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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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Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing: A Randomized Crossover Trial.
Yunker, AG, Alves, JM, Luo, S, Angelo, B, DeFendis, A, Pickering, TA, Monterosso, JR, Page, KA
JAMA network open. 2021;4(9):e2126313
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Added sweeteners are increasingly being used in foods to maintain the sweet taste without the added calories, however the health consequences of this are still unclear. Most of the research that exists is in men of normal weight, however women and individuals with obesity have shown to have differing appetite responses. This randomised crossover trial of 74 adults aimed to determine the effect of consuming sweetener compared to sugar on brain, hormone, and appetite responses and whether these differed by sex and obesity status. The results showed that women had increased food related brain responses and consumed greater calories following ingestion of an artificially sweetened drink. In those with obesity food related brain response was also increased following sweetener consumption. Blood glucose hormone response was decreased following sweetener consumption compared to sugar consumption. It was concluded that females and individuals with obesity have differing brain activity following consumption of sweetener. This study could be used by healthcare professionals to understand that the recommendation of artificial sweeteners for weight loss in women and those who are already suffering from obesity may lead to greater calorie consumption. However further research is needed to confirm this.
Abstract
Importance: Nonnutritive sweeteners (NNSs) are used as an alternative to nutritive sweeteners to quench desire for sweets while reducing caloric intake. However, studies have shown mixed results concerning the effects of NNSs on appetite, and the associations between sex and obesity with reward and appetitive responses to NNS compared with nutritive sugar are unknown. Objective: To examine neural reactivity to different types of high-calorie food cues (ie, sweet and savory), metabolic responses, and eating behavior following consumption of sucralose (NNS) vs sucrose (nutritive sugar) among healthy young adults. Design, Setting, and Participants: In a randomized, within-participant, crossover trial including 3 separate visits, participants underwent a functional magnetic resonance imaging task measuring blood oxygen level-dependent signal in response to visual cues. For each study visit, participants arrived at the Dornsife Cognitive Neuroimaging Center of University of Southern California at approximately 8:00 am after a 12-hour overnight fast. Blood was sampled at baseline and 10, 35, and 120 minutes after participants received a drink containing sucrose, sucralose, or water to measure plasma glucose, insulin, glucagon-like peptide(7-36), acyl-ghrelin, total peptide YY, and leptin. Participants were then presented with an ad libitum meal. Participants were right-handed, nonsmokers, weight-stable for at least 3 months before the study visits, nondieters, not taking medication, and with no history of eating disorders, illicit drug use, or medical diagnoses. Data analysis was performed from March 2020 to March 2021. Interventions: Participants ingested 300-mL drinks containing either sucrose (75 g), sucralose (individually sweetness matched), or water (as a control). Main Outcomes and Measures: Primary outcomes of interest were the effects of body mass index (BMI) status and sex on blood oxygen level-dependent signal to high-calorie food cues, endocrine, and feeding responses following sucralose vs sucrose consumption. Secondary outcomes included neural, endocrine, and feeding responses following sucrose vs water and sucralose vs water (control) consumption, and cue-induced appetite ratings following sucralose vs sucrose (and vs water). Results: A total of 76 participants were randomized, but 2 dropped out, leaving 74 adults (43 women [58%]; mean [SD] age, 23.40 [3.96] years; BMI range, 19.18-40.27) who completed the study. In this crossover design, 73 participants each received water (drink 1) and sucrose (drink 2), and 72 participants received water (drink 1), sucrose (drink 2), and sucralose (drink 3). Sucrose vs sucralose was associated with greater production of circulating glucose, insulin, and glucagon-like peptide-1 and suppression of acyl-ghrelin, but no differences were found for peptide YY or leptin. BMI status by drink interactions were observed in the medial frontal cortex (MFC; P for interaction < .001) and orbitofrontal cortex (OFC; P for interaction = .002). Individuals with obesity (MFC, β, 0.60; 95% CI, 0.38 to 0.83; P < .001; OFC, β, 0.27; 95% CI, 0.11 to 0.43; P = .002), but not those with overweight (MFC, β, 0.02; 95% CI, -0.19 to 0.23; P = .87; OFC, β, -0.06; 95% CI, -0.21 to 0.09; P = .41) or healthy weight (MFC, β, -0.13; 95% CI, -0.34 to 0.07; P = .21; OFC, β, -0.08; 95% CI, -0.23 to 0.06; P = .16), exhibited