8/06/2015. The Good News we are living longer! - but are we living healthier? National Research Priority: Preventive Healthcare

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Shawn Henderson
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June Life Expectancy in (CIA World Factbook) - but are we living healthier?

disability in Australia 99 "the science and art of preventing disease,

Leavell & EG Clark Functional capacity (physical & mental fitness) Early

Older Age Maintaining health and independence Disability threshold range of

disease and injury in Australia AIHW 7 WHO/HPS Geneva, Personalised

1 // The Good News we are living longer! Clinical Nutrition Research Centre University of Newcastle, Australia 7 th June Life Expectancy in (CIA World Factbook) - but are we living healthier? National Research Priority: Preventive Healthcare Increasing prevalence of disability in Australia 99 "the science and art of preventing disease, prolonging life and promoting physical and mental health and efficiency" HR Leavell & EG Clark Functional capacity (physical & mental fitness) Early Life Growth and development Adult Life Attaining highest level of function Older Age Maintaining health and independence Disability threshold range of function in individuals genes diet lifestyle Begg et al The burden of disease and injury in Australia AIHW 7 WHO/HPS Geneva, Personalised Diet/Lifestyle Guidelines (available on-line) Are the recommendations effective? December -9, Center for Nutrition Policy and Promotion, USDA,

// obesity Metabolic Syndrome mental fitness Estimates of dementia in Australia, Obesity Inflammation 9 s high blood glucose, insulin

in Australia Mental disorders.x risk of dementia if obese in middle age (K Anstey et al, ) http://www.aihw.gov.

inhibits cell adhesion/aggregation regulates vasomotor tone maintains barrier function (selective permeability) maintains vascular

Proteases fibronectin Thrombin laminin MMPs collagen I, II, III, IV, VIII, XVIII tpa proteoglycans Growth factors anti-,,

Vasorelaxation factors Factor V NO PAF PGI /E PAI-, PAI- EDHF Inflammatory Chemokines Vasoconstriction factors and Cytokines IL-, IL-,

Neuroinflammation ;: Endothelial dysfunction in metabolic syndrome smoking, high BP, high blood sugar, high blood fat, obesity, salt NO

of endothelial function flow mediated dilatation (FMD) expressed as % change in diameter ~% in healthy adults characterised by:-

vascular remodelling and hypertrophy (long term) Impaired Endothelial Function in Obesity Davison K et al, Journal of Obesity Obese Lean

±.. ±. <. DBP (mmhg) 7. ±. 7. ±. <. Large artery elasticity. ±.9. ±.. Small artery elasticity 7. ±. 7. ±..7 FMD (%). ±..7 ±.7 <.

2 // obesity Metabolic Syndrome mental fitness Estimates of dementia in Australia, Obesity Inflammation 9 s high blood glucose, insulin high blood pressure 7 Heart disease high blood fats Diabetes Prevalence of obesity in older Australians AIHW, % Prevalence of diabetes in Australia Mental disorders.x risk of dementia if obese in middle age (K Anstey et al, ) Prevalence of self-reported mental disorders AIHW, AIHW Year Metabolic syndrome is a circulatory disorder Roles of the endothelium inhibits cell adhesion/aggregation regulates vasomotor tone maintains barrier function (selective permeability) maintains vascular integrity (inhibits smooth muscle cell migration, proliferation) Endothelial Secretory/Expression Products Extracellular matrix factors Proteases fibronectin Thrombin laminin MMPs collagen I, II, III, IV, VIII, XVIII tpa proteoglycans Growth factors anti-,, pro-coagulation factors PDGF PGI EDGF thrombomodulin FGF AT III IGF Heparin sulfate TGF-β vwf GM-CSF TXA G-CSF thromboplastin Vasorelaxation factors Factor V NO PAF PGI /E PAI-, PAI- EDHF Inflammatory Chemokines Vasoconstriction factors and Cytokines IL-, IL-, IL- TXA /F a LTB, C, D, E EDCF MCP-, MCP- leukotrienes MHC II free radicals CAM endothelin Grammas J. Neuroinflammation ;: Endothelial dysfunction in metabolic syndrome smoking, high BP, high blood sugar, high blood fat, obesity, salt NO G Born & C Schwartz Vascular Endothelium Pulse wave analysis of arterial compliance with cardiovascular profiler Non-invasive assessment of endothelial function flow mediated dilatation (FMD) expressed as % change in diameter ~% in healthy adults characterised by:- Impaired vasodilatation (early) Production of inflammatory mediators (cytokines, adhesion molecules) Reduced arterial compliance due to vascular remodelling and hypertrophy (long term) Impaired Endothelial Function in Obesity Davison K et al, Journal of Obesity Obese Lean P Subjects 9 M, F M, F Age (yr) 9. ±.. ±.. Height (m).9 ±..7 ±.. Mass (kg).9 ±.. ±. <. BMI (kg/m). ±.9. ±. <. DEXA Body fat (%). ±. 7. ±. <. SBP (mmhg) 7. ±.. ±. <. DBP (mmhg) 7. ±. 7. ±. <. Large artery elasticity. ±.9. ±.. Small artery elasticity 7. ±. 7. ±..7 FMD (%). ±..7 ±.7 <. Circulatory effects of endothelial dysfunction endothelium Endothelial dysfunction obesity high blood pressure high blood sugar high blood fats (incl. cholesterol) smoking excess salt Inflammation impaired blood flow Can be improved/restored by regular aerobic exercise and supplementation with specific bioactive nutrients Cognitive decline depression neurodegenerative diseases hypertension stroke coronary disease angina heart failure physical incapacity impaired fat, glucose metabolism tissue inflammation

