A pinboard by
Edward Hill

PhD Student, Institute for Health & Ageing


To summarize the evidence relating diet and nutrition to the two hallmark biomarkers of AD

Approximately 44 million people worldwide have Alzheimer’s disease. Alzheimer’s disease (AD) is the leading cause of dementia, reporting an annual global cost of $605b USD and is therefore a global health priority. Currently, pharmaceuticals lack efficacy in the Alzheimer’s disease pathology and research is growing regarding the influence of diet on Alzheimer’s disease development. Diet and nutrition may play a crucial role in the Alzheimer’s disease symptomatology and offer great potential for non-pharmacological prevention. Summaries of the existing evidence reveal an association between diet and the incidence and prevalence of Alzheimer’s disease, yet few studies have investigated this relationship with respect to physical biomarkers. The aim of the current systematic review is to summarize the evidence relating diet and nutrition to the two hallmark biomarkers of Alzheimer’s disease; tau and beta-amyloid, to identify methodological constraints in these studies and provide to provide directions for future research.


High-intensity physical activity modulates diet effects on cerebrospinal amyloid-β levels in normal aging and mild cognitive impairment.

Abstract: We previously showed that amyloid-β 1-42 (Aβ(42)) levels in cerebrospinal fluid (CSF) were markedly altered in response to a 4-week dietary intervention in normal aging and mild cognitive impairment (MCI). Here, we re-examined the data to assess whether diet-induced effects on CSF Aβ(42) were modulated by high intensity physical activity (hi-PA). Normal older adults (n = 18, mean age = 68.6 ± 7.4 y) and adults with amnestic MCI (n = 23, mean age = 68.0 ± 6.5 y) received a low saturated fat/low glycemic index (LOW) diet or a high saturated fat/high glycemic index (HIGH) diet, and CSF levels of Aβ(42), tau, and IL-8 were measured at baseline and week 4. Pre-study activity levels were assessed using a 7-d questionnaire, and weekly duration of hi-PA was quantified. At baseline, increased hi-PA in normals predicted lower CSF levels of tau (r = -0.54, p = 0.020) and IL-8 (r = -0.70, p = 0.025). Diet-induced effects on CSF Aβ(42) during the intervention study were modulated by hi-PA, and the nature of this effect differed for normals and MCI (ANOVA, p = 0.039). That is, for normal adults, increased hi-PA attenuated the effects of the HIGH diet on CSF Aβ(42) whereas in MCI, increased hi-PA potentiated the effects of the LOW diet. Our results suggest that normal adults who engage in hi-PA are less vulnerable to the pathological effects of an unhealthy diet, while in MCI, the benefit of a healthy diet on Aβ modulation is greatest when paired with hi-PA. Exercise may thus interact with diet to alter pathological processes that ultimately modify risk of Alzheimer's disease.

Pub.: 06 Oct '11, Pinned: 19 Jan '18

Diet intervention and cerebrospinal fluid biomarkers in amnestic mild cognitive impairment.

Abstract: To compare the effects of a 4-week high-saturated fat/high-glycemic index (HIGH) diet with a low-saturated fat/low-glycemic index (LOW) diet on insulin and lipid metabolism, cerebrospinal fluid (CSF) markers of Alzheimer disease, and cognition for healthy adults and adults with amnestic mild cognitive impairment (aMCI).Randomized controlled trial.Veterans Affairs Medical Center clinical research unit.Forty-nine older adults (20 healthy adults with a mean [SD] age of 69.3 [7.4] years and 29 adults with aMCI with a mean [SD] age of 67.6 [6.8] years).Participants received the HIGH diet (fat, 45% [saturated fat, > 25%]; carbohydrates, 35%-40% [glycemic index, > 70]; and protein, 15%-20%) or the LOW diet (fat, 25%; [saturated fat, < 7%]; carbohydrates, 55%-60% [glycemic index, < 55]; and protein, 15%-20%) for 4 weeks. Cognitive tests, an oral glucose tolerance test, and lumbar puncture were conducted at baseline and during the fourth week of the diet.The CSF concentrations of β-amyloid (Aβ42 and Aβ40), tau protein, insulin, F2-isoprostanes, and apolipoprotein E, plasma lipids and insulin, and measures of cognition.For the aMCI group, the LOW diet increased CSF Aβ42 concentrations, contrary to the pathologic pattern of lowered CSF Aβ42 typically observed in Alzheimer disease. The LOW diet had the opposite effect for healthy adults, ie, decreasing CSF Aβ42, whereas the HIGH diet increased CSF Aβ42. The CSF apolipoprotein E concentration was increased by the LOW diet and decreased by the HIGH diet for both groups. For the aMCI group, the CSF insulin concentration increased with the LOW diet, but the HIGH diet lowered the CSF insulin concentration for healthy adults. The HIGH diet increased and the LOW diet decreased plasma lipids, insulin, and CSF F2-isoprostane concentrations. Delayed visual memory improved for both groups after completion of 4 weeks of the LOW diet.Our results suggest that diet may be a powerful environmental factor that modulates Alzheimer disease risk through its effects on central nervous system concentrations of Aβ42, lipoproteins, oxidative stress, and insulin.

