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Nutrients for Memory: the Hawaii Dementia Prevention Trial by Steve Blake

Nutrients for Memory

The Hawaii Dementia Prevention Trial

Steve Blake, ScD

July, 2017


"It was good meeting you today and
I very much appreciated your informative
discussion of nutritional approaches to
prevention and treatment of
Alzheimer's disease and related dementias."

BRENT P. FORESTER, MD Instructor in Psychiatry, Harvard.
Director Mood Disorders Division,
Geriatric Psychiatry Research Program and
Site Director, McLean Hospital,

Harvard Medical School.

$9.95 to download the entire 183 page book

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Please click above for a KITV news feature
about the author and clinical trial,

OR, click below for a 24-minute TV
show explaining Alzheimer's disease:



see below for the table of contents
and the scientific references.

Back cover of Nutrients for Memory: the Hawaii Dementia Prevention Trial by Steve Blake

Neuroscience nutrition foundation

Watch the video below to learn more about the book

Nutrients for Memory and what we used in the trial:




Nutrients for Memory Table of Contents


Introduction           2
Table of Contents                     4
Table of figures 11
Chapter 1: Diet can be powerful                           13
Age and delaying dementia               13
The Nurses’ Health Study                       13
The MIND diet   14
Rush Memory and Aging Project                           15
Supplements to improve cognition                 17
The Hawaii Dementia Prevention Trial     18
Chapter 2: Overview of Alzheimer’s disease             22
Changes to the brain in Alzheimer’s disease             23
What are amyloid plaques                   25
Meet tau tangles                         27
An epidemic of Alzheimer’s disease               29
Junk food, diabetes, and Alzheimer’s disease         30
Diabetes and dementia risk               31
Drugs and Alzheimer’s disease   31
Prevalence of dementia                             33
Chapter 3: Food and nutrient changes that worked                 36
Vitamin E                     36
Advanced glycation endproducts                         37
Berries for memory               39
Vascular dementia and saturated fat         40
Supplements used in the trial       42
Two B-vitamins 42
SAMe       42
Antioxidants           43
Vitamin E supplement used               44
Vitamin C supplement used             45
Coenzyme Q10 45
Four antioxidant minerals                     46
Two medical plants used                         48
Ginkgo biloba       48
Centella asiatica (gotu kola)               48
Chapter 4: Folate, vitamin B12, homocysteine, and SAMe                       50
How amyloid plaques are made                           50
How two B-vitamins reduce the formation of amyloid plaques     52
Folate and vitamin B12 transform homocysteine into SAMe.             54
Homocysteine and Alzheimer’s disease 55
Are we getting enough Folate and Vitamin B12?                             57
Getting enough vitamin B12             59
SAMe and Alzheimer’s disease   62
Chapter 5: Advanced Glycation Endproducts           65
Absorption of AGEs               66
Formation of AGEs                 67
AGEs as a cause of brain damage in Alzheimer’s disease                           70
Cooking methods to reduce AGEs in food                       72
Chapter 6: Antioxidants and Alzheimer’s disease                         74
Vitamins E and C protect brain cell membranes from free radical attack 75
Causes of excess free radicals       76
Radiation and medical testing as sources of free radicals                         77
Plant Antioxidants Defend Us from Free Radicals                         78
Vitamin E and Alzheimer’s disease                   79
Why synthetic vitamin E is ineffective         80
Food sources of vitamin E                     84
Vitamin C and Alzheimer’s disease                 86
Dietary sources of antioxidants 88
Plant antioxidants                   90
