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Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons.
Barnes, LL, Dhana, K, Liu, X, Carey, VJ, Ventrelle, J, Johnson, K, Hollings, CS, Bishop, L, Laranjo, N, Stubbs, BJ, et al
The New England journal of medicine. 2023;389(7):602-611
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Lifestyle interventions targeting diet are a possible approach that could affect public health. Most clinical trials have investigated comprehensive diets, in contrast to dietary manipulation of single foods or nutrients. The aim of this study was to evaluate the effects of a 3-year dietary intervention on cognitive decline and brain-imaging markers of dementia and Alzheimer’s disease in older, cognitively unimpaired adults at risk for dementia because of family history. This study was a 3-year, two-site, randomised, controlled trial. The participants were randomly assigned to follow the MIND diet with mild caloric restriction for weight loss or their usual diet with the same mild caloric restriction for weight loss (control diet). Participants were randomly assigned in a 1:1 ratio. Results showed that the participants who followed the MIND diet had small improvements in a global measure of cognition that were similar to those who followed a control diet with mild caloric restriction. Authors concluded that brain health, cognitive function and brain imaging outcomes (after 3 years) did not differ significantly between participants who followed the MIND diet and those who followed a control diet with a mild caloric restriction.
Abstract
BACKGROUND Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean-DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia. METHODS We performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)-derived measures of brain characteristics in a nonrandom sample of participants. RESULTS A total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, -0.022 to 0.092; P = 0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups. CONCLUSIONS Among cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.).
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The effect of weight loss following 18 months of lifestyle intervention on brain age assessed with resting-state functional connectivity.
Levakov, G, Kaplan, A, Yaskolka Meir, A, Rinott, E, Tsaban, G, Zelicha, H, Blüher, M, Ceglarek, U, Stumvoll, M, Shelef, I, et al
eLife. 2023;12
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Obesity is linked to premature brain ageing and subsequent development of diseases such as dementia and Alzheimer’s disease. Weight loss through lifestyle modifications may be able to attenuate brain ageing. This sub-study of 102 individuals from a randomised control trial known as the Dietary Intervention Randomised Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), aimed to determine the effect of 18 months lifestyle modifications and weight loss on brain age. The results showed that a decrease in BMI attenuated brain ageing and that 1% body weight loss reduced brain ageing by 8.9 months. Reduced brain age was also associated with decreased waist circumference and fat mass. Interestingly, reduced consumption of processed foods was also associated with reduced brain age. It was concluded that weight loss can be of benefit to brain health. This study could be used by healthcare professionals to understand that people with obesity are at a higher risk of brain related diseases, and that weight loss may be an effective way to prevent their development.
Abstract
BACKGROUND Obesity negatively impacts multiple bodily systems, including the central nervous system. Retrospective studies that estimated chronological age from neuroimaging have found accelerated brain aging in obesity, but it is unclear how this estimation would be affected by weight loss following a lifestyle intervention. METHODS In a sub-study of 102 participants of the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS) trial, we tested the effect of weight loss following 18 months of lifestyle intervention on predicted brain age based on magnetic resonance imaging (MRI)-assessed resting-state functional connectivity (RSFC). We further examined how dynamics in multiple health factors, including anthropometric measurements, blood biomarkers, and fat deposition, can account for changes in brain age. RESULTS To establish our method, we first demonstrated that our model could successfully predict chronological age from RSFC in three cohorts (n=291;358;102). We then found that among the DIRECT-PLUS participants, 1% of body weight loss resulted in an 8.9 months' attenuation of brain age. Attenuation of brain age was significantly associated with improved liver biomarkers, decreased liver fat, and visceral and deep subcutaneous adipose tissues after 18 months of intervention. Finally, we showed that lower consumption of processed food, sweets and beverages were associated with attenuated brain age. CONCLUSIONS Successful weight loss following lifestyle intervention might have a beneficial effect on the trajectory of brain aging. FUNDING The German Research Foundation (DFG), German Research Foundation - project number 209933838 - SFB 1052; B11, Israel Ministry of Health grant 87472511 (to I Shai); Israel Ministry of Science and Technology grant 3-13604 (to I Shai); and the California Walnuts Commission 09933838 SFB 105 (to I Shai). Obesity is linked with the brain aging faster than would normally be expected. Researchers are able to capture this process by calculating a person’s ‘brain age’ – how old their brain appears on