greater responsivity in the MFC and OFC to savory food cues after sucralose vs sucrose. Sex by drink interactions were observed in the MFC (P for interaction = .03) and OFC (P for interaction = .03) after consumption of sucralose vs sucrose. Female participants had greater MFC and OFC responses to food cues (MFC high-calorie vs low-calorie cues, β, 0.21; 95% CI, 0.05 to 0.37; P = .01; MFC sweet vs nonfood cues, β, 0.22; 95% CI, 0.02 to 0.42; P = .03; OFC food vs nonfood cues, β, 0.12; 95% CI, 0.02 to 0.22; P = .03; and OFC sweet vs nonfood cues, β, 0.15; 95% CI, 0.03 to 0.27; P = .01), but male participants' responses did not differ (MFC high-calorie vs low-calorie cues, β, 0.01; 95% CI, -0.19 to 0.21; P = .90; MFC sweet vs nonfood cues, β, -0.04; 95% CI, -0.26 to 0.18; P = .69; OFC food vs nonfood cues, β, -0.08; 95% CI, -0.24 to 0.08; P = .32; OFC sweet vs nonfood cues, β, -0.11; 95% CI, -0.31 to 0.09; P = .31). A sex by drink interaction on total calories consumed during the buffet meal was observed (P for interaction = .03). Female participants consumed greater total calories (β, 1.73; 95% CI, 0.38 to 3.08; P = .01), whereas caloric intake did not differ in male participants (β, 0.68; 95% CI, -0.99 to 2.35; P = .42) after sucralose vs sucrose ingestion. Conclusions and Relevance: These findings suggest that female individuals and those with obesity may be particularly sensitive to disparate neural responsivity elicited by sucralose compared with sucrose consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT02945475.
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The consequences of exercise-induced weight loss on food reinforcement. A randomized controlled trial.
Flack, KD, Hays, HM, Moreland, J
PloS one. 2020;15(6):e0234692
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Exercise is a long-standing remedy for nearly all of obesity’s comorbidities and often recommended as an economical and health-promoting option for weight loss and weight loss maintenance. The aim of this study was to investigate the effect of exercise on food reinforcement (reward-driven feeding), and to examine whether changes in body composition would be correlated with changes in food reinforcement. This study is randomized controlled trial with a total of 52 participants aged 18 to 40 years. Participants were randomly assigned to one of the three groups (six exercise sessions per week, two sessions per week, and sedentary control). Results indicate that there is great variability in individuals’ change in food reinforcement after a 12-week aerobic exercise intervention. Furthermore, those who did increase their food reinforcement were also those who lost the greatest amount of fat-free mass post-intervention. Authors conclude that preventing the loss of fat-free mass may be a valuable piece to a weight loss programme (with resistance training or dietary protein intake as adjunct therapy).
Abstract
BACKGROUND Obesity remains a primary threat to the health of most Americans, with over 66% considered overweight or obese with a body mass index (BMI) of 25 kg/m2 or greater. A common treatment option many believe to be effective, and therefore turn to, is exercise. However, the amount of weight loss from exercise training is often disappointingly less than expected with greater amounts of exercise not always promoting greater weight loss. Increases in energy intake have been prescribed as the primary reason for this lack of weight loss success with exercise. Research has mostly focused on alterations in hormonal mediators of appetite (e.g.: ghrelin, peptide YY, GLP-1, pancreatic polypeptide, and leptin) that may increase hunger and/or reduce satiety to promote greater energy intake with exercise training. A less understood mechanism that may be working to increase energy intake with exercise is reward-driven feeding, a strong predictor of energy intake and weight status but rarely analyzed in the context of exercise. DESIGN Sedentary men and women (BMI: 25-35 kg/m2, N = 52) were randomized into parallel aerobic exercise training groups partaking in either two or six exercise sessions/week, or sedentary control for 12 weeks. METHODS The reinforcing value of food was measured by an operant responding progressive ratio schedule task (the behavioral choice task) to determine how much work participants were willing to perform for access to a healthy food option relative to a less healthy food option before and after the exercise intervention. Body composition and resting energy expenditure were assessed via DXA and indirect calorimetry, respectively, at baseline and post testing. RESULTS Changes in fat-free mass predicted the change in total amount of operant responding for food (healthy and unhealthy). There were no correlations between changes in the reinforcing value of one type of food (healthy vs unhealthy) to changes in body composition. CONCLUSION In support of previous work, reductions in fat-free mass resulting from an aerobic exercise intervention aimed at weight loss plays an important role in energy balance regulation by increasing operant responding for food.
