1. Dementia Prevention Deborah Colson MSc DipION
Guildford GP Education – Update Week
Royal Surrey County Hospital, 6 November 2014

2. Background

3. Deborah Colson MSc DipION MBANT CNHC Nutritional Therapist
Specialist in nutrition / lifestyle for disorders of nervous system
Institute for Optimum Nutrition (DipION, 2002)
MSc Nutritional Therapy (University of Westminster, 2014)
Author of Optimum Nutrition for Your Child and Optimum Nutrition for your Child's Mind, Alzheimer's Prevention Plan
Professional Association: British Association for Applied Nutrition and Nutritional Therapy (BANT)
Regulator: Complementary and Natural Healthcare Council (CNHC) Professional Standards Authority Accredited Voluntary Register (AVR)

4. Clinical Practice Brain Bio Centre Re:Cognition Health
Clinic for nutritional treatment of mental health and neurological disorders (since 2003)
Wholly owned by charity Food for the Brain whose aim is to raise awareness of the link between nutrition and mental health
Re:Cognition Health
Multi-disciplinary cognitive health clinic
The Insight Network
Network of therapists and psychiatrists

5. What is Nutritional Therapy?
The application of nutrition and health science to enable individuals to maximise their health potential
Holistic therapy, complementary to medicine
Manages biochemical / nutritional imbalances which impact health
Genetic, environmental and psychosocial factors considered
Not homeopathy etc

6. How does Nutritional Therapy work?
Full case history
Biochemical / nutritional tests recommended
Practical dietary, lifestyle and supplement advice given, tailored to the individual
Optimise biochemistry
Address risk factors
Manage drug-nutrient interactions
Informed by evidence base
Favourable risk:benefit ratio
‘Wholistic’ – benefits are broad

7. Nutrition and lifestyle-related factors
blood glucose control
essential fatty acids
minerals
Mg, Se, Zn, Cr, Mn, I, Cu, Ca
vitamins
D, Bs, C, E, A, K
amino acids
phytonutrients
Mediterranean diet
microbiome
homocysteine
drug-nutrient interactions
food intolerances
oxidative stress
environmental toxins
stress
sleep
exercise
social activity

8. Well-established dementia risk factors
Modifiable?
Age X
Type II Diabetes √
Overweight
Hypertension (mid-life)
Dyslipidaemia (mid-life)
Smoking, ↓physical activity
↓Education, mental/social stimulation
Genetics – ApoE et al ?

9. Other nutrition & lifestyle risk factors
Modifiable?
↑ HbA1c (w/out diabetes) √
↓ Adherence to Mediterranean diet
↓Omega-3 / fish consumption
↑Homocysteine / ↓B vitamins
↓Vitamin D
↑Oxidative stress / ↓antioxidant nutrients
↑Alcohol
↓Polyphenols (curcumin et al)
↑Stress

10. Reversal of cognitive decline: A novel therapeutic program
Personalised intensive diet, lifestyle, supplement programme
10 pts (Alzheimer's, amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI))
9/10 showed subjective or objective improvement in cognition from 3-6 months (1/10 = very late stage AD).
6/10 had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance.
Improvements sustained. Longest follow-up is 2.5 years from initial treatment, with sustained and marked improvement.
Bredesen DE (2104) Reversal of cognitive decline: A novel therapeutic program. Aging (Albany NY) 6(9):
Aging (Albany NY) Sep;6(9):
Reversal of cognitive decline: A novel therapeutic program.
Bredesen DE.
Author information
Abstract
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.

11. Evidence base Limited due to:
Lack of pharmaceutical interest and non-pharmaceutical funding
Challenge of studying nutrients/diet in RCT setting
Synergy of nutrients often ignored

12. Evidence-based practice
“the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient. It means integrating individual clinical expertise with the best available external clinical evidence from systematic research.”
Sackett D, 1996
What is Evidence-Based Practice (EBP)? 
The most common definition of Evidence-Based Practice (EBP) is from Dr. David Sackett. EBP is “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of the individual patient. It means integrating individual clinical expertise with the best available external clinical evidence from systematic research.” (Sackett D, 1996)
EBP is the integration of clinical expertise, patient values, and the best research evidence into the decision making process for patient care. Clinical expertise refers to the clinician’s cumulated experience, education and clinical skills. The patient brings to the encounter his or her own personal preferences and unique concerns, expectations, and values. The best research evidence is usually found in clinically relevant research that has been conducted using sound methodology. (Sackett D, 2002)
The evidence, by itself, does not make the decision, but it can help support the patient care process. The full integration of these three components into clinical decisions enhances the opportunity for optimal clinical outcomes and quality of life. The practice of EBP is usually triggered by patient encounters which generate questions about the effects of therapy, the utility of diagnostic tests, the prognosis of diseases, and/or the etiology of disorders.

