Abstract: This is a case study on a 78 year old man with early Alzheimer’s dementia(AD) and mild cognitive impairment (MCI). He was already seeing a geriatrician and put on an anticholinesterase inhibitor. He had no dietary or environmental interventions when he came to see me and was found to have high cholesterol, high homocysteine. MTHFR heterozygous c665C and c1286A, a high copper: zinc ratio, gut dysbiosis and insomnia. The goal was to treat him as an integrative physician and reverse what I could using evidence based practice including reducing homocysteine and copper and repairing the gut. I have only been treating him for 2 months and will need at least 6-12 months to see if my interventions have made a difference. During this time I will continue monitoring him with MMSE and blood tests. He was treated with diet, exercise, lifestyle and supplements in order to reduce Alzheimer’s progression. Furthermore environmental toxins and body burden was reduced. Can anything be done about genetic predisposition to AD or has the horse bolted?
Alzheimer’s disease is characterised by memory impairment and according to the DSM must include at least one of the following; aphasia, apraxia, agnosia or disturbance in executive function. It interferes with daily function and characterised by a gradual onset and continuing decline. Traditionally western medicine has no effective treatments for this gut wrenching and costly ailment.(1)
AD is driven by two processes: extracellular deposition of beta amyloid-A? and intracellular accumulation of tau protein. Both these compounds are insoluble. A? is the main component of senile plaques and tau is the component of neurofibrillary tangles. A? deposition is specific for AD and is thought to be primary. Tau accumulation is also seen in other degenerative diseases and is thought to be secondary.
A? is toxic to neurons. It causes loss of long term potentiation, damages synapses, and kills neurons. Moreover, it shows selective neurotoxicity for the hippocampus and entorhinal cortex (areas that are severely affected in AD) while sparing cerebellar neurons. This damage is mediated by free radicals, which are generated when soluble A? is complexed with Zn, Cu, and Fe.
Tau aggregates as pairs of filaments that are twisted around one another (paired helical filaments). These deposits interfere with cellular functions by displacing organelles. By distorting the spacing of microtubules, they impair the axonal transport thus affecting the nutrition of axon terminals and dendrites.
Genetics accounts for 70% of the risk, and the most important genetic risk factor is the Apolipoprotein E (ApoE) genotype. ApoE is a protein that carries cholesterol in and out of cells. It occurs in three isoforms: ApoE2, ApoE3, and ApoE4. The gene for ApoE is on chromosome 19. One copy is inherited from each parent. The ApoE4 allele confers a high risk for AD, the rare ApoE2 confers a low risk, and the most common ApoE3 an intermediate risk. Persons who are homozygous for the ApoE4 allele develop AD at a mean age 70. Persons with other ApoE genotypes develop the disease later or not at all. However, having an ApoE4 allele does not mean that one will invariably develop AD. Furthermore, the role of ApoE4 in non-Europeans is not as well established. The ApoE4 allele is also a risk factor for hypercholesterolemia. High cholesterol levels during mid-life increase the risk of AD and lowering lipids lowers this risk.
The role of the environment, diet, and general state of health in AD is being actively explored. Chronic cellular damage from free radicals, excitotoxicity, nonenzymatic glycation of proteins, and other factors contributes to the loss of neurons and synapses that is associated with old age and aggravates the pathology of AD.
Neuroinflammation is an important factor involved in the pathogenesis of AD. Acute-phase proteins are elevated in serum and deposited in SPs; microglial cells accumulate around SPs; and complement components are present in SPs. APP is an acute phase protein which is released in brain tissue following trauma and other insults. The effects of neuroinflammation are mediated by activated microglial cells which are a source of cytokines and a potent generator of free radicals. Advanced molecular studies have revealed multiple aberrations in the microglial immune response in AD. These aberrations are triggered by A? and tau but, in turn, cause brain damage and accelerate A? and tau deposition.
