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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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A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study.
Vauzour, D, Scholey, A, White, DJ, Cohen, NJ, Cassidy, A, Gillings, R, Irvine, MA, Kay, CD, Kim, M, King, R, et al
The American journal of clinical nutrition. 2023;118(2):369-381
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At a population level, interventions that delay the onset of dementia by 2 years are predicted to reduce the number of dementia patients by 20%. Prospective cohort studies have consistently reported cognitive and neurophysiological benefits of the fish-derived omega-3 long-chain polyunsaturated fatty acids (PUFAs), EPA, and DHA and plant-derived flavanols (FLAVs). This study hypothesised that 12-month administration of a combination of 500 mg cocoa FLAVs with 1.5g omega-3 long-chain PUFAs would improve cognitive function in a mixed subjective cognitive impairment and mild cognitive impairment cohort. This study is based on the results of the CANN randomised controlled trial. A total of 258 participants were recruited and randomised to control or test intervention. Following baseline measurements, 125 participants were randomised into the active OM3FLAV intervention group and 121 into the control group. Results showed that the 1-year intervention with EPA and DHA and cocoa FLAVs did not improve cognition or protect the brain against atrophy in older adults with evidence of memory deficits. Authors concluded that given the complexity of neuropathological processes underpinning cognitive decline and dementia risk, multidomain, multinutrient, or whole diet approaches may be needed to positively impact the cognitive trajectory in the medium term (months to 3 years).
Abstract
BACKGROUND There is evidence that both omega-3 long-chain polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and cocoa flavanols can improve cognitive performance in both healthy individuals and in those with memory complaints. However, their combined effect is unknown. OBJECTIVES To investigate the combined effect of EPA/DHA and cocoa flavanols (OM3FLAV) on cognitive performance and brain structures in older adults with memory complaints. METHODS A randomized placebo-controlled trial of DHA-rich fish oil (providing 1.1 g/d DHA and 0.4 g/d EPA) and a flavanol-rich dark chocolate (providing 500 mg/d flavan-3-ols) was conducted in 259 older adults with either subjective cognitive impairment or mild cognitive impairment. Participants underwent assessment at baseline, 3 mo, and 12 mo. The primary outcome was the number of false-positives on a picture recognition task from the Cognitive Drug Research computerized assessment battery. Secondary outcomes included other cognition and mood outcomes, plasma lipids, brain-derived neurotrophic factor (BDNF), and glucose levels. A subset of 110 participants underwent structural neuroimaging at baseline and at 12 mo. RESULTS 197 participants completed the study. The combined intervention had no significant effect on any cognitive outcomes, with the exception of reaction time variability (P = 0.007), alertness (P < 0.001), and executive function (P < 0.001), with a decline in function observed in the OM3FLAV group (118.6 [SD 25.3] at baseline versus 113.3 [SD 25.4] at 12 mo for executive function) relative to the control, and an associated decrease in cortical volume (P = 0.039). Compared with the control group, OM3FLAV increased plasma HDL, total cholesterol ratio (P < 0.001), and glucose (P = 0.008) and reduced TG concentrations (P < 0.001) by 3 mo, which were sustained to 12 mo, with no effect on BDNF. Changes in plasma EPA and DHA and urinary flavonoid metabolite concentrations confirmed compliance to the intervention. CONCLUSIONS These results suggest that cosupplementation with ω-3 PUFAs and cocoa flavanols for 12 mo does not improve cognitive outcomes in those with cognitive impairment. This trial was registered at clinicaltrials.gov as NCT02525198.
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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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Mediterranean diet and structural neuroimaging biomarkers of Alzheimer's and cerebrovascular disease: A systematic review.