// Bioactive nutrients from plants >, Can flavonoids improve endothelial function (FMD)? Acute studies Hooper L et al AJCN ;: >, Chronic studies Generic antioxidants?

J Nutr 7;7:7S Favours placebo Favours flavanoid FMD responses to a flavanol-rich cocoa supplement Davison K, Coates AM, Buckley JD, Howe PRC.

3 // Bioactive nutrients from plants >, Can flavonoids improve endothelial function (FMD)? Acute studies Hooper L et al AJCN ;: >, Chronic studies Generic antioxidants? or Mediators of specific physiological functions? Erdman J et al. J Nutr 7;7:7S Favours placebo Favours flavanoid FMD responses to a flavanol-rich cocoa supplement Davison K, Coates AM, Buckley JD, Howe PRC. Int J Obesity ;:9 OH HO O OH OH +)-catechin OH (-)-epicatechin acute before chronic response Week 7 response hrs after 7 measured >hrs Week after previous FMD Week dose (%) LF mg HF 9mg LF mg HF 9mg Cocoa flavanols increase endothelial vasodilatation Davison et al, Int J Obesity lower blood pressure Davison K et al, J Hum Hypertens attenuate BP responses to stress Berry NM et al, Br J Nutr not due to antioxidant activity Engler M et al, JACN mediated by epicatechin NO Taubert D et al. JAMA 7 Regulation of Endothelial Nitric Oxide l-arginine l-arginase NO synthase urea nitric oxide (NO) free radical oxidation NO x Effects of chocolate and cocoa flavanols on FMD a systematic review and meta-analysis of randomized trials acute FMD responses chronic FMD responses % improvement in FMD = % lower risk Hooper of future et al. cardiac AJCN events Effect of Cocoa Intake on Blood Pressure: meta-analysis Desch S et al, Am J Hypertens Study Sample size Weight Change in SBP, 9% CI Study Sample size Weight Change in DBP, 9% CI The following wording reflects the scientific evidence:- Cocoa flavanols help maintain endothelium-dependent vasodilation, which contributes to normal blood flow. The Panel noted that cocoa flavanols consumed for weeks have been shown to increase fasting ED-FMD significantly in the target population (Davison et al, ) To obtain the claimed effect, mg of cocoa flavanols should be consumed daily Cocoa flavanols: dose-dependent reduction of hr ambulatory BP Davison K, Berry N, Misan G, Coates AM, Buckley JD, Howe PRC, J Human Hypertension

// Effects of chocolate or cocoa on Insulin Sensitivity Flavonoid Consumption Slows Cognitive Decline quartiles of intake in -7yr old men Letenneur et al Am J Epidemiol 7 In a prospective study, men

intake and cognitive assessments years later (avg yr old).

