Diet and Cognitive Aging

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1 Diet and Cognitive Aging Martha Clare Morris, Sc.D. Director, Section of Nutritional Epidemiology, Dept of Medicine Rush University Medical Center Institute of Medicine Public Workshop by the Committee on the Public Health Dimensions of Cognitive Aging, Arnold and Mabel Beckman Center of the National Academics, Irvine, CA, June 9, 2014

2 OVERVIEW 1. Identify nutrients and foods important in cognitive aging 2. Describe evidence and issues for study interpretation LEVEL OF NUTRIENT CRITICALLY IMPORTANT CONSIDERATION OF NUTRIENT INTERACTIONS AND CONFOUNDING 3. Identify gaps and future directions to advance the science

3 Summary: Nutrition for a Healthy Brain Evidence Strong NUTRIENT Dietary tocopherols (vitamin E) DHA Folate Saturate Fat U/S Fats Moderate / Limited Evidence Carotenoids (βcarotene, luteine, lycopene) Flavonoids Vitamin D Trans fats Monounsaturated fat Polyphenols FOOD SOURCES Nuts, oils, seeds, green leafy vegetables, whole grains Fish 1 meal /week Vegetables, whole grains Commercial products, baked goods, red meats, high fat dairy Green leafy vegetables, bright colored fruit, vegetables Berries, tea, chocolate, Fish, dairy Commercial products, baked goods Olive oil Olive oil, red wine, teas, vegs, fruits

4 Vitamin E and Other Antioxidant Nutrients VITAMIN E VITAMIN C CAROTENOIDS FLAVONOIDS

5 Antioxidant Nutrients Vitamin E potent antioxidant within cell membranes Numerous animal and laboratory studies have shown that vitamin E reduces βamyloid deposition lipid peroxidation DNA damage & mitochondrial dysfunction neurotoxicity loss of neurons dendrite degeneration neuroinflammation

6 ANTIOXIDANTS IN DIET PROSPECTIVE STUDIES Exposure Vit E Vit C βcar Flav Mangialasche, 2013 dementia Serum + Devore, 2012, 2012 cognitive change Devore, 2010 AD Diet Diet Wengreen, 2007 cognitive change total Dai, 2006, AD total Corrada, 2005, AD total + Helmer, 2003 dementia Commenges, 2000 plasma diet + + Luchsinger, 2003 AD diet Morris, 2002 cognitive change Morris, 2002 AD diet diet Englehart, 2002 AD diet Kalmijn, 1997 MMSE diet La Rue, 1997 cognition diet

7 VITAMIN SUPPLEMENTS: Prospective and RCT STUDY Vit E Vit C βcar Devore, 2013 cognitive change + Kang, 2009, cognitive change + Gray, 2007, AD, dementia Kang, 2006 cognitive change * Fillenbaum, 2005 AD Peterson, 2005 AD Zandi, 2004 AD + + Luchsinger, 2003 AD Laurin, 2002 AD,dementia Morris, 2002 cognitive change Morris, 2002 AD + + Englehart, 2002 AD Morris, 2000 AD

6 years cognitive change No effect overall Interaction with dietary

8 Women s Health Study Randomized Clinical Trial 600 IU αtocopherol versus placebo 9.6 years cognitive change No effect overall Interaction with dietary intake Below median <6.1 mg/d β=.05 (.01,.09)* Above median >6.1 mg/d β=.01(.06,.03) Kang JH et al. Arch Intern Med 2006; 166:24628

9 Fish and n3 Fatty Acids

10 Fish: Brain Food 50% to 60% Lipid DHA cerebral cortex synaptosomes mitochondria Function Structural and functional maintenance of neuronal membranes Neurotransmission Membrane fluidity Modulation of ion channels, receptors, ATPase

11 Prospective Studies: n3 FA/Fish and Cognitive Decline STUDY Exp Outcome n FY n3 FISH Ammann, 2013 WHICSA RBC Test Battery Ronnemaa, 2012 ULSAM Serum AD/dementia y Kroger, 2009 CHS Erythrocyte Dementia 663 5y Van de Rest, 2009 V.A. NAS Diet Test Battery y Samieri, City Plasma Dementia y Whalley, 2008 Erythrocyte Globcog 120 4y Eskelinen, 2008 CAIDE Diet Global/mem y p=.06 Roberts, 2010 Mayo Diet MCI y Beydoun, 2007 ARIC Plasma Globcog y Wd Fluency Van Gelder, 2007 Zutphen Diet MMSE 210 5y Heude, 2003 EVA Erythrocyte MMSE 246 4y Morris, 2003 CHAP Diet Globcog y

12 Fish intake and Risk of Alzheimer s disease Prospective Epidemiologic Studies Rotterdam 3City CHS 1 fish meal / week 23 fish meals/week vs none 2+ fish meals /week vs less Paquid 1 fish meal / week Framingham DHA in the upper 25% CHAP 1 fish meal / week ODDS RATIO

13 Fish Oil Randomized Trials Study Participants Result Van de Rest, Healthy DHA/EPA Andreeva, CVD DHA&EPA/ Bvits/placebo Gileijnse, Coronary DHA&EPA/ ALA/placebo Sinn, MCI DHA/ EPA / LA ***No trial restricted recruitment to nonfish consumers or limited fish intake to less than once per week

14 No effect Baseline nutrient level Treatment nutrient level Willett, WC: 1998; Nutritional Epidemiology

15 Large Effect Willett, WC: 1998; Nutritional Epidemiology

16 Other Dietary Fats

17 Background Dietary fats effect blood cholesterol high ratio of saturated to unsaturated fats increase LDL and decrease HDLcholesterol Animal models: High Sat Fat/Chol Diet impaired memory BBB dysfunction Aβ deposition neuroinflammation neurotoxicity brain lesions