13. Evidence-based practice

14. EBP: Hierarchy of evidence

15. BMJ Clinical Evidence
– Accessed September 2013

16. Dementia

17. Blood glucose Diabetes is a known risk factor
n = 2 067, mean age 76 yrs
In subjects without diabetes, higher glucose levels (6.4 vs 5.5 mmol/l) in preceding 5 years associated with increased risk of dementia HR 1.18 (95% CI ) p=0.01
In subjects with diabetes, higher glucose levels were also related to an increased risk of dementia (p=0.002)
glucose level 10.5 mmol/l vs 8.9 mmol/l, HR 1.40 (95% CI, )
Crane et al (2013) Higher glucose levels may be risk factor for dementia (even in absence of diabetes). NEJM 369(6):540-8
N Engl J Med Aug 8;369(6): doi: /NEJMoa
Glucose levels and risk of dementia.
Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, Haneuse S, Craft S, Montine TJ, Kahn SE, McCormick W, McCurry SM, Bowen JD, Larson EB.
Source
Department of Medicine, University of Washington, Seattle, WA, USA.
Abstract
BACKGROUND:
Diabetes is a risk factor for dementia. It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes.
METHODS:
We used 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2067 participants without dementia to examine the relationship between glucose levels and the risk of dementia. Participants were from the Adult Changes in Thought study and included 839 men and 1228 women whose mean age at baseline was 76 years; 232 participants had diabetes, and 1835 did not. We fit Cox regression models, stratified according to diabetes status and adjusted for age, sex, study cohort, educational level, level of exercise, blood pressure, and status with respect to coronary and cerebrovascular diseases, atrial fibrillation, smoking, and treatment for hypertension.
RESULTS:
During a median follow-up of 6.8 years, dementia developed in 524 participants (74 with diabetes and 450 without). Among participants without diabetes, higher average glucose levels within the preceding 5 years were related to an increased risk of dementia (P=0.01); with a glucose level of 115 mg per deciliter (6.4 mmol per liter) as compared with 100 mg per deciliter (5.5 mmol per liter), the adjusted hazard ratio for dementia was 1.18 (95% confidence interval [CI], 1.04 to 1.33). Among participants with diabetes, higher average glucose levels were also related to an increased risk of dementia (P=0.002); with a glucose level of 190 mg per deciliter (10.5 mmol per liter) as compared with 160 mg per deciliter (8.9 mmol per liter), the adjusted hazard ratio was 1.40 (95% CI, 1.12 to 1.76).
CONCLUSIONS:
Our results suggest that higher glucose levels may be a risk factor for dementia, even among persons without diabetes. (Funded by the National Institutes of Health.)

20. 2008, 5:51
J Neuroinflammation Nov 11;5:51. doi: /

21. Environmental factors
Biological factors
HTN, CVD, DM
hypoperfusion
Genetic factors
ApoE ε4 PSEN-1, -2, others
Environmental factors
Trauma, toxins, diet
Vascular compromise
Oxidative stress
Head trauma releases glutamate which is neurotoxic
HTN = hypertension
Impaired microvascular circulation = hypoperfusion
Amyloid plaques consist of a core of amyloid-B, peptide deposits, dystrophic neurites, activated microglia and reactive astrocytes
Neuroinflammation
Tau (hyperphosphorylation
βAmyloid