Free radicals and Oxidative stress, compounding with advancing age, causes mitochondrial DNA mutations, mitochondrial dysfunction and more oxidative stress. This process is accelerated in AD by the action of A? (a mitochondrial poison and free radical generator) and activated microglia, also a source of free radicals.
Type 2 diabetes is a risk factor for AD. AD patients have low levels of insulin and insulin resistance in the brain. These changes impair energy metabolism in neurons and adversely effect signalling pathways dependent on insulin and its receptors. Furthermore, nonenzymatic glycation of proteins produces neurotoxic derivatives that aggravate oxidative damage.
Traumatic brain injury is another risk factor. Dementia and parkinsonism develop sometimes in boxers, football players and other individuals who have had repeated cerebral concussions. The brain shows mainly NFTs. Diffuse and less frequently neuritic plaques are seen inconstantly.
Increased levels of homocysteine (also a risk factor for stroke) and decreased dietary folate potentiate these neurotoxic effects. Homocysteine increases with advancing age and is elevated in persons with polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR), an important enzyme involved in folate metabolism. Such polymorphisms are very common. Elevated homocysteine and decreased folate are associated with increased free radicals, cytosolic calcium, glutamate excitotoxicity, apoptosis, and decreased levels of ATP.
Alzheimer’s Disease International predicts Alzheimer’s rates will triple worldwide by 2050. The Alzheimer’s Association predicts long-term care costs start at $41,000 per year.
However, Alzheimer’s disease isn’t a natural part of aging and by staying active and moving plant-based foods to the centre of our plates, we have a fair shot at rewriting our genetic code.
The case below demonstrates a multi-faceted individualised evidence based approach to Alzheimer’s disease. It illustrates many variables involved in the treatment of AD and highlights how important the patient is when it comes to empowering them, or their carers, to take control of their health, environment and lifestyle and in effect become the ultimate patient for their own sake before it’s too late.
Mr S.N. is a 78 year old man with early Alzheimer’s dementia .He has been under the care of a geriatrician for the last few years and has been taking Aricept 10 mg. According to the geriatrician report there were no reversible causes of his dementia found including head trauma, drug toxicity, metabolic disturbances, hydrocephalus, mass lesions, infectious processes, collagen vascular diseases, endocrine disorders, COPD, Heart failure , liver disease or sleep apnoea. There was no family history of Alzheimer’s.
Past medical history also includes benign prostatic hypertrophy, vitamin d deficiency , hypercholesterolemia , herniotomy, cataract surgery, Left ankle fracture surgery .
Current medications included Aricept 10mg daily. Duodart 500mcg-400mcg 1 nocte .He was also taking a supplement from bioceuticals called advacal forte twice a day with a total per dose of elemental Calcium 334mg,phosphorus 88.3mg,vitamin D3 333IU ,vitamin K2 30mcg, Magnesium 58mg, Zinc 3.2mg Manganese 1mg Copper 200mcg Silicon 7.26mg Boron 1mg .He was also taking some fish oils and Blackmore’s magnesium.
Nutritional assessment was performed and his diet was inorganic and high in gluten, dairy, refined carbohydrates, artificial colours, flavours and preservatives .He would eat take away 2x/week. He would drink coffee 2x/day. He would drink alcohol 1 drink once a week and is a non smoker.
He is now retired but his occupational history was as a form worker in the building industry. He denied any current high stress levels. He says he walks 50 minutes a day and gets morning sun while exercising. He did not undertake any other forms of relaxation or hobbies. There was no significant travel history.
Significant findings on systems review included constipation, dental periodontitis,and cravings of sugar, dairy and gluten (namely bread) .
He denied any fatigue, depression or anxiety. He had good sleep (except for nocturia) and good dream recall.
He complained of chronic sinus congestion and occasional musculoskeletal cramps .He had some watery eyes and itchy ears.
MMSE; 24/30 indicating mild cognitive impairment.
