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Diet and dementia
Abstract
The ageing brain adapts to the accumulation of damage caused by oxidative stress and inflammation. Adaptive processes include neuroprotective and neurorestorative mechanisms. Individual differences in susceptibility to dementia arise when these mechanisms are impaired or are overwhelmed by the molecular pathology of Alzheimer's disease. Neuroprotection relies upon extrinsic and intrinsic defences. An adequate intake of antioxidant micronutrients (eg, vitamin C and vitamin E) and anti-inflammatory macronutrients (eg, omega-3 polyunsaturated fatty acids) forms an essential component of extrinsic defences against brain ageing. There are many epidemiological data to support an association between an inadequate intake of antioxidants and/or fish oils (an important source of omega-3 polyunsaturated fatty acids) and a greater than expected incidence of late onset dementia. These associations are confounded by established links between poverty, poor diet and failing health, especially in old age. Such links may be sufficient to explain some of the effects of an inadequate diet on the retention of cognitive function and increased risk of dementia in old age. More compelling is the association between increased plasma homocysteine concentration and later increased risk of dementia. This association is possibly caused by an inadequate intake of vitamin B(12)/folate.
... Meanwhile, Aβ induces oxidative stress and the generation of HNE, which is a neurotoxic lipid peroxidation product and associated with Aβ pathology in AD [26]. Several studies suggested that antioxidants vitamin E and vitamin C play a role in delaying the onset of AD [31] [32] [33] [34]. These studies further confirmed that oxidative stress is involved in the occurrence and progression of AD ( Figure 2). ...
... Researchers are looking for dietary patterns and specific nutrients that may enhance brain function and hence reduce the risk of developing dementia (Whalley et al. 2004). Dietary supplementation of walnut has been reported to improve learning and memory performance in transgenic animal model of Alzheimer's disease (Muthaiyah et al. 2014). ...
The brain is highly susceptible to the damaging effects of oxidative reactive species. The free radicals which are produced as a consequence of aerobic respiration can cause cumulative oxygen damage which may lead to age-related neurodegeneration. Scopolamine, the anti-muscarinic agent induces amnesia and oxidative stress similar to that observed in the older age. Studies suggest that antioxidants derived from plant products may provide protection against oxidative stress. Therefore, the present study was designed to investigate the attenuation of scopolamine-induced memory impairment and oxidative stress by walnut supplementation in rats. Rats in test group were administrated with walnut suspension (400 mg/kg/day) for four weeks. Both control and walnut-treated rats were then divided into saline and scopolamine-treated groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg dissolved in saline) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM), and novel object recognition task (NOR) followed by estimation of regional acetylcholine levels and acetylcholinesterase activity. In the next phase, brain oxidative status was determined by assaying lipid peroxidation, and measuring superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Results showed that scopolamine-treatment impaired memory function, caused cholinergic dysfunction, and induced oxidative stress in rats compared to that saline-treated controls. These impairments were significantly restored by pre-administration of walnut. This study demonstrates that antioxidant properties of walnut may provide augmented effects on cholinergic function by reducing oxidative stress and thus improving memory performance.
... It has been shown that dietary intake alters the progression of age-associated diseases such as memory loss, cardiovascular diseases and diabetes (Everitt et al., 2006). Researchers are looking for dietary patterns and specific nutrients that may enhance brain function and hence reduce the risk of developing dementia (Whalley et al., 2004;Luchsinger and Mayeux, 2004). Studies quercetin, quercitrin, kaempferol 3-O-rutinoside, isorhamnetin, and isorhamnetin 3-O-glucoside (Wijeratne et al., 2006). ...
Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond.
... Extensive reports using rodent models have identified that deficiency of DHA during growth and development causes significant learning and memory impairments [2,[9][10][11][12]. In addition to being critical for brain development [13][14][15][16][17] dietary DHA is particularly important during challenging situations such as aging [18][19][20][21], or brain injury [22,23]. Notably, low levels of DHA are associated with generalized anxiety [4] and supplementation with DHA has been shown to have anxiolytic effects [24][25][26][27]. ...