22. Carbs vs protein
n = 24, obese, premenopausal women (20-50yrs) no diabetes or prediabetes randomised to:
6 months, 500 kcal/day
HP (30% protein, 40% carbohydrates, 30% fat), or
HC (15% protein, 55% carbohydrates, 30% fat)
Kitabchi AE et al, (2013 ) Effects of high-protein versus high-carbohydrate diets on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in obese, premenopausal women without diabetes: a randomized controlled trial. Diabetes Care 36(7):
Diabetes Care Jul;36(7): doi: /dc Epub 2013 Feb 12.
Effects of high-protein versus high-carbohydrate diets on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in obese, premenopausal women without diabetes: a randomized controlled trial.
Kitabchi AE, McDaniel KA, Wan JY, Tylavsky FA, Jacovino CA, Sands CW, Nyenwe EA, Stentz FB.
Source
Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Abstract
OBJECTIVE:
To study the effects of high-protein versus high-carbohydrate diets on various metabolic end points (glucoregulation, oxidative stress [dichlorofluorescein], lipid peroxidation [malondialdehyde], proinflammatory cytokines [tumor necrosis factor-α and interleukin-6], adipokines, and resting energy expenditure [REE]) with high protein-low carbohydrate (HP) and high carbohydrate-low protein (HC) diets at baseline and after 6 months of dietary intervention.
RESEARCH DESIGN AND METHODS:
We recruited obese, premenopausal women aged years with no diabetes or prediabetes who were randomized to HC (55% carbohydrates, 30% fat, and 15% protein) or HP (40% carbohydrates, 30% fat, and 30% protein) diets for 6 months. The diets were provided in prepackaged food, which provided 500 kcal restrictions per day. The above metabolic end points were measured with HP and HC diet at baseline and after 6 months of dietary intervention.
RESULTS:
After 6 months of the HP versus HC diet (12 in each group), the following changes were significantly different by Wilcoxon rank sum test for the following parameters: dichlorofluorescein (-0.8 vs µmol/L, P < ), malondialdehyde (-0.4 vs μmol/L, P = ), C-reactive protein (-2.1 vs mg/L, P = ), E-selectin (-8.6 vs ng/mL, P = ), adiponectin (1,284 vs. 504 ng/mL, P = ), tumor necrosis factor-α (-1.8 vs pg/mL, P < ), IL-6 (-1.3 vs pg/mL, P < ), free fatty acid (-0.12 vs mmol/L, P = ), REE (259 vs. 26 kcal, P < ), insulin sensitivity (4 vs. 0.9, P < ), and β-cell function (7.4 vs. 2.1, P < ).
CONCLUSIONS:
To our knowledge, this is the first report on the significant advantages of a 6-month hypocaloric HP diet versus hypocaloric HC diet on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in normal, obese females without diabetes.
PMID:
[PubMed - in process]
PMCID:
PMC
[Available on 2014/7/1]

23. High protein (HP) vs high carbohydrate (HC)
CRP ( -2.1 vs mg/L, P = )
inflammation √
TNFα (-1.8 vs pg/mL, P < )
IL-6 (-1.3 vs pg/mL, P < )
E-selectin (-8.6 vs ng/mL, P = )
β-cell function (7.4 vs. 2.1, P < )
metabolic/obesity/DM
insulin sensitivity (4 vs. 0.9, P < )
adiponectin (1,284 vs. 504 ng/mL, P = )
free fatty acid (-0.12 vs mmol/L, P = )
dyslipideamia
REE (259 vs. 26 kcal, P < )
metabolism
dichlorofluorescein (-0.8 vs µmol/L, P < )
cellular oxidative stress
malondialdehyde (-0.4 vs μmol/L, P = )
lipid peroxidation
Adiponectin associated with lean mass
Diabetes Care Jul;36(7): doi: /dc Epub 2013 Feb 12.
Effects of high-protein versus high-carbohydrate diets on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in obese, premenopausal women without diabetes: a randomized controlled trial.
Kitabchi AE, McDaniel KA, Wan JY, Tylavsky FA, Jacovino CA, Sands CW, Nyenwe EA, Stentz FB.
Source
Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Abstract
OBJECTIVE:
To study the effects of high-protein versus high-carbohydrate diets on various metabolic end points (glucoregulation, oxidative stress [dichlorofluorescein], lipid peroxidation [malondialdehyde], proinflammatory cytokines [tumor necrosis factor-α and interleukin-6], adipokines, and resting energy expenditure [REE]) with high protein-low carbohydrate (HP) and high carbohydrate-low protein (HC) diets at baseline and after 6 months of dietary intervention.
RESEARCH DESIGN AND METHODS:
We recruited obese, premenopausal women aged years with no diabetes or prediabetes who were randomized to HC (55% carbohydrates, 30% fat, and 15% protein) or HP (40% carbohydrates, 30% fat, and 30% protein) diets for 6 months. The diets were provided in prepackaged food, which provided 500 kcal restrictions per day. The above metabolic end points were measured with HP and HC diet at baseline and after 6 months of dietary intervention.
RESULTS:
After 6 months of the HP versus HC diet (12 in each group), the following changes were significantly different by Wilcoxon rank sum test for the following parameters: dichlorofluorescein (-0.8 vs µmol/L, P < ), malondialdehyde (-0.4 vs μmol/L, P = ), C-reactive protein (-2.1 vs mg/L, P = ), E-selectin (-8.6 vs ng/mL, P = ), adiponectin (1,284 vs. 504 ng/mL, P = ), tumor necrosis factor-α (-1.8 vs pg/mL, P < ), IL-6 (-1.3 vs pg/mL, P < ), free fatty acid (-0.12 vs mmol/L, P = ), REE (259 vs. 26 kcal, P < ), insulin sensitivity (4 vs. 0.9, P < ), and β-cell function (7.4 vs. 2.1, P < ).
CONCLUSIONS:
To our knowledge, this is the first report on the significant advantages of a 6-month hypocaloric HP diet versus hypocaloric HC diet on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in normal, obese females without diabetes.
PMID:
[PubMed - in process]
PMCID:
PMC
[Available on 2014/7/1
Kitabchi AE et al (2013 ) Diabetes Care 36(7):