Examination revealed an endomorphic body type. Happy affect and normal gait. He had some nasolabial redness and flakiness. His hair was thinning. He had crimson crescents in his pharynx and a coated strawberry tipped and creviced tongue. His hands showed collapsed finger pulps and small muscle wasting. His nails were bitten and brittle and showed vertical grooves and white spots. His skin was dry .His abdomen was soft and non tender .His central nervous system revealed no further abnormality.
CT sinuses showed complete opacification right maxillary antrum,rhinitis and sphenoidal encroachment on the nasopharyngeal airway.
CT chest shows stable lymph nodes in the mediastinum and degenerative changes in the thoracic spine. Lymph nodes being followed up 6-12 monthly with CT by his GP.
FBC showed platelets 146 x10^9/L(low) ,lymphocytes 1.1 x10^9/L (low normal), basophils 0.0 x10^9/L MCV 91 fL
Sodium/potassium ratio 30.8mmol/L,
Urea 7.4 mmol/L , Creatinine 83 umol/L urea/creatinine 89 umol/L
Cholesterol 6.1mmol/L (high) Triglyceride 1.1mmol/L
Ca/PO4 2.28 mmol/L Corrected ca 2.26, PO4 0.99
TSH 1.30 mIU/L
Fasting glucose 4.9 mmol/L, Insulin 4mU/L
Iron 15.9 umol/L ,Transferrin 2.0 g/L (low normal), Ferritin 103 ug/L
Vitamin D 78 nmol/L
Homocysteine 12.3 umol/L (high normal)
Active B12 >128 pmol/L .Note on 12/11/16 B12 was 9 and has been replaced with imtramuscular injections.
Serum folate 25 nmol/L
ANA not detected
MTHFR c665cT and 1286ac both heterozygous
Plasma zinc 9.2 umol/L(low normal)
Se Copper 15 umol/L
Copper/zinc; 1.63 umol/L
Histamine 0.5 umol/L
A dexa scan was performed and was osteopenic T score 1.8 Z score 2.5
A bioscreen was also ordered and revealed a high aerobe: anaerobe ratio with an overgrowth of e.coli ,streptococcus, staphylococcus and enterococcus. He also had an overgrowth of lactobacillus, and undergrowth of bifidobacterium and eubacterium .
Early Alzheimer’s dementia with memory loss and cognitive decline with some disturbance in executive function. High copper :zinc ratio. High Homocysteine. MTHFR heterozygous.
Mr S.N. was advised to reduce his body burden. This included eating an organic diet with no artificial colours, flavours or preservatives.
He was advised to avoid any PCBs and BPAs i.e. plastic containers and canned foods. He was advised to avoid paints ,solvents, sealants and pesticides.
He did not eat any fish and was advised to eat wild caught fish (salmon size or smaller), organic or free range meat ,chicken and eggs and fruit and vegetables (2 and 5 serves/day respectively).
Other dietary considerations included drinking only filtered water, cooking with stainless steel ,avoiding aluminium and Teflon frying pans, avoiding hydrogenated vegetable oils and using olive oil for cooking , using more natural chemical free options with perfumes, antiperspirants, detergents, sunscreens and washing powders.
He was put on a low stress diet i.e. avoid sugar, gluten, dairy, take away foods, and advised to eat more low stress foods i.e. nutrient rich, low GI, high antioxidant fruits, vegetables, salads, legumes, nuts and seeds. Gluten free grains i.e. corn, rice, millet and quinoa were advised . He was advised to include more essential fatty acids in his diet and flavanoids.
With regards to his gut he was advised to increase his intake of fructo-oligosaccharide (FOS) and actually put on an FOS supplement (1/2-2 tablespoons/day) to reduce E.Coli and promote bifidobacteria growth.
He was also put on a supplement containing Glutamine, zinc, vitamin A, vitamin D3 ,boswellia, aloe vera and arabinogalactan for leaky gut and bifidobacteria promotion..
