Kyle J. Norton (Scholar)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
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Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
Abstract
Dementia is defined as neuro degeneration syndrome among elder, affecting memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement over 47 millions
of worldwide population, mostly in the West. The evaluation of the syndrome by holistic medicine has been lacking, especially through conventional medicine research and studies. The aim of this essay is to provide accurate information of how effective of holistic medicine in prevention, management and treatment of dementia through searching data base of PubMed.
This is the third time, a research paper has been written this way to general public that you will not find any where in the net. We would like to provide more of this kind of research, but unfortunately, it is time consuming and burdened financially, we have run out of time and the site will be shut down Monday(July 6, 2015). If you like what you read, please donate generously to our site.
at http://kylejnorton.blogspot.ca/
Kyle J. Norton
Contents
Most common diseases of elders - Nutrients Requirements for elder
I. The Types
II. Causes
1. The Deficient Causes of Dementia
2. Free radical causes of dementia (Alzheimer’s disease)
3. Free radical causes of Parkinson's disease
4. Free radical causes of dementia (Parkinson's disease, PD)
5. Free radical causes of dementia (Multiple Sclerosis, MS)
6. Free radical causes of dementia (Lou Gehrig's disease(Amyotrophic lateral sclerosis))
7. Diseases causes of dementia
8. Hormonal Causes of Dementia
9. Substance Abused Causes of Dementia
10. Diet Causes of Dementia
11. Medication Causes of Dementia
12. Life Style Causes of Dementia
13. Genetic mutation Causes of Dementia
III. The Diseases's symptoms and Complications
14. Symptoms of Dementia
15. Complications of Dementia
III. The preventions and managements
16. The Preventive Do's and Do Not's list
17. The Preventive Antioxidant enzymes
18. The Preventive Metals Binding Proteins
19. The Preventive Common Free Radical Scavengers
20. The Preventive Phytochemical Rosemarinol
21. The Preventive Phytochemicals Gingerole and Naringenin
22. The Preventive Phytochemicals Tangeritin and Curcumin
23. The Preventive Phytochemicals Gallic acid and Cinnamic acid
24. The Preventive Phytochemicals Tyrosol and Silymarin
IV. Treatments
A. In conventional Medicine
25. Treatments of Alzheimer's disease and Diminished quality of acetylcholine
26. Treatments of Wernicke-Korsakoff Syndrome due to long-term alcohol abuse
27. Treatments of Dementia associated with Parkinson's disease
28. Treatments of Dementia associated with Creutzfeldt-Jakob disease (CJD)
29. Treatments of Dementia associated with Multi-infarct dementia
30. Treatments of Dementia associated with Subdural hematoma
B. In Herbal Medicine
31. Herbal Treatments: Ginkgo Biloba(bai Guo)
32. Herbal Treatments: Lemon Balm
33. Herbal Treatments: Lavender
34. Herbal Treatments: Huperzine A.
35. Herbal Treatments: Bacopa
36. Herbal Treatments: Other Potential Herbs
C. In Traditional Chinese Medicine
The herbs
38. Treatments in Traditional Chinese Herbal Medicine Poria cocos(Fu Ling)
39. Treatments in Traditional Chinese Herbal Medicine Radix polygalae(Yuan Zhi)
40. Treatments in Traditional Chinese Herbal Medicine: Radix glycyrrhizae(Gan Cao)
41.Treatments in Traditional Chinese Herbal Medicine: Radix Angelica Sinensis(Dang Qui)
42. Treatments in Traditional Chinese Herbal Medicine: Radix rehmanniae(Di Huang)
Dementia caused by Kidney Qi deficiency
43. TCM Herbal treatments of Dementia Caused by Kidney Qi Deficiency
Dementia caused by Heart Qi deficiency
44. TCM Dan shen treatments of Dementia Caused by Heart Qi Deficiency
45. TCM Ren shen (Ginseng) treatments of Dementia Caused by Heart Qi Deficiency
46. TCM XI Yang Shen (American Ginseng) treatments of Dementia Caused by Heart Qi Deficiency
47. TCM Sang Shen (Mulberry Fruit) treatments of Dementia Caused by Heart Qi Deficiency
Dementia Caused by Spleen Qi Deficiency
48. TCM Herbal Peony (Chi Shao) treatments of Dementia Caused by Spleen Qi Deficienc
49. TCM Herbal Chai Hu (Bupleurum) in treatments of Dementia Caused by Spleen Qi Deficiency
50. TCM Herbal Safflower (Hong Hua) treatments of Dementia Caused by Spleen Qi Deficiency
51. TCM Herbal Cinnamonin treatments of Dementia Caused by Spleen Qi Deficiency
Dementia caused by Blood Stasis
52. TCM Herbal Gou Qi treatments of Dementia Caused by Blood Stasis
53. TCM Herbal Polygonum multiflorum (He shou wu) treatments of Dementia Caused by Blood Stasis
Dementia Caused by Toxins accumulation
54. TCM herbal Shui Fei Zi (Milk thistle) treatments of Dementia Caused by Toxin Accumulation
55. TCM herbal Xiu Hui Xiang (Fennel) treatments of Dementia Caused by Toxin Accumulation
56. TCM herbal Da Suan (Garlic) treatments of Dementia Caused by Toxin Accumulation
Dementia due to aging Kidney essence gradual depletion
57. TCM herbal Dong Chong Cao(Cordyceps) treatments of Dementia Caused by Kidney Jing Depletion
58. TCM herbal Shi Hu(Dendrobium) treatments of Dementia Caused by Kidney Jing Depletion
59. TCM herbal Du Zhong(Eucommia bark) treatments of Dementia Caused by Kidney Jing Depletion
60. TCM herbal Huang Qi(Astragalus) treatments of Dementia Caused by Kidney Jing Depletion
Nutrients Requirements for elder
Consuming foods and drinks, containing protein and a specific range of vitamins, minerals and trace elements are necessary to provide sources of energy (calories). Especially plant food phytochemicals with various groups of structure include 3000-4000 individual compounds with possession of a number of different properties(175)
Daily intakes for micro nutrients recommended by the Department of Health DRVs (Dietary Reference Values)(176)
A. Nutrient and Recommended daily intake
1. Calcium (mg) 700
2. Phosphorus (mg) 550
3. Magnesium (mg) 270
4. Sodium (mg) 1600
5. Potassium (mg) 3500
6. Chloride (mg) 2500
7. Iron (mg) 14.8
8. Zinc (mg) 9
9. Copper (mg) 1.2
10. Selenium (μg) 60
11. Iodine (μg) 140
12. Vitamin A (μg) 600
13. Thiamin (mg) 0.8
14. Riboflavin (mg) 1.1
15. Niacin (mg) 12
16. Vitamin B6 (mg) 1.2
17. Vitamin B12 (μg) 1.5
18. Folate (μg) 200
19. Vitamin C (mg) 40
20. Vitamin D* (μg) 10
B. Estimated Average Requirements (EARs) for energy
Age (years), Estimated energy requirement for males (kcals per day), Estimated energy requirement for females (kcals per day)
51-59 2550 1900
60-64 2380 1900
65-74 2330 1900
75+ 2100 1810
C. Proteins
Age (years) Estimated protein requirement for males (kcals per day) For females
51+ 53.3 46.5
Types of dementia
1. Alzheimer's disease
Alzheimer's disease is a brain disorder named for German physician Alois Alzheimer(1). Alzheimer's destroys brain cells, causing problems with memory, thinking and behavior severe enough to affect language communication, memory, lifelong hobbies or social life. Alzheimer's gets worse over time, and it is fatal(2). Over 1 million people in US alone are currently afflicted by Alzheimer's disease because of degeneration of hippocampus and cerebral cortex(3) of the brain where memory, language and cognition(4) are located. With this mental disorder, brain cells gradually die and generate fewer and fewer chemical signals day by day resulting in diminished of functions. Overtime memory thinking as well as behavior deteriorates. Today, there is no known cure.