Pub.: 15 Jun '11, Pinned: 19 Jan '18

Effect of apolipoprotein E genotype and diet on apolipoprotein E lipidation and amyloid peptides: randomized clinical trial.

Abstract: Sporadic Alzheimer disease (AD) is caused in part by decreased clearance of the β-amyloid (Aβ) peptide breakdown products. Lipid-depleted (LD) apolipoproteins are less effective at binding and clearing Aβ, and LD Aβ peptides are more toxic to neurons. However, not much is known about the lipid states of these proteins in human cerebrospinal fluid.To characterize the lipidation states of Aβ peptides and apolipoprotein E in the cerebrospinal fluid in adults with respect to cognitive diagnosis and APOE ε4 allele carrier status and after a dietary intervention.Randomized clinical trial.Veterans Affairs Medical Center clinical research unit.Twenty older adults with normal cognition (mean [SD] age, 69 [7] years) and 27 with amnestic mild cognitive impairment (67 [6] years).Randomization to a diet high in saturated fat content and with a high glycemic index (High diet; 45% of energy from fat [>25% saturated fat], 35%-40% from carbohydrates with a mean glycemic index >70, and 15%-20% from protein) or a diet low in saturated fat content and with a low glycemic index (Low diet; 25% of energy from fat [<7% saturated fat], 55%-60% from carbohydrates with a mean glycemic index <55, and 15%-20% from protein).Lipid-depleted Aβ42 and Aβ40 and apolipoprotein E in cerebrospinal fluid.Baseline levels of LD Aβ were greater for adults with mild cognitive impairment compared with adults with normal cognition (LD Aβ42, P = .05; LD Aβ40, P = .01). These findings were magnified in adults with mild cognitive impairment and the ε4 allele, who had higher LD apolipoprotein E levels irrespective of cognitive diagnosis (P < .001). The Low diet tended to decrease LD Aβ levels, whereas the High diet increased these fractions (LD Aβ42, P = .01; LD Aβ40, P = .15). Changes in LD Aβ levels with the Low diet negatively correlated with changes in cerebrospinal fluid levels of insulin (LD Aβ42 and insulin, r = -0.68 [P = .01]; LD Aβ40 and insulin, r = -0.78 [P = .002]).The lipidation states of apolipoproteins and Aβ peptides in the brain differ depending on APOE genotype and cognitive diagnosis. Concentrations can be modulated by diet. These findings may provide insight into the mechanisms through which apolipoprotein E4 and unhealthy diets impart risk for developing AD.

Pub.: 20 Jun '13, Pinned: 19 Jan '18

A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults.

