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Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.
Kim, CS, Cha, L, Sim, M, Jung, S, Chun, WY, Baik, HW, Shin, DM
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;76(1):32-40
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Aging is characterized by progressive decline in biological functions of the organism. Diet is one of the critical lifestyle factors for physical and mental well-being throughout the life span, including later life. The aim of this study was to investigate the effects of probiotics consumption on intestinal and brain health in elders over the age of 65. This study is a randomised, double-blind, placebo-controlled, multicentre trial. All participants, study coordinators, and researchers were blinded throughout the entire study. Sixty-three participants were randomized, with 31 and 32 subjects in the placebo and probiotics group, respectively. Results demonstrate that probiotics have system-wide effects on the gut–brain axis in healthy community-dwelling older adults by promoting cognitive and mental health and changing the gut microbial composition. Authors conclude that their findings provide evidence that probiotics have health-promoting properties as part of a healthy diet in the general population of independently living older adults.
Abstract
Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the beneficial role of probiotics in brain functions of healthy older adults remains unclear. Therefore, a randomized, double-blind, and placebo-controlled multicenter trial was conducted to determine the effects of probiotics on cognition and mood in community-dwelling older adults. Sixty-three healthy elders (≥65 years) consumed either placebo or probiotics containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Brain functions were measured using the Consortium to Establish a Registry for Alzheimer's disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule. Blood brain-derived neurotrophic factor (BDNF) was determined using enzyme-linked immunosorbent assay. Relative abundance of inflammation-causing gut bacteria was significantly reduced at Week 12 in the probiotics group (p < .05). The probiotics group showed greater improvement in mental flexibility test and stress score than the placebo group (p < .05). Contrary to placebo, probiotics significantly increased serum BDNF level (p < .05). Notably, the gut microbes significantly shifted by probiotics (Eubacterium and Clostridiales) showed significant negative correlation with serum BDNF level only in the probiotics group (RS = -0.37, RS = -0.39, p < .05). In conclusion, probiotics promote mental flexibility and alleviate stress in healthy older adults, along with causing changes in gut microbiota. These results provide evidence supporting health-promoting properties of probiotics as a part of healthy diet in the older adults.
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Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer's disease: a cross-sectional study of middle-aged adults from the broader New York City area.
Mosconi, L, Walters, M, Sterling, J, Quinn, C, McHugh, P, Andrews, RE, Matthews, DC, Ganzer, C, Osorio, RS, Isaacson, RS, et al
BMJ open. 2018;8(3):e019362
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Alzheimer’s disease (AD) is the most common form of dementia, affecting nearly 34 million people worldwide. It has been estimated that one in every three cases of AD may be attributable to diet and lifestyle factors. The aim of this study was to investigate the effects of lifestyle and vascular-related risk factors for AD. Researchers studied the brain scans of 116 healthy adults aged 30-60 years. They collected information on factors related to lifestyle, such as diet, physical activity and intellectual enrichment. They also looked at markers for vascular risk such as body mass index (BMI), cholesterol and homocysteine, as well as cognitive function. The researchers found that a Mediterranean-style diet and good insulin sensitivity were both associated with a healthier brain structure. A better score for intellectual enrichment and lower BMI were both associated with better cognition. They concluded that adopting a Mediterranean-style diet and maintaining a healthy weight might reduce the risk of developing AD.
Abstract
OBJECTIVE To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults. DESIGN Cross-sectional, observational. SETTING Broader New York City area. Two research centres affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. PARTICIPANTS We studied 116 cognitively normal healthy research participants aged 30-60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition. RESULTS Adherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: βs≥0.26, insulin sensitivity βs≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (βs≥0.25 P≤0.001), as were those between overweight and lower cognition (βs≥-0.22, P≤0.01). CONCLUSIONS In cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.
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Cognitive Effects of Intentional Weight Loss in Elderly Obese Individuals With Mild Cognitive Impairment.