2. Absence of acetylcholine
If the nerves located in front of the brain perish(5), caused by diminished quality of acetylcholine due long term alcohol abused may result of cognitive dysfunction(6) causes of language difficulty, memory loss, concentration problem, and anxiety- and depression-like behaviors(8),reduced moblile skills because of lacking reaction in muscular activity and refection(7).
3. Dementia due to long-term alcohol abuse
Dementia is common in patients with alcoholism(9). Most classic is the Korsakoff's dementia resulted in extremely poor short term memory(10) and often associated with the memory losses of confabulations due to diminished processing resources and/or an encoding or retrieval deficit(11).
4. Multi-infarct dementia
Also known as vascular dementia, is the second most common form of dementia after Alzheimer's disease in older adults caused by different mechanisms all results in vascular lesions(12) of the brain(13).
5. Dementia associated with Parkinson's disease
Parkinson disease (PD) is a disabling, progressive condition, causes of cognitive deficits due to the interruption of frontal-subcortical loops that facilitate cognition and parallel the motor loop(15)(16) due to loss of substantia nigra pars compacta (SNc) dopamine (DA) neurons(14).
6. Creutzfeldt-Jakob disease (CJD)
People who have eaten contaminated beef(18) for many years may be infected without even knowing it. Creutzfeldt-Jakob disease is a quickly progressing and fatal disease consisted of dementia(19), muscle abnormal functions(17).
7. Subdural hematoma
It is the accumulation of blood beneath the outer cover of the brain resulted from the rupture of blood vessel(20)(21). Subdural hemorrhages may increase intracranial pressure(22), causing compression and damage to delicate brain tissue. Acute subdural hematoma has a high mortality rate(23).
Other types of dementia include metabolic disorders, dementia due to long-term substance abuse, hypothyroidism, and hyperethyroidism.
Causes of dementia
A. Deficient cause of dementia due to aging
1. Vitamin D and 1,25-dihydroxyvitamin D(3) deficiency
Vitamin D levels not only plays an important role in the pathogenesis of many age-associated diseases including cancer, heart disease, type 2 diabetes
mellitus and stroke, but also associate with increased risk of prevalent cognitive dysfunction. According to number of studies, raising vitamin D plays a role in decreased cognitive dysfunction and dementia(24). Evidence from epidemiological also insisted the association between 25(OH)D concentrations and systolic blood pressure, risk for CV disease-related deaths, symptoms of depression, cognitive deficits, and mortality(25).
2. Folic acid with vitamin B12 deficiency
Folates are vitamins essential to the development of the central nervous system. Deficiency of folate can increase the risk of dementia. According to Cochrane Dementia and Cognitive Improvement Group, folic acid plus vitamin B12 were effctive in reducing the serum homocysteine concentrations, with no adverse effects(26).
3. Vitamin B12 deficiency
An association between neuropsychiatric disorders and vitamin B12deficiency has been recognized since 1849. Deficiency of Vitamin B12 are found in many elders and might contribute to age-associated cognitive impairment, according to the Scientist at Cochrane Dementia and Cognitive Improvement Group(27).
4. Vitamin B6 deficiency
Vitamin B6 supplementation showed to reduce the risk of developing cognitive impairment in older healthy people, and improve cognitive functioning of people with cognitive decline and dementia, according the study conducted by Cochrane Dementia and Cognitive Improvement Group(28).
5. Deficiency of Insulin-like growth factor (IGF)-1and growth hormones
Deficiency of Insulin-like growth factor (IGF)--1 hormone may contribute to the genesis of cognitive impairment and dementia in the elderly patients. Old age, in the absence of circulating IGF-1, a hormone with a complex role in brain function has seen to link to an acceleration of neurological diseases(29) Growth hormone and IGF-1 replacement showed to increase neurogenesis, vascular density, and glucose utilization, and alter NMDA receptor subunit composition in brain areas implicated learning and memory, in animal (30)and children(31) studies.
8. Deficiency of cerebrospinal fluid melatonin
Melatonin plays an essential role in ventricular system via choroid plexus portals. In Alzheimer's disease, inadequate melatonin increases risk of the neuropathological changes due to hydroxyl radicals cause of damage mitochondria and initiated cascade of oxygen radicals(32).
9. Decreased dehydroepiandrosterone (DHEA)
Dehydroepiandrosterone sulfate (DHEAS) concentrations
DHEA, a neurosteroid secreted by the adrenal cortex. is also a neurosteroid. The levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrationsare decline in concentration with age(33).
10. Etc.
B. Free radical causes of dementia
B.1. Alzheimer’s disease
1. Free radical and Alzheimer’s disease
Free radicals causes of Alzheimer’s disease is well defined in many researches(25)(26). Oxidative stress-induced injury involved the selective modification of different intracellular proteins may lead to the neurofibrillary degeneration of neurons in the brain(27)(28).
2. Antioxidants and Alzheimer’s disease
a. Docosahexaenoic acid (DHA)
Change of brain aging in DHA metabolism, was found in patients withAlzheimer's disease(29). DHA, a naturally occurring component found in every cell membrane(29) with ability to increase phosphatidylserine(30)(31) is important in decreased production of proinflammatory omega-6 eicosanoids causes of Alzheimer's disease(31) and in improved the memory of animals with Alzheimer's disease by suppressing oxidative damage in the brain(32).
b. Vitamin E
Vitamin E, and drugs(memantine) reduced generalized inflammation, may slow the decline of mental and physical abilities in people with Alzheimer's disease (AD) over the long term(33). Also vitamin E inhibited cells damage and cells death caused by beta-amyloid(34)(35), which is toxic to brain cells(36).
c. Phosphatidylserine
Patients who had Alzheimer’s disease taken100 milligrams per day (mg/day) of phosphatidylserine scored significantly better on standardized memory tests at the end of the 12-week trial period than patients without(37)(38).
d. Antioxidants
Antioxidant are found at much lower levels for patients with Alzheimer’s disease(39)(40)(41), such as serum of vitamin A, C, E, zinc and transfferin.
e. Muscarinic cholinergic receptors
Alzheimer’s disease patients showed to exhibit the significant loss of muscarinic cholinergic receptors neurons(42) causes of reduced volume of neural transmission that can lead to loss of memory(43).