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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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Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.
Cooke, GE, Wetter, NC, Banducci, SE, Mackenzie, MJ, Zuniga, KE, Awick, EA, Roberts, SA, Sutton, BP, McAuley, E, Kramer, AF
PloS one. 2016;11(2):e0149552
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As survival rates of breast cancer increase, the long-term cognitive effects of disease and required treatment are emerging. The underlying pathways of cancer-related cognitive impairment involve accelerated aging of the brain, low levels of physical activity and decreased cognitive function, however these links have not been adequately explored. The aim of this study was to investigate the link between physical activity, white matter lesion volume and cognition in 30 breast cancer survivors and 28 age-matched controls. The results of this study showed that brain structure significantly predicted cognitive function. This study provided evidence suggesting that moderate physical activity may help reduce the treatment related risks associated with breast cancer.
Abstract
Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.
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Inhalational Alzheimer's disease: an unrecognized - and treatable - epidemic.
Bredesen, DE
Aging. 2016;8(2):304-13
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Alzheimer’s disease (AD) is the third leading cause of death in the USA, with around 5.2 million Americans diagnosed with AD. Effective treatment with medications has yet to be found. A recent multiple therapy programme (originally known as MEND, now called ReCODE) proposed by Professor Bredesen and team, has shown some promising anecdotal results. Identifying sub-types of AD has been proposed as a means to develop targeted protocols for treatment. Recently, 3 sub-types of AD have been described: Type 1 (inflammatory), Type 2 (non-inflammatory or decreasing brain size) and Type 3 (damage to the outer layer of the cerebrum). This report describes 7 patients with Type 3 AD. Type 3 AD is characterised by exposure to specific toxins (usually inhaled) and is often associated with Chronic Inflammatory Response Syndrome (CIRS). The report provides the symptoms, signs and laboratory values representative of Type 3 AD and could be used by Nutrition Practitioners to help with implementation of appropriate nutrition protocols when working with clients with AD.
Abstract
Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave.
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Reversal of cognitive decline in Alzheimer's disease.
Bredesen, DE, Amos, EC, Canick, J, Ackerley, M, Raji, C, Fiala, M, Ahdidan, J
Aging. 2016;8(6):1250-8
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Alzheimer’s disease is the third leading cause of death and is one of the most significant global healthcare problems of modern times. It leads initially to cognitive decline – inability to recall words and faces, do mental calculations, navigate on familiar routes – and eventually to complete loss of memory and ability to perform routine daily tasks. Conventional therapy focuses on single drug therapies and success with these has been limited. This case study report details the results of 10 patients experiencing differing degrees of cognitive decline and early Alzheimer’s disease. Each patient followed a personalised, multiple therapy programme for 5 months to 2 years, based on their genetics, markers for blood glucose management, lipid profile, homocysteine, Vitamin D and inflammation, amongst others. Each case reports a quantified improvement in brain function, as well as subjective improvements reported by the carers and patients. The authors call for funding for a randomised controlled trial and for early detection and treatment using a multi-faceted protocol. Nutrition Practitioners working with cognitive decline can use the case study reports to inform their testing choices and personalised nutrition and lifestyle protocols.
Abstract
Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4-, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype.
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Metabolic profiling distinguishes three subtypes of Alzheimer's disease.