He was prescribed amoxicillin 500mg bd for 2 weeks to suppress enterococcus, streptococcus and lactobacillus .
All lactobacillus and lactic acid producing probiotics were ceased . A bifidobacterium probiotic was started (5 billion bd between antibiotic doses for 1 month).
Arginine was also started to promote eubacterium species.
He was started on some antioxidants including vitamin c 2gm, mixed tocopherols 400mg, coq10 300mg, l-carnitine 2gm, R-alpha lipoic acid 600mg as total daily elemental doses .
He was also put on curcumin 350mg bd , and another formula containing ;Omega 3; 2.3 gm, EPA 253 mg, DHA 1gm ,lecithin 1.5gm, phosphatydil choline 520mg, phosphatydil serine 150mg, tocotrienols 80mg and vitamin D3 500iu.
He was put on melatonin 1gm nocte + 5HTP 100mg nocte to help with sleep.
To reduce copper and homocysteine and improve zinc, further compounded nutritional supplements given included riboflavin-5- phosphate 100mg , nicotinamide 100mg, P5P 50mg, methylcobalamin 1000mcg, methyl folate 1000mcg, zinc(as picolinate) 40mg, chromium 400mcg, magnesium (as glycinate) 400mg, molybdenum 100mcg, selenium 100mcg and manganese 15mg. All elemental doses.
He could continue his Ginko Biloba.
It was recommended he continue physical exercise and also play some brain games.
Future considerations include APOE testing and heavy metals testing post chelation . This patient has some financial concerns so this testing was not performed at this time .
Cholesterol triglyceride HDL levels
serum B12 folate levels
Serum copper plasma zinc
Note; acetyl l-carnitine although usually well tolerated but can cause nausea, vomiting, depression, mania, confusion, and aggression in AD patients.
The most important questions in Mr S.N.’s case is why did he develop Alzheimer’s disease, how can we prevent it progressing and can we reverse it?
According to his geriatrician he has Alzheimer’s however on examination he seems to be functioning well and continues to drive. Does he have mild cognitive impairment or age related memory impairment? Studies show a probable increase to Alzheimer’s at 10-15%/year anyway and the treatment principles remain the same .(2)
Mr S.N.’s risk factors include his age (2% aged 75-79), low educational attainment(3), hyperlipidaemia (4) and an elevated homocysteine level (5) .
He was supplemented with folate, B6 and B12 and it is noteworthy that these are essential cofactors for the methylation of homocysteine. In one study of older individuals with elevated homocysteine levels and cognitive decline the supplementation of these 3 vitamins maintained memory performance and reduced the rate of brain atrophy. He was also advised to have a high plant based diet which is rich in B vitamins.(6)
He is also MTHFR heterozygous further justifying supplementation with B2, methylfolate, methylcobalamin and B6.(7). He lacks any basophils which can also indicate B3, folate and B12 deficiency. (8)
His platelets reflect likely an essential fatty acid imbalance and his diet lacks omega 3’s.One study showed deficiency in docosahexaenoic acid (DHA), a brain-essential omega-3 fatty acid, is associated with cognitive decline.(9). In human neuronal cells DHA attenuates amyloid beta secretion which is accompanied by the formation of NPD1 which promotes brain cell survival by inducing neuroprotective gene expression. Hence he was supplemented with DHA. This supplement also contained phosphatydilserine . Phosphatidylserine (PS) is a key constituent of brain and nerve cell membranes and may help to improve memory in people with age-related cognitive decline. A double-blind, placebo controlled study using 494 patients, over the age of 65, examined the benefits of 300 mg of PS on men and women with moderate to severe age-related cognitive decline. Significant improvements in behaviour and cognitive performance, including memory recall, were distinguished in the PS group, compared to placebo.(10)