B.2. Parkinson's disease
1. Free radicals and Parkinson's disease
Patients with Parkinson's disease have low levels of polyunsaturated fat in the substania nigra(44)(45). Also patients with the disease found to contain waste pigments of lipofusion(46) and other polymers in the neurons(47) where dopamine is most active.
2. Aging and Parkinson's disease
According to Julius-Maximilians-University, physiological aging and OS-dependent aggregation of proteins, accompanied with environment toxins(49) are found to associate to the progression of the disease(48).
3. Antioxidants and Parkinson's disease
Antioxidants play an vital role for patients with Parkinson's disease.
a. Superoxide dismutase
Researcher found that the progression of the disease may be associated with the decrease levels of superoxide dismutase, a antioxidant enzyme(50). According to University of Thessaloniki, patients with advanced Parkinson' diseases showed a statistically significant decrease of SOD activity in whole blood and in red blood cells(51).
b. NADH ubiquinone reductase
Levels of NADH ubiquinone reductase is decreased in the substania nigra(52) in patients with PD, causing neurons apoptosis, but this can be treated with antioxidants Acetyl-L-carnitine (53) and alpha lipoic acid(54).
c. Uric acid
People with a high blood level of the natural antioxidant uric acid have a lower risk of developing Parkinson's disease(55) than do people with lower levels(56), but high levels of uric acid increases the risk of kidney diseases(57) and gout(58).
d. Glutathione
Glutathoine showed to deactivate the harmful product HNE of lipid peroxidation(59).
f. Etc.
B.3. Multiple Sclerosis
1. Free radicals and Multiple Sclerosis
Free radical activity is a contributory factors in MS(60) due to proinflammatory cytokines in free radicals production in the peripheral immune and central nervous system (CNS)(60).
2. Antioxidants and Multiple sclerosis
Antioxidants protect the neural tissues from damage against inflammation caused by oxidative stress.
a. TNFalpha
TNFalpha, an imflammatory cytokine showed to associate with MS inhibited by antioxidants(61)) of green tea(62), and curcumin(63).
b. Melatonin
Melatonin functions as an antioxidant has the ability to protect neurons(65)(66) from free radicals cause of lipid peroxidation(64).
c Selenium
Some studies found that the level of selenium in the blood of people with MS was lower than in that of people without(67)(68). In patients with MS, all abnormalities may be normalized by daily intake of selenium(69),
d. Niacin
Niacin acting as antioxidant is a key to the successful treatment of multiple sclerosis, profoundly prevents the degeneration(70) of demyelinated axons and improves the behavioral deficits(71).
e. Vitamin D
Serum of 25(OH)D level showed to regulate expression dynamics of a large gene-gene interaction system in immune modulatory processes of MSactivity(72). According to the study published by the journal Neurology, group receiving vitamin D supplement demonstrated a remarkable 41 percent reduction in new MS events with no meaningful side effects(73).
f. Etc.
B.4. Lou Gehrig's disease(Amyotrophic lateral sclerosis)
1. Free radicals and Lou Gehrig's disease
Researchers found that glutamate in the synapses enhances the production of free radicals(77) only in motor nerve cells but spares other nerve cells(74) such as cells control senses and other body functions, causing disruption of astrocytes in regulated glutamate levels(76).
2. Antioxidants and Lou Gehrig's disease
a. Vitamin B12 (methylcobalamin)
High doses of vitamin B12 as an antioxidant have shown to improve or slow muscle wasting in the later stages of patients with ALS disease(78)(79).
b. Vitamin E
Vitamin E protected against cell membranes from lipid peroxidation damage(80) in reduced the risk of breakdown of the cell membrane cause of ALS(81).
c. Superoxide dismutase enzyme
Mutations in the superoxide dismutase enzyme can increase the risk ALS(82) in catalyzing the dismutation of superoxide into oxygen and hydrogen peroxide(83).
d. Cerebral cortex
Oxidative stress and DNA alternation triggered neurons damage(84) were found in elevating levels in mice with ALS(85).
e. Amino acids
Diet high in amino acids as antioxidants have shown some promising effect in treating ALS(86)(87).
C. Diseases Causes of Dementia
1. Alzheimer's disease
Alzheimer's disease is a brain disorder named for German physician Alois Alzheimer. Alzheimer's destroys brain cells, effecting memory, thinking and behavior severe enough to affect language communication, memory, lifelong hobbies or social life.
2. Stroke (Vascular problems)
Strokes caused by uncontrolled diet with high in saturated and trans fats, can lead to bad cholesterol building up(88) in blocking the circulation of blood to the body, thus increasing volume of infarction, in the brain(89). If oxygen is not delivered to the brain cells, some cells die off and can not reproduce(90), causing stroke(89). Others happen, when a blood vessel in the brain ruptures(91), it causes the cells in your brain deprived of oxygen with symptoms of vascular dementia(92)(93)(94).
According to the prevalence, incidence, and factors associated with pre-strokeand post-stroke dementia by University Department of Clinical Neurology, 10% of patients had dementia before first stroke, 10% developed newdementia soon after first stroke, and more than a third had dementia after recurrent stroke(95).
3. Dementia with Lewy bodies
Lewy bodies is a condition of spherical masses displaced other cell components with symptoms of fluctuating cognitive ability with pronounced variations in attention and alertness, recurrent visual hallucinations and spontaneous motor features, including akinesia, rigidity and tremor(97). Abnormal aggregates of protein develop inside nerve cells are also found in Parkinson's disease (PD), Lewy Body Dementia and some other disorders.(96). According to Mayo Clinic in MRI analysis of the characterizing the tissue abnormalities characteristic of Alzheimer disease and DLB, loss of tissues due to increased amygdalar diffusivity in dementia with Lewy bodies(DLB) may be related to small cavity in the cytoplasm of a cell, a common pathology associated with Lewy body disease(98).
4. Fronto-temporal dementia
Fronto-temporal dementia (FTD) or Pick's disease is clinical syndrome caused by degeneration of the frontal lobe(lobes of the brain lying immediately behind the forehead) of the brain, lead to symptoms ofdepression and executive dysfunction triggering the loss of autonomy, the risk of fall and of malnutrition in elderly patients(100). Early diagnosis of fronto-temporal dementia (FTD) is often difficult because of the non-specific presentation, a delayed-gross estimation of injury or dysfunction of the frontal lobe(99).
5. Progressive supranuclear palsy
Progressive supranuclear palsy, a condition of a movement disorder occurred as a result of damage to certain nerve cells with relatively specific patterns of atrophy, involving the brainstem, the latter frontoparietal regions, pontine tegmentum and the left frontal eye field(102) in the brain may lead to serious and progressive problems with control of gait and balance, including an inability to aim the eyes properly(101).