detailed scans, regardless of chronological age. This approach also helps to monitor how certain factors, such as lifestyle, can influence brain aging over relatively short time scales. It is not clear whether lifestyle interventions that promote weight loss can help to slow obesity-driven brain aging. To answer this question, Levakov et al. studied 102 individuals who met the criteria for obesity and took part in a lifestyle intervention aimed to improve diet and physical activity levels over 18 months. The participants received a brain scan at the beginning and the end of the program; additional tests and measurements were also conducted at these times to capture other biological processes impacted by obesity, such as liver health. Levakov et al. used the brain scans taken at the start and end of the study to examine the impact of the lifestyle intervention on the aging trajectory. The results revealed that a reduction in body weight of 1% led to the participants’ brain age being nearly 9 months younger than the expected brain age after 18 months. This attenuated aging was associated with changes in other biological measures, such as decreased liver fat and liver enzymes. Increases in liver fat and production of specific liver enzymes were previously shown to negatively impact brain health in Alzheimer’s disease. Finally, examining more closely the food consumption reports completed by participants showed that reduced consumption of processed food, sweets and beverages were linked to attenuated brain aging. The findings show that lifestyle interventions which promote weight loss can have a beneficial impact on the aging trajectory of the brain observed with obesity. The next steps will include determining whether slowing down obesity-driven brain aging results in better clinical outcomes for patients. In addition, the work by Levakov et al. demonstrates a potential strategy to evaluate the success of lifestyle changes on brain health. With global rates of obesity rising, identifying interventions that have a positive impact on brain health could have important clinical, educational and social impacts.
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Insufficient sleep predicts poor weight loss maintenance after 1 year.
Bogh, AF, Jensen, SBK, Juhl, CR, Janus, C, Sandsdal, RM, Lundgren, JR, Noer, MH, Vu, NQ, Fiorenza, M, Stallknecht, BM, et al
Sleep. 2023;46(5)
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Short sleep duration, defined as less than 6 hours/night, is associated with all-cause mortality, cardiovascular diseases, hypertension, diabetes, and obesity. Sleep restriction causes metabolic and behavioural changes suggesting that short sleep duration may contribute to the development of obesity. The aim of this study was to investigate associations between short sleep duration or poor sleep quality and weight regain after weight loss. This study is based on data from the S-LiTE randomised, controlled trial. Participants followed a low-calorie diet (800 kcal/day) for eight weeks prior to randomisation. Those who lost at least 5% of initial weight were randomised to the control or intervention group. Results showed that participants with objectively measured short sleep duration after a diet-induced weight loss had less success during weight loss maintenance than those with longer sleep duration. Worse sleep quality was associated with less weight loss during a low-calorie diet and subsequent weight maintenance. Authors conclude that insufficient sleep predicts weight regain during interventional efforts to maintain weight loss. Exercise maintained low-calorie diet-induced improvements in sleep quality during 1 year of weight loss maintenance, and liraglutide transiently increased sleep duration.
Abstract
STUDY OBJECTIVES Insufficient sleep may attenuate weight loss, but the role of sleep in weight loss maintenance is unknown. Since weight regain after weight loss remains a major obstacle in obesity treatment, we investigated whether insufficient sleep predicts weight regain during weight loss maintenance. METHODS In a randomized, controlled, two-by-two factorial study, 195 adults with obesity completed an 8-week low-calorie diet and were randomly assigned to 1-year weight loss maintenance with or without exercise and liraglutide 3.0 mg/day or placebo. Sleep duration and quality were measured before and after the low-calorie diet and during weight maintenance using wrist-worn accelerometers (GENEActiv) and Pittsburgh Sleep Quality Index (PSQI). To test associations between insufficient sleep and weight regain, participants were stratified at randomization into subgroups according to sleep duration (≥6 h/night) or sleep quality (PSQI score ≤/>5). RESULTS After a diet-induced 13.1 kg weight loss, participants with short sleep duration at randomization regained 5.3 kg body weight (p = .0008) and had less reduction in body fat percentage compared with participants with normal sleep duration (p = .007) during the 1-year weight maintenance phase. Participants with poor sleep quality before the weight loss regained 3.5 kg body weight compared with good quality sleepers (p = .010). During the weight maintenance phase, participants undergoing liraglutide treatment displayed increased sleep duration compared with placebo after 26 weeks (5 vs. -15 min/night) but not after 1 year. Participants undergoing exercise treatment preserved the sleep quality improvements attained from the initial weight loss. CONCLUSIONS Short sleep duration or poor sleep quality was associated with weight regain after weight loss in adults with obesity.