Gregory, S, Pullen, H, Ritchie, CW, Shannon, OM, Stevenson, EJ, Muniz-Terrera, G
Experimental gerontology. 2023;172:112065
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Nearly a million people in the UK have Alzheimer's disease, the most common type of dementia. Mediterranean diet (MedDiet) adherence is associated with healthy brain ageing, a reduced stroke risk, and a lower incidence of dementia. Seven studies were included in this review to evaluate the effects of MedDiet on hippocampal volume and white matter hyperintensity volume, predictors of stroke and dementia. This systematic review did not reveal any associations between MedDiet adherence and hippocampal volume. However, there was a significant negative relationship between MedDiet adherence and white matter hyperintensity volume in two of the studies included. It is necessary to conduct more robust studies to investigate the associations between MedDiet adherence and structural brain imaging findings and understand the mechanisms behind dementia and other cerebrovascular diseases. This study could provide healthcare professionals with valuable information about the effects of increased MedDiet adherence on brain health, including its potential to delay neurodegenerative disease progression.
Expert Review
Conflicts of interest:
None
Take Home Message:
Due to inconclusive results on the associations between MedDiet adherence and AD and cerebrovascular related structural neuroimaging findings, specific recommendations for the MedDiet cannot be made on the basis of this study until further research has been completed.
Evidence Category:
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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:
Background:
Changes in hippocampal volume (HV) and white matter intensity volume (WMIV) have been identified as structural neuroimaging biomarkers of neurodegenerative disease such as Alzheimer’s Disease (AD) and Cerebrovascular disease (CVD) respectively. Evidence has shown adherence to the Mediterranean Diet (MedDiet) has been associated with reduced risk for strokes. This review evaluated the MedDiet in relation to HV and WMIV.
Methods:
The review followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in seven studies published between 2012 and 2022, which met the inclusion criteria. Six studies analysed cross-sectional data and one analysed longitudinal data. The NIH Quality Assessment Tool for Observational and Cross-Sectional Studies was used to assess risk of bias.
Overall, the studies were rated as low-risk of bias with details of the research question, participant group exposure and outcome variables included. Due to moderate to high heterogeneity in some studies, a meta-analysis was deemed unsuitable and narrative synthesis was conducted to present the results.
Results:
Mean participant age ranged from 53.19 to 80.3 years and volunteers were healthy or had subjective cognitive decline and a few participants had dementia (n=46).
Hippocampal Volume:
Four studies included 20,077 participants and found no significant associations between MedDiet adherence and hippocampal volume. All four studies were cross-sectional from larger cohort studies. To establish causative relationships longitudinal and RCT trials are required.
White Matter Hyperintensity Volumes:
Four studies included 1938 participants. Two studies found a significant negative association between MedDiet and WMHV, demonstrating higher Mediterranean Scores were associated with lower level of WHMV. The other two studies found no significant associations.
Although the review methodology with a piloted search strategy was considered a key strength, the lack of meta-analysis as planned in the a priori protocol, due to minimal eligible studies and high heterogeneity was a limitation as well as the restriction of brain imaging outcomes.
Conclusion:
Overall, these results are inconclusive on the associations between the MedDiet and HV and WMHV, and identify a gap in the knowledge, therefore further research such as RCT’s remains a priority to further understand the impact diet may have on neuroimaging markers of AD and CVD.
Clinical practice applications:
There were no significant associations between MedDiet adherence and HV, which was surprising given the evidence stating adherence to the MedDiet is associated with a lower incidence of dementia and stroke. However all four studies were cross-sectional studies and in order to detect causal associations, longitudinal and RCT’s are needed. Two studies did show a significant association between higher MedDiet adherence and lower WMHV, whereas two studies reported no significant associations.
Caution needs to be taken when recommending the MedDiet specifically for a reduction in HV and WMHV until further research has been undertaken.
Considerations for future research:
Future research should consider:
- larger cohorts and participants from the Mediterranean region where lifelong adherence to the MedDiet is more likely.
- looking at other risk factors to include obesity, lack of activity, poor sleep quality and stress.
- evaluating different socio-economic status, which has been shown to impact dietary behaviour.