6. Korsakoff's syndrome
Korsakoff's syndrome, named after Sergei Korsakoff, a Russian neuropsychiatris, a neurological disorder caused by deficiency of Vitamin B1 (thiamine) in the brain and associated closely to chronic alcohol abuse and/or severe malnutrition, can lead to spontaneous alternation performance impaired in PTD accompanied by a significant reduction (30%) in phosphorylated synapsin I(103). Korsakoff's syndrome has been linked to neurotoxic effect of chronic alcohol consumption causes of medial thalami, mammillary bodies, and corpus callosum(104)
According to University of Campinas (Unicamp), the main causes of thiamine deficiency and viral infection or toxins in the blood, other adjunct factors, include magnesium depletion and chronic alcohol misuse, in the development of Korsakoff's syndrome(105)
7. Binswanger's disease
Binswanger disease also known as subcortical vascular dementia is a type of small vessel vascular dementia caused by microscopic areas of damage to the deep layers of white matter in the brain, including mostly of glial cells and myelinated axons in transmitting signals from one region of the cerebrum to another and between the cerebrum and lower brain centers.
Binswanger's disease frequency increased with age, independent of other risk factors, is associated with white matter hyperintensities (WMHs) deficits in selected cognitive functions(106). The disease is considered as
a progressive dementia, depression and "subcortical" dysfunction such as gait abnormalities, rigidity and neurogenic bladder(107). Control of hypertension may help prevent further progression of white matter disease(107).
8. Acquired immunodeficiency syndrome (AIDS)
Acquired immunodeficiency syndrome (AIDS) is a condition of the progressive failure of the immune system caused by HIV, a lentivirus, originated HIV invasion of CNS by crossing the blood-brain barrier (BBB), through progression of chronic inflammation induced dysfunction in neurons and astrocytes(star-shaped glial cells in the brain)(108). The presence of tumor necrosis factor-alpha (in systemic inflammation) may also increase the risk of the development of neurological dysfunction(109).
9. Creutzfeldt-Jakob disease (CJD)
Creutzfeldt-Jakob disease (CJD) is a form of incurable, fatal, degenerative neurological disorder cause of rapid decrease of mental function and movement due to the infectious replicate protein, including symptoms of Mild Cognitive Impairment resembled the final stages of Alzheimer's disease,inexplicable visual disturbances(110).
10. Parkinson's disease
Parkinson's disease is a condition of a degenerative disorder of the central nervous system causes of shaking (tremors) and difficulty with walking, movement, etc. with dementia commonly occurring in the advanced stages of the disease. According to study, in a survey of all stages of disease and 18.38 % demented from patients, caregiver and both, spychotic symptoms, mood/Apathy, and impulse control disorders are accounted for 66.63 % of the variance(111).
11. Huntington's disease
Huntington's disease is a condition of a neurodegenerative genetic disorder affected the muscle coordination causes of cognitive decline and psychiatric problems(17). Impairments of patients with Huntington's disease include speed of processing, initiation, and attention measuresin linear regression(112).
12. Motor Neurone disease (MND)
Motor neuron disease is a group of neurological disorders affected the motor neurones, located in the central nervous system (CNS), causes of cognitive and behavioural changes(113)
13. Multiple Sclerosis
Multiple Sclerosis is a condition of an inflammatory disease due to the damage of the fatty myelin sheaths around the axons of the brain and spinal cord, responded to vision, speech, walking, writing, and memory(114).
14. Obesity
Midlife and late-life obesity may increase the risk of dementia. In 480 persons with incident dementia, risk of dementia was associated to patients with for obese (BMI >30) and uderweight persons (BMI <20) but not overweight (BMI >25-30)(115).
D. Hormonal Causes of Dementia
1. Growth hormone
According to Universidad de Barcelona, Barcelona, physiological decline of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis due to ageing, may involve in the progression of cognitive deficits(116), probably due to ability of both hormones in stimulation of beta amyloid release from neurons and IGF-I involved on brain amyloid clearance(117).
2. Estrogen
According to Scientist at the Kings College London, the decreased production of estrogen due to aging in menopausal women may be association to the risk of dementia(118). Estrogen-replacement therapy has shown to reduce prevalence of Alzheimer's disease in postmenopausal women, but weighing risks and benefits of estrogen-replacement therapy must be taken into account(119)
3. Testosterone
Lower androgen levels in aging are associated with increased plasma Abeta 40 in older men with memory loss or dementia, according to the comparison of levels of serum total testosterone and sex hormone binding globulin (SHBG) and plasma levels of amyloid beta peptide 40(120).
4. DHEA
A decreased concentration of dehydroepiandrosterone sulfate (DHEA-S) and lower DHEA-S/DHEA ratio are associated to risk of Alzheimer's disease (AD)(121)(122).
5. Sex-hormone binding globulin
Gonadotropins may be involved in processes and contribution to the etiology/pathogenesis of AD due to its involvement on inflammation, cholesterol homeostasis, and insulin status(123).
6. Etc.
E. Substance Abused Causes of Dementia
Illicit drug used may cause nervous system impairment due to their direct and indirect effects on the integrity and function of nervous system tissue, probably through immune altered effects(124). Injection drug users has shown to increase risk of dementia, up to 40% of patients with HIV infection(125)
1. Heroin
Heroin (diacetylmorphine or morphine diacetate (INN)), also known as diamorphine (BAN), an opiate drug extracted from the seed pod of the Asian opium poppy plant, showed to induce dysfunction of different components of cortico-striatal (forebrain) circuitry in response to recognition memory, spatial working memory, planning, sequence generation, visual discrimination learning, and attentional set-shifting of groups of subjects(126).
2. Cocaine and Methamphetamine
Cocaine (benzoylmethylecgonine) (INN), a crystalline tropane alkaloid obtained from the leaves of the coca plant showed to induce rapidly accelerating HIV dementia accompanied by seizures and an unusual movement disorder(127).
3. Lysergic acid diethylamide (LSD)
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug used to treat patients with mental disorders may temporarily alter the thinking processes, closed and open eye visuals, synaesthesia, an altered sense of time, etc.(128), but regain the ability to judge, to acquire competence and new learning, to focus attention and concentrate, to recall and retrieve relevant information(129)
4. Ecstasy (3,4-methylenedioxymethamphetamine, or MDMA
Ecstasy, a highly addictive drug, is a powerful CNS stimulant with chemically similar to the stimulant methamphetamine and hallucinogen mescaline induced confusion, depression, sleep problems, drug craving, and severe anxiety(130).
5. Other illicit drugs
According to the study at University of Rostock, Dr. Büttner A., drug abuse represents a significant health issue. The major substances abused substances including cannabis, opiates, cocaine, amphetamine, methamphetamine and 'ecstasy'. altered intracellular messenger pathways, transcription factors and immediate early genes within the brain reward system may lead to cardiovascular complications, psychiatric and neurologic symptoms due to their widespread disturbances within the complex network of central nervous system in cell-to-cell interaction(131).
