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Recruitment and Baseline Characteristics of Participants in the AgeWell.de Study-A Pragmatic Cluster-Randomized Controlled Lifestyle Trial against Cognitive Decline.
Röhr, S, Zülke, A, Luppa, M, Brettschneider, C, Weißenborn, M, Kühne, F, Zöllinger, I, Samos, FZ, Bauer, A, Döhring, J, et al
International journal of environmental research and public health. 2021;(2)
Abstract
Targeting dementia prevention, first trials addressing multiple modifiable risk factors showed promising results in at-risk populations. In Germany, AgeWell.de is the first large-scale initiative investigating the effectiveness of a multi-component lifestyle intervention against cognitive decline. We aimed to investigate the recruitment process and baseline characteristics of the AgeWell.de participants to gain an understanding of the at-risk population and who engages in the intervention. General practitioners across five study sites recruited participants (aged 60-77 years, Cardiovascular Risk Factors, Aging, and Incidence of Dementia/CAIDE dementia risk score ≥ 9). Structured face-to-face interviews were conducted with eligible participants, including neuropsychological assessments. We analyzed group differences between (1) eligible vs. non-eligible participants, (2) participants vs. non-participants, and (3) between intervention groups. Of 1176 eligible participants, 146 (12.5%) dropped out before baseline; the study population was thus 1030 individuals. Non-participants did not differ from participants in key sociodemographic factors and dementia risk. Study participants were M = 69.0 (SD = 4.9) years old, and 52.1% were women. The average Montreal Cognitive Assessment/MoCA score was 24.5 (SD = 3.1), indicating a rather mildly cognitively impaired study population; however, 39.4% scored ≥ 26, thus being cognitively unimpaired. The bandwidth of cognitive states bears the interesting potential for differential trial outcome analyses. However, trial conduction is impacted by the COVID-19 pandemic, requiring adjustments to the study protocol with yet unclear methodological consequences.
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Effectiveness and Safety Profile of Ginkgo biloba Standardized Extract (EGb761®) in Patients with Amnestic Mild Cognitive Impairment.
Băjenaru, O, Prada, G, Antochi, F, Jianu, C, Tudose, C, Cuciureanu, A, Docu, AA, Perrot, V, Avram, M, Tiu, C
CNS & neurological disorders drug targets. 2021;(4):378-384
Abstract
BACKGROUND Ginkgo biloba is a common symptomatic treatment for cognitive impairment, although data on its efficacy are controversial. OBJECTIVE The aim of the current study was to evaluate the effectiveness of standardized Ginkgo biloba extract EGb761® (Tanakan®) for the improvements of cognitive functions over 24 months in a local cohort of patients diagnosed with amnestic mild cognitive impairment (aMCI). METHODS This multicentre non-interventional study included 500 eligible patients with a MCI treated with 120 mg/day standardized Ginkgo biloba extract EGb761® (Tanakan®). Patients were evaluated using several scales for assessment of cognition, memory, activities of daily living, and depression (MMSE, FAQ, CGI, HAM-D) at baseline and every 6 months after that for a 24-month period. The median change in MMSE at the 24-month follow-up was the primary outcome of the study. RESULTS A statistically significant increase of 2 points in the median MMSE score was obtained. In patients with other concomitant cognitive disorders, the improvement in MMSE was less significant. Tanakan® improved memory impairment (using the delayed recall test) and the ability to accomplish activities of daily living (mean FAQ score, 1.7); it also decreased the severity of depression (mean HAM-D score, 2.4) at the end of the study. More than 80% of the patients showed minimal improvement of their condition as assessed by the CGI-Improvement Scale. CONCLUSION The administration of EGb761® (Tanakan®) led to a significant improvement of cognitive decline, memory, activities of daily living, and depression in subjects with aMCI over 24 months.
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The Japan-Multimodal Intervention Trial for Prevention of Dementia (J-MINT): The Study Protocol for an 18-Month, Multicenter, Randomized, Controlled Trial.