- alternative imaging outcomes such as cortical thinning, PET amyloid and tau.
- . gold standard for methodology in particular dietary analysis and scanning and outcome derivation.
Abstract
Previous studies have demonstrated an association between adherence to the Mediterranean diet (MedDiet) and better cognitive performance, lower incidence of dementia and lower Alzheimer's disease biomarker burden. The aim of this systematic review was to evaluate the evidence base for MedDiet associations with hippocampal volume and white matter hyperintensity volume (WMHV). We searched systematically for studies reporting on MedDiet and hippocampal volume or WMHV in MedLine, EMBASE, CINAHL and PsycInfo. Searches were initially carried out on 21st July 2021 with final searches run on 23rd November 2022. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Of an initial 112 papers identified, seven papers were eligible for inclusion in the review reporting on 21,933 participants. Four studies reported on hippocampal volume, with inconclusive or no associations seen with MedDiet adherence. Two studies found a significant association between higher MedDiet adherence and lower WMHV, while two other studies found no significant associations. Overall these results highlight a gap in our knowledge about the associations between the MedDiet and AD and cerebrovascular related structural neuroimaging findings.
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A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia.
Aarsland, D, Khalifa, K, Bergland, AK, Soennesyn, H, Oppedal, K, Holteng, LBA, Oesterhus, R, Nakling, A, Jarholm, JA, de Lucia, C, et al
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2023;31(2):141-151
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A growing body of evidence suggests that some modifiable factors, including cardiometabolic disorders such as hypertension, diabetes and hypercholesterolemia, as well as lifestyle factors such as physical exercise and diet, are associated with an increased risk of developing dementia. Anthocyanins, a flavonoid subclass found in dark berries and fruits, are among the dietary factors that may have positive effects on the pathogenesis of Alzheimer’s disease. The aim of this study was to assess whether anthocyanins can improve cognition and reduce the risk of dementia. This study is a 24-week randomised, double-blind, placebo-controlled Phase II study. Two-hundred and six participants were randomly assigned to one of the two groups: anthocyanins (n=106) or placebo (n=100). Results show that there wasn’t any significant group difference at the end of the study (24 weeks) in episodic memory (primary analysis) or for the secondary cognitive outcomes. However, there was a significant difference in slopes during weeks 8−24 where the anthocyanin group improved while the placebo group worsened. Furthermore, anthocyanin capsules were well-tolerated and safe to use. Authors conclude that future studies need to explore the potential mechanisms leading to cognitive improvement, how they relate to bioavailability of anthocyanins and metabolites, the optimal dosage, and the duration of treatment.
Abstract
IMPORTANCE Identifying nutritional compounds which can reduce cognitive decline in older people is a hugely important topic. OBJECTIVE To study the safety and effect of anthocyanins in maintaining cognitive functioning in people at increased risk for dementia. DESIGN, SETTING, AND PARTICIPANTS Participants (206 individuals, aged 60-80 years) diagnosed with either mild cognitive impairment (MCI) or two or more cardiometabolic disorders (i.e., diabetes, hypertension, obesity) were enrolled at three different centres in Norway. INTERVENTION Participants were randomly assigned to four capsules with a total of 320 mg/d of naturally purified anthocyanins or placebo 1:1 for 24 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was the Quality of Episodic Memory composite measure (0-100) from an online cognitive test battery CogTrack, which was administered at baseline and monthly for the next 24 weeks. Secondary outcomes included other cognitive scores from the CogTrack battery. We applied mixed effects models with a baseline test score, group, time and their interaction as fixed effects, as well as other predefined baseline covariates. The primary comparison was the group difference at week 24 based on a modified intention-to-treat principle. RESULTS The primary analysis did not show a significant group difference at 24 weeks (78.2 versus 76.8; adjusted mean difference 1.4 (95% confidence interval -0.9-3.7); effect size 0.15; p = 0.23). However, there was a significant difference in slopes during weeks 8-24 (p = 0.007); the anthocyanin group improved while the placebo group worsened. No differences were found for the secondary cognitive outcomes. Anthocyanin capsules were well-tolerated and safe to use. CONCLUSION Anthocyanin supplementation for 24 weeks was safe and well tolerated in people with MCI or cardiometabolic disorders. We found no significant group difference in episodic memory at the end of the study but statistically significant differences in slopes. Further studies are warranted to explore whether anthocyanins supplementation can reduce cognitive decline in people at increased risk of dementia. TRIAL REGISTRATION ClinicalTrials.gov, (Identifier NCT03419039). http://www. CLINICALTRIALS gov/, NCT03419039.
