neurogranin, shows a significant change in a stage of AD characterized by low Aβ42 and normal CSF tau and CSF NfL levels, thus suggesting that synaptic changes may precede overt neuronal (axonal) damage. CSF NPTX2 is a robust biochemical reflection of cognitive decline, as defined by California Verbal Learning Tests and Mattis Dementia Rating Scale and in contrast to all other fluid markers, it is not age‐dependent in control individuals.ConclusionExploring all these biochemical markers in observational longitudinal studies suggests changes might delineate different stages in the disease process: (1) intracellular synaptic markers such as VAMP2, SNAP25 and neurogranin precede neuronal degeneration as defined by increased CSF tau and CSF NfL levels, while NPTX2 only begins to decrease towards late clinical stages, showing a robust correlation to cognitive decline. When further verified and/or validated in other well‐designed longitudinal studies, such prognostic biomarkers might define specific stages and predict the onset of specific pathophysiological progression during the long course of the disease.
Does sex impact neuropsychiatric symptom burden in APOε4 carriers with at‐risk cognitive conditions?
Authors: Dissanayake Andrew S , Bowie Christopher R , Butters Meryl A , Flint Alastair , Gallagher Damien , Golas Angela C , Herrmann Nathan , Kennedy James L , Kumar Sanjeev , Lanctot Krista L , Mah Linda , Mulsant Benoit H , Pollock Bruce G , Rajji Tarek K , Schweizer Tom A , Munoz David G , Fischer Corinne E ,   PACT‐MD Research Group
Published: December 2020

AbstractBackgroundThe Apolipoprotein E (APOE) ε4 allele is a well‐established genetic risk factor of Alzheimer's disease (AD). While sex may play an important modulatory role in the association between APOε4 and certain neuropsychiatric symptoms (NPS) in AD1, it is unclear whether or not this risk extends to cognitively at‐risk populations with Mild Cognitive Impairment (MCI) or a history of Major Depressive Disorder (MDD). This cross‐sectional analysis compared NPS burden between males and females in a cohort of APOε4 carriers with at‐risk cognitive conditions of AD.MethodWe analyzed the Neuropsychiatric Inventory Questionnaire (NPI‐Q) data of 51 symptomatic APOε4 carriers (age = 71.9 ± 5.2) from the PACt‐MD cohort which was comprised of older persons from three at‐risk groups of AD: MCI; MDD without MCI; and MDD with MCI. We stratified participants by sex to compare their NPS severity. We tested whether there was a significant association between sex and i) NPI‐Q total score, and ii) NPI‐Q severity score. We chose not to stratify by zygosity or diagnosis due to the sample size.ResultFemale APOε4 carriers (n = 33, MNPI Total= 2.27, MNPI Severity = 3.55 ) had significantly higher NPI‐Q total scores(t = 2.15, df = 43.67, p = 0.037, d = 0.50) and significantly higher NPI‐Q severity scores (t = 2.06, df = 45.37, p = 0.044, d = 0.48) than male carriers (n = 18 , MNPI Total = 1.72, MNPI Severity = 2.44). There were no significant differences in the prevalence of certain NPS between male and female carriers.ConclusionOur findings support the need to further investigate whether sex influences the effect of APOε4 on NPS burden. Although female carriers showed significantly higher levels of NPS burden, aligning with previous findings1, our analysis was limited by the small number of symptomatic male carriers (n = 18). Thus, further studies with larger samples are needed to elucidate the interaction between sex and APOε4 status on NPS burden. References: Kim, J., Fischer, C. E., Schweizer, T. A., & Munoz, D. G. (2017). Gender and Pathology‐ Specific Effect of Apolipoprotein E Genotype on Psychosis in Alzheimer's Disease. Current Alzheimer research, 8, 834–840.