Dietary deficiency of docosahexaenoic acid (C22: 6n-3; DHA) is linked to the neuropathology of several cognitive disorders, including anxiety. DHA, which is essential for brain development and protection, is primarily obtained through the diet or synthesized from dietary precursors, however the conversion efficiency is low. Curcumin (diferuloylmethane), which is a principal component of the spice turmeric, complements the action of DHA in the brain, and this study was performed to determine molecular mechanisms involved. We report that curcumin enhances the synthesis of DHA from its precursor, α-linolenic acid (C18: 3n-3; ALA) and elevates levels of enzymes involved in the synthesis of DHA such as FADS2 and elongase 2 in both liver and brain tissue. Furthermore, in vivo treatment with curcumin and ALA reduced anxiety-like behavior in rodents. Taken together, these data suggest that curcumin enhances DHA synthesis, resulting in elevated brain DHA content. These findings have important implications for human health and the prevention of cognitive disease, particularly for populations eating a plant-based diet or who do not consume fish, a primary source of DHA, since DHA is essential for brain function and its deficiency is implicated in many types of neurological disorders.
Neurodegenerative diseases (NDDs) comprise a broad range of progressive neurological disorders with multifactorial etiology contributing to disease pathophysiology. Evidence of the microbiome involvement in the gut-brain axis urges the interest in understanding metabolic interactions between the microbiota and host physiology in NDDs. Systems Biology offers a holistic integrative approach to study the interplay between the different biologic systems as part of a whole, and may elucidate the host–microbiome interactions in NDDs. We reviewed direct and indirect pathways through which the microbiota can modulate the bidirectional communication of the gut-brain axis, and explored the evidence of microbial dysbiosis in Alzheimer’s and Parkinson’s diseases. As the gut microbiota being strongly affected by diet, the potential approaches to targeting the human microbiota through diet for the stimulation of neuroprotective microbial-metabolites secretion were described. We explored the potential of Genome-scale metabolic models (GEMs) to infer microbe-microbe and host-microbe interactions and to identify the microbiome contribution to disease development or prevention. Finally, a systemic approach based on GEMs and ‘omics integration, that would allow the design of sustainable personalized anti-inflammatory diets in NDDs prevention, through the modulation of gut microbiota was described.
There is an increasing attention toward the role played by certain nutritional components found in foods, including dietary flavonoids, in fruit, vegetables and beverages in the prevention of age-related decreases in cognitive, memory and learning tasks. Thus, aging is a major risk factor for neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). An unbalanced overproduction of reactive oxygen species (ROS) may give rise to oxidative stress, which can induce neuronal damage, ultimately leading to neuronal death by apoptosis or necrosis. A large body of evidence indicates that oxidative stress is involved in the pathogenesis of AD, PD and ALS. An increasing number of studies show that nutritional antioxidants (especially vitamin E and polyphenols) can block neuronal death in vitro, and may have therapeutic properties in animal models of neurodegenerative diseases including AD, PD and ALS. Moreover, clinical data suggest that nutritional antioxidants might exert some protective effect against AD, PD and ALS. In this chapter, the biochemical mechanisms by which nutritional antioxidants can reduce or block neuronal death occurring in neurodegenerative disorders are reviewed. Particular emphasis will be given to the role played by the nuclear transcription factor- κ B (NF κ B) in apoptosis, and in the pathogenesis of neurodegenerative disorders, such as AD, PD and ALS. The effects of ROS and antioxidants on NF κ B function and their relevance in the pathophysiology of neurodegenerative diseases will also be examined.
Oxidative stress and low-grade inflammation stimulate the ageing brain to adapt to accumulated damage. Neuroprotection relies on intrinsic/extrinsic defences to which specific nutrients may contribute. Food intakes are often reinforced with supplements containing high concentrations of nutrients, in amounts that equal or exceed recommended daily allowances. This practice is often followed by those who have least need to reinforce their diets in this way. This brief review examines some psychosocial aspects of food supplement use in old age and examines the scant evidence of its efficacy in promoting the retention of cognitive function in old age. Presently, there is insufficient evidence that the use of food supplements should be recommended to prevent cognitive decline in old age.