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The impact of Dietary Weight loss, Aerobic Exercise, and Daylong Movement on Social Cognitive Mediators of Long-term Weight loss.
Fanning, J, Nicklas, B, Furlipa, J, Rejeski, WJ
Journal of behavioral medicine. 2023;46(3):499-508
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Obesity in older adults predisposes individuals to physical disability, a host of chronic diseases, and premature mortality. A strong body of evidence indicates that well-designed structured exercise interventions increase older adults’ self-efficacy and satisfaction with their physical functioning, and these are important social cognitive outcomes closely linked with quality of life and health behaviour change. The main aim of this study was to investigate changes in walking self-efficacy and satisfaction after the 6-month intensive phase of the intervention. This study was a secondary analysis of the Empowered with Movement to Prevent Obesity and Weight Regain (EMPOWER) study, which was an 18-month, three-group, single-blind randomised trial. A total of 183 participants were randomly assigned to one of the three treatment arms: weight loss + structured exercise (WL+EX), WL+ sitting less and moving more across the day (SL), or WL+EX+SL. Results showed that: - participants demonstrated improvements in self-efficacy and satisfaction following the 6-month intervention weight loss and physical activity intervention. - participants who received an exercise intervention focused on sustained walking demonstrated significantly better self-efficacy for walking relative to those who did not (WL+SL). - both WL+EX and WL+EX+SL regressed to baseline levels of self-efficacy for walking by month 18, only WL+SL did not significantly decrease self-efficacy scores, sustaining a significant increase over baseline. Authors conclude that programs focused on daylong movement may contribute to improved self-efficacy and satisfaction. Thus, health promotion professionals should demonstrate flexibility in the ways in which physical activity is prescribed for older adults since not everyone resonates with traditional structured exercise.
Abstract
This report contrasts the impact of a dietary weight loss intervention (WL) paired with aerobic exercise (EX) and/or sitting less and moving throughout the day (SL) on self-efficacy for walking (hereafter walking self-efficacy) and satisfaction with physical functioning (hereafter satisfaction). Additional analyses examined dose-response associations between change in weight and changes in these key outcomes. Older adults (N = 112; age = 70.21[Formula: see text]4.43) were randomized to 6 months of WL+EX, WL+SL, or WL+EX+SL followed by a 12-month maintenance period. All groups reported increases in walking self-efficacy at month 6 with greater improvements in WL+EX and WL + EX+SL. Only WL+SL demonstrated improved walking self-efficacy at month 18. All conditions demonstrated improved satisfaction scores at both time points. Changes in walking self-efficacy and satisfaction were negatively associated with change in weight over the 6-month intervention and after the maintenance period. These results support the utility of WL + SL for improving key social cognitive outcomes in aging.
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Habitual daily intake of a sweet and fatty snack modulates reward processing in humans.