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Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial.
Wood, E, Hein, S, Mesnage, R, Fernandes, F, Abhayaratne, N, Xu, Y, Zhang, Z, Bell, L, Williams, C, Rodriguez-Mateos, A
The American journal of clinical nutrition. 2023;117(6):1306-1319
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The risk of developing both cardiovascular and neurodegenerative diseases increases with aging. Growing evidence from epidemiological and human intervention trials indicates that (poly)phenols may have cardioprotective properties as well as the ability to improve cognitive function. The aim of this study was to investigate the effects of daily wild blueberry (WBB) (poly)phenol consumption on vascular function and cognitive performance in healthy older individuals. This study was a randomised, double-blinded, placebo-controlled parallel design study. A total of 61 healthy older individuals were recruited and randomly assigned to one of the two arms; placebo intervention or blueberry intervention group. Results showed that long-term consumption of a dietary achievable amount of WBB enhanced vascular and cognitive function in older adults. Authors conclude that gut microbiota and vascular blood flow may play important roles in mediating the cognitive benefits shown by the consumption of (poly)phenol-rich foods.
Abstract
BACKGROUND Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. METHODS A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry. RESULTS A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found. CONCLUSIONS Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.
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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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Effects of iron supplementation on neural indices of habituation in Bangladeshi children.
Larson, LM, Feuerriegel, D, Hasan, MI, Braat, S, Jin, J, Tipu, SMU, Shiraji, S, Tofail, F, Biggs, BA, Hamadani, JD, et al
The American journal of clinical nutrition. 2023;117(1):73-82
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Adversity during early life, including malnutrition, may influence the long-term cognitive development of children. Micronutrients, especially iron, may play a critical role in the developing infant brain The aim of this study was to determine the effects of supplementation with iron syrup and iron containing multiple micronutrient powders (MNPs) on neural indices of habituation in Bangladeshi children. This neurocognitive substudy was nested within the Benefits and Risks of Iron Supplementation in Children (BRISC) trial. BRISC was a 3-arm, double-blind, double-dummy, individual randomised, superiority trial. Children were randomly assigned to 1 of the 3 arms using a 1:1:1 allocation. Results showed that iron supplementation (provided through 2 different modes) did not affect neural indices of habituation. There wasn’t any identification of treatment effects for any of the outcomes measured, despite finding improvements in haemoglobin and ferritin concentrations for children given iron syrup or MNPs. Authors conclude that despite established links between iron availability and neurophysiological development, increased iron availability in children under one year of age does not lead to measurable changes in neural indices of habituation.