Horie, NC, Serrao, VT, Simon, SS, Gascon, MR, Dos Santos, AX, Zambone, MA, Del Bigio de Freitas, MM, Cunha-Neto, E, Marques, EL, Halpern, A, et al
The Journal of clinical endocrinology and metabolism. 2016;101(3):1104-12
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Several studies have elucidated that midlife obesity increases the risk of dementia later in life. While the neuroprotective effects of caloric restriction have been widely demonstrated, they have not yet been investigated in patients with mild cognitive impairment (MCI). The aim of this trial was to evaluate the effect of intentional weight loss in elderly adults with mild cognitive impairment (MCI). Eighty participants aged over 60 were randomly allocated to receive either nutritional counselling or medical care alone for 12 months. The findings of this study indicated that intentional weight loss through diet was associated with cognitive improvement in patients with MCI, and this association was strongest in younger adults and APOE4 carriers. As this was the first clinical trial exploring these effects in patients with MCI further research is warranted.
Abstract
CONTEXT Obesity in midlife is a risk factor for dementia, but it is unknown if caloric restriction-induced weight loss could prevent cognitive decline and therefore dementia in elderly patients with cognitive impairment. OBJECTIVE To evaluate the cognitive effect of intentional weight loss in obese elderly patients with mild cognitive impairment (MCI), considering the influence of age, apolipoprotein E (APOE) genotype, physical activity, biochemical markers, and diet. DESIGN Single-center, prospective controlled trial. SETTING Academic medical center. PARTICIPANTS Eighty obese patients with MCI, aged 60 or older (68.1 ± 4.9 y, body mass index [BMI] 35.5 ± 4.4 kg/m(2), 83.7% women, 26.3% APOE allele ϵ4 carriers). INTERVENTION Random allocation to conventional medical care alone (n = 40) or together with nutritional counselling (n = 40) in group meetings aiming to promote weight loss through caloric restriction for 12 months. OUTCOME MEASUREMENTS clinical data, body composition, neuropsychological tests (main outcome), serum biomarkers, APOE genotype, physical performance, dietary recalls. RESULTS Seventy-five patients completed the follow-up. BMI, on average, decreased 1.7 ± 1.8 kg/m(2) (P = .021), and most of the cognitive tests improved, without difference between the groups. In analysis with linear generalized models, the BMI decrease was associated with improvements in verbal memory, verbal fluency, executive function, and global cognition, after adjustment for education, gender, physical activity, and baseline tests. This association was strongest in younger seniors (for memory and fluency) and in APOE allele ϵ4 carriers (for executive function). Changes in homeostasis model assessment-estimated insulin resistance, C-reactive protein, leptin and intake of energy, carbohydrates, and fats were associated with improvement in cognitive tests. CONCLUSIONS Intentional weight loss through diet was associated with cognitive improvement in patients with MCI.
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Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects.
Ford, HE, Peters, V, Martin, NM, Sleeth, ML, Ghatei, MA, Frost, GS, Bloom, SR
European journal of clinical nutrition. 2011;65(4):508-13
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There have been significant advances in the understanding of how hormonal signals released from the gastrointestinal (GI) tract interact with circuits within the central nervous system to control appetite and energy intake. The aim of this study is to investigate whether oral ingestion of sucralose, at a dose that would be consumed in a normal diet, increases circulating gut hormones (glucagon-like peptide [GLP-1] or peptide YY [PYY] concentrations in man. This study is a randomised, single-blinded, crossover design study. Subjects were randomly assigned to receive one of four solutions on four separate study sessions. Eight normal-weight, healthy volunteers were recruited, all of which were non-smokers, aged 22–27 years (seven females and one male) with a stable body weight. Results indicate that oral ingestion of the artificial sweetener sucralose does not increase plasma GLP-1 or PYY concentrations nor does it affect subjective feelings of appetite or energy intake at the next meal in healthy volunteers. Based on their findings, authors conclude that a dietary dose of sucralose does not stimulate the sweet-taste receptor in the GI tract to release GLP-1 and PYY.