F. Diet Causes of dementia
Midlife characteristics of nonsmoking, body mass index (BMI) less than 25.0 kg/m(2), physically active, and having a healthy diet (based on alcohol, dairy, meat, fish, fruits, vegetables, cereals, and ratio of monounsaturated tosaturated fat) are associated to reduce risk of dementia(132)
1. Saturated fat and Trans fat(145)
Saturated fat is important for energy, hormone production, cellular membranes, especially in signalling and stabilization processes in the body, but over consumption can cause cholesterol building up in the arteries leading to heart diseases, stroke, diabetes, etc. A high saturated fat and cholesterol intake has shown to increase the risk of dementia, whereas fish consumption may decrease this risk(135)(145), probably due to involvement in the β-oxidation process of long-chain fatty acids, very-long-chain fatty acids, and branched-chain fatty acids of peroxisome(133)(145) in the breaks down molecules into smaller units to release energy of very long chain fatty acids(134). Intake of trans fat is also found to potentially increase the AD risk or cause an earlier onset of the disease due to its effects in increased production of amyloid beta (Aβ) peptides, main components of senile plaques(136).
2. Artificial sweetener
Artificial sweetener can cause obesity risk of dementia independent of diabetes and cardiovascular comorbidities(137). and induced increasing consumption of fat(138).
3. Fast Foods
Fast foods, unwholesome foods, containing high amounts of artificial ingredients, with an aim to be cooked fast and handed over to the customer in minutes may induce anxiety, tension, depression, difficulty in concentration, and memory of that can lead to onset of senile dementia(139).
4. Artificial ingredients
A standard American diet containing high amount of MSG and aspartame may induce the early onset of neurodegenerative disease(140)
5. Alcohol
Moderate alcohol drinking is associated with a reduced risk of unspecified incident dementia and AD(141)(145), but excessive consumption of alcohol not only causes liver damage but also increases risk of neuro-degeneration, including onset of dementia due to its neurotoxic and neuroprotective effect(142).
6. Low intake of fruits and Vegetables
Nutrition plays a role in the ageing process of the brain and suboptimal nutrient. According to The Chinese University of Hong Kong, older people with questionable dementia have lower intakes of vegetables, fruits(145) and fluid than those who were cognitively normal(143)
7. Meat
The typical American diet containing high amounts of red meat has shown to increase risk of cholesterol building up in the blood vessels and capillaries in causation of heart diseases and stroke(144) and cognitive impairment(135).
8. Etc.
G. Medication Causes of Dementia
As aging, accumulation of toxins of certain medication used to treat certain diseases, such as antidepressants, sedatives, cardiovascular drugs and anti-anxiety medications may cause increased risk of cognitive dysfunction, including dementia-like symptoms(146).
1. Antidepressants, selective serotonin reuptake inhibitors, antipsychotics and benzodiazepines
An Antidepressant is a psychiatric medication used to treat mood disorders, such as major depression and dysthymia and anxiety disorders. According toJohns Hopkins Bayview Medical Center. all antidepressants, selective serotonin reuptake inhibitors (SSRIs), antipsychotics (atypical and typical), and benzodiazepines overtime of medication exposure, induced more rapid cognitive and functional decline in AD(147).
2. Anti-inflammatory drugs (NSAIDs)
Risks for AD and all-cause dementia were lower significantly with the use of any NSAIDs, but there is a weak link associated between usage of NSAIDs and the risk of cognitive impairment but not dementia(148).
3. Cannabis
Cannabis has been used for the treatment of a number of conditions, including neuropathic pain, spasticity associated with multiple sclerosis, and chemotherapy-induced nausea, etc,. Chronic use of cannabis may impair intellectual abilities, probably through some causal pathways(149).
4. Hallucinogens
Hallucinogens, psychedelic drugs, used primary action in altered cognition and perception, may cause distortion of sensory perception, and other psychic and somatic effects, including sweating, heart palpitations, blurring of vision, memory loss, trembling, and itching(150).
5. Risperidone
The most prescribed antipsychotic medication has shown to increase risk of dementia(152) and other cognitive dysfunction, depending to overtime chronic exposure(151).
5. Others
a. Corticosteroids
Corticosteroids are synthetic drugs closely resemble cortisol, a steroid hormones produced by the adrenal glands to assist the physiologic processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, behavior, etc., but an excessive usage may induce risk of progressive cognitive decline(153)(154).
b. Antibiotics
Antibiotics are medication taken to treat a variety of infections found to be associated with increased risk of psychomotor deceleration, delirium and psychosis in elderly patients(155)(156).
c. H2-receptor antagonists
H2-receptor antagonists are medicines taken to reduce the amount of acid in the stomach by blocking one important producer of histamine2, may cause acute and chronic cognitive impairments(157)(158).
d. Etc.
H. Life Style causes of Dementia
1. Unhealthy diet
Unhealthy lifestyle choices lead to an increasing incidence of obesity, diabetes mellitus type II, hypertension and disorder of the metabolic syndrome(159)(160), are found to associate to risk of AD. Recent research supports the hypothesis that calorie intake, among other non-genetic factors, can influence the risk of clinical dementia(161).
2. Psychological and Neurological effects
Dysfunctional mind may be associated to dementia due to its effects on the cognitive profile of ALS, a subclinical behavioural-variant frontotemporaldementia (bvFTD(162). Stress, anxiety, depression(163), negative thoughts(162), unhealthy life style(159)(160), unwholesome diet(161), can cause memory, intellect, attention, thinking, comprehension and personality, with preservation of normal level of consciousness deficits(164)
3. Excessive alcohol drinking
Moderate alcohol drinking of less than 2 cups for men and 1 cups for women of red wine are said to offer possible health benefits(165), but binge drinkingin midlife and excessive alcohol usages are associated with an increased risk of dementia, according to the follow-up, 103 participants had developeddementia(166), including central pontine myelinolysis, Marchiafava-Bignami disease(167).
4. Smoking
Smoking is a risk factor for several life-threatening diseases, but its long-term afflicts of dementia is controversial and understudied. According to University of Eastern Finland, heavy smoking in midlife was found to associate with a greater than 100% increase in risk of dementia, AD, and VaD more than 2 decades later, in a follow up study of a total of 5367 people diagnosed withdementia (including 1136 cases of AD and 416 cases of VaD)(168).
5. Etc.
I. Genetic Mutation causes of dementia
Genetic mutation is a condition of changes of DNA structure and alteration in the inherited nucleic acid sequence of the genotype(169). There are always a concern of some dementia patients with inherited trails for passing them to their children.
1. Linkage of Dementia with Lewy bodies (DLB) to 2q35-q26
Genetic mutation of chromosome 2q35-q36 Lewy bodies (DLB) are multiplex, due to its complex mechanism than generally monogenic disorders. Identifying the first familial DLB gene may contribute to an entry point of DLB pathology, according to Belgian family,researchers(170)
2. VCP gene R155H mutation
Some patients in the same family with frontotemporal dementia (FTD) have been diagnosed with high risk of cognitive decline due to the recurrent R155Hmutation, according to University of Genova(171).