24. Omega-3 Omega-6 EPA 20:5 ω-3 DHA 22:6 ω-3 ALA 18:3 ω−3 LA 18:2 ω−6
linseeds, walnuts and their oils, green veg
nuts, seeds seed oil
ALA 18:3 ω−3
LA 18:2 ω−6
∆6 desaturase Mg, Zn, B3, B6, C trans fats, alcohol, stress, sat fats
Evening Primrose Oil / borage oil
GLA 18:3 ω−6
∆5 desaturase Mg, Biotin trans fats, alcohol, stress, sat fats
DGLA 20:3 ω−6
EPA 20:5 ω-3
eicosanoids (anti-inflammatory)
Ratio in hunter-gatherer diets
Half:life
AA: years
DHA: years
EPA: 2 weeks
meat dairy
AA 20:4 ω-6
oily fish
eicosanoids, resolvins (anti-inflammatory)
eicosanoids (pro-inflammatory)
DHA 22:6 ω-3
resolvins, protectins (anti-inflammatory)

25. RBC omega-3 and brain ageing
Lower RBC DHA levels are associated with smaller brain volumes and a “vascular” pattern of cognitive impairment even in persons free of clinical dementia
Tan Z.S. et al., 2012 Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology, 78(9):
Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging
Z.S. Tan, MD, MPH, W.S. Harris, PhD, A.S. Beiser, PhD, R. Au, PhD, J.J. Himali, MS, S. Debette, MD, A. Pikula, MD, C. DeCarli, MD, P.A. Wolf, MD, R.S. Vasan, MD, S.J. Robins, MD and S. Seshadri, MD
Neurology, February 28, 2012 vol. 78 no
Abstract
Objective: Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort.
Methods: We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1,575; 854 women, age 67 ± 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE ϵ4 and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D).
Results: Participants with RBC DHA levels in the lowest quartile (Q1) when compared to others (Q2–4) had lower total brain and greater white matter hyperintensity volumes (for model A: β ± SE = −0.49 ± 0.19; p = 0.009, and 0.12 ± 0.06; p = 0.049, respectively) with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and ω-3 index (RBC DHA+EPA) levels (Q1 vs Q2–4) also had lower scores on tests of visual memory (β ± SE = −0.47 ± 0.18; p = 0.008), executive function (β ± SE = −0.07 ± 0.03; p = 0.004), and abstract thinking (β ± SE = −0.52 ± 0.18; p = 0.004) in model A, the results remaining significant in all models.
Conclusion: Lower RBC DHA levels are associated with smaller brain volumes and a “vascular” pattern of cognitive impairment even in persons free of clinical dementia.