He has a high copper: zinc ratio and this is a risk factor and should be rectified (11). Excess copper, causes neuronal toxicity. Also zinc deficiency, causes neuronal damage. Brewer et al presents evidence that Alzheimer's disease (AD) has become an epidemic in developed, but not undeveloped, countries and that the epidemic is a new disease phenomenon, beginning in the early 1900s and exploding in the last 50 years. This leads to the conclusion that something in the developed environment is a major risk factor for AD. They hypothesized that the factor is inorganic copper, leached from the copper plumbing, the use of which coincides with the AD epidemic. They present a web of evidence supporting this hypothesis. Regarding zinc, they have shown that patients with AD are zinc deficient when compared with age-matched controls. Zinc has critical functions in the brain, and lack of zinc can cause neuronal death. A non-blinded study about 20 years ago showed considerable improvement in AD with zinc therapy, and a mouse AD model study also showed significant cognitive benefit from zinc supplementation. In a small blinded study they carried out, analysis revealed that 6 months of zinc therapy resulted in significant benefit relative to placebo controls in cognition. These two factors may be linked in that zinc therapy significantly reduced free copper levels. Thus, zinc may act by lowering copper toxicity or by direct benefit on neuronal health, or both.(12) Mr S.N. was placed on zinc, molybdenum, manganese, vitamin c, chromium and magnesium to reduce copper. He was also advised to drink filtered water only and avoid any copper in his vitamins.
He eats a highly processed diet which lacks antioxidants (13) and flavanoids (14).
In a cross sectional study of 2031 patients aged 70-74 the consumption of 10g/day of chocolate and 75ml/d of red wine resulted in superior cognitive performance. Hence he was educated on flavanoids and advised to incorporate them into his daily dietary routine.(14)
Antioxidants protect neurons from free radical and reactive oxygen damage.(15) Vitamin E and C in particular protected against dementia and was associated with reduced Alzheimer’s prevalence ( OR 0.22).(16) He was supplemented with both (mixed tocopherols) and there may be merit in this preventing further decline in cognition.
A RCT of 613 patients with mild to moderate AD over 5 years showed on 2000iu/day of alpha tocopherol there was a 19% delay in clinical progression compared with placebo.(17) He was also advised to get more of these vitamins in his diet i.e. seeds, nuts, green leafy vegetables, some fruits and whole grains as dietary sources were more protective.(18)
With regards to his Bioscreen data increased distribution of lactic acid bacteria (Streptococcus, Enterococcus sp.) may lower the colonic pH (19) and has been reported to modify faecal microbial metabolism particularly the Bacteroides and Bifidobacterium spp, resulting in a decreased production of volatile fatty acids (20), and also alter intestinal epithelial barrier function increasing passive intestinal permeability to small and large molecules. Although this consideration requires further study he was still treated for leaky gut.
High colonization of faecal lactic acid bacteria (Streptococcus, Enterococcus sp.) significantly and positively correlate with cognitive dysfunctions (nervousness, memory loss, forgetfulness, confusion, mind going blank)(220.127.116.11) and sleep patterns.
Also he had high levels of Lactobacillus spp. in the anaerobic microbial flora. Metabolic acidosis and neurological dysfunction (depressed conscious state, confusion, aggressive behaviour, slurred speech and ataxia) have been reported in patients with increased level of lactobacilli in the anaerobic faecal flora (25).
FOS was started to reduce E.Coli and promote bifidobacteria growth. (26)
Hence it is imperative to treat his gut dysbiosis.
Mr S.N. has a very good vitamin D level however I maintained him on about 3500 iu /day. This is because a studies suggest that lower vitamin D concentrations are associated with poorer cognitive function and a higher risk of AD.(27) Vitamin D insufficiency may be a modifiable risk factor for dementia as the role of vitamin D in brain function is becoming clearer. At the molecular level, the brain has the ability to synthesize the active form of vitamin D (1,25-dihydroxyvitamin D) with predominance in the hypothalamus and the substantia nigra. Vitamin D regulates genes allowing cells to synthesize relevant products in response to routine signals. Vitamin D contributes to neuroprotection by modulating the production of nerve growth factor (NGF), neurotrophin 3, glial cell derived neurotrophic factor (GDNF), nitric oxide synthase (iNOS), and choline acetyl transferase.