3. Genetic mutation and Alzheimer's disease
4 genes have been identified to affect development of AD. with the amyloid precursor protein (APP ) gene, presenillin gene (PSEN-1), and presenillin gene (PSEN-1)) affect younger people, and apolipoprotein E (APOE ) iaffects older people(172).
4. Chromosome 3 (FTD-3) caused by a truncating mutation in CHMP2B
Presymptomatic CHMP2B mutation was found to associate to significantly decreased cerebral blood flow (CBF) affecting brain capillaries(173) and contributing to the early on set of dementia.
5. Mutations in the NOTCH3
Mutations in the NOTCH3 gene are responsible for hereditary stroke disorder, contributed to an adult onset of hereditary ischemic stroke, vascular dementiaand psychiatric disorders(174).
6. Etc.
Symptoms and Complications of Dementia
Dementia is a neuropsychiatric disorder induced of cognitive impairment andbehavioral disturbances. The behavioral and psychological symptoms ofdementia (BPSD) are common, with a progressive loss of memory and other mental abilities, affecting a person's ability to perform usual tasks in everyday life.
A. Symptoms
A.1. Symptoms of Alzheimer's disease
Alzheimer's disease is a brain disorder, affecting over 1 million people in US alone with well known symptoms of lack of concentration (56%), tremors (56%), depression (44%), lack of cooperation (36%), and delusions (32%), psychotic symptoms (delusions, hallucinations, and delirium) and tremors, and emotional symptoms (tearfulness and apathy, lack of concentration and appetite change), according to Hospital de Cruces, Plaza de Cruces s/n, Barakaldo in a study of total of 1014 patients(177). Other symptoms include
1. Increasing forgetfulness(178)
2. Communication difficulty(179)
3. Anxiety(180)
4. Mood and personal change(181)
5. Delay recall(183)
6. Repeat question(183)
7. Memory loss(182)
8 Aberrant motor behavior (184)
9. Sleep problems (184)
10. Eating problems (184) and
11. Agitation/aggression (184)
10. Etc.
A.2. Symptoms of Diminished quality of acetylcholine
If the nerves located in front of the brain perish, diminished quality of acetylcholine, it can cause language difficulty, memory loss, concentration problem and reduce mobile skills because of lacking reaction in muscular activity and refection.
Symptoms of deficiency of acetylcholine include(185)
1. Difficulty remembering names and faces after meeting people
2. Difficulty remembering peoples birthdays and numbers
3. Difficulty remembering lists, directions or instructions
4. Forgetting common facts
5. Trouble understanding spoken or written language
6. Forget where I put things
7. Slowed and/or confused thinking
8. Difficulty finding the right words before speaking
9. Disorientation
10. Prefer to do things alone than in groups / social withdrawal
11. Rarely feel passionate
12. Feel despair and lack joy
13. Lost some of my creativity / lack imagination
14 Dry mouth
15. Etc.
A.3. Dementia due to long-term alcohol abuse
Dementia is common in patients with alcoholism. Most symptoms of alcohol dementia are also presented in other types of dementia, with a few qualitative differences(186) involved both cortical and subcortical pathology. According to the article, "What's alcohol-related dementia?" Alcohol dementia induced deterioration in intellectual function with memory not being specifically affected, such as disinhibition, loss of planning, and executive functionsand a blithe disregard for the consequences of their behaviour, affecting mostly of women in the ages between 30 - 70 with the better rates better than for Korsakoff's Psychosis(187).
Other symptoms in deficits are most frequently observed on tasks of visuospatial function, memory(188) and higher-order (executive) tasks(189)
A.4. Multi-infarct dementia
Also known as vascular dementia, is the second most common form of dementia after Alzheimer's disease in older adults, caused by different mechanisms, affecting the vascular lesions in the brain.with major neurovegetative symptoms of depression accompanied by depressed mood/anhedonia in patients with clinically-diagnosed Alzheimer's disease (AD) and multi-infarct dementia (MID)(190).
Symptoms include memory deficits(192) such as
1. Confusion
2. Memory problems
3. Wandering Getting lost
and
4. At least one of behavioural or psychological symptom, such as appetite disturbances irritability and anxiety and emotional suppresion(such as laughing inappropriately, crying inappropriately)
(193), and
5. Difficulty following instructions, and
6. Bladder incontinence
7. Bowel incontinence(191)
A.5. Dementia associated with Parkinson's disease
Parkinson disease (PD) is a disabling, progressive condition cause of cognitive deficits due to the interruption of frontal-subcortical loops that facilitate cognition and that parallel the motor loop, affecting motor function.These include olfactory deficit, sleep problems such as rapid eye movement behaviour disorder, constipation and male erectile dysfunction.(194).
Other symptoms due to dopamine (DA) deficiency, include, dysexecutive behaviors(196), such as planning, abstract thinking, flexibility and behavioural control and postural disabilities(197) and
1. Constipation
2. Difficulty swallowing
3. Choking, coughing, or drooling
4. Excessive salivation
5. Excessive sweating
6. Loss of bowel and/or bladder control(195)
A.6. Creutzfeldt-Jakob disease (CJD)
People who have eaten contaminated beef in many years, may be infected with Creutzfeldt-Jakob disease (CJD) without even knowing it. Creutzfeldt-Jakob disease is a quickly progressing and fatal disease, characterized by rapidly progressive dementia. Initially, individuals experience problems withmuscular coordination, personality changes, including impaired memory,judgment, and thinking and impaired vision. People with the disease also may experience insomnia, depression, or unusual sensations.(198).
A.7. Subdural hematoma
Subdural hemorrhages, the accumulation of blood beneath the outer cover of the brain resulted from the rupture of blood vessel may cause an increase in tracranial pressure, leading compression and damage to delicate brain tissue. Acute subdural hematoma has a high mortality rate.
Other symptoms include
1. Intermittent numbness and weakness of extremity(199) and
2. Loss of consciousnes(201)
3. Irritability
4. Seizures
5. Pain
6. Headache
7. Dizziness
8. Disorientation
9. Weakness
10. Weakness or lethargy
11. Nausea or vomiting
12. Loss of appetite
13. Personality changes
14. Confused speech
15. Difficulty with balance or walking
16. Altered breathing patterns
17. Hearing loss or hearing ringing (tinnitus)
18. Blurred Vision
19. Deviated gaze, or abnormal movement of the eyes(200)
B. The Complications
According to physical complications of patients with dementia occurred in the 12 months from April 2007 to March 2008 recorded in Ichinomiya CityHospital, Ichinomiya, the physical complications can be divided into two categories:
** Serious emergencies occurred with a possible high risk of mortality within a few days (e.g. pneumonia and upper airway obstruction); and
**Life-threatening complications arising required diagnosis and treatment by specialists from other medical departments (e.g. bone fracture andcancer)(202).
1. Pneumonia
Pneumonia is common among patients with advanced dementia, especially toward the end of life, due to microbial infection, according to Beth IsraelDeaconess Medical Center(203).