Antioxidants made in your body                           94
Protecting our little energy factories, the mitochondria   96
Coconut oil, ketones, and mitochondrial function                       97
Coenzyme Q10, the only fat-soluble antioxidant made in the body                   99
Are statins related to memory loss?             101
Antioxidant content in diets             104
Chapter 7: Saturated fat and dementia   106
Saturated fat in diets         109
Blood cholesterol and risk of Alzheimer’s disease                       111
Oxidized dietary cholesterol and vascular dementia               112
Crystallized cholesterol 117
Lowering cholesterol using phytosterols                           119
Fiber and blood cholesterol               121
Chapter 8: Medical plants to treat Alzheimer’s disease     123
Ginkgo biloba       123
How does ginkgo work?                           123
How ginkgo protects brain cells 125
Ginkgo and bleeding           126
Ginkgo and memory           126
Gotu kola                     127
Gotu kola as an antioxidant               128
Gotu kola improves memory scores             128
Gotu kola for memory in healthy elders 129
Chapter 9: Exercise and Alzheimer’s disease             130
Exercise and vascular dementia 131
Muscle strength and Alzheimer’s disease                       131
Exercise decreases brain shrinkage                 132
Exercise can reduce risk of dementia           132
Exercise can cut risk of dementia in half                             133
More exercise cuts risk further   133
Chapter 11: Environmental toxins and Alzheimer’s disease                 135
Seafood, mercury, and DHA             135
Organophosphate pesticides and dementia               137
Organochlorines and dioxins         138
Aluminum, does it cause Alzheimer’s disease?     139
Chapter 12: Nutritional approaches to Alzheimer’s disease                 141
Acknowledgements               144
Index       145
Reference citations               150
Table of figures
Figure 1   Three supplements helped cognition     18
Figure 2   Improvement in our trial                     19
Figure 3   No degeneration was noted with food changes                           20
Figure 4   Normal decline of memory score                   20
Figure 5   Normal brains on the left and advanced Alzheimer’s disease on the right                           23
Figure 6   Amyloid plaques look like fuzz balls between neurons.                             25
Figure 7     Amyloid plaques and tau tangles                   26
Figure 8   Tangled neuron looks like a fried egg     27
Figure 9   The great increase in Alzheimer's death rate       29
Figure 10 Dementia forecast for less developed countries                       33
Figure 11 Forecast increase in Alzheimer's disease                   34
Figure 12 Types of dementia graph                 40
Figure 13 Folate and vitamin B12 and amyloid plaque       51
Figure 14 How amyloid plaque is formed                         52
Figure 15 Homocysteine and B-vitamins                             54
Figure 16 Folate can be low on an American diet                           57
Figure 17 Folate in food from the Diet Doctor         59
Figure 18 Folate and vitamin B12 in diets                         61
Figure 19 List of foods highest in AGEs     69
Figure 20 Synthetic vitamin E structure   82
Figure 21 Nut and seed sources of vitamin E             85
Figure 22 Vitamin E in some common foods             86
Figure 23 Vitamin C in food graph                     88
Figure 24 Antioxidants in common diets                           89
Figure 25 A tiny amount of manganese on an Atkin's diet                       96
Figure 26 Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study.                     105
Figure 27 Saturated fat in various food servings 108
Figure 28 A mostly clogged artery                       110
Figure 29 LDL diagram showing signaling proteins                       115
Figure 30 Cholesterol crystals in plaque 118
Figure 31 Sources of plant sterols to block cholesterol       120


Reference Citations:


Dietary intakes of berries and flavonoids in relation to cognitive decline, Devore, Elizabeth E., et al. Annals of neurology 72.1 (2012): 135-143.
MIND diet associated with reduced incidence of Alzheimer's disease, Morris, Martha Clare, et al. Alzheimer's & Dementia 11.9 (2015): 1007-1014.
Nutrition and risk of dementia: overview and methodological issues, Morris, Martha Clare, Annals of the New York Academy of Sciences 1367.1 (2016): 31-37.
Fruit and vegetable consumption and cognitive decline in aging women, Kang et al., Annals of Neurology 57.5 (2005): 713-720.
Effects of vitamins E and C combined with carotene on cognitive function in the elderly, Li, Yonghua, et al. Experimental and therapeutic medicine 9.4 (2015): 1489-1493.
Proteolytically Inactive Insulin-Degrading Enzyme Inhibits Amyloid Formation Yielding Non-Neurotoxic Ab Peptide Aggregates, Tullio et al., PLoS ONE, April 2013, Volume 8, Issue 4, e59113.
Insulin Resistance and Alzheimer´s Disease: Molecular Links & Clinical Implications, Neumann et al., Current Alzheimer Research, 2008, Vol. 5, No. 5.
Alzheimer’s beta-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme, Kurochkin et al., Federation of European Biochemical Societies Letters 345 (1994) 33-37.
Midlife cardiovascular risk factors and risk of dementia in late life, Whitmer, Rachel A., et al. Neurology 64.2 (2005): 277-281.
Diabetes, Alzheimer disease, and vascular dementia A population-based neuropathologic study, Ahtiluoto, S., et al. Neurology 75.13 (2010): 1195-1202.
Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer Disease, Clarke, et al.
Archives of Neurology, November 1998, volume 55.
Homocysteine, folate, and vitamin B-12 on mild cognitive impairment, Alzheimer Disease, and vascular dementia, Quadri, et al. American Journal of Clinical Nutrition, Vol. 80, No. 1, 114-122, July 2004.
Homocysteine and folate as risk factors for dementia and Alzheimer Disease, Ravaglia, et al.
American Journal of Clinical Nutrition, Vol. 82, No. 3, 636-643, September 2005.
Protein Phosphatase 2A Methyltransferase Links Homocysteine Metabolism with Tau and Amyloid Precursor Protein Regulation, Sontag et al. The Journal of Neuroscience, March 14, 2007, 27(11):2751-2759.
S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production, Fuso et al. Molecular and Cellular Neuroscience 28 (2005) 195- 204.
Protein Phosphatase 2A Methyltransferase Links Homocysteine Metabolism with Tau and Amyloid Precursor Protein Regulation, Sontag et al. The Journal of Neuroscience, March 14, 2007, 27(11):2751-2759.
S -Adenosylmethionine Is Decreased in the Cerebrospinal Fluid of Patients with Alzheimer’s Di sease. Linnebank et al. Neurodegenerative Dis 2010;7:373-378.
S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. Najm et al. BMC Musculoskeletal Disorders 2004, 5.
Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype? Semba et al. J Gerontol A Biol Sci Med Sci. 2010 September;65A(9):963-975.
Orally absorbed reactive glycation products (glycotoxins): An environmental risk factor in diabetic nephropathy, Koschinsky et al. Proc. Natl. Acad. Sci. USA 94 (1997).
Active glycation in neurofibrillary pathology of Alzheimer disease: N-(Carboxymethyl) lysine and hexitol-lysine, Castellani et al. Free Radical Biology and Medicine Volume 31, Issue 2, 15 July 2001, Pages 175-180.
Advanced Glycosylation End Products and Nutrition-A Possible Relation with Diabetic Atherosclerosis and How to Prevent It, Xanthis, Vol. 72, Nr. 8, 2007, Journal of Food Science.
Dietary Advanced Glycation End Products and Aging, Luevano-Contreras et al. Nutrients 2010, 2, 1247-1265.
Active glycation in neurofibrillary pathology of Alzheimer disease: N-(Carboxymethyl) lysine and hexitol-lysine, Castellani et al. Free Radical Biology and Medicine Volume 31, Issue 2, 15 July 2001, Pages 175-180.