Sugimoto, T, Sakurai, T, Akatsu, H, Doi, T, Fujiwara, Y, Hirakawa, A, Kinoshita, F, Kuzuya, M, Lee, S, Matsuo, K, et al
The journal of prevention of Alzheimer's disease. 2021;(4):465-476
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BACKGROUND/OBJECTIVES The Japan-multimodal intervention trial for prevention of dementia (J-MINT) is intended to verify the effectiveness of multi-domain interventions and to clarify the mechanism of cognitive improvement and deterioration by carrying out assessment of dementia-related biomarkers, omics analysis and brain imaging analysis among older adults at high risk of dementia. Moreover, the J-MINT trial collaborates with partnering private enterprises in the implementation of relevant interventional measures. This manuscript describes the study protocol. DESIGN/SETTING Eighteen-month, multi-centered, randomized controlled trial. PARTICIPANTS We plan to recruit 500 older adults aged 65-85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the dynamic allocation method with all subjects stratified by age, sex, and cognition. INTERVENTION The multi-domain intervention program includes: (1) management of vascular risk factors; (2) group-based physical exercise and self-monitoring of physical activity; (3) nutritional counseling; and (4) cognitive training. Health-related information will be provided to the control group every two months. MEASUREMENTS The primary and secondary outcomes will be assessed at baseline, 6-, 12-, and 18-month follow-up. The primary outcome is the change from baseline to 18 months in a global composite score combining several neuropsychological domains. Secondary outcomes include: cognitive change in each neuropsychological test, incident dementia, changes in blood and dementia-related biomarkers, changes in geriatric assessment including activities of daily living, frailty status and neuroimaging, and number of medications taken. CONCLUSIONS This trial that enlist the support of private enterprises will lead to the creation of new services for dementia prevention as well as to verify the effectiveness of multi-domain interventions for dementia prevention.
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A randomized phase II remote study to assess Bacopa for Gulf War Illness associated cognitive dysfunction: Design and methods of a national study.
Cheema, AK, Wiener, LE, McNeil, RB, Abreu, MM, Craddock, T, Fletcher, MA, Helmer, DA, Ashford, JW, Sullivan, K, Klimas, NG
Life sciences. 2021;:119819
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AIMS: Gulf War Illness (GWI) is a chronic, debilitating, multi-symptom condition affecting as many as one-third of the nearly 700,000 U.S. troops deployed to the Middle East during the 1990-1991 Gulf War (GW). The treatment of GWI relies on symptom management. A common challenge in studying the efficacy of interventions for symptom management is participant recruitment related to factors such as the burden of travelling to study sites and the widespread dispersion of Veterans with GWI. The goal of this study is to assess the efficacy of a novel low-risk therapeutic agent, Bacopa monnieri, for cognitive function in Veterans with GWI and to evaluate the utility of a remote patient-centric study design developed to promote recruitment and minimize participant burden. MAIN METHODS To promote effective participant recruitment, we developed a remote patient-centric study design. Participants will be recruited online through social media and through a web-based research volunteer list of GW Veterans. An online assessment platform will be used, and laboratory blood draws will be performed at clinical laboratory sites that are local to participants. Furthermore, the assigned intervention will be mailed to each participant. SIGNIFICANCE These study design adaptations will open participation to Veterans nearly nationwide and reduce administrative costs while maintaining methodologic rigor and participant safety in a randomized, placebo-controlled phase II clinical trial.
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The effects of six months Persicaria minor extract supplement among older adults with mild cognitive impairment: a double-blinded, randomized, and placebo-controlled trial.