Edwin Thanarajah, S, DiFeliceantonio, AG, Albus, K, Kuzmanovic, B, Rigoux, L, Iglesias, S, Hanßen, R, Schlamann, M, Cornely, OA, Brüning, JC, et al
Cell metabolism. 2023;35(4):571-584.e6
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The prolific amount of sugar and fat in modern Western diets is regarded as a significant contributor to overeating and consequential weight gain. Dopamine, a neurotransmitter involved in learning and reward signalling, is also important in regulating food intake. Energy-dense foods, often high in both sugar and fat, stimulate pleasure-signalling dopamine to encourage eating, even if no more energy is needed. It is acknowledged that in many cases of obesity, the function of dopamine appears to be altered. Yet it is uncertain whether this was pre-existing to obesity, a result of obesity or whether it was re-shaped though exposure to high sugar and high-fat diets. To gain more insights, this study evaluated whether adding a high-fat/high-sugar (HF/HS) snack or a low-fat/low-sugar (LF/LS) snack to a regular diet could change the candidates liking for fat, their brain responses to likeable foods like fat and sugar and if it impacted on sensory associative learning. The randomised controlled study was conducted for 8-weeks and included 49 people of normal-weight. The candidates were also monitored for any changes in weight and body fat, insulin resistance, leptin levels, and blood fats, and all completed self-reported dietary intake forms. The findings demonstrated that repeated exposure to HF/HS food reduced the preference for low-fat foods and up-regulated the brain responses when anticipating and consuming such highly palatable, energy-dense foods. Beyond increased brain response to HF/HS food, HF/HS exposure also induced a general rewiring of the brain by enhancing new sensory associations and behavioural adaptations that were unrelated to food. Notably, these changes all occurred independent of weight gain or alterations in metabolic function, thus suggesting that repeated exposure to HF/HS foods can change the physiology in healthy weight individuals to reduce their liking of healthier foods whilst at the same time increasing the reward responses to more palatable HF/ HS foods. The authors highlighted this as a risk for overeating and weight gain, arguing that reducing the exposure to energy-dense HF/HS food items therefore is critical in the prevention and management of obesity.
Abstract
Western diets rich in fat and sugar promote excess calorie intake and weight gain; however, the underlying mechanisms are unclear. Despite a well-documented association between obesity and altered brain dopamine function, it remains elusive whether these alterations are (1) pre-existing, increasing the individual susceptibility to weight gain, (2) secondary to obesity, or (3) directly attributable to repeated exposure to western diet. To close this gap, we performed a randomized, controlled study (NCT05574660) with normal-weight participants exposed to a high-fat/high-sugar snack or a low-fat/low-sugar snack for 8 weeks in addition to their regular diet. The high-fat/high-sugar intervention decreased the preference for low-fat food while increasing brain response to food and associative learning independent of food cues or reward. These alterations were independent of changes in body weight and metabolic parameters, indicating a direct effect of high-fat, high-sugar foods on neurobehavioral adaptations that may increase the risk for overeating and weight gain.
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HOMEFOOD randomised trial - Six-month nutrition therapy improves quality of life, self-rated health, cognitive function, and depression in older adults after hospital discharge.
Blondal, BS, Geirsdottir, OG, Halldorsson, TI, Beck, AM, Jonsson, PV, Ramel, A
Clinical nutrition ESPEN. 2022;48:74-81
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It is well known that older people are at a higher risk for nutritional inadequacy which is accompanied by depression, impaired cognitive function, and poor overall health. In this secondary analysis of a randomised controlled assessor-blinded dietary intervention trial, the authors examined the effects of six months of nutritional therapy on quality of life, self-rated health, cognitive function, and depression in elderly patients aged 65 years and over. The participants in the intervention group received nutritional therapy (HOMEFOOD) education to overcome malnutrition, which included dietary recommendations to ensure an adequate nutritional intake of energy and protein through diet and additional supplemental protein and energy-rich foods. After six months of nutritional therapy, the intervention group showed improvement in cognitive function, self-rated health, depression score, and quality of life scores, as well as improvements in measures related to weight gain. Further studies need to be conducted in order to determine if nutritional therapy provides additional benefits to older people. However, healthcare professionals can use the results of this study to better understand how nutritional therapy can improve the quality of life and health of older people in comparison to standard care, so they can better advise their patients.
