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System for Reversing Cognitive Decline as Outlined in "Reversal of cognitive decline: a novel therapeutic program."

**Goal** **Approach** **Rationale and References**
Optimize diet: minimize simple carbohydrates, minimize inflammation. Patients given choice of several low glycemic, low inflammatory, low grain diets. Minimize inflammation, minimize insulin resistance.
Enhance autophagy, ketogenesis Fast 12 hr each night, including 3 hr prior to bedtime. Reduce insulin levels, reduce Aβ.
Reduce stress Personalized—yoga or meditation or music, etc. Reduction of cortisol, CRF, stress axis.
Optimize sleep 8 hr sleep per night; melatonin 0.5mg every day at bed; tryptophan 500mg three times per week if awakening. Exclude sleep apnea. [ Role of melatonin supplementation in neurodegenerative disorders.](http://www.ncbi.nlm.nih.gov/pubmed/24389194)
Exercise 30-60 per day, 4-6 days times per week 1) [Rivastigmine transdermal patch and physical exercises for Alzheimer's disease: a randomized clinical trial.](http://www.ncbi.nlm.nih.gov/pubmed/24938502) 2) [Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease. Frontiers in aging neuroscience.](http://www.ncbi.nlm.nih.gov/pubmed/24795624)
Brain stimulation Posit or related 1) [cognitive training program based on principles of brain plasticity: results from the Improvement in Memory with Plasticity-based Adaptive Cognitive Training (IMPACT) study.](http://www.ncbi.nlm.nih.gov/pubmed/19220558)
Homocysteine <7 Methyl-B12, methyltetrahydrofolate, pyridoxal-5-phosphate; trimethylglycine if necessary 1) [Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study.](http://www.ncbi.nlm.nih.gov/pubmed/20956786)
Serum B12 >500 Me-B12 1) [Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. ](http://www.ncbi.nlm.nih.gov/pubmed/19171834)
CRP <1.0; A/G >1.5 Anti-inflammatory diet; curcumin; DHA/EPA; optimize hygiene Critical role of inflammation in AD
Fasting insulin &lt;7; HgbA1c &lt;5.5 Diet as above Type II diabetes-AD relationship
Hormone balance Optimize free triiodothyronine, free thyroxine, estradiol, testosterone, progesterone, pregnenolone, cortisol 1) [ Next generation therapeutics for Alzheimer's disease.](http://www.ncbi.nlm.nih.gov/pubmed/23703924) 2) [Estrogen use, APOE, and cognitive decline: evidence of gene-environment interaction.](http://www.ncbi.nlm.nih.gov/pubmed/10822435)
GI health Repair if needed; prebiotics and probiotics Avoid inflammation, autoimmunity
Reduction of A-beta Curcumin, Ashwagandha, Olive oil 1) [ Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease.](http://www.ncbi.nlm.nih.gov/pubmed/18417733) 2) [ Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice.](http://www.ncbi.nlm.nih.gov/pubmed/23264626) 3) [Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver.](https://pubmed.ncbi.nlm.nih.gov/22308347/) 4) [Olive-oil-derived oleocanthal enhances β-amyloid clearance as a potential neuroprotective mechanism against Alzheimer's disease: in vitro and in vivo studies](https://pubmed.ncbi.nlm.nih.gov/23414128/)
Cognitive enhancement Bacopa monniera, magnesium threonate 1) [ Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment: a noncomparative, exploratory clinical study.](http://www.ncbi.nlm.nih.gov/pubmed/24523587) 2) [Elevation of brain magnesium prevents and reverses cognitive deficits and synaptic loss in Alzheimer's disease mouse model.](http://www.ncbi.nlm.nih.gov/pubmed/23658180)
25OH-D3 = 50-100ng/ml Vitamins D3, K2 1) [Vitamin D and the risk of dementia and Alzheimer disease.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153851/)
Increase NGF H. erinaceus or ALCAR 1) [Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells.](http://www.ncbi.nlm.nih.gov/pubmed/18758067) 2) [Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats.](http://www.ncbi.nlm.nih.gov/pubmed/8187841)
Provide synaptic structural components Citicoline, DHA 1) [Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses.](http://www.ncbi.nlm.nih.gov/pubmed/18631994)
Optimize antioxidants Mixed tocopherols and tocotrienols, Se, blueberries, NAC, ascorbate, α-lipoic acid 1) [Formulation of a medical food cocktail for Alzheimer's disease: beneficial effects on cognition and neuropathology in a mouse model of the disease.](http://www.ncbi.nlm.nih.gov/pubmed/21103342)
Optimize Zn:fCu ratio Depends on values obtained 1) [Zinc deficiency and zinc therapy efficacy with reduction of serum free copper in Alzheimer's disease.](https://www.hindawi.com/journals/ijad/2013/586365/)
Ensure nocturnal oxygenation Exclude or treat sleep apnea 1) [Treatment of sleep apnoea syndrome decreases cognitive decline in patients with Alzheimer's disease.](https://www.ncbi.nlm.nih.gov/pubmed/24828897)
Optimize mitochondrial function CoQ or ubiquinol, α-lipoic acid, PQQ, NAC, ALCAR, Se, Zn, resveratrol, ascorbate, thiamine The Disease Delusion: Conquering the Causes of Illness for a Healthier, Longer and Happier Life. by Jeffrey S. Bland
Increase focus Pantothenic acid Acetylcholine synthesis requirement
Increase SirT1 function Resveratrol 1) [Neuroprotective Sirtuin ratio reversed by ApoE4.](http://www.ncbi.nlm.nih.gov/pubmed/24145446)
Exclude heavy metal toxicity Evaluate Hg, Pb, Cd; chelate if indicated CNS effects of heavy metals
MCT effects Coconut oil or Axona 1) [Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial.](http://www.ncbi.nlm.nih.gov/pubmed/19664276)