Abstract
BACKGROUND/OBJECTIVE The sweet-taste receptor (T1r2+T1r3) is expressed by enteroendocrine L-cells throughout the gastrointestinal tract. Application of sucralose (a non-calorific, non-metabolisable sweetener) to L-cells in vitro stimulates glucagon-like peptide (GLP)-1 secretion, an effect that is inhibited with co-administration of a T1r2+T1r3 inhibitor. We conducted a randomised, single-blinded, crossover study in eight healthy subjects to investigate whether oral ingestion of sucralose could stimulate L-cell-derived GLP-1 and peptide YY (PYY) release in vivo. METHODS Fasted subjects were studied on 4 study days in random order. Subjects consumed 50 ml of either water, sucralose (0.083% w/v), a non-sweet, glucose-polymer matched for sweetness with sucralose addition (50% w/v maltodextrin+0.083% sucralose) or a modified sham-feeding protocol (MSF=oral stimulation) of sucralose (0.083% w/v). Appetite ratings and plasma GLP-1, PYY, insulin and glucose were measured at regular time points for 120 min. At 120 min, energy intake at a buffet meal was measured. RESULTS Sucralose ingestion did not increase plasma GLP-1 or PYY. MSF of sucralose did not elicit a cephalic phase response for insulin or GLP-1. Maltodextrin ingestion significantly increased insulin and glucose compared with water (P<0.001). Appetite ratings and energy intake were similar for all groups. CONCLUSIONS At this dose, oral ingestion of sucralose does not increase plasma GLP-1 or PYY concentrations and hence, does not reduce appetite in healthy subjects. Oral stimulation with sucralose had no effect on GLP-1, insulin or appetite.
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Hormonal and psychobehavioral predictors of weight loss in response to a short-term weight reduction program in obese women.
Hainer, V, Hlavatá, K, Gojová, M, Kunešová, M, Wagenknecht, M, Kopský, V, Pařízková, J, Hill, M, Nedvídková, J
Physiological research. 2008;57 Suppl 1:S17-S27
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Among the many factors that influence weight loss and weight management, metabolic and hormonal parameters have been increasingly explored as important predictors. The aim of this study was to reveal potential psycho-behavioural and hormonal factors as predictors of weight loss. A group of 67 overweight women were enrolled in a 3-week weight management programme in which food intake and physical activity were under strict control. This study indicated that a short-term weight management programme induced favourable changes in anthropometric, psycho-behavioural and hormonal indices. Changes in several hormone concentrations were significantly associated with the reduction of anthropometric parameters, however psycho-behavioural factors did not contribute to weight change in the programme.
Abstract
Among the factors influencing weight loss and maintenance, psychobehavioral, nutritional, metabolic, hormonal and hereditary predictors play an important role. Psychobehavioral factors influence adherence to lifestyle changes and thus weight loss maintenance. The outcome of short-term weight reduction treatment is mainly affected by changes in energy and nutrient intake and physical activity and thus the impact of hormones can possibly be obscured. In order to reveal hormonal determinants of weight loss, a 4-week in-patient comprehensive weight reduction program was introduced in which food intake and physical activity were under the strict control. Women (n = 67, BMI: 32.4+/-4.4 kg; age: 48.7+/-12.2 years) who exhibited stable weight on a 7 MJ/day diet during the first week of weight management were given a hypocaloric diet yielding daily energy deficit 2.5 MJ over the subsequent 3-week period. This treatment resulted in a mean weight loss of 3.80+/-1.64 kg. Correlation analysis revealed that baseline concentrations of several hormones were significantly associated either with a higher (free triiodothyronine, C-peptide, growth hormone, pancreatic polypeptide) or with a lower (insulin-like growth factor-I, cortisol, adiponectin, neuropeptide Y) reduction of anthropometric parameters in response to weight management. In a backward stepwise regression model age, initial BMI together with baseline levels of growth hormone, peptide YY, neuropetide Y and C-reactive protein predicted 49.8 % of the variability in weight loss. Psychobehavioral factors (items of the Eating Inventory, Beck Depression score) did not contribute to weight change induced by a well-controlled short-term weight reduction program.