4 // Effects of chocolate or cocoa on Insulin Sensitivity Flavonoid Consumption Slows Cognitive Decline quartiles of intake in -7yr old men Letenneur et al Am J Epidemiol 7 In a prospective study, men without dementia and with reliable dietary assessment were tested four times over a -year period Another prospective study of 7 adults Kesse-Guyot et al J Nutr found associations between polyphenol intake and cognitive assessments years later (avg yr old). Total flavonoids, catechins, theaflavines, flavonols, and phenolic acids were associated with long-term language and verbal memory capacities. Nurses' Health Study - Devore E et al Ann Neurol tests of cognitive function were conducted at,, years in, women aged 7 years. Verbal memory composite score, telephone interview of cognitive status and global composite score were strongly correlated with flavonoid intake (esp. from bluberries and strawberries). Hooper et al. AJCN Feb Berry fruits modulate endothelial cell migration and angiogenesis Tulio AZ et al. J Agric Food Chem. Anthocyanin extracts of strawberry, wild blueberry and cranberry extracts dose-dependently activated Akt via PI kinase and induced cell migration and angiogenesis in vitro in human umbilical endothelial cells. Cerebral blood flow is reduced in mild cognitive impairment Blood flow is measured in cerebral arteries using Transcranial Doppler Ultrasound (TCD). Significantly lower in middle and anterior cerebral arteries in adults with MCI compared to controls. Sun Z et al Eur J Neurol 7 A: Pericallosal Artery B: Anterior Cerebral Artery C: Middle Cerebral Artery D: Anterior Choroidal Artery E: Ophthalmic Artery F: Internal Carotid Artery G: Posterior Cerebral Artery Flavonoids can act via endothelium to increase cerebral blood flow enhance cerebral angiogenesis suppress inflammatory mediators restore blood-brain barrier function Cocoa flavanols increase cerebral blood flow Fisher N et al (J Cardiovasc Pharmacol ) found an % increase of blood flow velocity in the middle cerebral artery after one week of daily intake of flavanol-rich cocoa. Cocoa flavanols enhance cognition Scholey et al (J Psychopharmacol ) were the first to report acute cognitive improvements in healthy adults taking cocoa flavanols. Field et al (Physiol Behav ) confirmed acute cognitive benefit of cocoa flavanols and also reported improved visual contrast sensitivity. Desideri et al (Hypertension ) reported cognitive improvements associated with increases in insulin sensitivity with regular consumption of cocoa flavanols for wks. Effects of soy isoflavones on FMD and cognitive function % increase in diameter Soy isoflavones enhance FMD chronically ( weeks), possibly via ERβ The main soy isoflavone, genistein, is a selective ERβ agonist ERβ are localised in brain regions associated with learning and memory (Resnick et al ) Estrogen acts on both ERα and ERβ to increase cerebral blood flow (Duckles & Krause 7) Flow mediated dilatation (n=) P<. Dairy S/D Soy A Thorp et al. AJCN ;:9 J Hypertens 9;7(Suppl ):S prefrontal important cortex in spatial working memory basal forebrain ER β hypothalamus ER α ER β Limbic System pituitary ER α & ER β amygdala ER α We have shown that isoflavone supplementation for weeks can enhance spatial working memory in men Thorp A, Sinn N, Buckley J, Coates A, Howe P. Br J Nutr 9 cerebral cortex ER α & ER β cerebellum ER β hippocampus important in visuospatial tasks & memory recall Is the cognitive benefit attributable to enhanced cerebral perfusion? ER β Can we assess vasodilator function in the brain? A: Pericallosal Artery B: Anterior Cerebral Artery C: Middle Cerebral Artery D: Anterior Choroidal Artery E: Ophthalmic Artery F: Internal Carotid Artery G: Posterior Cerebral Artery Vasodilator response to breathing % CO Fisher et al. J CardiovascPharm;7:S

// Wild green oat Vasodilator effect of wild green oat extract Avena sativa (oat) herb purportedly reduces heart disease risk, raises energy levels, improves mood, reduces anxiety, helps to cope with

It can acutely enhance EEG indices of mental alertness (resting δ and θ activity). We have also reported dose-related acute increases in performance of the Stroop CWT.

there was no improvement of mood or cognition.

Pharmacol Combats oxidative stress (anti-aging) Trans-resveratrol Cancer protection Reduces chronic inflammation Placebo WGOE Placebo WGOE Wong et al J Hypertens Protects against bone loss Improves

Adapted from Li & Forstermann, CardiovascDrugs Ther 9 Resveratrol enos production NO inactivation NO bioavailability Endothelial vasodilator function Cerebral perfusion Xia et al, Molecules Cognitive

