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From Smart Drugs II, copyright (c) 1993 by Smart Publications. Used with permission.

Smart Drug Update

Recommended Combination-Therapies
for Alzheimer’s Disease

From the book Smart Drugs II: The Next Generation
by Ward Dean, M.D., John Morgenthaler, and Steven Wm. Fowkes

Table of Therapies

Thiamine (B-1) (50-500 mg 3 times daily)
Nutrition adjunct [Hoffer, 1993].

Niacin (B-3) (100-500 mg 3 times daily)
Enhanced cerebral circulation; nutritional adjunct [LaBrecque & Goldberg, 1967; Loriaux, et al., 1985; Hoffer, 1993].

Pyridoxine (B-6) (20-60 mg 3 times daily)
Support of methylation metabolism, co-factor in neurotransmitter synthesis [Imagawa, 1990; Deijen, et al., 1992].

Cobalamin (B-12) (1 mg weekly, by injection, or 1 mg daily, by mouth)
Age-associated loss of intrinsic factor; support of methylation metabolism [Shaw, et al., 1971; Roberts, 1982].

Folic acid (5 mg daily)
Support of methylation metabolism [Shaw, et al., 1971; Hoffer, 1993].

Vitamin B-complex (100% RDA 3-4 times daily)
Metabolic support, correction of nutritional deficiencies [Whitman, 1966; Altman, et al., 1973].

Lecithin (high phosphatidylcholine) (10 grams daily)
Membrane stabilization; acetylcholine precursor [Etienne, 1981].

or Choline chloride (3 grams daily)
Acetylcholine precursor [Thal, et al., 1981].

DMAE (dimethylaminoethanol) (100-1000 mg daily)
Precursor for choline and acetylcholine; lipofuscin removal [Fisman, et al., 1981; Ferris, 1981].

or Centrophenoxine (600 mg 2 times daily)
Cholinergic enhancement; lipofuscin removal [Ferris, 1981; Gedye, et al., 1972].

Ascorbate (vitamin C) (500 mg 3 times daily, up to 2000 mg 12X daily (up to bowel tolerance))
Nutritional support, water-soluble antioxidant support, sulfhydryl-reducing agent [Altman, et al., 1973; Roberts, 1982; Hoffer, 1993].

Vitamin E (400-1000 IU daily)
Antioxidant; lipid-membrane stabilization [Roberts, 1982].

Glutathione (100-1000 mg daily)
Sulfhydryl antioxidant [Roberts, 1982].

and/or Cysteine (500-1500 mg daily)
Sulfhydryl antioxidant and glutathione precursor [Fowkes, 1993].

CoEnzyme Q-10 (60-180 mg daily)
Support of energy metabolism [Imagawa, 1990; Imagawa, et al., 1990; Roberts, 1982].

Zinc (preferably as zinc aspartate) (25 mg daily)
Immune enhancement; nutritional support [Czerwinski, et al., 1974; Constantinidis, 1990a, 1990b].

Magnesium (500 mg 2 times daily)
Nutritional support; calcium-channel inhibition [Glick, 1990a, 1990; Landfield, 1986].

Acetyl-L-carnitine (1000 mg 2-3 times daily)
Cerebral metabolic enhancement [see SDII].

Aspirin (300 mg daily)
Anti-clotting agent; anti-inflammatory agent [Hoffer, 1993].

Deprenyl (5 mg twice daily (breakfast and lunch))
Dopaminergic neuroprotection; neuroendocrine regulation [Knoll, 1989; Dilman and Dean, 1992].

Diapid (vasopressin) (and DDAVP) (2-3 times daily)
Neuropeptide neurostimulation [Laczi, et al., 1982; Durso, et al. 1982].

DHEA (1 gram daily)
Steroid precursor; cyclic GMP stimulation [Bonnet and Brown, 1992; Roberts, 1990].

Estrogen (for women) (0.5-1.0 mg per day, days 1-25)
Hormone replacement [Fillit, et al., 1986].

Ginkgo biloba (40-120 mg 3 times daily)
Cerebral metabolic enhancement; cerebral circulation enhancement [see SD&N references].

Hydergine (6-12 mg daily (divided doses))
Neural metabolic enhancement [see SD&N references; Kugler, et al., 1978].

Melatonin (3-15 mg daily, 8-12 P.M.)
Circadian rhythm enhancement; sleep enhancement, neuroendocrine regulation [Arendt, et al., 1986; Dilman and Dean, 1992].

Nimodipine (30 mg twice daily)
Calcium-channel inhibition; vasodilation [see SDII: Nimodipine chapter].

Phosphatidylserine (100 mg 3 times daily)
Phospholipid nutrient support; membrane stabilization; methylation enhancement; membrane fluidization [see SDII: Phosphatidylserine chapter].