Abstract
BACKGROUND AND AIMS Malnutrition is common among older adults and is related to quality of life, cognitive function, and depression. To what extent nutrition interventions can improve these outcomes remains unclear. The aim of this study was to investigate the effect of nutrition therapy on health-related quality of life (EQ-5D), self-rated health, cognitive function, and depression in community dwelling older adults recently discharged from hospital. METHODS Participants (>65 years) were randomised into an intervention (n = 53) and a control group (n = 53). The intervention group received individualised nutrition therapy based on the nutrition care process including 5 home visits and 3 phone calls, in combination with freely delivered energy- and protein-rich foods and oral nutrition supplements for six months after hospital discharge. EQ-5D, self-rated health, Mini-Mental-State-Examination (MMSE), and the Centre for Epidemiologic Studies Depression - IOWA (CES-D) scale were measured at baseline and at endpoint. RESULTS Two subjects dropped out, one from each arm. The control group experienced an increase in depressive symptoms and a decrease in self-rated health during the study period, while the intervention group experienced increases in cognitive function, self-rated health, and EQ-5D resulting in significant endpoint differences between the groups: EQ-5D (0.102, P = 0.001); self-rated health: 15.876 (P < 0.001); MMSE 1.701 (P < 0.001); depressive symptoms: - 3.072 (P < 0.001); all in favour of the intervention group. Improvements during the intervention in MMSE, self-rated health, and CES-D were significantly related to body weight gain in a linear way. CONCLUSION Cognitive function and mental well-being worsen or stagnate in older adults who receive standard care after hospital discharge. However, a six-month nutrition therapy improves these outcomes leading to statistically and clinically significant endpoint differences between the groups. As improvements were related to body weight gain after hospital discharge, we conclude that the increase in dietary intake, with focus on energy and protein density, and changes in body weight might have contributed to better cognitive function and mental well-being in older adults after the intervention.
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Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people: the FINGER trial.
Lehtisalo, J, Rusanen, M, Solomon, A, Antikainen, R, Laatikainen, T, Peltonen, M, Strandberg, T, Tuomilehto, J, Soininen, H, Kivipelto, M, et al
European heart journal. 2022;43(21):2054-2061
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Older people are at high risk of cardiovascular disease, and 90% of the risk factors can be modified, including an unhealthy diet, poor physical activity, obesity, smoking, and obesity-related comorbidities. This randomised controlled trial examined a multifactorial approach combining several lifestyle modifications in 1259 older adults between 60 and 77 years of age to reduce the risk of cardiovascular disease. Participants were randomly assigned to intensive multi-domain lifestyle intervention or regular health advice control groups. The multifactorial lifestyle intervention incorporated dietary counselling, exercise training, cognitive training, and managing CVD and metabolic risk factors. Dietary interventions included tailored strategies that considered increased consumption of fruits, berries, vegetables, whole grains, margarine, oil, and fish. Physical exercise interventions included strength training, balance exercises, and aerobic exercises. Cognitive interventions and intensive strategies to manage metabolic factors were also implemented. In the multifactorial lifestyle intervention group, cerebrovascular events were lower after two years than in the control group. In addition, cardiovascular disease and stroke incidence were lower in the elderly with a history of cardiovascular disease. Healthcare professionals can use the results from this study to understand the benefits of multifactorial lifestyle interventions on cardiovascular disease. However, there is a need for longer-term robust studies since the evidence is sparse.
Abstract
AIMS: Joint prevention of cardiovascular disease (CVD) and dementia could reduce the burden of both conditions. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated a beneficial effect on cognition (primary outcome) and we assessed the effect of this lifestyle intervention on incident CVD (pre-specified secondary outcome). METHODS AND RESULTS FINGER enrolled 1259 individuals aged 60-77 years (ClinicalTrials.gov NCT01041989). They were randomized (1:1) to a 2-year multi-domain intervention with diet, physical and cognitive activity, and vascular monitoring (n = 631), or general health advice (n = 628). National registries provided data on CVD including stroke, transient ischaemic attack (TIA), or coronary heart event. During an average of 7.4 years, 229 participants (18%) had at least one CVD diagnosis: 107 in the intervention group and 122 in the control group. The incidence of cerebrovascular events was lower in the intervention than the control group: hazard ratio (HR) for combined stroke/TIA was 0.71 [95% confidence interval (CI): 0.51-0.99] after adjusting for background characteristics. Hazard ratio for coronary events was 0.84 (CI: 0.56-1.26) and total CVD events 0.80 (95% CI: 0.61-1.04). Among those with history of CVD (n = 145), the incidence of both total CVD events (HR: 0.50, 95% CI: 0.28-0.90) and stroke/TIA (HR: 0.40, 95% CI: 0.20-0.81) was lower in the intervention than the control group. CONCLUSION A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those who had history of CVD.
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Effects of a multicomponent resistance-based exercise program with protein, vitamin D and calcium supplementation on cognition in men with prostate cancer treated with ADT: secondary analysis of a 12-month randomised controlled trial.