Curcumin has many modes of action in AD including antioxidant effects, metal chelation, actions on glial cells including decreased proliferation of neuroglial cells and increased oligodendrocyte activity. It also has anti inflammatory effects and reduces beta amyloid plaques.(28) Research indicates the prevalence of AD among adults aged 70-79 years in India is 4.4 times less than that of adults aged 70-79 years in the United States most likely due to high curcumin consumption .(29) I maintained Mr S.N. on 350mg bd.
Mr S.N. was already on Ginko Biloba and I urged him to keep taking this. Studies show it protects against neuronal damage and improves blood viscosity. Various in vivo and in vitro preclinical studies support the notion that Ginkgo biloba extract may be effective in the treatment and prevention of AD. Anti-oxidation, anti-apoptosis, anti-inflammation, protection against mitochondrial dysfunction, amyloidogenesis and A? aggregation, ion homeostasis, modulation of phosphorylation of tau protein and even induction of growth factors are possible mechanisms of action.(30)
Coq10 improves nerve and glial cell energy metabolism however there are no RCT’s.(31) He was supplemented with 300mg/d.
L-carnitine is a scavenger of free radicals in the mitochondria, a cell membrane stabiliser and stimulates nerve growth factor.(32) It improves fatigue and physical and mental function in the elderly and improves both the cognitive status and physical functions.(33)
Melatonin is shown to decline in AD patients resulting in circadian disorganization and decreased sleep and cognitive dysfunction. Melatonin also has antioxidant, antiamyloidogenic and mitochondrial effects indicating its potentiality to interfere with the onset of the disease. This is of particularly importance in mild cognitive impairment (MCI) hence supplementation has a definite add on role. Melatonin replacement has been shown to be effective in treating sundowning and other sleep wake disorders in AD patients.(34)
There is not much data on 5HTP however as a precursor to serotonin and melatonin it also aids in sleep.
Alpha lipoic acid is an antioxidant that has positive effects on glucose metabolism, oxidative stress and energy depletion which are characteristic of AD. In one small study 600mg/day was given to 9 patients with AD who were also receiving standard treatment with acetylcholinesterase inhibitors over about a year. Results showed stabilisation of cognitive function measured by MMSE and ADAScog. Alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD and related dementias.(35)
Oleocanthal, a phenolic component of extra-virgin olive oil, has been recently linked to reduced risk of Alzheimer's disease (AD). The mechanism in in vitro and in vivo studies is the clearance of B amyloid at the blood brain barrier.(36). 1 litre of extra virgin olive oil /week resulted in better cognition. (37) Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer’s disease.(38) So Mr S.N. was advised a diet high in olive oil, omega 3 from fish, low in saturated fat, high in plant phenols, high vegetable and moderate fruit to improve oxidation and inflammation and switch on nitric oxide and change gene expression.
Mr S.N was also advised to continue to remain active. In one study 12 weeks of moderate exercise improved neural efficiency in mild cognitive impairment as measured by functional MRI .(39)
In terms of general body burden BPAs, PCBs, pesticides, phthalates, mercury, aluminium, lead, and cadmium should all be avoided. (40,41,42,43,44)
If he fails to improve it is worth while doing a post-chelation heavy metals challenge urine test and considering chelation or detoxification if he has high heavy metals. Aluminium and mercury have been demonstrated in the brains of AD patients.(40,44) In areas of high aluminium water contamination there is a higher prevalence of AD(44). Significant memory deficits were found in 32 out of 40 studies on individuals exposed to inorganic mercury.(44) We know mercury interferes with polymerization of microtubules, increases secretion of Abeta proteins, promotes hyperphosphorylation of tau protein, changes mitochondrial structure, interferes with cell-maturation, DNA repair, glutathione level and linkage and structure of microtubules .(44)
ApoE4 is the major genetic risk factor for Alzheimer‘s .How apoE4 influences AD onset and progression has yet to be proven. It has probable effects on Abeta aggregation and clearance which plays a major role in AD pathogenesis. It possibly modulates tau phosphorylation, as well as plays a role in synaptic plasticity and neuroinflammation. (45).