Amplifiers of Systemic Inflammation- The Role Advanced Glycation and Lipoxidation End Products in Foods,
Stig Bengmark, Kuwait Medical Journal 2008, 40 (1): 3-17.
Age- and Stage-dependent Accumulation of Advanced Glycation End Products in Intracellular Deposits in Normal and Alzheimer’s Disease Brains, Luth 2005 Cerebral Cortex February 2005;15:211-220.
Advanced Glycosylation End Products and Nutrition-A Possible Relation with Diabetic Atherosclerosis and How to Prevent It, Xanthis, Vol. 72, Nr. 8, 2007, Journal of Food Science.
Gofman, J. W. and E. O’Conner. X-Rays: Health Effects of Common Exams. San Francisco: Sierra Club Books, 1985.
A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease, Sano et al. April 24, 1997, JAMA Volume 336 Number 17.
Molecular bases of the treatment of Alzheimer’s disease with antioxidants: prevention of oxidative stress, Jose Vina, et al. Molecular Aspects of Medicine 25 (2004) 117-123.
Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study, Morris et Al. JAMA, June 26, 2002-Vol 287, No. 24.
High plasma levels of vitamin E forms and reduced Alzheimer’s disease risk in advanced age, Journal of Alzheimer’s Disease, volume 20, #4 2010.
Vitamins and Minerals Demystified, Blake, McGraw-Hill, 2008.
Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change, Morris et al. Am J Clin Nutr 2005;81:508 -14.
Vitamin E Forms in Alzheimer's Disease: A Review of Controversial and Clinical Experiences, Usoro and Mousaa, Critical Reviews in Food Science and Nutrition Volume 50, Issue 5, 2010, Pages 414 - 419.
Lowered plasma vitamin C, but not vitamin E, concentrations in dementia patients. Charlton et al. The Journal of Nutrition Health & aging, 2004, vol. 8, no2, pp. 99-107.
Vitamin E and vitamin C supplement use and risk of incident Alzheimer’s disease, Morris et al. Alzheimer Disease & Associated Disorders: September 1998 - Volume 12 - Issue 3.
Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Masaki et al. Neurology 2000;54:1265-1272.
Dietary Intake of Antioxidants and Risk of Alzheimer Disease, Engelhart et al. JAMA. 2002;287:3223-3229.
The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide, Carlsen et al. Nutrition Journal 2010, 9:3.
Grape juice, berries, and walnuts affect brain aging and behavior, Joseph et al. Journal of Nutrition 139: 1813S-1817S 2009.
Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment, Krikorian et al. British Journal of Nutrition (2010), 103, 730-734.
Nutritional status of selenium in Alzheimer's disease patients, Cardoso et al. British Journal of Nutrition (2010), 103: 803-806 .
Coenzyme Q10 Attenuates -Amyloid Pathology in the Aged Transgenic Mice with Alzheimer Presenilin 1 Mutation, Yang et al. J Mol Neurosci (2008) 34:165-171.
Review: Fosslien, “Mitochondrial Medicine - Molecular Pathology of Defective Oxidative Phosphorylation,” Annals of Clinical & Laboratory Science, vol. 31, no. 1, 2001.
Catarina et al., “Coenzyme Q and Mitochondrial Disease,” Dev Disabil Res Rev. 2010 June ; 16(2): 183-188. doi:10.1002/ddrr.108.
Review: Fosslien, “Mitochondrial Medicine - Molecular Pathology of Defective Oxidative Phosphorylation,” Annals of Clinical & Laboratory Science, vol. 31, no. 1, 2001.
Rojas-Fernandez and Cameron, “Is Statin-Associated Cognitive Impairment Clinically Relevant? A Narrative Review and Clinical Recommendations,” Ann Pharmacother 2012;46:549-57.
Hyttinen et al., “Long-Term Statin Therapy is Associated with Better Episodic Memory in Aged Familial Hypercholesterolemia Patients in Comparison with Population Controls,” Journal of Alzheimer’s Disease 21 (2010) 611-617.
Dolga et a., “Statins - increasing or reducing the risk of Parkinson's disease?,” Experimental Neurology 228 (2011) 1-4.
Shintani et al., “Obesity and cardiovascular risk intervention through the ad libitum feeding of traditional Hawaiian diet,” Am J Clin Nutr 1991:53:1647S-51S.
Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study, Eha Nurk, British Journal of Nutrition (2010), 104, 1190-1201.
Nonoptimal Lipids Commonly Present in Young Adults and Coronary Calcium Later in Life: The CARDIA (Coronary Artery Risk Development in Young Adults), Pletcher et al. Annals of Internal Medicine, August 3, 2010, vol. 153 no. 3 137-146.
Mechanisms by which Dietary Fatty Acids Modulate Plasma Lipids, Fernandez and West, J. Nutr. 135:2075-2078, September 2005.
Food Combination and Alzheimer Disease Risk, A Protective Diet, Yian Gu et al. Arch Neurol. 2010;67(6).
Dietary Fats and the Risk of Incident Alzheimer Disease, Morris et al. Archives of Neurology 2003; 60: 194-200.
Apolipoprotein E4 Allele, Elevated Midlife Total Cholesterol Level, and High Midlife Systolic Blood Pressure Are Independent Risk Factors for Late-Life Alzheimer Disease, Kivipelto et al. Annals of Internal Medicine 2002, vol. 137, no3, pp. 149-155.
Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late-Onset Alzheimer Disease, Reitz et al. Archives of Neurology. 2010;67(12):1491-1497.
Independent inhibition of Alzheimer’s disease B- and G-Secretase cleavage by lowered cholesterol levels, Grimm et al. The Journal of Biological Chemistry Vol. 283, No. 17, pp. 11302-11311, April 25, 2008.
Oxysterols: A world to explore, Otaegui-Arrazola et al., Food and Chemical Toxicology 48 (2010) 3289-3303.
Oxidized Cholesterol in the Diet Accelerates the Development of Aortic Atherosclerosis, Staprans et al., Arteriosclerosis, Thrombosis, and Vascular Biology. 1998;18:977-983.
Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation, Abela, Journal of Clinical Lipidology (2010) 4, 156-164.
Continuous Dose-Response Relationship of the LDL-Cholesterol-Lowering Effect of  Phytosterol Intake. Demonty et al. Journal of Nutrition 139: 271-284, 2009.
The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial, Lin et al., European Journal of Clinical Nutrition (2010) 64, 1481-1487.
Plant sterol consumption frequency affects plasma lipid levels and cholesterol kinetics in humans, AbuMweis et al., European Journal of Clinical Nutrition (2009) 63, 747-755.
Phytosterol Composition of Nuts and Seeds Commonly Consumed in the United States, Phillips et al., J. Agric. Food Chem., 2005, 53 (24), pp 9436-9445.
Ginkgo biloba for dementia: a systematic review of double-blind placebo-controlled trials, Ernst E, Pittler, Clinical Drug Investigation.1999;17:301-8.
Flavonoids as modulators of memory and learning: molecular interactions resulting in behavioural effects, Rendeiro et al. Proceedings of the Nutrition Society 71.2 (2012): 246-262.
Radioprotection by plant products: present status and future prospects, Arora et al. Phytotherapy Research 19.1 (2005): 1-22.
The neuroprotective potential of flavonoids: a multiplicity of effects, Vauzour et al. Genes & nutrition 3.3-4 (2008): 115-126.
The ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by €amyloid, Bastianetto et al. European Journal of Neuroscience 12.6 (2000): 1882-1890.
Ginkgo biloba, Sierpina et al. Am Fam Physician, 2003 Sept 1 68(5) 923-926.
Ginkgo  biloba and Donepezil: a comparison in the treatment of Alzheimer’s dementia in a randomized placebo-controlled double-blind study, Mazza et al. European Journal of Neurology 2006, 13: 981-985.
Effects of Gingko biloba supplementation in Alzheimer's disease patients receiving cholinesterase inhibitors: data from the ICTUS study, Canevelli et al. Phytomedicine 21.6 (2014): 888-892.
Centella asiatica Extract Selectively Decreases Amyloid  Levels in Hippocampus of Alzheimer’s Disease Animal Model, Dhanasekaran et al. Phytotherapy Research. 23, 14-19 (2009).
Effect of different extracts of Centella asiatica on cognition and markers of oxidative stress in rats,
Kumar and Gupta, Journal of Ethnopharmacology, Volume 79, Issue 2, February 2002, Pages 253-260.