Hyperhomocysteinemia (HHcy), an oxidative stress inducer, has been implicated in several oxidative-related neurodegenerative diseases. The present study evaluated the neuroprotective effects of folic acid or Dioscorea alata on different regions of the brain in HHcy-induced brain oxidative stress of rats with methionine (Met) loading. Rats were divided into control, Met, Met with folic acid and Met with Dios. HHcy promoted oxidative stress in brain by providing evidences that an elevation of ROS level occurred in the striatum and cerebellum in the Met group as well as the activities of SOD in the same region. A marked depletion of GSH content in the striatum was also observed in HHcy rats. Neuroprotective effect of folic acid supplement was more efficient than D. alata at reducing HHcy-induced ROS production and SOD activities, but effect of restoring striatal GSH content was less prominent. Our results provided that folic acid or D. alata supplement exhibited differentially neuroprotective effects.
There is growing evidence that oxidative stress (OS) may play an important role in the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Cells normally have a number of mechanisms to resist against damage induced by cellular free radicals during OS. The major antioxidant defenses consist of antioxidant scavengers such as glutathione (GSH), vitamin C (ascorbic acid), vitamin E (α-tocopherol), carotenoids, polyphenols, flavonoids, and antioxidant enzymes. This chapter focuses on the actions of in vitro application of natural nutritional antioxidants in experimental models of neurodegenerative disorders. The capability of these compounds to counteract the damaging effects of reactive oxygen species (ROS) and the relevance of this biochemical effect in their putative neuroprotective action are examined in the chapter. Among the numerous biochemical effects of ROS and antioxidants, particular emphasis is given to their interference with the transcriptional factor NF-κB function, whose role in the pathophysiology of neurodegenerative disorders is gaining increasing attention. The chapter reviews the effects of the administration of pharmacological doses of nutritional antioxidants in animal models and in patients with AD, PD, and ALS. A detailed analysis of the role of dietary intake of polyphenols and other antioxidant vitamins in the prevention of AD and PD is discussed in the chapter.
Background
Previous studies have reported that elevated total homocysteine levels are associated with cognitive dysfunction. However, few studies have examined the radiological markers of associated neuropathology in Alzheimer's disease (AD). We hypothesized that elevated levels of homocysteine are associated with cerebral grey matter volume loss. We compared the grey matter in a high homocysteine group and a normal homocysteine group using an optimized voxel-based morphometry.Methods
The study included 79 patients with AD who were divided into two groups: a high homocysteine group and a normal homocysteine group. The participants underwent brain magnetic resonance imaging using a standardized protocol and neurocognitive evaluation. Homocysteine tests and other routine laboratory examinations for dementia assessment were carried out in all patients.ResultsThere was no significant difference in grey matter volume between the patients with high homocysteine levels and those with normal homocysteine levels. A multiple regression analysis also revealed that the levels of homocysteine were not associated with the grey matter volume in patients with AD. Homocysteine levels were not correlated significantly with Mini-Mental State Examination, Global Deterioration Scale, or Clinical Dementia Rating.Conclusion
Our results showed that elevated homocysteine levels are not associated with reduced cerebral grey matter volume in AD. Larger samples will be needed to assess potential correlations between homocysteine and neuroanatomical pathology in the future.
To examine prospective changes in food habits and nutrient intakes in a representative New Zealand sample of community dwelling adults aged 70 y and over.
Longitudinal study with food intake data collected in 1988/89 and again in 1995/96. In an attempt to distinguish age, time and cohort effects, data were analysed longitudinally, cross-sectionally and time-sequentially.
The sample for study consisted of all non-institutionalised people aged 70 years and over registered with the Mosgiel Health Centre in 1988. In 1988/89, 678 adults completed a dietary survey (85% of those eligible) and 248 adults participated again in 1995/96 (66% of those eligible).