26. Omega-3 and fish
Prospective study, Chicago Health and Aging Project (CHAP), , followed up 3.9 years for development of AD
n = 815 community-dwelling, years, free from AD
131 developed AD
Fish ≥ 1/week: 60% less risk of AD vs non-consumers (RR, 0.4; 95% CI, )
Total intake of omega-3, and DHA intake associated with reduced risk of AD. EPA not associated with AD
Conclusion:  Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce risk of incident Alzheimer disease.
M. Morris, et al.. (2003) Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol, 60:
Prospective cohort, 815 community-dwelling elderly, free from AD at baseline. Fish once or more a week = 60% less risk of AD. Total omega-3 intake and DHA associated with reduced risk of AD.
M. Morris, et al., Arch Neurol, vol 60, pp (2003)

27. Omega-3 and fish Prospective cohort, 210 elderly
Fish consumers had significantly less 5-y subsequent cognitive decline than nonconsumers (p = 0.01)
Linear trend for relation between the intake of EPA+DHA and cognitive decline (p = 0.01)
An average difference of 380 mg/d in EPA+DHA intake was associated with a 1.1-point difference in cognitive decline (p = 0.01).
van Gelder et al., (2007) Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study, Am J Clin Nutr. 85(4):1142-7
Am J Clin Nutr Apr;85(4):  
Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study.
van Gelder BM et al
Background: Indications have been seen of a protective effect of fish consumption and the intake of n–3 fatty acids on cognitive decline. However, studies are scarce and results inconsistent.
Objective: The objective of the study was to examine the associations between fish consumption, the intake of the n–3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish and other foods, and subsequent 5-y cognitive decline.
Design: Data on fish consumption of 210 participants in the Zutphen Elderly Study, who were aged 70–89 y in 1990, and data on cognitive functioning collected in 1990 and 1995 were used in the study. The intake of EPA and DHA (EPA+DHA) was calculated for each participant. Multivariate linear regression analysis with multiple adjustments was used to assess associations.
Results: Fish consumers had significantly (P = 0.01) less 5-y subsequent cognitive decline than did nonconsumers. A linear trend was observed for the relation between the intake of EPA+DHA and cognitive decline (P = 0.01). An average difference of 380 mg/d in EPA+DHA intake was associated with a 1.1-point difference in cognitive decline (P = 0.01).
Conclusions: A moderate intake of EPA+DHA may postpone cognitive decline in elderly men. Results from other studies are needed before definite conclusions about this association can be drawn.

28. Cochrane Review: Omega-3
“Direct evidence on the effect of omega-3 PUFA on incident dementia is lacking”
Sydenham E et al., (2012) Cochrane Database Syst Rev. Omega 3 fatty acid for the prevention of cognitive decline and dementia. 13;6:CD
Omega 3 fatty acid for the prevention of cognitive decline and dementia.
Cochrane Database Syst Rev Jun 13;6:CD doi: / CD pub3.
Sydenham E, Dangour AD, Lim WS.
Source
Abstract
Cochrane Injuries Group, London School of Hygiene & Tropical Medicine, London,
BACKGROUND:
Evidence from observational studies suggests that diets high in omega-3 long-chain polyunsaturated fatty acids (PUFA) may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomised controlled trials.
OBJECTIVES:
To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people.
SEARCH METHODS:
We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 6 April 2012 using the terms: "omega 3", PUFA, "fatty acids", "fatty acid", fish, linseed, eicosapentaenoic, docosahexaenoic.
SELECTION CRITERIA:
Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials.
DATA COLLECTION AND ANALYSIS:
The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD) or standardised mean differences (SMD) and 95% confidence intervals (CI) on an intention-to-treat basis, and summarised narratively information on safety and adherence.
MAIN RESULTS:
Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up.In two studies participants received gel capsules containing either omega-3 PUFA (the intervention) or olive or sunflower oil (placebo) for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies had cognitive health as their primary outcome; one study of cardiovascular disease included cognitive health as an additional outcome.None of the studies examined the effect of omega-3 PUFA on incident dementia. In two studies involving 3221 participants there was no difference between the omega-3 and placebo group in mini-mental state examination score at final follow-up (following 24 or 40 months of intervention); MD (95% CI to 0.10). In two studies involving 1043 participants, other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced either small or no cognitive declines during the studies.The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems. Overall, minor adverse events were reported by fewer than 15% of participants, and reports were balanced between intervention groups. Adherence to the intervention was on average over 90% among people who completed the trials. All three studies included in this review are of high methodological quality.
AUTHORS' CONCLUSIONS:
Direct evidence on the effect of omega-3 PUFA on incident dementia is lacking. The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people. Omega-3 PUFA supplementation is generally well tolerated with the most commonly reported side-effect being mild gastrointestinal problems.Further studies of longer duration are required. Longer-term studies may identify greater change in cognitive function in study participants which may enhance the ability to detect the possible effects of omega-3 PUFA supplementation in preventing cognitive decline in older people.