Mundell, NL, Owen, PJ, Dalla Via, J, Macpherson, H, Daly, RM, Livingston, PM, Rantalainen, T, Foulkes, S, Millar, J, Murphy, DG, et al
BMJ open. 2022;12(6):e060189
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Androgen deprivation therapy (ADT) for local and advanced prostate cancer (PCa) is effective at reducing androgens, and thus inhibiting tumour progression. However, testosterone reduces the production of a highly neurotoxic protein (amyloid beta peptide 40), which is linked with the development of dementia and Alzheimer’s disease. The aim of this study was to investigate the effects of a multi-component resistance-based exercise programme with daily protein, vitamin D and calcium supplementation on cognitive function compared with usual care in PCa survivors treated with ADT. This study is a secondary analysis of a 12-month single-blinded, two-arm randomised controlled trial. Participants (n = 70) were randomised (1:1 ratio) to either: (a) multi-component exercise intervention including progressive resistance training, body-weight impact and balance exercises, as well as a daily nutritional supplement containing whey protein, calcium and vitamin D, or (b) usual care control receiving 1000 IU vitamin D only. Results show that a multicomponent exercise training and nutritional supplementation intervention did not improve cognitive function in men treated with ADT for PCa compared with usual care. Authors conclude that cognitive decline associated with ADT may mechanistically differ to that of general age-related cognitive declines, thus it is important that future studies also examine other intervention modalities.
Abstract
OBJECTIVES The aim of this preplanned secondary analysis of a 12-month randomised controlled trial was to investigate the effects of a multicomponent exercise programme combined with daily whey protein, calcium and vitamin D supplementation on cognition in men with prostate cancer treated with androgen deprivation therapy (ADT). DESIGN 12-month, two-arm, randomised controlled trial. SETTING University clinical exercise centre. PARTICIPANTS 70 ADT-treated men were randomised to exercise-training plus supplementation (Ex+ Suppl, n=34) or usual care (control, n=36). INTERVENTION Men allocated to Ex + Suppl undertook thrice weekly resistance training with weight-bearing exercise training plus daily whey protein (25 g), calcium (1200 mg) and vitamin D (2000 IU) supplementation. PRIMARY AND SECONDARY OUTCOME MEASURES Cognition was assessed at baseline, 6 and 12 months via a computerised battery (CogState), Trail-making test, Rey auditory-verbal learning test and Digit span. Data were analysed with linear mixed models and an intention-to-treat and prespecified per-protocol approach (exercise-training: ≥66%, nutritional supplement: ≥80%). RESULTS Sixty (86%) men completed the trial (Ex + Suppl, n=31; control, n=29). Five (7.1%) men were classified as having mild cognitive impairment at baseline. Median (IQR) adherence to the exercise and supplement was 56% (37%-82%) and 91% (66%-97%), respectively. Ex + Suppl had no effect on cognition at any time. CONCLUSIONS A 12-month multicomponent exercise training and supplementation intervention had no significant effect on cognition in men treated with ADT for prostate cancer compared with usual care. Exercise training adherence below recommended guidelines does not support cognitive health in men treated with ADT for prostate cancer. TRIAL REGISTRATION NUMBER Australian and New Zealand Clinical Trial Registry (ACTRN12614000317695, registered 25/03/2014) and acknowledged under the Therapeutic Goods Administration Clinical Trial Notification Scheme (CT-2015-CTN-03372-1 v1).
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Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle interventions: secondary analyses of the "MIMOSA" randomized clinical trial.
Georgoulis, M, Yiannakouris, N, Kechribari, I, Lamprou, K, Perraki, E, Vagiakis, E, Kontogianni, MD
Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2022;18(5):1251-1261
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Obstructive sleep apnoea (OSA) represents one of the most common and serious sleep-related breathing disorders. Excess body weight has emerged as the strongest modifiable predictor of the onset and severity of OSA. The aim of this study was to explore the dose-response relationship between the degree of weight loss and improvements in OSA severity. This study is a secondary analysis of the Mediterranean diet/lifestyle Intervention for the Management of Obstructive Sleep Apnea (MIMOSA) study, which was designed as a single-centre, single-blind, parallel, randomised, controlled clinical trial. Results show that respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Authors conclude that their findings indicate a dose-response relationship between the degree of weight loss and improvement in OSA severity and symptoms. However, further research is needed to gather more data on the optimal degree of weight loss and appropriate weight-loss interventions for managing the wide spectrum of OSA severity to guide clinical practice.
