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Association of Concomitant Use of Cholinesterase Inhibitors or Memantine With Cognitive Decline in Alzheimer Clinical Trials: A Meta-analysis.
Kennedy, RE, Cutter, GR, Fowler, ME, Schneider, LS
JAMA network open. 2018;(7):e184080
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Abstract
IMPORTANCE Clinical trials in Alzheimer disease (AD) generally allow participants to continue receiving concomitant medications, including cholinesterase inhibitors (ChEIs) and memantine, if the dose is stable. Previous analysis of observational studies indicates such individuals experience greater rate of decline on cognitive testing than those not receiving such medications. OBJECTIVE To investigate whether concomitant use of ChEIs or memantine is associated with cognitive outcomes in AD clinical trials. DATA SOURCES Meta-database of 18 studies from the Alzheimer Disease Cooperative Study and Alzheimer Disease Neuroimaging Initiative. STUDY SELECTION All studies with data on ChEI and memantine use that included assessment of specified outcome measures. DATA EXTRACTION AND SYNTHESIS The analysis estimated annual rate of decline on the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) using linear mixed-effects models, and compared rates for participants receiving ChEIs and memantine, alone and combined, with participants not receiving either medication using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES Annual rate of change on the ADAS-cog. RESULTS Across 10 studies, of 2714 participants, the mean (SD) age was 75.0 (8.2) years, 58% were female, and 9% were racial/ethnic minorities. There were 906 participants (33.4%) receiving ChEIs, 143 (5.3%) receiving memantine, 923 (34.0%) receiving both, and 742 (27.3%) receiving neither. Meta-analysis showed those receiving ChEIs or memantine were associated with significantly greater annual rate of decline on the ADAS-cog than those receiving neither medication (1.4 points/y; 95% CI, 0.1-2.7). CONCLUSIONS AND RELEVANCE Similar to observational studies, many participants in AD clinical trials receiving ChEIs or memantine experience greater cognitive decline. This difference is nearly as large as the hypothesized effect sizes of the treatments investigated in the trials. Concomitant use of ChEIs or memantine may be confounded with outcomes on the ADAS-cog and should be considered in design of clinical trials of potential therapeutic agents for AD. Post hoc analyses stratifying by ChEIs or memantine must be interpreted cautiously given the potential for confounding.
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Uric Acid and Cognitive Function in Older Individuals.
Tana, C, Ticinesi, A, Prati, B, Nouvenne, A, Meschi, T
Nutrients. 2018;(8)
Abstract
Hyperuricemia has been recognized as an independent cardiovascular risk factor in epidemiological studies. However, uric acid can also exert beneficial functions due to its antioxidant properties, which may be particularly relevant in the context of neurodegenerative diseases. In this paper, we critically revise the evidence on the relationship between serum uric acid levels and cognitive function in older individuals, focusing on the etiology of cognitive impairment (Alzheimer's disease, Parkinson's dementia, and vascular dementia) and on the interactive connections between uric acid, dementia, and diet. Despite high heterogeneity in the existing studies, due to different characteristics of studied populations and methods of cognitive dysfunction assessment, we conclude that serum uric acid may modulate cognitive function in a different way according to the etiology of dementia. Current studies indeed demonstrate that uric acid may exert neuroprotective actions in Alzheimer's disease and Parkinson's dementia, with hypouricemia representing a risk factor for a quicker disease progression and a possible marker of malnutrition. Conversely, high serum uric acid may negatively influence the disease course in vascular dementia. Further studies are needed to clarify the physio-pathological role of uric acid in different dementia types, and its clinical-prognostic significance.
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Effects of vitamin D3 supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial.
Hu, J, Jia, J, Zhang, Y, Miao, R, Huo, X, Ma, F
Journal of neurology, neurosurgery, and psychiatry. 2018;(12):1341-1347
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Musical practice as an enhancer of cognitive function in healthy aging - A systematic review and meta-analysis.