Comparison on Cognitive Effects of Centella Asiatica in Healthy Middle Age Female and Male Volunteers, Dev et al. European Journal of Scientific Research Vol.31 No.4 (2009), pp.553-565.
Effect of centella asiatica on mild cognitive impairment (MCI) and other common age-related clinical problems, Tiwari et al. Digest Journal of Nanomaterials and Biostructures Vol. 3, No.4, December 2008, p. 215 - 220.
Exercise Plus Behavioral Management in Patients With Alzheimer Disease: A Randomized Controlled Trial,
Teri et al. JAMA. 2003;290(15):2015-2022.
Physical Activity, Diet, and Risk of Alzheimer Disease, Scarmeas et al. JAMA, August 12, 2009-Vol 302, No. 6.
Effects of Aerobic Exercise on Mild Cognitive Impairment, A Controlled Trial, Laura D. Baker et al. Arch Neurol. 2010;67(1):71-79.
Association of muscle strength with the risk of Alzheimer disease and the rate of cognitive decline in community-dwelling older persons, Boyle, et al. (2009) Arch Neurol 66, 1339-1344.
Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease, Smith et al."Frontiers in Aging Neuroscience 6 (2014).
Physical activity, diet, and risk of Alzheimer disease. Scarmeas et al., (2009) JAMA 302, 627-637.
Alzheimer’s disease - the ways of prevention. Kivipelto and Solomon (2008) J Nutr Health Aging 12, 89S-94S.
Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Larson et al., (2006) Ann Intern Med 144, 73-81.
Physical activity and risk of cognitive impairment and dementia in elderly persons. Laurin et al., (2001) Arch Neurol 58, 498-504.
Physical exercise and mild cognitive impairment: A population-based study, Geda et al. Archives of Neurology, Vol 67 (NO. 1), JAN 2010, 80-86.
Effect of mercury levels and seafood intake on cognitive function in middle-aged adults, Masley et al., Integrative Medicine 11.3 (2012): 32.
No Effect of DHA Supplementation in Slowing Alzheimer's Progression, Quinn et al. JAMA. 2010;304:1903-1911, 1952-1953.
Low level methylmercury exposure affects neuropsychological function in adults, Yokoo et al. Environmental Health 2.1 (2003): 8.
Neurodegenerative Memory Disorders: A Potential Role of Environmental Toxins, Caban-Holt et al. Neurologic Clinics 23 (2005) 485-521.
Consumption of organic meat does not diminish the carcinogenic potential associated with the intake of persistent organic pollutants (POPs) Hernández et al. Environmental Science and Pollution Research 24.5 (2017): 4261-4273.
Organochlorine pesticide levels and risk of Alzheimer’s disease in north Indian population Singh et al. Human & experimental toxicology 32.1 (2013): 24-30.
Elevated serum pesticide levels and risk for Alzheimer disease Richardson, Jason et al. JAMA neurology 71.3 (2014): 284-290.
Low aluminum levels in the human brain from controls and Alzheimer patients, Delacourte et al. The Journal of Applied Neuroscience, Vol.2005.1-14.
Brain aluminum in aging and Alzheimer disease, John R. McDermott et al. Neurology, May 10, 2011, 76 (19).
Content of Brain Aluminum Is Not Elevated in Alzheimer Disease, Bjertness et al. Alzheimer Disease & Associated Disorders: Fall 1996 - Volume 10 - Issue 3.
Trace copper levels in the drinking water, but not zinc or aluminum influence CNS Alzheimer-like pathology, Sparks et al. The Journal of nutrition, health & aging 2006, vol. 10, no4, pp. 247-254.
Evidence for Participation of Aluminum in Neurofibrillary Tangle Formation and Growth in Alzheimer’s Disease, Walton, Journal of Alzheimer’s Disease 22 (2010) 65-72.
Link between Aluminum and the Pathogenesis of Alzheimer's Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses, Kawahara and Kato-Negish, International Journal of Alzheimer’s Disease. 2011; v2011.
Aluminum in the Diet and Alzheimer's Disease: From Current Epidemiology to Possible Disease-Modifying Treatment, Frisardi et al. Journal of Alzheimer's Disease, Volume 20, Number 1 / 2010.