Expert Review
Conflicts of interest:
None
Take Home Message:
Important from a public health perspective:
- This study has confirmed that even a small degree of weight loss can have a beneficial effect on respiratory events and oxygen desaturation in moderate-to-severe OSA, but clinicians should preferably aim at a ≥ 5% weight loss, and ideally a ≥ 10% weight loss, to achieve clinically meaningful reductions in OSA severity.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
OSA represents one of the most common and serious sleep-related breathing disorders, with a high worldwide prevalence of almost 1 billion people. OSA has numerous well-established cardiometabolic consequences.
The authors highlight that weight loss is essential for obstructive sleep apnea (OSA) management. However, the optimal degree of weight loss for improving OSA severity or eliminating sleep-disordered breathing has not been extensively studied. The aim of this study was to explore the dose-response relationship between the degree of weight loss and improvements in OSA severity.
Methods
This is a secondary analysis of the Mediterranean diet/lifestyle Intervention for the Management of Obstructive Sleep Apnea (MIMOSA) study. This study was designed as a single-center, single-blind, parallel, randomised, controlled clinical trial to evaluate the effectiveness of a weight-loss Mediterranean dietary/lifestyle intervention on managing OSA.
This 6-month long clinical trial included 180 adult, overweight/obese moderate-to-severe OSA patients (45 patients per study group plus a 29% dropout rate). All patients were prescribed the standard of care continuous positive airway pressure (CPAP) therapy and were randomised to 3 arms: standard care; Mediterranean diet; Mediterranean lifestyle
Based on percent change in weight at 6 months, participants were categorised into a weight-stable/gain (WS/GG) group or one of 3 weight-loss groups (WLG): < 5%WLG; 5%–10%WLG; ≥ 10%WLG. Polysomnographic data and OSA symptoms were also evaluated preintervention and postintervention.
Results
Results confirm a dose-response relationship between the degree of weight loss achieved through a dietary/lifestyle intervention and improvements in OSA severity.
- Respiratory events and oximetry indices improved only in patients who lost weight. Improvements were proportional to the degree of weight loss.
- Median percent change in apnea-hypopnea index (AHI) was −11.7%, − 37.9%, and − 49.3% in the < 5%WLG, 5%–10%WLG, and ≥ 10%WLG, respectively (P < .001).
- Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use–adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23–0.87) in the 5%–10%WLG and 0.32 (0.17–0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22–0.82]).
- Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss.
- The dose-response relationship between weight loss and improvement in OSA severity was evident regardless of self-reported CPAP use.
Conclusions
The authors conclude that even a < 5% weight loss was sufficient for improvements in respiratory events and oximetry indices, but the prevalence of severe OSA reduced only after a ≥ 5% weight loss, and patients achieving a ≥ 10% weight loss exhibited the greatest benefits compared to weight-stable/gain patients.
Clinical practice applications:
These findings might be useful for Nutritional Therapists and Clinical Practitioners:
- Clinicians should aim for a ≥ 5% weight loss, and ideally a ≥ 10% weight loss, to achieve clinically meaningful reductions in OSA severity.
- Improvements after weight loss were significant even though a healthy body weight was not achieved.
Considerations for future research:
- The study sample consisted of predominantly male, overweight, otherwise healthy patients with moderate-to-severe OSA. Therefore, findings cannot be generalised to the whole OSA population and further research is required with broader, diverse, study samples.
- 6 months is a short duration period, therefore longer trials are required.
- Self-reported CPAP use by participants is a limitation of this study. Further robust analysis methods should be considered for future trials.
- Participants were advised to abstain from CPAP therapy for 2 days prior to the follow-up PSG but this was not evaluated or confirmed in this study and should be in future research.