Lau, H, Shahar, S, Mohamad, M, Rajab, NF, Yahya, HM, Din, NC, Hamid, HA
BMC complementary medicine and therapies. 2020;(1):315
Abstract
BACKGROUND Persicaria minor extract exhibits antioxidant and anti-inflammatory properties and has potential effects on cognitive function and mood. However, the effects of P.minor on brain activation and biomarkers have not been studied among older adults. This multicentre, randomized, double-blinded, placebo-controlled study aimed to investigate the effect of 6 months P.minor extract supplement (Biokesum®) on cognition, mood, biomarkers, and brain activation among older adults with Mild Cognitive Impairment (MCI). METHOD A total of 36 Malaysian community-dwelling older adults with MCI (60-75-year-old) were randomized into Biokesum® (n = 18) and placebo group (n = 18). Each subject consumed one capsule of Biokesum® (250 mg/capsule) or placebo (maltodextrin, 280 mg/capsule) twice daily for 6 months. Cognitive function and mood were assessed at baseline, 3rd, and 6th-month using neuropsychological tests (MMSE, Digit Span, RAVLT, Digit Symbol, and Visual Reproduction) and Profile of Mood State (POMS) questionnaire. Blood lipid profile, fasting blood glucose, and biomarkers (MDA, LPO, COX-2, iNOS, and BDNF) were measured at baseline and 6th month. By the end of the intervention, there were 30 compliers (Biokesum®: N = 15; Placebo: N = 15) and 6 dropouts. For brain activation assessment, 15 subsamples (Biokesum®: N = 8; Placebo: N = 7) completed N-back and Stroop tasks during fMRI scanning at baseline and 6th month. The dorsolateral prefrontal cortex (Brodmann's area 9 and 46) was identified as a region of interest (ROI) for brain activation analysis using SPM software. RESULTS Two-way mixed ANOVA analysis showed significant improvements in Visual Reproduction II (p = 0.012, partial η2 = 0.470), tension (p = 0.042, partial η2 = 0.147), anger (p = 0.010, partial η2 = 0.207), confusion (p = 0.041, partial η2 = 0.148), total negative subscales (p = 0.043, partial η2 = 0.145), BDNF (p = 0.020, partial η2 = 0.179) and triglyceride (p = 0.029, partial η2 = 0.237) following 6 months of Biokesum® supplementation. Preliminary finding also demonstrated significant improvement at 0-back task-induced right DLPFC activation (p = 0.028, partial η2 = 0.652) among subsamples in Biokesum® group. No adverse events were reported at the end of the study. CONCLUSION Six months Biokesum® supplementation potentially improved visual memory, negative mood, BDNF, and triglyceride levels among older adults with MCI. Significant findings on brain activation at the right DPLFC must be considered as preliminary. TRIAL REGISTRATION Retrospectively registered on 30th August 2019 [ ISRC TN12417552 ].
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Plasma metabolomics in early Alzheimer's disease patients diagnosed with amyloid biomarker.
Peña-Bautista, C, Roca, M, Hervás, D, Cuevas, A, López-Cuevas, R, Vento, M, Baquero, M, García-Blanco, A, Cháfer-Pericás, C
Journal of proteomics. 2019;:144-152
Abstract
An untargeted metabolomics study has been carried out using plasma samples from patients with Mild Cognitive Impairment due to Alzheimer's disease patients (MCI-AD, n = 29) and healthy people (n = 29)). They have been classified following the National Institute on Aging and Alzheimer's Association (NIA-AA) recommendations and cerebrospinal fluid biomarkers. The analytical method was based on liquid chromatography coupled to high resolution mass spectrometry. The data process from the corresponding metabolic profiles retained 1158 molecular features in positive and 424 in negative ionization mode. Differences between metabolomic profiles from MCI-AD patients and healthy participants were investigated using a penalized logistic regression analysis (ElasticNet), and being able to select automatically the most informative variables (53 molecular features). From the molecular features selected for the elastic net models, 16 variables were preliminarily identified by The Human Metabolome Database (amino acids, lipids…). However, only 4 of these variables were tentatively identified by MS/MS and all ions fragmentation modes, being choline the only confirmed metabolite. Regarding their metabolic pathways, they could be involved in cholinergic system, energy metabolism, amino acids and lipids pathways. To conclude, this is a reliable approach to early AD mechanisms, and choline has been identified as a promising AD diagnosis metabolite. SIGNIFICANCE The untargeted analysis carried out in human plasma samples from early Alzheimer's disease patients and healthy individuals, and the use of sophisticated statistical tools, identified some metabolic pathways and plasma biomarkers. Preliminarily, cholinergic system, energy metabolism, and aminoacids and lipids pathways may be involved in early Alzheimer's disease development.