5 // Wild green oat Vasodilator effect of wild green oat extract Avena sativa (oat) herb purportedly reduces heart disease risk, raises energy levels, improves mood, reduces anxiety, helps to cope with stress, increases physical performance. Neuravena is an oat extract rich in avenanthramides, phytoalexins and flavonoids (vitexin and isovitexin) with possible inhibitory effects on MAO-B and PDE. It can acutely enhance EEG indices of mental alertness (resting δ and θ activity). We have also reported dose-related acute increases in performance of the Stroop CWT. Chronic Neuravena supplementation ( mg/day for weeks) in healthy older adults caused equal % increases in both FMD and CVR, indicating sustained improvement of cerebral endothelial function, although there was no improvement of mood or cognition. FMD % CVR % WGO Extract Cardiovascular protection Protects against neurodegenerativ e disorders Red Multi-faceted wine and the benefits French of Paradox resveratrol from Chachay et al Br J Clin Pharmacol Combats oxidative stress (anti-aging) Trans-resveratrol Cancer protection Reduces chronic inflammation Placebo WGOE Placebo WGOE Wong et al J Hypertens Protects against bone loss Improves fat regulation & metabolism Improves insulin sensitivity Resveratrol enhances NO production and prevents NO breakdown Can Resveratrol improve brain function? Adapted from Li & Forstermann, CardiovascDrugs Ther 9 Resveratrol enos production NO inactivation NO bioavailability Endothelial vasodilator function Cerebral perfusion Xia et al, Molecules Cognitive performance Acute effects of Resveratrol on FMD Wong et al Nutr Metab Cardiovasc Disease Chronic vasodilator effects of Resveratrol R Wong et al J Hypertens FMD response (%) % +.% +.7% +.% +.% +.9% +.% Red wine Cocoa Tea (ml) EGCG polyphenol flavanols (mg) extract (9mg) (mg). Lekakis et al Eur J Card Prev Rehab ;:9 FMD (%) 7 P=..% (% increase) Change in FMD (%) (resveratrol placebo) (r = -.9; P =.) 9 7 Resveratrol dose (mg) Davison et al Int J Obes: ;:9 Widlansky et al Free Rad Bio Med: ;:99 Widlansky et al J Am Coll Nutr: 7;:9 Chronic FMD response Placebo Resveratrol % improvement in FMD = % lower risk of future cardiac events

// Chronic effects of Resveratrol on cognition R Wong et al J Hypertens Stroop Word reading trial Resveratrol Placebo Resveratrol -Placebo P 9% CI of change d Time taken (sec) 9.9 ±. 9.9 ±. -.9 ±.9.9 -.

±.97 -. ±.9. -.7.. Resveratrol improves cerebrovascular responsiveness to cognitive stimulus Kennedy D et al Am J Clin Nutr healthy college men (-9 years old) Acute effects of,, mg doses of

stimulus No effect on cognition Functional Near Infra-Red Spectroscopy Functional Magnetic Resonance Imaging Stroop Colour naming trial Time taken (sec).9 ± 7.. ±. -.7 ±.7. -7.7..9 Uncorrected errors.

.. Even though subjects were not cognitively impaired, there was a trend toward improved word reading performance (speed and accuracy) with resveratrol Can resveratrol influence cerebral blood flow?

org Effects of Resveratrol on Memory Performance and Hippocampal Functional Connectivity AV Witte et al J Neurosci pairwise matched overweight older adults took resveratrol ( mg/d plus quercetin) or