Abstract
STUDY OBJECTIVES Lifestyle-induced weight loss is a complementary therapeutic approach for obstructive sleep apnea (OSA). We aimed at identifying the dose-response relationship between weight loss and OSA severity improvement. METHODS This is a secondary analysis of a 6-month clinical trial in 180 adult, overweight/obese moderate-to-severe OSA patients. Participants were randomized to a standard care, a Mediterranean diet, or a Mediterranean lifestyle arm. All patients were prescribed with continuous positive airway pressure (CPAP), while intervention arms additionally participated in a weight-loss dietary/lifestyle intervention. Based on percent change in weight at 6 months, participants were categorized into a weight-stable/gain (WS/GG) group or 3 weight-loss groups (WLG): < 5%WLG, 5%-10%WLG, and ≥ 10%WLG. Polysomnographic data and OSA symptoms were evaluated preintervention and postintervention. RESULTS Respiratory events and oximetry indices improved only in patients who lost weight and improvements were proportional to the degree of weight loss. Median percent change in apnea-hypopnea index (AHI) was -11.7%, - 37.9%, and - 49.3% in the < 5%WLG, 5%-10%WLG, and ≥ 10%WLG, respectively (P < .001). Compared to the WS/GG, the age-, sex-, baseline-, and CPAP use-adjusted relative risk (95% confidence interval) of severe OSA (AHI ≥ 30 events/h) was 0.45 (0.23-0.87) in the 5%-10%WLG and 0.32 (0.17-0.64) in the ≥ 10%WLG; the risk was also lower in the ≥ 10%WLG vs the < 5%WLG (0.42 [0.22-0.82]). Insomnia and daytime sleepiness also improved more in participants exhibiting ≥ 5% weight loss. CONCLUSIONS Even a < 5% weight loss can reduce respiratory events, but a ≥ 5% and ideally ≥ 10% weight loss is necessary for reducing the prevalence of severe OSA. CLINICAL TRIAL REGISTRATION Registry: ClinicalTrials.gov; Name: Mediterranean Diet/Lifestyle Intervention in Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT02515357; Identifier: NCT02515357. CITATION Georgoulis M, Yiannakouris N, Kechribari I, et al. Dose-response relationship between weight loss and improvements in obstructive sleep apnea severity after a diet/lifestyle intervention: secondary analyses of the "MIMOSA" randomized clinical trial. J Clin Sleep Med. 2022;18(5):1251-1261.
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10.
Celiac Disease, Beyond the Bowel: A Review of Its Neurological Manifestations.
Patel, SC, Shreya, D, Zamora, DI, Patel, GS, Grossmann, I, Rodriguez, K, Soni, M, Joshi, PK, Sange, I
Cureus. 2021;13(12):e20112
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Plain language summary
Coeliac disease (CD) is an autoimmune condition in which genetically predisposed individuals develop an immunologic reaction to ingested gluten, a protein found in barley, wheat, and rye, destroying the intestinal villi. The aims of this review are to: (i) underline the pathogenic mechanism of the involvement of CD and its neurological manifestations; (ii) establish a clinical relationship between CD and its neurological manifestations; (iii) explore the existing screening and upcoming management guidelines of CD. This review shows that: - the most common neurological manifestations of CD include gluten ataxia, gluten neuropathy, and epilepsy. These conditions are strongly associated with a lower quality of life and a higher rate of hospitalisation. - neurological features of CD should be kept in mind in order to raise an adequate amount of clinical suspicion to perform screening for gluten sensitivity with the aim of reducing the time it takes for diagnosis, and thus patient suffering is kept to a minimum. Authors conclude that further thorough studies about neurological manifestations of CD are needed so that alternative treatment modalities are offered to provide a more holistic treatment approach to a patient with CD.
Abstract
Celiac disease (CD) is a multi-systemic autoimmune condition that causes a hyperinflammatory response when gluten is ingested. There has been a shift in the clinical presentation of CD from a mere malabsorption disorder to an autoimmune condition that affects multiple organ systems, which could increase the rate of hospitalizations and a decreased quality of life. This article has compiled various studies that have explored the neurological manifestations of celiac disease, their epidemiology, possible pathogenic mechanisms, diagnosis, and treatment. The most common neurological conditions include gluten ataxia (GA), gluten neuropathy, gluten encephalopathy, and epilepsy which usually present as sporadic diseases which are difficult to diagnose in the absence of gastrointestinal (GI) symptoms. The treatment for most of these conditions is a gluten-free diet (GFD) regardless of GI involvement.