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Self and Informant Memory Reports in FINGER: Associations with Two-Year Cognitive Change.
Vaskivuo, L, Hokkanen, L, Hänninen, T, Antikainen, R, Bäckman, L, Laatikainen, T, Paajanen, T, Stigsdotter-Neely, A, Strandberg, T, Tuomilehto, J, et al
Journal of Alzheimer's disease : JAD. 2019;(3):785-795
Abstract
BACKGROUND Subjective memory complaints (SMCs) may be the first sign of cognitive decline in aging. OBJECTIVE To examine whether SMCs reported by oneself and informant predict cognitive change over 2 years among at-risk elderly people, and to determine the relationship of different types of SMCs (prospective and retrospective memory complaints) and change in cognitive function. METHODS This investigation is part of the FINGER project, which is a multicenter randomized controlled trial aiming at preventing cognitive decline in cognitively healthy older adults with increased risk of dementia. A subsample of 303 control-group participants (aged 60-80 years) and their informants (n = 261) rated the frequency of SMCs, using the Prospective and Retrospective Memory Questionnaire (PRMQ). Cognitive performance was measured at baseline and at 1- and 2-year follow-up visits using a neuropsychological test battery. RESULTS Participants who reported more SMCs improved less in global cognition, executive function, and memory during the subsequent 2 years in the fully-adjusted analyses. Self-reported retrospective memory problems predicted less improvement in all cognitive domains, whereas prospective memory problems did not. Informant-reported memory problems were not linked to subsequent change in cognition. CONCLUSION Our results indicate that self-reported SMCs, measured with PRMQ, predict future cognitive change in several cognitive domains. By contrast, reports by informants were not linked to changes in cognition. Among cognitively healthy at-risk elderly individuals, the persons themselves observe more easily problems relevant for their future cognitive trajectories than their informants.
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Altered Eating Attitudes in Nursing Home Residents and Its Relationship with their Cognitive and Nutritional Status.
María Pérez-Sánchez, C, Nicolás Torres, D, Hernández Morante, JJ
The journal of nutrition, health & aging. 2018;(7):869-875
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BACKGROUND although eating disorders are usually linked to young adolescents, these mental disorders can also appear in the elderly, especially in those living in nursing homes, which might be associated or not with the cognitive decline; however, there are few data regarding elderly subjects. OBJECTIVES the objective of the present work was to evaluate the presence of abnormal eating attitudes in nursing home residents and its relation with several cognitive, nutritional and psychological factors that could be influencing their nutritional state. DESIGN AND SETTING a observational experimental study was carried out at several nursing homes of Murcia, Spain. SUBJECTS 139 nursing home residents. METHODS EAT-26 test was used to screen classic eating disorders (anorexia and bulimia). Blandford's scale was employed to determine aversive eating attitudes. Moreover, subjective appetite sensations, body image perception, nutritional (MNA and diet composition) and biochemical data were also evaluated. RESULTS 33% of the subjects had malnutrition. No subject showed symptoms of anorexia or bulimia; however, subjects with cognitive decline frequently showed aversive feeding behaviours (21.6%). Albumin values were significantly lower in subjects with cognitive impairment. CONCLUSIONS our data showed a clear relation between cognitive impairment and altered eating attitudes, which was reflected by both biochemical (albumin) and nutritional parameters, while no classic eating disorder was observed in residents with normal cognitive-status. These data confirm the need to strengthen our efforts towards maintaining the nutritional status of the subjects with cognitive impairment.