Bredesen, DE
Aging. 2015;7(8):595-600
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The causes of Alzheimer’s Disease (AD) remain incompletely defined and there are currently no truly effective drug therapies available. However, there is growing evidence that disordered blood glucose management and hormonal changes and deficiencies, amongst other things, are implicated in symptom onset. Optimising these various metabolic processes, therefore, may be used as a comprehensive way to avoid cognitive decline or achieve cognitive improvements in symptomatic individuals. This report provides the metabolic results of 3 case studies and suggests 3 different types of AD classification, depending on the individual metabolic profile. Further studies are required to elaborate on the metabolic profiles suggested in this report, however Nutrition Practitioners working with cognitive decline, can use this report as a basis for individualised nutrition protocols to optimise metabolic processes in clients with cognitive decline.
Abstract
The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization.
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Sleep restriction increases the neuronal response to unhealthy food in normal-weight individuals.
St-Onge, MP, Wolfe, S, Sy, M, Shechter, A, Hirsch, J
International journal of obesity (2005). 2014;38(3):411-6
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Sleep patterns influence eating behaviour and the body’s response to food. Previous studies suggest that short sleep duration leads to increased caloric intake and a desire for high-fat foods, however the specific neural mechanisms explaining how sleep restriction modulates this response is unknown. The aim of this study was to determine whether a specific area of the brain is activated in response to unhealthy compared with healthy foods. 25 participants were included, all of which were normal weight and had normal sleeping patterns. Each participant was tested after five nights of either 4 or 9 hours in bed by functional magnetic resonance imaging (fMRI). The test was performed while the participant was shown healthy and unhealthy food photos in the fasted state. This study found that after a period of restricted sleep compared with habitual sleep, unhealthy foods led to greater activation in brain regions associated with reward compared with healthy foods. This finding provides a model of neuronal mechanisms relating short sleep duration to obesity and cardio-metabolic risk factors and warrants further investigation.
Abstract
CONTEXT Sleep restriction alters responses to food. However, the underlying neural mechanisms for this effect are not well understood. OBJECTIVE The purpose of this study was to determine whether there is a neural system that is preferentially activated in response to unhealthy compared with healthy foods. PARTICIPANTS Twenty-five normal-weight individuals, who normally slept 7-9 h per night, completed both phases of this randomized controlled study. INTERVENTION Each participant was tested after a period of five nights of either 4 or 9 h in bed. Functional magnetic resonance imaging (fMRI) was performed in the fasted state, presenting healthy and unhealthy food stimuli and objects in a block design. Neuronal responses to unhealthy, relative to healthy food stimuli after each sleep period were assessed and compared. RESULTS After a period of restricted sleep, viewing unhealthy foods led to greater activation in the superior and middle temporal gyri, middle and superior frontal gyri, left inferior parietal lobule, orbitofrontal cortex, and right insula compared with healthy foods. These same stimuli presented after a period of habitual sleep did not produce marked activity patterns specific to unhealthy foods. Further, food intake during restricted sleep increased in association with a relative decrease in brain oxygenation level-dependent (BOLD) activity observed in the right insula. CONCLUSION This inverse relationship between insula activity and food intake and enhanced activation in brain reward and food-sensitive centers in response to unhealthy foods provides a model of neuronal mechanisms relating short sleep duration to obesity.
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Reversal of cognitive decline: a novel therapeutic program.
Bredesen, DE
Aging. 2014;6(9):707-17
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Alzheimer’s Disease (AD) is estimated to affect 30 million individuals globally, with projections as high as 150 million by 2050 if no effective treatment is found. This report describes a personalised, multi-modal, therapeutic programme used with 10 individuals with various degrees of cognitive decline. The goal was to optimise metabolic parameters and lifestyle factors and was personalised based on laboratory test results. 9 out of 10 of the case study patients experienced improvement in cognitive abilities, beginning within 3-6 months of starting the programme. These effects were sustained at 2.5 year follow up. The 1 patient who did not benefit had advanced AD, in comparison to the other patients with subjective or mild cognitive decline. The authors call for a more extensive trial of the therapeutic programme.
Abstract
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.