18 Prospective Studies of Fats and Cognitive Decline STUDY Exposure Outcome SAT TRANS MUFA PUFA U/S Okereke, 2012 WHS Diet Global Devore, 2009 NHS Diet Global Eskelinen, 2008 Finland Diet Global Beydoun, 2007 ARIC Plasma Global Morris, 2006 CHAP Diet Global Solfrizzi, 2006 ILSA Diet MMSE Heude, 2003 EVA Erythro MMSE Bowman, 2012 Oregon Plasma Global Roberts, 2012 MAYO Diet MCI Vercambre, 2010 WACS Diet Global Naqvi, 2011 WHI Diet

19 Example: Fat Correlations in CHAP Sat Fat PUFA MUFA Trans Sat Fat 1.0 PUFA MUFA Trans

20 Folate and Vitamin B12

BACKGROUND BGroup Vitamin Insufficiencies Vitamin

myelin Folate : increased homocysteine, impaired

in these nutrients may account for inconsistencies

21 BACKGROUND BGroup Vitamin Insufficiencies Vitamin B12: dementia, neuropathy, increased homocysteine, myelin Folate : increased homocysteine, impaired DNA repair Population differences in deficiencies in these nutrients may account for inconsistencies in study findings 1998 US grain fortification with folic acid

22 BVitamins and Incident Alzheimer s Disease Study n FU Exposure Folate B12 Kivipelto, y plasma Nelson, y diet Luchsinger, y diet Kim, y serum Morris MC, y diet Ravaglia, y serum Corrada, y diet Seshadri, y serum Wang, y serum Hinterberger, y Serum

23 Prospective Studies of BVitamins and Cognitive Decline Study n Exposure Cognitive Folate B12 Morris, MS 549 Plasma MMSE x Clarke, Serum MMSE Kang, serum globcog Moojaart, diet globcog Morris, diet globcog Tucker, plasma /diet mem/lang spatial copy Kado, plasma globcog Garcia, serum stroop Teunissen, serum cog battery McCaddon, mmse,adas

24 Prospective Studies of BVitamins and Cognitive Decline Study n Exposure Cognitive Folate B12 Morris, MS, Plasma MMSE x Clarke, Serum MMSE Kang, serum globcog Moojaart, diet globcog Morris, diet globcog Tucker, plasma /diet mem/lang spatial copy Kado, plasma globcog Garcia, serum stroop Teunissen, serum cog battery McCaddon, mmse,adas

25 Prospective Studies of BVitamins and Cognitive Decline Study n Exposure Cognitive Folate B12 Morris, MS 549 Plasma MMSE x Clarke, Serum MMSE Kang, serum globcog Moojaart, diet globcog Morris, diet globcog Tucker, plasma /diet mem/lang spatial copy Kado, plasma globcog Garcia, serum stroop Teunissen, serum cog battery McCaddon, mmse,adas

26 Randomized Trials of Vitamin B12 and Cognition Study n Sample Treatment Effect (tests) Hvas, Cog Imp (CI) B12 4 wk (1/4) Eussen, Low B12 CI B12 24 wk (2/16) Bryan, Normal B12 5 wk ND Seal, Low B12, norm. B12 4 wk ND Van Asselt, Low B12 B12 IM 5 mo + (3/9) Kwok, Low B12, norm. B12 IM 36mo + (1/8) Kral, Normal B12 3.5mo ND

27 Randomized Trials of Folic Acid and Cognition Study n Sample Treatment Effect (tests) Fiorvanti, low FA, CI FA 8 wk + (4/16) Bryan, normal FA 5 wk ND Durga, low FA FA 3 y + (5/6)

28 RCT of Combined BVitamins and Cognition Study n Sample Treatment Period Effect McMahon, High Hcy, normal 2 y Stott, VasDis, normal 3.5mo Lewerin, Normal 4 mo Eussen, CI, B12 low 6 mo Kang, CVD, normal 10 y ND overall + Low B vit De Jager, MCI, normal 2 y + (1/4 tests) Walker, Distressed, normal 2 y + Hankey, Stroke, normal 2.8 y

29 State of the Science: Diet and Dementia Cognitive Decline Alzheimer Disease Future Research Vitamin E Fish, n3 FA Other antioxidants Fats RCT; low vitamin status RCT; nonfish consumers Epidemiologic studies; focus on nutrient level Epidem studies; other fat adjust B12 and Folate Folate RCT; deficiency B12FA interaction

30 BRAIN HEALTHY DIET Foods to Include in Your Diet: Vegetable oils Nuts Whole grains Vegetables (green leafy) Fish Poultry Berries Foods to Avoid: High fat dairy products Fatty meats Fried foods Processed foods

31 FUTURE DIRECTIONS Additional epidemiological and animal studies on carotenoids, flavonoids, and other nutrients Report and determine levels of effect RCT designed to test nutrient supplementation at nutrient insufficiency RCT of diet patterns and of individual or functional foods (e.g. berries, nuts, cacao

The MIND Diet. Dr. Morris has no relevant conflicts of interest to disclose OVERVIEW 11/26/2018. to prevent dementia

The MIND Diet. Dr. Morris has no relevant conflicts of interest to disclose OVERVIEW 11/26/2018. to prevent dementia The MIND Diet to prevent dementia Martha Clare Morris, Sc.D. Director, Rush Institute for Healthy Aging and The MIND Center for Brain Health Rush University Medical Center Illinois Osteopathic Medical