29. BDNF Brain-derived neurotrophic factors
Neurogenesis occurs throughout life
New neurons are fragile and survival is uncertain
BDNF supports survival of these neurons and synaptic connections
Exercise, vitamin D, omega-3 promote BDNF

30. Vitamin D
Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease
Oudshoorn et al, Dement Geriatr Cogn Disord. (2008)
Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults
Wilkins et al, Am J Geriatr Psychiatry (2006)
Vitamin D inversely associated with increased odds of cognitive impairment (p for linear trend = .001)
Llewellyn et al, (2009) Serum 25-Hydroxyvitamin D Concentration and Cognitive Impairment. J Geriatr Psychiatry Neurol.
In cognitive decline, there are a number of studies showing an association between low D levels and worse cognitive function. There also appears to be a higher prevalence of VDR polymorphisms in Alzheimer's patients according to a recent Turkish study. And, of course, inflammation is a hallmark of Alzheimer's so the anti-inflammatory properties in vitamin D may have a part to play here too.
Vitamin D may be of interest in the prevention of cognitive impairment, though previous findings are inconclusive. Participants were 1766 adults aged 65 years and older from the Health Survey for England 2000, a nationally representative population-based study. Cognitive impairment was assessed using the Abbreviated Mental Test Score. The cross-sectional relation of serum 25-hydroxyvitamin D quartiles to cognitive impairment was modeled using logistic regression. In all, 212 participants (12%) were cognitively impaired. Odds ratios (95% confidence intervals) for cognitive impairment in the first (8-30 nmol/L), second (31-44 nmol/L), and third (45-65 nmol/L) quartiles of serum 25-hydroxyvitamin D compared with the fourth ( nmol/L) were 2.3 ( ), 1.4 ( ), and 1.1 ( ), after adjustment for age, sex, education, ethnicity, season of testing, and additional risk factors for cognitive impairment (P for linear trend = .001). Our data suggest low serum 25-hydroxyvitamin D is associated with increased odds of cognitive impairment.

31. Vitamin D Hypovitaminosis D is prevalent among older adults
Stimulates neurotrophin release (BDNF)
Protects the brain by buffering antioxidant and anti-inflammatory defences against vascular injury and improving metabolic and cardiovascular function
Cherniack EP et al., (2009) Some new food for thought: the role of vitamin D in the mental health of older adults. Curr Psychiatry Rep. 11:12-9
Cherniack EP, Troen BR, Florez HJ, Roos BA, Levis S. (2009) Some new food for thought: the role of vitamin D in the mental health of older adults. Curr Psychiatry Rep. 11:12-9
Geriatrics Institute and Division of Gerontology and Geriatric Medicine, Miller School of Medicine, University of Miami, and Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL 33125, USA.
Vitamin D, a multipurpose steroid hormone vital to health, has been increasingly implicated in the pathology of cognition and mental illness. Hypovitaminosis D is prevalent among older adults, and several studies suggest an association between hypovitaminosis D and basic and executive cognitive functions, depression, bipolar disorder, and schizophrenia. Vitamin D activates receptors on neurons in regions implicated in the regulation of behavior, stimulates neurotrophin release, and protects the brain by buffering antioxidant and anti-inflammatory defenses against vascular injury and improving metabolic and cardiovascular function. Although additional studies are needed to examine the impact of supplementation on cognition and mood disorders, given the known health benefits of vitamin D, we recommend greater supplementation in older adults.