Román-Caballero, R, Arnedo, M, Triviño, M, Lupiáñez, J
PloS one. 2018;(11):e0207957
Abstract
Aging is accompanied by cognitive decline, although recent research indicates that the rate of decline depends on multiple lifestyle factors. One of such factors is musical practice, an activity that involves several sensory and motor systems and a wide range of high-level cognitive processes. This paper describes the first systematic review and meta-analysis, to our knowledge, of the impact of musical practice on healthy neurocognitive aging. The inclusion criteria for the review required that studies were empirical works in English or Spanish that they explored the effects of musical practice on older people; they included an assessment of cognitive functions and/or an assessment of brain status; and they included a sample of participants aged 59 years or older with no cognitive impairment or brain damage. This review led to the selection of 13 studies: 9 correlational studies involving older musicians and non-musicians and 4 experimental studies involving short-term musical training programs. The results of the meta-analysis showed cognitive and cerebral benefits of musical practice, both in domain-specific functions (auditory perception) and in other rather domain-general functions. Moreover, these benefits seem to protect cognitive domains that usually decline with aging and boost other domains that do not decline with aging. The origin of these benefits may reside, simultaneously, in the specific training of many of these cognitive functions during musical practice (specific training mechanism), in the improvement of compensatory cognitive processes (specific compensatory mechanism), and in the preservation of general functions with a global influence on others, such as perceptual capacity, processing speed, inhibition and attention (general compensatory mechanism). Therefore, musical practice seems to be a promising tool to reduce the impact of cognitive problems associated to aging.
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Evaluating Mediterranean diet and risk of chronic disease in cohort studies: an umbrella review of meta-analyses.
Galbete, C, Schwingshackl, L, Schwedhelm, C, Boeing, H, Schulze, MB
European journal of epidemiology. 2018;(10):909-931
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Abstract
Several meta-analyses have been published summarizing the associations of the Mediterranean diet (MedDiet) with chronic diseases. We evaluated the quality and credibility of evidence from these meta-analyses as well as characterized the different indices used to define MedDiet and re-calculated the associations with the different indices identified. We conducted an umbrella review of meta-analyses on cohort studies evaluating the association of the MedDiet with type 2 diabetes, cardiovascular disease, cancer and cognitive-related diseases. We used the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) checklist to evaluate the methodological quality of the meta-analyses, and the NutriGrade scoring system to evaluate the credibility of evidence. We also identified different indices used to define MedDiet; tests for subgroup differences were performed to compare the associations with the different indices when at least 2 studies were available for different definitions. Fourteen publications were identified and within them 27 meta-analyses which were based on 70 primary studies. Almost all meta-analyses reported inverse associations between MedDiet and risk of chronic disease, but the credibility of evidence was rated low to moderate. Moreover, substantial heterogeneity was observed on the use of the indices assessing adherence to the MedDiet, but two indices were the most used ones [Trichopoulou MedDiet (tMedDiet) and alternative MedDiet (aMedDiet)]. Overall, we observed little difference in risk associations comparing different MedDiet indices in the subgroup meta-analyses. Future prospective cohort studies are advised to use more homogenous definitions of the MedDiet to improve the comparability across meta-analyses.
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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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Abstract
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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Reducing Burden for Caregivers of Older Adults With Mild Cognitive Impairment: A Systematic Review.
Domingues, NS, Verreault, P, Hudon, C
American journal of Alzheimer's disease and other dementias. 2018;(7):401-414
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BACKGROUND/RATIONALE This systematic review aims to evaluate the efficacy of the nonpharmacological interventions reducing burden, psychological symptoms, and improving quality of life of caregivers of individuals with mild cognitive impairment (MCI). METHOD Databases reviewed included Medline, Cochrane Library, Embase, PsycNet, AgeLine, and ProQuest Dissertations and Theses. Studies using an experimental/quasi-experimental design including nonpharmacological intervention were included. Four studies were included, and no meta-analysis was conducted. RESULTS Calendar training and note-taking (cognitive intervention) significantly decreased caregiver's depressive symptoms and prevented worsening of subjective burden 6 months posttreatment. Daily engagement of meaningful activity combined with problem-solving therapy and educational material reduced depressive symptoms 3 months posttreatment. Moreover, educational intervention and social conversation phone calls decreased caregiver burden 3 months posttreatment. CONCLUSION Studies suggest that nonpharmacological interventions can support caregivers of older adults with MCI, but the few published articles present some bias and are inconclusive. Randomized-controlled trials targeting specifically caregivers are needed to determine the most efficient type of interventions for those individuals.
