Alzheimer s Disease (AD) and Dietary Supplementation George C. SPATHARAKIS

Transcription

1 Alzheimer s Disease (AD) and Dietary Supplementation George C. SPATHARAKIS Geriatrician Gerontologist, Thessaloniki, george_spatharakis@yahoo.com

2 INTRODUCTION Although it is well established that AD constitutes a multifactorial, chronic, degenerative disease, a simple search on the mass media will soon reveal a profusion of information and proposals of treatments with certain magic pills alias elixirs that promise miraculous results on the stopping of progression or even inversion of the disease and representing a flourishing industry

3 INTRODUCTION However, only a small fraction of these claims, are supported by sound and adequate scientific research

4 PROTECTION from WEIGHT LOSS in AD PATIENTS An area where scientific proof is sound is that of caloric and/or protein supplementation of Alzheimer s patients in the process of losing or at high risk of losing body weight as it is known that weight loss is accompanied with worsening of the cognitive status.

5 EPIDEMIOLOGY of WEIGHT LOSS in AD PATIENTS Weight loss affects 30 to 45% of AD patients, mainly roaming people, and it worsens with the evolution of the disease - Raynaud-Simon A, Lesourd B. Dénutrition du sujet âgé. Conséquences cliniques.presse Méd 2000; 29 : Gillette-Guyonnet S, Abellan Van Kon G, Alix E, Andrieu S, Belmin J, Berrut G et al. IANA (International Academy on Nutrition and Aging) Expert Group: weight loss and Alzheimer s disease. J Nutr Health Aging 2009;13: Shah RC. Medical foods for Alzheimer s disease. Drugs Aging 2011;28:

6 WORSENING of AD PATIENTS Presenting With WEIGHT LOSS Vellas B et al, J Nutr Health Aging. 2005;9(2):75-80 Impact of nutritional status on the evolution of Alzheimer's disease and on response to acetylcholinesterase inhibitor treatment AD patients living at home with a caregiver are frequently at risk of undernutrition. Undernourished patients seem to present more rapid aggravation of the disease

7 PREVENTION of WEIGHT LOSS in AD PATIENTS Energy-rich and especially Protein-rich oral nutritional supplements can help preventing and fighting malnutrition among AD patients Shah RC. Medical foods for Alzheimer s disease. Drugs Aging 2011;28: Salva A, Andrieu S, Fernandez E, Schiffrin EJ, Moulin J, Decarti B et al. Health and nutrition promotion program for patients with dementia (NutriAlz): cluster randomized trial. J Nutr Health Aging 2011:15:822-30

8 DIETARY SUPPLEMENTATION MEDICAL FOODS DEFINITION Industry research is interested, among others, in the discovery and development of medical foods that is of foods formulated for enteral taken under physician supervision, and intended to meet the distinctive nutritional requirements identified for a disease or condition

9 DIETARY SUPPLEMENTATION LEVEL of EVIDENCE The kind and level of available supporting evidence for each one of these substances is different and varies from experimental in vitro studies and animal models to epidemiological studies Few are the available observational and intervention studies and even lesser the randomized control trials (RCTs) or the metaanalyses Substances are briefly presented using a critical approach of the available publications

10 DIETARY SUPPLEMENTATION LIST of SUBSTANCES The list of substances used so far include: n-3 polyunsaturated fatty acids (PUFAs) Gingko biloba leaf extracts Antioxidant flavonoids and non-flavonoid polyphenols (like lycopene, quercetin, resveratrol, curcumin, etc.) Antioxidant Vitamins (like β-carotene, C and E) Vitamin D certain Vitamins of the B complex Selenium Choline S-adenosyl methionine (SAM)

11 n-3 P U F A Level of Evidence: META-ANALYSIS of RCTs Citations Controlled: 3692 Studies included: 34 Participants: 12,999 (1031 infants, 1517 children, 3657 adults, and 6794 elderly individuals) CONCLUSION: n-3 PUFA supplements may significantly improve cognitive development in infants but do not improve cognitive performance in children, adults, or the elderly. BUN S. et al, J Alzheimers Dis Dec 16.