32. Sources of vitamin D
Full-body exposure to UVB 10,000 iu D3 (15 to 20 minutes at midday in summer, fair skin, no sun-block) Cooked tuna sardines, mackerel 200 – 360 iu D3 or salmon (3-3.5 oz) Shitake mushrooms 100 iu D2 (fresh 3.5 oz) Egg yolk 20 iu D2 or D3 Cod liver oil (1 tbspn) 1,360 iu D3 200 iu = 5µg 10,000 iu = 250µg

33. Vitamin D – how much?
5000 iu/day vitamin D3 for 12 months increased serum D to > 74 nmol/l for 92% of 45 nursing home residents.
Average level 125 nmol/l.
No adverse effects seen
Mocanu V et al., (2009) Long-term effects of giving nursing home residents bread fortified with 125 µg(5000 IU) vitamin D(3) per daily serving. Am J Clin Nutr. 89(4):1132-7
Mocanu V, Stitt PA, Costan AR, Voroniuc O, Zbranca E, Luca V, Vieth R. (2009) Long-term effects of giving nursing home residents bread fortified with 125 microg (5000 IU) vitamin D(3) per daily serving. Am J Clin Nutr. 89(4): – ABSTRACT ONLY
BACKGROUND: In older adults, a serum 25-hydroxyvitamin D [25(OH)D] concentration >75 nmol/L lowers the risk of fracture. An oral intake of 125 microg (5000 IU) vitamin D(3)/d may be required to achieve this target. OBJECTIVE: The objective was to characterize the safety and efficacy of fortifying bread with a biologically meaningful amount of vitamin D(3). DESIGN: In a single-arm design, 45 nursing home residents consumed one bun daily that had been fortified with 125 microg (5000 IU) vitamin D(3) and 320 mg elemental calcium. RESULTS: The initial mean (+/-SD) serum 25(OH)D concentration was / nmol/L. After 12 mo, the 25(OH)D concentration was / nmol/L, and it exceeded 74 nmol/L in 92% of the patients. At every 3-mo follow-up, serum parathyroid hormone was lower than at baseline (P = 0.001). No changes in serum calcium or cases of hypercalcemia were observed at the follow-up assessments. Both mean total urinary calcium and the mean urinary calcium-creatinine ratio increased from baseline at one follow-up time point (P < 0.05). Between baseline and the 12-mo visit, z scores for bone mineral density at the lumbar spine and the hip both increased significantly (P < 0.001). CONCLUSIONS: Fortification of bread with much more vitamin D than used previously produced no evident adverse effects on sun-deprived nursing home residents and improved bone density measures. Fortification of bread with 5000 IU vitamin D(3)/d provided reasonable assurance that vitamin D-deficient older adults attained a serum 25(OH)D concentration greater than the desirable objective of >75 nmol/L. This trial was registered at (ClinicalTrials.gov) as: NCT

34. Homocysteine
“77 cross-sectional studies on >34,000 subjects and 33 prospective studies on >12,000 subjects have shown associations between cognitive deficit or dementia and homocysteine and/or B vitamins”
Smith AD (2008) The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 29(2 Suppl):S143-72
“Dementia has reached epidemic proportions, with an estimated 4.6 million new cases worldwide each year. With an aging world population, the prevalence of dementia will increase dramatically in the next few decades. Of the predicted 114 million who will have dementia in 2050, about three-quarters will live in less developed regions. Although strongly age-related, dementia is not an inevitable part of aging but is a true disease, caused by exposure to several genetic and nongenetic risk factors. Prevention will be possible when the nongenetic risk factors have been identified. Apart from age, more than 20 nongenetic risk factors have been postulated, but very few have been established by randomized intervention studies. Elevated blood concentrations of total homocysteine and low-normal concentrations of B vitamins (folate, vitamin B12, and vitamin B6) are candidate risk factors for both Alzheimer's disease and vascular dementia. Seventy-seven cross-sectional studies on more than 34,000 subjects and 33 prospective studies on more than 12,000 subjects have shown associations between cognitive deficit or dementia and homocysteine and/or B vitamins. Biologically plausible mechanisms have been proposed to account for these associations, including atrophy of the cerebral cortex, but a definite causal pathway has yet to be shown. Raised plasma total homocysteine is a strong prognostic marker of future cognitive decline, and is common in world populations. Low-normal concentrations of the B vitamins, the main determinant of homocysteine concentrations, are also common and occur in particularly vulnerable sections of the population, such as infants and elderly. Large-scale randomized trials of homocysteine-lowering vitamins are needed to see if a proportion of dementia in the world can be prevented” – AD Smith
Smith AD (2008) The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 29(2 Suppl):S143-72