Piracetam (800 mg 3 times daily)
Cerebral metabolic enhancement [see SDII: Piracetam Update; see SD&N references].

Brewer's yeast / RNA (up to 15 grams, as tolerated)
Memory enhancement; nutritional support [Dalderup, et al., 1970; Munch-Petersen, et al., 1974].

Possible Adjuctive Strategies

Krebs-cycle intermediates (as directed)
Support of energy metabolism [Davies, 1981].

Pyritinol (200 mg 3 times daily)
Vasodilation; cerebral metabolic activation; cholinergic activation; cerebral circulation enhancement [Cooper and Magnus, 1980; Seyfried, 1989].

AL 7:2:1 (egg-lipid preparation) (10 grams daily (up to 30 grams daily))
Membrane fluidization; membrane stabilization [Shinitzky, et al., 1983].

L-Dopa (250-4,000 mg daily)
Dopamine precursor loading [Kristensen, et al. 1977; Jellinger, et al., 1980].

Tyrosine and/or phenylalanine (500-2000 mg, in A.M.) Noradrenergic precursor loading [Gelenberg, et al., 1980].

Bromocriptine (1.25-2.5 mg daily)
Dopamine receptor stimulation; prolactin suppression [Phuapradit, et al., 1978].

Ondansetron (0.25-1.0 mg 2 times daily)
Serotonin re-uptake inhibition (of 5-HT3 receptors) [see Ondansetron chapter references].

L-Tryptophan (500-2000 mg before sleep)
Serotonin precursor loading [Smith, Stromgren, et al., 1984].

Cylert (pemoline) (18-75 mg daily)
Psychostimulation [Bartus, 1979; Ferris, 1981].

TRH (as prescribed)
Neuropeptide stimulation [Hollister, 1986].

Thyroid hormone (0.25-0.5 mg daily)
Hormone replacement therapy [Barnes and Galton, 1976].

Chelation therapy (as administered)
Heavy-metal elimination; removal of aluminum and calcium cross-links [Cranton, 1992].

Gangliosides (as prescribed)
Miscellaneous.

Hyperbaric oxygen (as administered)
Improved oxygenation; metabolic enhancement [Raskin, et al., 1978].

or Oxygen (normobaric) (as administered or directed)
Improved oxygenation; metabolic enhancement [Jacobs, et al., 1969].

or H2O2 (intravenous) (as administered)
Improved oxygenation; metabolic enhancement [Roberts, 1981].

Trental (as prescribed)
Increase RBC elasticity [Harwart, 1979].

Tacrine (THA, Cognex) (25-200 mg, maximum tolerated dose)
Cholinergic enhancement, acetylcholinesterase inhibition [Farlo, 1992; Molloy, 1991].

Adapted and extensively revised from Bagne, et al., 1986.

References

Arendt J, Aldhous M, and Marks V. Alleviation of jet lag by melatonin: Preliminary results of controlled, double-blind trial. Brit Med J 292: 1170, 1986.

Dilman VM and Dean W. The Neuroendocrine Theory of Aging and Degenerative Disease, Center for Bio-Gerontology, Pensacola, FL, 1992.

Farlo M, Gracon SI, Hershey LA, et al. A controlled trial of tacrine in Alzheimer's disease. JAMA 268: 2523-29, 1992.

Fowkes, SW. Personal communication.

Gedye JL, Exton-Smith AN and Wedgewood J. A method for measuring mental performance in the elderly and its use in a pilot clinical trial of meclofenoxate in organic dementia. Age and Ageing 1: 74-80, 1972.

Gelenberg, et al. Tyrosine for the treatment of depression. Am J Psychiatry 137(5): 622-3, 1980.

Hollister LE. Summary and conclusions. In: Treatment Development Strategies for Alzheimer's Disease, by Crook T, Bartus R, Ferris S, and Gershon S (Eds.), Mark Powley Associates, Madison, CT, 1986, pp. 671-77.

Knoll J. The pharmacology of selegiline ((-)deprenyl). New Aspects. Acta Neurol Scand 126: 83-91, 1989.

Kugler, et al., 1978.

Molloy DW, Guyatt GH, Wilson DB, et al. Effect of tetrahydroaminoacridine on cognition function and behavior in Alzheimer's disease. Canadian Medical Association Journal 144: 29-34, 1991.

Roberts E. DHEA and its sulfate (DHEAS) as neurofacilitators: Effects on brain tissue in culture and on memory in young and old mice. A cyclic-GMP hypothesis of action of DHEA and DHEAS in nervous system and other tissues. In: The Biologic Role of DHEA, Kalimi M and Regelson W (Eds.), deGruyter, New York, 1990, pp. 13-42.

Shinitzky M, et al., Intervention in membrane aging — the development and application of Active Lipid. Intervention in the Aging Process: Basic Research and Preclinical Screening, New York: Alan R. Liss, 1983.