2. Obstructive Sleep Apnea Syndrome (OSAS)
The prevalence of OSAS increased with aging, occurring in up to 25% of older adults and up to 48% in patients with Alzheimer's disease, showed to induce symptoms of hypoxia, fragmented sleep, daytime sleepiness, cognitive dysfunction, functional decline, and brain damage, due to reduced cerebral blood flow, ischemic brain lesions, microvascular reactivity, white matter lesions, and grey matter loss(204)
3. Bone fracture
Bone mass and dementia in elderly hip fracture patients may be associated to levels of different aluminium concentrations in water supplies in the areas affecting the negative calcium balance of age-related osteoporosis together predispose to senile dementia.(205)
4. Urinary incontinence
Urinary incontinence is a common problem in dementia. Almost invariably, the person with dementia will develop incontinence as the diseaseprogresses. However, the primary reasons for incontinence are often not because of any significant pathology in the urinary system. Rather, it is due to factors outside the urinary system, including insertion of tube in assisting urinary flow(206)
5. Venous thromboembolism
Venous thromboembolism (VTE), caused by a blood clot breaking loose and traveling in the blood, in patients with dementia had a high incidence of fatal pulmonary embolism (PE) and fatal bleeding, according to the study of 37988 patients with 1316 (3.5%) having dementia(207).
6. Etc.
Prevention and Management
A. The Do's and Do Not's list
1. Mediterranean diet
If you are typical American dieter, you are at increased risk for the development of dementia, in advanced age, as the diet is classified as one of the most unhealthy diet in the existence, according to studies. Mediterraneandiet, high monounsaturated fatty acids energy intake appeared to be associated with a high protection against cognitive decline and reduced the prevalence of AD in older people(208). Also recent research supports the hypothesis of calorie intake, among other non-genetic factors, in influence of the risk of clinical dementia.(209).
2. Yoga
Senile dementia is the mental deterioration, such as loss of intellectual ability associated with old age. Yoga is believed to have beneficial effects on cognition, probably through attenuation of emotional intensity and stress reduction. Yoga participation showed to improve the memory performance, and all other psychophysiological parameters, in patient with dementia, including intellect, attention, thinking, comprehension and personality, with preservation of normal level of consciousness(210), according to G.J. PatelAyurved College.
3. Aging of theory of mind
According to Aging of theory of mind, educational level and cognitiveprocessing are two factors, influencing the pattern of the aging. Younger and older group with equally high education showed to outperform the older group with less education in false-belief and faux-pas tasks, with younger group outperformed the other two groups in the cognitive processing tasks(211).
3. Moderate alcohol drinking
Moderate alcohol drinking of less than 2 cups for men and 1 cups of red wine for women are said to offers possible health benefits, but Binge drinking (ie,alcohol exceeding the amount of 5 bottles of beer or a bottle of wine on 1 occasion at least monthly) in midlife is associated with an increased risk ofdementia, according to the follow-up, 103 participants had developeddementia(212).
4. Stop Smoking or never smoke before
Smoking is a risk factor for several life-threatening diseases, but its long-term association with dementia is controversial and somewhat understudied. According to a total of 5367 people (25.4%), heavy smoking in midlife was associated with a greater than 100% increase in risk of dementia, AD, and VaD more than 2 decades later(213).
5. Drink your tea and coffee
Caffeine in tea and coffee may enhance cognitive function acutely, but its link to dementia is somewhat inconsistent, but most studies support coffee's favourable and protective effects against cognitive decline, dementia or AD. Coffee drinking of 3-5 cups per day at midlife was associated with a decreased risk of dementia/AD by about 65% at late-life(214).
6. Eat your fruits and veggies
Fruits and veggies containing high amounts of antioxidant enhance the immune system in fighting against forming of free radicals cause to damage to the brain cells in induced early onset of dementia. Vitamin E and vitamin C supplements in combination were associated with reduced prevalence and incidence of AD, according to The Johns Hopkins University(215).
7. Regular and moderate exercise for elder
Regular and moderate exercise may attenuate the cognitive dysfunction, but theirs' induced changes in cognition were not correlated with changes in mood/anxiety, probably through some separate neural systems mediation(216).
8. Avoid nutritional deficiency with balance diet
a. Beyond our believe, an excess of dietary carbohydrates, particularly fructose, alongside a relative deficiency in dietary fats and cholesterol,may lead to the development of Alzheimer's disease(217).
b. For more of Avoid nutritional deficiency with balance diet, please visit(218)
9. Avoid environment risk of dementia
Certain environment toxins produced as a result of industrialization or naturally have been linked to cognitive degenerative diseases. According to University of British Columbia, novel environmental toxins: steryl glycosides, a potential etiological factor for age-related neurodegenerative diseases, showed signs of mimicked ALS-PDC, including progressive deficits in motor, cognitive, and olfactory functions associated with neuron loss in the spinal cord, nigrostriatal system, cortex, hippocampus, and olfactory bulb in fed mice(219).
10. No illicit drug, please(220)
Illicit drug used may cause nervous system impairment as a result of direct and indirect effects on the integrity and function of nervous system tissue and, potentially, through immune effects, especially, up to 40% risk of nervous system impairment for patients with HIV-1 infection.
11. Prevent prolonged period of using certain drugs
As aging, accumulation of toxins of certain medication used to treat certain diseases, such as antidepressants, sedatives, cardiovascular drugs and anti-anxiety medications may cause increased risk of cognitive dysfunction causes of dementia-like symptoms(221).
12. Etc.
B. Antioxidants and Dementia
B.1. Antioxidant enzymes
Antioxidant enzymes, chemical substances found in plants, protect the body from damage of free radicals by terminating the chain reactions through removing free radical intermediates and inhibiting oxidation reactions.
1. Catalase
Catalase is an enzyme, found in most living organisms exposed to oxygen for action of converse hydrogen peroxide (free radicals)(226) to water and oxygen. The antioxidants showed to protect cells against the toxic effects of hydrogen peroxide in pathogenesis of oxidative stress-related diseases(222) inducted early stages of aggregation of the amyloid peptides(225), including neurodegeneration(224) such as Alzheimer's diseas(223).
2. Glutathione peroxidase
The function of glutathione peroxidase is to protect the organism from oxidative damage and induced neurodegenerative diseases, such as Alzheimer's disease(228) by removing lipid hydroperoxides(227), causes of oxidation of lipid cell membranes. probably through its major cellular peroxide scavenging enzyme(228) and maintaining the oxidative phosphorylation system and protecting mitochondria(229) and oxidative injury and amyloid toxicity of cortical neurons(230).