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Disclosure of amyloid positron emission tomography results to individuals without dementia: a systematic review.
de Wilde, A, van Buchem, MM, Otten, RHJ, Bouwman, F, Stephens, A, Barkhof, F, Scheltens, P, van der Flier, WM
Alzheimer's research & therapy. 2018;(1):72
Abstract
BACKGROUND Disclosure of amyloid positron emission tomography (PET) results to individuals without dementia has become standard practice in secondary prevention trials and also increasingly occurs in clinical practice. However, this is controversial given the current lack of understanding of the predictive value of a PET result at the individual level and absence of disease-modifying treatments. In this study, we systematically reviewed the literature on the disclosure of amyloid PET in cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) in both research and clinical settings. METHODS We performed a systematic literature search of four scientific databases. Two independent reviewers screened the identified records and selected relevant articles. Included articles presented either empirical data or theoretical data (i.e. arguments in favor or against amyloid status disclosure). Results from the theoretical data were aggregated and presented per theme. RESULTS Of the seventeen included studies, eleven reported empirical data and six provided theoretical arguments. There was a large variation in the design of the empirical studies, which were almost exclusively in the context of cognitively normal trial participants, comprising only two prospective cohort studies quantitatively assessing the psychological impact of PET result disclosure which showed a low risk of psychological harm after disclosure. Four studies showed that both professionals and cognitively normal individuals support amyloid PET result disclosure and underlined the need for clear disclosure protocols. From the articles presenting theoretical data, we identified 51 'pro' and 'contra' arguments. Theoretical arguments in favor or against disclosure were quite consistent across population groups and settings. Arguments against disclosure focused on the principle of non-maleficence, whereas its psychological impact and predictive value is unknown. Important arguments in favor of amyloid disclosure are the patients right to know (patient autonomy) and that it enables early future decision making. DISCUSSION Before amyloid PET result disclosure in individuals without dementia in a research or clinical setting is ready for widespread application, more research is needed about its psychological impact, and its predictive value at an individual level. Finally, communication materials and strategies to support disclosure of amyloid PET results should be further developed and prospectively evaluated.
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Necrotizing Enterocolitis and Neurodevelopmental Outcome.
Adams-Chapman, I
Clinics in perinatology. 2018;(3):453-466
Abstract
Necrotizing enterocolitis is a serious complication of prematurity that is associated with an increased risk for adverse neurodevelopmental outcome secondary to a complex relationship between various morbidities that increase the risk for central nervous system injury. Affected infants are exposed to a variety of circulating cytokines known to be associated with white matter injury. These infants also have an increased risk of secondary blood stream infections and nutritional compromise.
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Association between mental disorders, cognitive disturbances and vitamin D serum level: Current state.
Lerner, PP, Sharony, L, Miodownik, C
Clinical nutrition ESPEN. 2018;:89-102
Abstract
BACKGROUND & AIMS Vitamin D deficiency has been identified as a global problem. Approximately 14% of the world population has inadequate vitamin D levels. This vitamin has been usually associated with bone disorders such as rickets, osteomalacia, and osteoporosis. However, these disorders present only a small part of all the disturbances which can be induced by its deficiency. Low serum vitamin D is associated with development of cardiovascular diseases, hypertension, neurodegenerative diseases, diabetes mellitus, metabolic syndrome and even cancer. This vitamin may be an important factor in the development of psychiatric illnesses, therefore clinicians should not leave this serious issue unresolved. The aim of this review is to describe the current data concerning the association between vitamin D serum levels, cognition and mental disorders. METHODS We conducted a systematic bibliographical research, of PubMed, MedLine literature and Cochrane database without language restriction to identify all publications concerning this issue from 1995 to the first quarter of 2017. RESULTS We found 48,937 articles concerning vitamin D, published during the last 22 years and 3 months (1995-2017). We selected only those publications focused on the association between vitamin D serum deficiency and mental disturbances (depression, schizophrenia, cognitive disturbances, attention deficit disorder, and autism). One hundred and sixty-seven papers were found suitable to our selection criteria. Careful evaluation of the relevant literature demonstrates that addition of vitamin D to conventional antidepressive agents can improve antidepressive effect in contrast to placebo. Regarding other mental conditions there are no clear-cut conclusions. CONCLUSIONS An association between low vitamin D serum levels and different mental disorders was found. Yet, nonetheless there is no clear consensus that addition of vitamin D improves or is related to a beneficial effect on mental health. More randomized clinical control trials should be performed in order to reach evidence based conclusions.