Energy intakes declined longitudinally in men only; however, this decline appeared not to be an aging effect as energy intake was not found to decrease with age cross-sectionally. Percentage of energy from protein increased by 0.7% in women (95% confidence interval 0.2-1.2) in both the longitudinal and time-sequential analysis, suggesting a time effect. The percentage of energy from saturated fat decreased 0.7% (95% confidence interval -1.4 to -0.1) and percentage of energy from polyunsaturated fat increased 0.4% (95% confidence interval 0.0-0.7) in women, and appears to be a time effect. However, the increase in saturated fat and decrease in polyunsaturated fat with advancing age seen cross-sectionally suggests a cohort effect also occurring. In 1995/96, more people were using margarine as a spread and vegetable oils to cook meat. Milk and milk product consumption increased (not significantly), and meat intake decreased significantly by 5 and 4 servings per month in men and women, respectively. There was an increase in the proportion of people who ate breakfast cereal at least once a week, and more women ate brown or wholemeal bread in 1995/96.
Over the 6 y follow-up period studied, there was no indication of an age effect on nutrient intakes in adults aged 70 y and older; however, the changes occurring over time demonstrate that older adults, particularly women, are making changes towards healthier food choices.
Vitamin B-12 deficiency is usually accompanied by elevated concentrations of serum total homocysteine (tHcy) and methylmalonic acid (MMA). Folate deficiency also results in elevated tHcy. Measurement of these metabolites can be used to screen for functional vitamin B-12 or folate deficiency.
We assessed the prevalence of vitamin B-12 and folate deficiency in a population-based study (n = 1562) of older persons living in Oxford City, United Kingdom.
We postulated that, as vitamin B-12 or folate concentrations declined from adequate to impaired levels, tHcy (or MMA) concentrations would increase. Individuals were classified as being at high risk of vitamin B-12 deficiency if they had low vitamin B-12 (< 150 pmol/L) or borderline vitamin B-12 (150-200 pmol/L) accompanied by elevated MMA (> 0.35 micromol/L) or tHcy (> 15.0 micromol/L). Individuals were classified as being at high risk of folate deficiency if they had low folate (< 5 nmol/L) or borderline folate (5-7 nmol/L) accompanied by elevated tHcy (> 15 micromol/L).
Cutoffs of 15.0 micro mol/L for tHcy and 0.35 micro mol/L for MMA identified persons with normal or elevated concentrations. Among persons aged 65-74 and >or= 75 y, respectively, approximately 10% and 20% were at high risk of vitamin B-12 deficiency. About 10% and 20%, respectively, were also at high risk of folate deficiency. About 10% of persons with vitamin B-12 deficiency also had folate deficiency.
Use of tHcy or MMA among older persons with borderline vitamin concentrations may identify those at high risk of vitamin B-12 deficiency who should be considered for treatment.
to examine the prevalence of vitamin B12 deficiency and folate deficiency in later life in representative samples of the elderly population in the United Kingdom.
a population-based cross-sectional analysis of 3,511 people aged 65 years or older from three studies was used to estimate the age-specific prevalence of vitamin B12 deficiency and of folate deficiency. Vitamin B12 deficiency is conventionally diagnosed if serum vitamin B12 < 150 pmol/l ('low vitamin B12'). We defined 'metabolically significant vitamin B12 deficiency' as vitamin B12 < 200 pmol/l and blood total homocysteine >20 micro mol/l. Folate deficiency, which usually refers to serum folate <5 nmol/l, was defined as 'metabolically significant' if serum folate was <7 nmol/l and homocysteine >20 micro mol/l.
the prevalence of vitamin B12 deficiency, whether defined as low vitamin B12 or metabolically significant vitamin B12 deficiency increased with age in all three studies, from about 1 in 20 among people aged 65-74 years to 1 in 10 or even greater among people aged 75 years or greater. The prevalence of folate deficiency also increased with age, and was similar to that for vitamin B12 deficiencies, but only about 10% of people with low vitamin B12 levels also had low folate levels.
the high prevalence of vitamin B12 and folate deficiency observed in older people indicates a particular need for vigilance for deficiency of these vitamins. Reliable detection and treatment of vitamin deficiency could reduce the risk of deficiency-related disability in old age.