6 // Chronic effects of Resveratrol on cognition R Wong et al J Hypertens Stroop Word reading trial Resveratrol Placebo Resveratrol -Placebo P 9% CI of change d Time taken (sec) 9.9 ±. 9.9 ±. -.9 ± Uncorrected errors. ±..7 ±. -. ± Corrected errors. ±.7. ± ± Resveratrol improves cerebrovascular responsiveness to cognitive stimulus Kennedy D et al Am J Clin Nutr healthy college men (-9 years old) Acute effects of,, mg doses of resveratrol Cognitive tasks: Serial subtraction & Rapid Visual Information Processing Cerebral blood flow: Functional near-infrared spectroscopy Resveratrol improved blood flow response to cognitive stimulus No effect on cognition Functional Near Infra-Red Spectroscopy Functional Magnetic Resonance Imaging Stroop Colour naming trial Time taken (sec).9 ± 7.. ±. -.7 ± Uncorrected errors.9 ±.7.7 ±.. ± Corrected errors. ±.9. ±.. ± Even though subjects were not cognitively impaired, there was a trend toward improved word reading performance (speed and accuracy) with resveratrol Can resveratrol influence cerebral blood flow? Matthew Vita, Gallaudet University H Tsunashima, K Yanagisawa ComputIntell Neurosci 9 en.wikipedia.org Effects of Resveratrol on Memory Performance and Hippocampal Functional Connectivity AV Witte et al J Neurosci pairwise matched overweight older adults took resveratrol ( mg/d plus quercetin) or placebo for mths. Memory was tested at and mths; functional connectivity, volume and microstructure of the hippocampus were evaluated by MRI. r =., P =. Effects of resveratrol on biomarkers of TDM Liu et al Am J Clin Nutr Effect on HOMA-IR Effect on HbAC (%) Improved memory retention was related to enhanced functional connectivity P<. Markers of glucose metabolism, inflammation, lipids and neurotrophic factors were tested in fasting blood. Reduction of HbAc was also related to enhanced functional connectivity TDM is associated with accelerated cognitive decline. Tests of executive function, working memory and psychomotor and attentional functions are selectively impaired. (R Wong et al. Curr Diab Rep ) Is this attributable to impaired cerebrovascular responsiveness? Cerebrovascular responsiveness (CVR) to cognitive stimuli in TDM assessed by TCD Preliminary comparison of adults with TDM and age/gender matched healthy controls % increase N-back Letter number sequencing functional TCD Controls (n=) TDM (n=9) Left MCA Right MCA Mean SD Mean SD P Digit span backward Digit span forward Serial subtraction 7 Concept shifting task Digit symbol coding B Digit symbol coding A Stroop colour Increases of blood flow velocity in middle cerebral arteries of adults with Type diabetes during selected cognitive tasks (preliminary data from Wong, Howe et al) Stroop word Age (years) Duration of diabetes (years) Fasting HbAc (%) Fasting glucose (mmol/l) Fasting insulin (miu/l) HOMA-IR BMI (kg/m) Waist circumference (cm) Systolic blood pressure (mmhg)..... Diastolic blood pressure (mmhg) Mini-Mental State Examination (MMSE) Cerebral blood flow velocity (cm/s) (left) Cerebral blood flow velocity (cm/s) (right) Pulsatility Index (left) Pulsatility Index (right) (preliminary data from Wong, Howe et al)

7 // CVR (%) P<. Evaluation of CVR to cognitive stimuli in TDM Left MCA TDM Non-TDM CVR (%) (preliminary data from Wong, Howe et al) P<. Right MCA We are now conducting clinical trials in TDM and others at risk of cerebrovascular dysfunction to see whether both CVR and cognition can be improved with resveratrol or omega- (fish oil) Potential benefits of Long Chain Omega- (EPA, DHA) Enhancing early infant development & growth Promoting fitness (physical, mental, reproductive) Counteracting chronic disease (prevention, treatment) Cardiovascular, metabolic lipids (TG, HDL) endothelial dilatation arterial compliance blood pressure heart rate, HRV platelet aggregation anti-arrhythmic ischemic heart disease sudden cardiac death heart failure stroke insulin resistance abdominal adiposity Anti-inflammatory psoriasis/dermatitis rheumatoid arthritis inflammatory bowel disease immune renal disease periodontal disease osteoporosis? asthma? COPD? Cognitive, behavioural cognitive impairment, ADHD depression, bipolar disorder schizophrenia? autism? Omega- and Mental Health across the Lifespan Effects of omega- supplementation in ADHD 7- year olds with Attention Deficit Hyperactivity Disorder Comparison of EPA-rich oil, DHA-rich oil, LA-rich oil (placebo) Baseline red blood cell omega- status:- higher DHA = better word reading higher n- PUFA = less anxiety/shyness higher n- PUFA = poorer reading, vocabulary, spelling those with learning difficulties (7/7) had lower DHA (Milte C, Sinn N, Buckley JD, Coates AM, Young RM, Howe P. J Child Health Care ) Effects of month intervention:- increasing DHA improved word reading, ability to switch attention and parent ratings of behaviour, esp. in subgroup with learning difficulties (Milte C, Sinn N, Buckley JD, Coates AM, Young RM, Howe P. Nutrition ) Omega- and cognition in older adults with MCI (-month RCT) Lower red blood cell EPA in adults with MCI than controls at baseline (Milte C, Sinn N, Street S, Buckley J, Coates A, Howe P. PLEFA ) Both EPA and DHA improved depression scores Omega- Index in ADHD, Depression, Dementia - toward an omega - index for mental health? (Sinn N, Milte C, Street S, Buckley J, Coates A, Petkov J, Howe P. Br J Nutr ) DHA supplementation improved verbal letter fluency DHA improved health-related quality of life, Milte C, Sinn N, Howe P. Nutr Rev 9 which also contributed to the improvement of mood Omega- supplementation has a multifaceted influence on physical and mental wellbeing. Is improved circulatory function a common underlying mechanistic link? Consuming Hi-Oleic Peanuts for weeks Enhances Cerebral Vasodilator Responsiveness and Cognition JA Barbour, PRC Howe, JA Buckley, J Bryan, AM Coates (unpublished) D C B A Systematic review included 7 studies measuring effects of nut consumption on glucoregulation, blood pressure, inflammation, endothelial function, arterial compliance and cognition as epidemiological (A), uncontrolled (B) or randomised controlled trials with primary (C) or secondary (D) outcomes. Oleic acid Arginine Fibre Vitamin E Folate Magnesium Potassium Polyphenols (Resveratrol) Low GI Low Na Improve CV and metabolic risk factors Lipids Glucose Insulin Blood Pressure Inflammation Body weight Cerebral Endothelial Function Cognition Weighted mean percent changes unsalted Hi-oleic peanuts (with skins on) g/day for men and g/day for women versus nut free diet 7