Abstract
BACKGROUND Iron deficiency and anemia have been associated with poor cognition in children, yet the effects of iron supplementation on neurocognition remain unclear. OBJECTIVE We aimed to examine the effects of supplementation with iron on neural indices of habituation using auditory event-related brain potentials (ERPs). METHODS This substudy was nested within a 3-arm, double-blind, double-dummy, individual randomized trial in Bangladesh, in which 3300 8-mo-old children were randomly selected to receive 3 mo of daily iron syrup (12.5 mg iron), multiple micronutrient powders (MNPs) (including 12.5 mg iron), or placebo. Children were assessed after 3 mo of intervention (mo 3) and 9 mo thereafter (mo 12). The neurocognitive substudy comprised a randomly selected subset of children from the main trial. Brain activity elicited during an auditory roving oddball task was recorded using electroencephalography to provide an index of habituation. The differential response to a novel (deviant) compared with a repeated (standard) sound was examined. The primary outcome was the amplitude of the mismatch response (deviant minusstandard tone waveforms) at mo 3. Secondary outcomes included the deviant and standard tone-evoked amplitudes, N2 amplitude differences, and differences in mean amplitudes evoked by deviant tones presented in the second compared with first half of the oddball sequence at mo 3 and 12. RESULTS Data were analyzed from 329 children at month 3 and 363 at mo 12. Analyses indicated no treatment effects of iron interventions compared with placebo on the amplitude of the mismatch response (iron syrup compared with placebo: mean difference (MD) = 0.07μV [95% CI: -1.22, 1.37]; MNPs compared with placebo: MD = 0.58μV [95% CI: -0.74, 1.90]) nor any secondary ERP outcomes at mo 3 or 12, despite improvements in hemoglobin and ferritin concentrations from iron syrup and MNPs in this nested substudy. CONCLUSION In Bangladeshi children with >40% anemia prevalence, iron or MNP interventions alone are insufficient to improve neural indices of habituation. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.
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Mediterranean and Western diet effects on Alzheimer's disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial.
Hoscheidt, S, Sanderlin, AH, Baker, LD, Jung, Y, Lockhart, S, Kellar, D, Whitlow, CT, Hanson, AJ, Friedman, S, Register, T, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022;18(3):457-468
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There is a current understanding that Alzheimer’s disease (AD) development is related to a high intake of saturated fat and simple carbohydrates, which are found in abundance in the so-called Western Diet (WD). In contrast the consumption of low saturated fat and simple carbohydrates characteristic of the Mediterranean Diet (MD), has been associated with a reduced risk for the development of AD. This study aimed to look at the association of the MD and WD with AD in a more robust way using the randomised control method in 84 individuals both with and without mild memory impairment. The results showed that depending on whether an individual has mild brain impairment determines their response to the MD or WD after 4 weeks. In those without brain impairment the adoption of the WD resulted in a shift towards increasing the risk for AD development and the reverse following the MD. Whereas in those with brain impairment, the adoption of the WD was protective against the development of AD and the MD moved individuals towards worse disease outcomes. It was concluded that diet can be of importance in the prevention or progression of AD and that further studies are required to determine the possible mechanisms through which these two diets can act differentially. This study could be used by health care professionals to understand that diet can have a large impact on AD.
Expert Review
Conflicts of interest:
None
Take Home Message:
- A Med-diet may be beneficial for supporting brain health, cognitive function. metabolic health and reduce the risk of an AD pathology in middle-aged adults with normal cognitive function
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
Epidemiological studies have associated a Western diet (West-diet) with an increased risk of Alzheimer’s disease (AD) and other dementias. This study aimed to examine the impact of a Mediterranean-diet (Med-diet) versus a West-diet on AD pathology, cognition, vascular function and metabolic markers in middle aged adults with normal cognitive (NC) function compared to adults with mild cognitive impairment (MCI).
Methods
N=41 NC adult females completed the Med-diet and N=43 adult females with MCI completed the West-diet arm of this study. The average age of the participants was 56y. All participants received isocaloric diets which were either high or low in saturated fat, sodium and glycaemic index (GI) for 4 weeks. Statistical analyses were conducted per dietary arm as well as per cognitive function (NC vs MCI).
Results
- NC Participants were found to have decreased cerebro-spinal fluid (CSF) biomarkers (p=.026) following the Med-diet and increased levels following the West-diet. Whereas, cerebral perfusion increased following the med-diet and decreased after the West-diet (p=.003). These results indicate a reduced AD risk. The MCI group showed no changes to CSF or cerebral perfusion for either dietary group.