12 GINKGO BILOBA Level of Evidence: META-ANALYSIS Studies included: 9 Participants: 2,372 individuals Duration: weeks CONCLUSION: the SMDs in change scores for cognition were in favor of GB compared to placebo (-0.58, 95% confidence interval [CI] ; -0.01, p = 0.04), but did not show a statistically significant difference from placebo for activities in daily living (ADLs) (SMD = -0.32, 95% CI -0.66; 0.03, p = 0.08) Weinmann S et al, BMC Geriatr Mar 17;10:14

13 GINKGO BILOBA -- RESULTS Heterogeneity among studies was high. For the Alzheimer subgroup, the SMDs for ADLs and cognition outcomes were larger than for the whole group of dementias with statistical superiority for GB also for ADL outcomes (SMD = -0.44, 95% CI -0.77; -0.12, p = 0.008). Drop-out rates and side effects did not differ between GB and placebo. No consistent results were available for quality of life and neuropsychiatric symptoms, possibly due to the heterogeneity of the study populations

14 GINKGO BILOBA Level of Evidence: META-ANALYSIS Studies included: 36 Participants: 2,016 individuals CONCLUSION: The results of the more recent trials showed inconsistent results for cognition, activities of daily living, mood, depression and carer burden. Of the 4 most recent trials to report results 3 found no difference between GB and placebo, and 1 found very large treatment effects in favour of GB Birks J, Grimley Evans J, Cochrane Database Syst Rev Jan 21;(1):CD003120

15 GINKGO BILOBA -- RESULTS Level of Evidence: META-ANALYSIS Studies included: 36 Participants: 2,016 individuals CONCLUSION: There are no significant differences between GB and placebo in the proportion of participants experiencing adverse events A subgroup analysis including only patients diagnosed with Alzheimer's disease (925 patients from 9 trials) also showed no consistent pattern of any benefit associated with GB Birks J, Grimley Evans J, Cochrane Database Syst Rev Jan 21;(1):CD003120

16 FLAVONOID CHEMICAL SUBGROUPS and RELATIVE FOOD SOURCES Mecocci P. et al, Front. Pharmacol., 2014, June

17 FLAVONOID and NON-FLAVONOID ANTIOXIDANTS' USE RCTs Mecocci P. et al, Front. Pharmacol., 2014, June

18 ANTIOXIDANT VITAMINS Vitamin E Farina N et al, Cochrane Database Syst Rev Nov Vitamin E for Alzheimer's dementia and mild cognitive impairment Level of Evidence: META-ANALYSIS Studies included: 3 for AD and 1 for MCI CONCLUSION: No convincing evidence that vit. E is of benefit in the treatment of AD or MCI. Future trials assessing vitamin E treatment in AD should not be restricted to alpha-tocopherol

19 ANTIOXIDANT VITAMINS No Vitamins C and E Boothby LA, Doering PL, Ann Pharmacother Dec;39(12): Vitamin C and vitamin E for Alzheimer's disease CONCLUSIONS: In the absence of prospective, RCTs documenting benefits that outweigh recently documented morbidity and mortality risks, vit. E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vit. C are lower than those with vit. E, the lack of consistent efficacy data for vit. C in preventing or treating AD should discourage its routine use for this purpose

20 VITAMIN D Balion C, Neurology 2012 Sep 25;79(13): Vitamin D, cognition, and dementia: a systematic review and meta-analysis lower vitamin D concentrations are associated with poorer cognitive function and a higher risk of AD. Further studies are required to determine the significance and potential public health benefit of this association

21 VITAMINS B Complex Clarke R, Am J Clin Nutr 2014 Aug;100(2): Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging

22 NEW DOMAIN of RESEARCH FIXED COMBINATIONS of SELECTED SUBSTANCES HOPE for SYNERGISTIC PROTECTIVE EFFECTS

23 SOUVENAID R Eicospentaenoic acid (EPA) 300 mg Docosahexaenoic acid (DHA) 1200 mg Phospholipids 106 mg Choline, 400 mg Uridine monophosphate 625 mg Vitamin E (alpha-tocopherol equivalents) 40 mg Selenium, 60 µg Vitamin B12, 3 µg Vitamin B6, 1 mg Folic acid, 400 µg Vitamin C, 80 mg

24 SOUVENAID R Scheltens P et al. "Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial". Alzheimers Dement Jan 2010': 6 (1): 1 10 Scheltens P et al. Souvenaid improves memory in drug-naïve patients with mild Alzheimer's disease: results from a randomized, controlled, double-blind study (Souvenir II) CtAD Nov 2011; J Nutr Health Aging 2011;15 (Suppl 1) S13

25 Combination of n-3 PUFAs + GINGKO BILOBA + LYCOPENE Bun S, J Alzheimers Dis Dec A Combination of Supplements May Reduce the Risk of Alzheimer's Disease in Elderly Japanese with Normal Cognition