// Cerebrovascular responsiveness % Difference in CVR Peanuts vs control Left Outcomes completed study 9 male/ female, age ± yrs, BMI ± kg/m² Right.7...... p <.

Memory Executive function Verbal fluency Processing speed Correlations between changes in CVR and Cognition RAVLT target Excluded letter P=.

LCVR This is the first study to directly link enhanced cerebrovascular function to improvements in cognitive performance with regular consumption of a

com/images/fruits berri es/berries_mixed/berries-.

(FMD) consistently in individuals with CVD risk and hypertension." Swift et al Br J Sports Med Sep ".

scant evidence suggesting that physical activity may in fact reduce the risk of dementia and Alzheimer's disease.

clinical trials". Lautenschlager & Almeida. Curr Opinion Psychiatry Lautenschlager et al.

were randomized to a moderate physical activity program ( x min/week) or 'usual care' for months, with months follow up.

There were also modest improvements in word list delayed recall and Clinical Dementia Rating.

8 // Cerebrovascular responsiveness % Difference in CVR Peanuts vs control Left Outcomes completed study 9 male/ female, age ± yrs, BMI ± kg/m² Right p <. Composite cognitive scores Difference in composite score peanut vs control. Memory Executive function Verbal fluency Processing speed Correlations between changes in CVR and Cognition RAVLT target Excluded letter P=. P=.9 LCVR LCVR RAVLT delay P=. LCVR This is the first study to directly link enhanced cerebrovascular function to improvements in cognitive performance with regular consumption of a functional food High salt intake impairs FMD in salt-resistant adults DuPont J et al, J Hypertens com/images/fruits berri es/berries_mixed/berries-.jpg Aerobic exercise improves circulatory function and cognition "Aerobic exercise training as an intervention has been shown to improve endothelial function (FMD) consistently in individuals with CVD risk and hypertension." Swift et al Br J Sports Med Sep "... cohort studies show that physical activity is associated with better cognitive function and less cognitive decline in later life, although there is only scant evidence suggesting that physical activity may in fact reduce the risk of dementia and Alzheimer's disease. Data to support the systematic introduction of physical activity programs to reduce the risk of dementia in later life are not as yet available from randomized clinical trials". Lautenschlager & Almeida. Curr Opinion Psychiatry Lautenschlager et al. JAMA Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease subjects aged > years with subjective memory impairment were randomized to a moderate physical activity program ( x min/week) or 'usual care' for months, with months follow up. The 'Change in Alzheimer Disease Assessment Scale - Cognitive Subscale' improved. points in the active group versus a. decline in the 'usual care' group. There were also modest improvements in word list delayed recall and Clinical Dementia Rating. Conclusions Impaired endothelial function may link age-related deficits in mood and cognition with metabolic syndrome, diabetes and heart disease. Regular consumption of marine omega- and certain plant polyphenols (esp. flavonoids) can improve endothelial function and arterial health. These vasoactive nutrients may also enhance mood and counteract cognitive decline by improving circulatory function in the brain. Evidence of optimal dose requirements is still rudimentary and the potential to develop judicious combinations is yet to be explored. The potentially adverse effect of high sodium intake should be recognised. Together with regular aerobic exercise, supplementing these nutrients can help to maintain a healthy circulation and prevent the increased risk of cardiovascular disease, diabetes, depression and dementia in our ageing population.

Nutrients and Circulatory Function

Clinical Nutrition Research Centre Nutrients and Circulatory Function Peter Howe Clinical Nutrition Research Centre University of Newcastle Nutritional Physiology Research Centre University of South Australia