Abstract: Background: Little is known about the relation between dietary intake and cerebral amyloid accumulation in aging.Objective: We assessed the association of dietary glycemic measures with cerebral amyloid burden and cognitive performance in cognitively normal older adults.Design: We performed cross-sectional analyses relating dietary glycemic measures [adherence to a high-glycemic-load diet (HGLDiet) pattern, intakes of sugar and carbohydrates, and glycemic load] with cerebral amyloid burden (measured by florbetapir F-18 positron emission tomography) and cognitive performance in 128 cognitively normal older adults who provided eligibility screening data for the University of Kansas's Alzheimer's Prevention through Exercise (APEX) Study. The study began in November 2013 and is currently ongoing.Results: Amyloid was elevated in 26% (n = 33) of participants. HGLDiet pattern adherence (P = 0.01), sugar intake (P = 0.03), and carbohydrate intake (P = 0.05) were significantly higher in participants with elevated amyloid burden. The HGLDiet pattern was positively associated with amyloid burden both globally and in all regions of interest independently of age, sex, and education (all P ≤ 0.001). Individual dietary glycemic measures (sugar intake, carbohydrate intake, and glycemic load) were also positively associated with global amyloid load and nearly all regions of interest independently of age, sex, and educational level (P ≤ 0.05). Cognitive performance was associated only with daily sugar intake, with higher sugar consumption associated with poorer global cognitive performance (global composite measure and Mini-Mental State Examination) and performance on subtests of Digit Symbol, Trail Making Test B, and Block Design, controlling for age, sex, and education.Conclusion: A high-glycemic diet was associated with greater cerebral amyloid burden, which suggests diet as a potential modifiable behavior for cerebral amyloid accumulation and subsequent Alzheimer disease risk. This trial was registered at clinicaltrials.gov as NCT02000583.

Pub.: 27 Oct '17, Pinned: 19 Jan '18

Modulation Of Inflammation As A Way Of Delaying Alzheimer's Disease Progression: The Diet's Role.

Abstract: Most of the recent reports suggest that inflammatory mediators play a central role in the etiopathogenesis of Alzheimer's disease (AD) and that the conditions leading to a chronic low-grade inflammation, such as stress, depression, obesity and metabolic syndrome, increase the odds of developing Mild Cognitive Impairment (MCI) and AD. Microglia cells are the main actors in the AD process: stimuli from the microenvironment may induce microglia cells to switch to a classically activated inflammatory phenotype M1, or, on the contrary to an alternatively activated M2 phenotype characterized by the secretion of different types of cytokines. Many attempts are currently being made in order to delay the progression of AD by reducing inflammatory mechanisms underlying the disease. Several studies support a relationship among neuroinflammation and nutrients, foods or dietary patterns, taking into account the synergistic or antagonistic biochemical interactions among nutrients as well as the different food sources of the same nutrient. Natural antioxidant and anti-inflammatory compounds found in plant food matrices, like fruits, especially berries (such as strawberry, bilberry, blackcurrant, blackberry, blueberry and mulberry) offer a possible neuroprotective effects. It is still unclear whether the dietary bioactive compounds enter the Blood Brain Barrier (BBB) playing a direct anti-inflammatory or pro-inflammatory effect on microglia and/or other Central Nervous System (CNS) cells. Another hypothesis is that they may trigger a peripheral reaction that induce indirectly a CNS' response. The subsequent synthesis of cytokines may drive microglia polarization by different ways. So, via an indirect route microglia detects and responds to signals emerging from immune-to-brain signaling pathways. This review summarizes current evidence about the potential mechanisms of the interaction among diet, neuroinflammation and AD.

Pub.: 30 Aug '17, Pinned: 19 Jan '18

Alzheimer's disease and diet: a systematic review.

Abstract: Purpose/Aim: Approximately 44 million people worldwide have Alzheimer's disease (AD). Numerous claims have been made regarding the influence of diet on AD development. The aims of this systematic review were to summarize the evidence considering diet as a protective or risk factor for AD, identify methodological challenges and limitations, and provide future research directions.Medline, PsycINFO and PsycARTICLES were searched for articles that examined the relationship between diet and AD.On the basis of the inclusion and exclusion criteria, 64 studies were included, generating a total of 141 dietary patterns or "models". All studies were published between 1997 and 2015, with a total of 132 491 participants. Twelve studies examined the relationship between a Mediterranean (MeDi) diet and AD development, 10 of which revealed a significant association. Findings were inconsistent with respect to sample size, AD diagnosis and food measures. Further, the majority of studies (81.3%) included samples with mean baseline ages that were at risk for AD based on age (>65 years), ranging from 52.0 to 85.4 years. The range of follow-up periods was 1.5-32.0 years.The mean age of the samples poses a limitation in determining the influence of diet on AD; given that AD has a long prodromal phase prior to the manifestation of symptoms and decline. Further studies are necessary to determine whether diet is a risk or protective factor for AD, foster translation of research into clinical practice and elucidate dietary recommendations. Despite the methodological limitations, the finding that 50 of the 64 reviewed studies revealed an association between diet and AD incidence offers promising implications for diet as a modifiable risk factor for AD.

Pub.: 19 Feb '16, Pinned: 19 Jan '18