To determine whether supplementation with vitamins and trace elements in modest amounts influences cognitive function in apparently healthy, elderly subjects.
The study was designed as a randomized, double-blind, placebo-controlled trial. Ninety-six, apparently healthy, independent men and women older than 65 y of age were recruited and randomized to receive a supplement of trace elements and vitamins or a placebo daily for 12 mo. Blood-nutrient levels were estimated at baseline and at the end of the study. The major outcome measure assessed was cognitive function consisting of immediate and long-term memory, abstract thinking, problem-solving ability, and attention.
Eighty-six subjects completed the 1-y trial. The supplemented group showed a significant improvement in all cognitive tests (P < 0.001 to 0.05) except long-term memory recall (P > 0.1). Those whose blood-nutrient levels were below the reference standard showed lower responses on cognitive tests. There was no significant correlation between individual nutrient levels and performance on various cognitive function tests.
Cognitive functions improved after oral supplementation with modest amounts of vitamins and trace elements. This has considerable clinical and public health significance. We recommend that such a supplement be provided to all elderly subjects because it should significantly improve cognition and thus quality of life and the ability to perform activities of daily living. Such a nutritional approach may delay the onset of Alzheimer's disease.
Demographic changes, together with improvements in nutrition, general health, and life expectancy, will greatly change the social and economic structures of most industrialized and developing countries in the next 50 years. Extended life expectancy has increased the number of chronic illnesses and disabilities, including cognitive impairments. Inflammatory processes and vascular dysfunctions appear to play important roles in the pathogenesis of age-associated pathologies including Alzheimer's and Parkinson's disease. A large body of evidence shows that both vitamins E and C are important for the central nervous system and that a decrease in their concentrations causes structural and functional damage to the cells. Several studies reveal a link between diets rich in fruits and vegetables containing generous amounts of vitamins E and C and lower incidence of certain chronic diseases.
We studied 82 non-demented old people and, using MRI, derived measures of grey and white matter and intracranial volumes. Controlling for sex and intracranial volume, we related grey and white matter volumes to plasma concentrations of vitamins C, B(12), folate, homocysteine, cholesterol, triglycerides, high density and low density (LDL) lipoproteins, and to red blood cell folate and glycated haemoglobin concentrations (HbA1(c)). We found that lower grey matter volume was associated with lower plasma vitamin C and higher homocysteine, cholesterol and LDL. Lower blood cell folate was also associated with lower grey matter volume but HbA1(c) was not. These data are consistent with the putative benefits of dietary vitamin C and folate intake and the role of cholesterol in age related neurodegeneration.
This analysis considers factors that underlie the leading causes of death and disability for adult women in the United States and changes in those factors over the previous decade.
1991-2001 Behavioral Risk Factor Surveillance System (BRFSS) data are used to review changes over the decade in the most important indicators of women's health. Estimates are weighted by demographic characteristics and selection probabilities. Sample sizes ranged from 50,875 women in 1991 to 121,456 in 2001.
State-level maps show dramatic changes in obesity prevalence over the previous decade. Obesity prevalence increased to 21.5% in 2001 from 12.4% in 1991. Reports of exercise, never smoking, and binge drinking remained essentially level. The percentage of women who currently smoke cigarettes declined slightly but significantly. Reports of ever being told they had high blood pressure increased significantly for women aged > or =65 years. There was a significant and substantial change in the percentage of women aged > or =40 who reported having a mammogram in the past 2 years (62.7% in 1991, 76.2% in 2001).
Findings show that we are at a critical juncture in public health. Some changes are stunning (e.g., rising obesity), others remain stubbornly static (e.g., smoking), and still others demonstrate positive trends (e.g., mammogram screening). The increase in obesity foretells similar future increases in obesity-related chronic conditions unless public health efforts can stem the tide. It is imperative that effective strategies to change behavior are developed, especially those that are women focused, to improve quality and length of life.