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Co-occurrence and Severity of Neurodevelopmental Burden (Cognitive Impairment, Cerebral Palsy, Autism Spectrum Disorder, and Epilepsy) at Age Ten Years in Children Born Extremely Preterm.
Hirschberger, RG, Kuban, KCK, O'Shea, TM, Joseph, RM, Heeren, T, Douglass, LM, Stafstrom, CE, Jara, H, Frazier, JA, Hirtz, D, et al
Pediatric neurology. 2018;:45-52
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BACKGROUND This study aims to determine the prevalence of neurodevelopmental impairments at age ten years among children born extremely preterm (less than 28 weeks gestational age) and to offer a framework for categorizing neurological limitations. METHODS A multicenter, prospective cohort follow-up study recruited 889 ten-year-old children born from 2002 to 2004. We assessed prevalence of cognitive impairment, measured by intelligent quotient and tests of executive function, cerebral palsy (CP), autism spectrum disorder (ASD), and epilepsy singly and in combination. The three levels of impairment severity were: category I-no major neurodevelopmental impairment; category II-normal cognitive ability with CP, ASD, and/or epilepsy; and category III-children with cognitive impairment. RESULTS A total 214 of 873 children (25%) had cognitive impairment, 93 of 849 children (11%) had CP, 61 of 857 children (7%) had ASD, and 66 of 888 children (7%) had epilepsy. Further, 19% of all children had one diagnosis, 10% had two diagnoses, and 3% had three diagnoses. Decreasing gestational age was associated with increasing number of impairments (P < 0.001). Half the children with cognitive impairment and one third of children with CP, ASD, or epilepsy had a single impairment. Six hundred one (68% [95% CI, 64.5%-70.7%]) children were in category I, 74 (8% [95% CI, 6.6%-10.3%]) were in category II, and 214 (24% [95% CI 21.7%-27.4%]) were in category III. CONCLUSIONS Three quarters of children had normal intellect at age ten years; nearly 70% were free of neurodevelopmental impairment. Forty percent of children with impairments had multiple diagnoses.
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Designing an Internet-Based Multidomain Intervention for the Prevention of Cardiovascular Disease and Cognitive Impairment in Older Adults: The HATICE Trial.
Barbera, M, Mangialasche, F, Jongstra, S, Guillemont, J, Ngandu, T, Beishuizen, C, Coley, N, Brayne, C, Andrieu, S, Richard, E, et al
Journal of Alzheimer's disease : JAD. 2018;(2):649-663
Abstract
BACKGROUND Many dementia and cardiovascular disease (CVD) cases in older adults are attributable to modifiable vascular and lifestyle-related risk factors, providing opportunities for prevention. In the Healthy Aging Through Internet Counselling in the Elderly (HATICE) randomized controlled trial, an internet-based multidomain intervention is being tested to improve the cardiovascular risk (CVR) profile of older adults. OBJECTIVE To design a multidomain intervention to improve CVR, based on the guidelines for CVR management, and administered through a coach-supported, interactive, platform to over 2500 community-dwellers aged 65+ in three European countries. METHODS A comparative analysis of national and European guidelines for primary and secondary CVD prevention was performed. Results were used to define the content of the intervention. RESULTS The intervention design focused on promoting awareness and self-management of hypertension, dyslipidemia, diabetes mellitus, and overweight, and supporting smoking cessation, physical activity, and healthy diet. Overall, available guidelines lacked specific recommendations for CVR management in older adults. The comparative analysis of the guidelines showed general consistency for lifestyle-related recommendations. Key differences, identified mostly in methods used to assess the overall CVR, did not hamper the intervention design. Minor country-specific adaptations were implemented to maximize the intervention feasibility in each country. CONCLUSION Despite differences in CVR management within the countries considered, it was possible to design and implement the HATICE multidomain intervention. The study can help define preventative strategies for dementia and CVD that are applicable internationally.