Is it worthwhile testing APO-E in this patient and will it make a difference to the treatment outcome? In one study MCI subjects carrying the APOE 4 allele showed distinct cognitive and imaging profiles, which appeared to resemble those of early Alzheimer patients. APOE4 genotype was associated with greater impairments in memory and functional activities as well as hippocampal atrophy.(46) So if he was APOE4 positive he would have a worse prognosis but what can we do about it that is different to what we are already doing?
In another study B-amyloid was measured in the CSF of those with MCI and APOE4 and found to be higher in those on a high saturated fat /high GI diet compared to those on a low saturated fat/ low GI diet .When the diet changed to a low one the levels went down. (47) If the patient can afford the test he should do one to confirm his prognosis. In any case he has to stay on a healthy diet. APOE4 testing may be more useful in the asymptomatic patient who is considering making lifestyle changes to avoid dementia and many other cardiovascular morbidities and mortalities.
There are many factors that contribute to Alzheimer’s disease and multiple modalities which need to be addressed and rectified to effectively treat Alzheimer’s in order to prevent it progressing. At the very least one should follow the lifestyle recommendations of the “physicians committee for responsible medicine.” This includes eating plant based foods predominantly i.e. vegetables, legumes (beans, peas, and lentils), fruits, and whole grains should replace meats and dairy products as primary staples of the diet. Further to this consume 15mg of vitamin E daily through seeds, nuts, green leafy vegetables, and whole grains. Avoid trans and saturated fats. Take a B12 supplement. Avoid vitamins with iron and copper. Avoid aluminium e.g. in cookware, antacids and baking powder. Exercise aerobically for 120 minutes/week. I would add to this a diet high in olive oil like the Mediterranean one and include lots of flavanoids. Also vitamin D is very important so advise the patient to get 30 minutes of morning sun every day.(48)
Without the necessary lifestyle changes supplements will not make a difference however they can get the patient cognitively stable more quickly with the right lifestyle. Ultimately the patient is in control of their own health.
From a physicians point of view control all the risk factors you can including reducing homocysteine, cholesterol and copper . Manage the gut and detoxify any heavy metals .
2.Grundman, M., R. Petersen, et al. (2004). "Mild Cognitive Impairment Can Be Distinguished From Alzheimer Disease and Normal Aging for Clinical Trials." Arch Neurol 61(1): 59-66.
3.Farfel, J., R. Nitrini, et al. (2013). "Very low levels of education and cognitive reserve: a clinicopathologic study." Neurology 81(7): 650-7.
4.Tan ZS, Seshadri S, Beiser A, et al. Plasma total cholesterol level as a risk factor for Alzheimer disease: The Framingham Study. Ann Intern Med 2002; 137:149–155.
Sudha Seshadri, M.D., Alexa Beiser, Ph.D., Jacob Selhub, Ph.D., Paul F. Jacques, Sc.D., Irwin H. Rosenberg, M.D., Ralph B. D'Agostino, Ph.D., Peter W.F. Wilson, M.D., and Philip A. Wolf, M.D.N Engl J Med 2002; 346:476-483 February 14, 2002 .
. Biofactors. 2012 Mar-Apr;38(2):107-13.
large intestine. Journal of Applied Bacteriology 1993;?75:373-80.
39.. Smith JC1, Nielson KA, Antuono P, Lyons JA, Hanson RJ, Butts AM, Hantke NC, Verber MD. Semantic memory functional MRI and cognitive function after exercise intervention in mild cognitive impairment. J Alzheimer’s Dis. 2013;37(1):197-215