- Cognition tended to improve for the NC Med-diet and remain the same for the NC West-diet group. No changes were found for the MCI groups.
- Total cholesterol levels were increased following the West-diet and decreased following the Med-diet for both groups (p=0.0001).
- Glucose and HbA1C were unchanged in the NC group following the Med-diet, increased for the West-diet (p=.049) and decreased for the MCI group (p=<.001). whereas fasting insulin was increased in the NC Med-diet group and decreased in the MCI Med-diet (p=.0.12) and West diet groups.
Conclusion
The results of this study found that diet may modulate AD pathology, cognitive and metabolic function in middle-aged adults. A West-like diet may increase risk of AD through its effects on impairing cognitive function, reducing cerebral infusion and negatively influencing metabolic health in NC adults. Conversely, A Med-diet may promote brain function and metabolic health. However, surprisingly, in this study the results were reversed for MCI middle aged adults, the results showed improvement in metabolic and cerebrospinal fluid biomarkers for the West-diet. These results require further confirmation.
No conflicts of interest were declared.
Clinical practice applications:
- A Med-diet may be beneficial for supporting brain health, cognitive function, metabolic health and reducing the risk of an AD pathology in middle-aged adults with normal cognitive function but not for those with MCI.
Considerations for future research:
The authors acknowledged several limitations to this study.
- These results require further confirmation through longer and larger studies, particularly the surprising finding that a West-diet may confer beneficial effects on metabolic and brain health for middle-aged adults with MCI.
Abstract
INTRODUCTION Mid-life dietary patterns are associated with Alzheimer's disease (AD) risk, although few controlled trials have been conducted. METHODS Eighty-seven participants (age range: 45 to 65) with normal cognition (NC, n = 56) or mild cognitive impairment (MCI, n = 31) received isocaloric diets high or low in saturated fat, glycemic index, and sodium (Western-like/West-diet vs. Mediterranean-like/Med-diet) for 4 weeks. Diet effects on cerebrospinal fluid (CSF) biomarkers, cognition, and cerebral perfusion were assessed to determine whether responses differed by cognitive status. RESULTS CSF amyloid beta (Aβ)42/40 ratios increased following the Med-diet, and decreased after West-diet for NC adults, whereas the MCI group showed the reverse pattern. For the MCI group, the West-diet reduced and the Med-diet increased total tau (t-tau), whereas CSF Aβ42 /t-tau ratios increased following the West-diet and decreased following the Med-diet. For NC participants, the Med-diet increased and the West-diet decreased cerebral perfusion. DISCUSSION Diet response during middle age may highlight early pathophysiological processes that increase AD risk.
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Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project.
Toups, K, Hathaway, A, Gordon, D, Chung, H, Raji, C, Boyd, A, Hill, BD, Hausman-Cohen, S, Attarha, M, Chwa, WJ, et al
Journal of Alzheimer's disease : JAD. 2022;88(4):1411-1421
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Plain language summary
Neurodegenerative diseases such as Alzheimer’s disease are without effective therapeutics. The aim of this study was to compare the effects of a precision medicine approach to historical controls in patients with mild cognitive impairment or early dementia. This study is a proof-of-concept study which recruited twenty-five patients with Alzheimer’s disease or mild cognitive impairment, aged between 50–76 years. Patients were treated for nine months with a personalised, precision medicine protocol that addressed each patient’s identified potentially contributory factors. Results show that a precision medicine approach to the cognitive decline of Alzheimer’s disease and mild cognitive impairment may be an effective strategy, especially with continued optimization over time. Authors conclude that their findings indicate that it is possible to reverse cognitive decline in mild cognitive impairment and early dementia with a personalised, precision medicine (/systems medicine) protocol. This is a small study that requires larger scale initiatives, including examining the practicalities of integrating this approach into healthcare systems.
Abstract
BACKGROUND Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy. OBJECTIVE To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. METHODS Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months. RESULTS All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. CONCLUSION Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.