3. Glutathione reductase
Glutathione reductase, an antioxidant enzyme capable to regenerate Gglutathione (GSH) levels at 24h(233), and reduced pair of sulfur atoms glutathione to a organosulfur compound form of antioxidant (consisting of three amino acids joined by peptide bonds) may play an important role in prevention of damage of important cellular components induced neurodegenerative diseases such as PD(231)(232), caused by free radicalsand peroxides. probably through its antioxidant and anti-inflammatory properties(231)
4. Super oxide dismutase (both Cu-Zn and Mn)
Super oxide dismutase is an important antioxidant and immune defence(224) in nearly all cells exposed to oxygen by converting superoxide into oxygen and hydrogen peroxide, depending on the metal cofactor such as both Cu-Zn and Mn(225), probably through the attenuation of superoxide dismutases (SODs) and catalases (CATs)(225) in enhanced protection of biochemical/molecular/neurobiological function(226).
B.2. Metals binding proteins
1. Ceruloplasmin
Ceruloplasmin, the major copper-carrying protein in the blood, plays a role iniron metabolism(227). Decreased level of ceruloplasmin impaired ferroportin stability(229)(230)may induce progressive action tremor, and cognitive decline(227), causing the forming of superoxide anion radicals(231) and iron overload in the brain, liver, pancreas, and other organs(232).
2. Ferritin
Ferritin, the protein produced by almost all living organisms, acts as a component to fight against iron deficiency and iron overload(233)(234). In a soluble and non-toxic form, the protein is transported to the body needs, including organs(236) for enhancement of the immune system in the presence of an infection(237), against proliferation of lymphoid and myeloid cells(235), cancer(238) and prevention of the infectious agent in attempt of binding iron to form free radicals(239) in most cellular oxidation reactions(239).
3. Lactoferrin
Lactoferrin, a multifunctional protein of the transferrin family, is one of the components of the immune system(240) of the body used for fighting against foreign invasion of bacteria and virus(241)(242) and lipid oxidation(243) by inhibiting oxidation in a concentration-dependent manner even at concentrations beyond its capacity(244).
4. Metallothionein
Metallothionein, a family of cysteine-rich(24), low molecular weight proteins binds both physiological heavy metals(245) through detoxified fraction of accumulation(245) by capturing harmful superoxide and hydroxyl radicals(246) through binding the metal ions(247)(248) bounded to cysteine(249).
5. Transferrin
Transferrin, a glycoprotein binded iron very tightly but reversibly, enhances the immune system in fighting against infection, inflammation(250) by creating an environment low in free iron(251) impeded to cell oxidation(253)(254), through rapidly evolving sites reverse to bacterial binding in counteract bacterial iron piracy(250). Transferrin deformation and aggregation are found to associate to neurological disorders such as Parkinson's and Alzheimer's disease(252).
6. Hemoglobin
Hemoglobin, the protein molecule in red blood cells enhances the carrying of oxygen from the lungs to the body's tissues and return CO2 from the tissues to the lungs(255)(256). During oxidate stress, the cell membrane is protected by intraerythrocytic hemoglobin from the forming of free radicals(259), probably through regulating NO(258) and auxin homeostasis(257).
7. Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates. The binding of oxygen by myoglobin(260) through interaction with pathogens establishment of successful infection and survival is probably through peroxidase activity(261) in reducing the free radicals damage caused by oxidate stress(261)(262).
8. Etc.
B.3. Common Free Radical Scavengers
1. Bilirubin
Bilirubin is a prosthetic group with a unique function in breaking down molecules into smaller units for releasing energy, excreted in bile and urine(263). As a cellular antioxidant, it protected against diseases associated with oxidative stress, through mildly elevated serum bilirubin levels and activation of heme oxygenase(264) and reverted to biliverdin, a green tetrapyrrolic bile pigment, through antioxidant redox cycle in inhibition of the effects of mutagens when oxidized(265). A significant reduction of levels ofbilirubin, has shown to associate to patients with Alzheimer's disease(AD)(266).
2. Carotenoids
Carotenoids are organic pigments, occurred in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria. The antioxidant has been under intense scrutiny studies for finding of their potential in modulated chronic disease risk and prevention of vitamin A deficiency(267). Plasma levels of HDL and carotenoids have shown to lower in patients with dementia related vascular disorders(268) and Alzheimer's disease(AD)(269).
Beta-Carotene, an organic compound is classified as a terpenoid, a strongly-coloured red-orange pigment in plants and fruits.
Beta-Carotene is not toxic and stored in liver for the production of vitamin A(270) showed to inhibit cancer cell in experiment(271)(272). Its anti oxidative effects has shown to cover the main pathways for formation, transformation, and decay of free radicals(273), through its relation to the antioxidant/pro-oxidant properties(274). According to Yale University, the decreased non-enzymatic antioxidants in blood, including β-carotene showed a significant oxidative damage in the process of neurodegeneration(275).
3. Flavonoids
Flavonoid also known as Vitamin P and citrinare, is a yellow pigments having a structure similar to that of flavones occurred in varies plants. The antioxidant has been in human history for over thousands of years and discovered by A. S. Szent-Gyorgi in 1930. Vitamin C and flavonoids combination has shown to expressed wound healing in animal model(276).
Flavonoids process a property as antioxidants in inhibition of cell growth, differentiation and development, and overexpressed in gastric cancer, colorectal cancer, pancreatic cancer, etc., probably through cell cycle arrest and induced apoptosis(277). Intake of antioxidant flavonoids is associated to the reduced risk of incident dementia(278) and mild cognitive impairment(279).
Although nitric oxide is considered a free radical produced by immune system to destroy microbial(281) and cancerous cells(282)(283). Over produced NO, showed to induce inflammation(280). Flavonoids processed an ability in inhibited NO production of peroxynitrite(284) found to induce mitochondrial dysfunction associated with PD progression(285) and cause of inappropriate damage to blood and tissues(284).
4. Vitamin A, C, E
a. Vitamin A
Vitamin A occurred in the form retinol is best known for its function in maintaining a critical role in vertebrate development, cell differentiation, reproduction, vision and immune system(286). The vitamin also acts as an the major peroxyl radical scavenger role in biological lipid phases such as membranes or low-density lipoproteins (LDL)(291)(288), including incidence of bronchopulmonary dysplasia (BPD) with respiratory failure(290), in fighting the increased free radicals activity by radiation(287), and enhancement of the productions of insulin pancreas(289).
b. Vitamin C
Vitamin C, presencted in aqueous compartments (e.g. cytosol, plasma, and other body fluids)(292) plays an important role in synthesis of collagen, carnitine, catecholamine and the neurotransmitter norepinephrine(293). As an water soluble vitamin, vitamin C can be easily carried in blood, operated in many parts of body. By recycling vitamin E, vitamin C also helps to fight against forming of free radicals(294). By enhancing the immune system(295)(296), it promotes against the microbial and viral(298) and irregular cell growth causes of infection and inflammation(297).
Vitamin C also is a free radical scavenger in inhibiting pollution cause of oxidation(299).
c. Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds, including both tocopherols and tocotrienols(300), discovered by researchers Herbert Evans and Katherine Bishop. The vitamin not only is important in protecting muscle weakness(300), repairing damage tissues(302) caused by oxidation(303), and promoting blood clotting in healing wound(302), etc., it also, moved into the fatty medium to prevent lipid
peroxidatio