36. Homocysteine
Treatment with B vitamins (FA, B6, B12) for 24 months significantly slowed the rate of brain atrophy in elderly subjects with MCI
Rate of atrophy per year (p =0.001)
B vitamins = 0.76% [95% CI, 0.63–0.90]
placebo = 1.08% [0.94–1.22]
Greater rate of atrophy was associated with lower final cognitive test scores
Smith AD et al. (2010) Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE
Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, et al. (2010) Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE 5(9): e doi: /journal.pone
Abstract
Background: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins.
Objective: To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN ).
Methods and Findings: Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans.
Results: A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94– 1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine .13 mmol/L was 53% lower in the active treatment group (P = 0.001). A greater
rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category.
Conclusions and Significance: The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer’s disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer’s disease, trials are needed to see if the same treatment will delay the development of Alzheimer’s disease.

37. Homocysteine-lowering nutrients
Folic acid 400µg Green, leafy veg, pulses
Vitamin B12 100µg Animal products (eggs, meat, dairy etc)
Vitamin B6 20mg Eggs, cheese, fish, mushrooms, broccoli, lentils, yoghurt, nuts
Vitamin B2 10mg Wholemeal bread, oily fish, walnuts, lentils, bananas, chicken
Zinc 5 mg Sardines, eggs, tofu, oysters, lamb, seeds, nuts
These levels may be found in a good multi or B-complex

38. How much B12?
50µg/day effective in restoring normal B12 status in people over the age of 50
10µg/day no more effective than placebo
UK RDA = 1.5µg/day
Seal et al., (2002) A Randomized, Double-Blind, Placebo-Controlled study of Oral Vitamin B12 Supplementation in Older Patients with Subnormal or Borderline Serum Vitamin B12 Concentrations Journal of the American Geriatric Society, vol 50, pp

39. How much B12 ?
Dose-finding RCT to determine lowest oral dose of cyanocobalamin to normalize biochemical markers of vitamin B12 deficiency in older people with mild vitamin B12 deficiency
defined as a serum vitamin B12 level of 100 to 300 pmol/L ( pg/mL) and a methylmalonic acid (MMA) level of 0.26 µmol/L or greater.
n = 120, 16 weeks, daily oral doses used: 2.5, 100, 250, 500, and 1000 µg
Mean reductions in MMA: 16%, 16%, 23%, 33%, and 33%, respectively
µg/d cyanocobalamin associated with 80% - 90% of estimated maximum reduction in MMA
Conclusion:  Lowest dose of oral cyanocobalamin required to normalize mild vitamin B12 deficiency is more than 200 times greater than the Dutch RDA, which is approximately 3 µg daily.
Eussen et al., (2005) Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial, Arch Intern Med
n = 120, 16 wks. Dose-finding trial. The lowest dose of oral B12 required to normalize mild vitamin B12 deficiency is 600 µg daily. UK RDA is 1.5 µg.
S. J. Eussen et al., Arch Intern Med, vol 165(10), pp (2005)
Vitamin B12 deficiency symptoms include neuropsychiatric
Some drugs interfere with B12 absorption (proton-pump inhibitors, H2 antagnonists, metformin) – commonly used in elderly. B12 needs to complex with intrinsic factor in stomach in order to absorbed in the colon.
Frequently deficient in the elderly. Vegans at high risk of deficiency. Gut flora manufactures some B12.
UK RDA 1 µg
Supplementing folic acid masks a B12 deficiency (blood parameters and symptoms)
Note: measures of B12 – best is MMA
Alternatives:
High dose oral - perhaps
sub-lingual (not in BNF)
Monthly injections – disadvantage: administration (staff, patients don’t like), water-soluble vitamin so doesn’t last long in the body
B12 is co-factor for methylmalonyl-coenzyme A mutase enzyme which converts methylmalonyl-coenzyme A to succinyl-coenzyme A. if inadequate B12, then methylmalonyl-coenzyme A is instead hydrolyzed into methylmalonic acid (MMA). So low B12 = high MMA
S. J. Eussen et al., Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial, Arch Intern Med, vol 165(10), pp (2005)

40. Mediterranean diet
Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease.
Lourida et al, (2013) Mediterranean diet, cognitive function, and dementia: a systematic review. Epidemiology
Epidemiology Jul;24(4): doi: /EDE.0b013e
Mediterranean diet, cognitive function, and dementia: a systematic review.
Lourida I, Soni M, Thompson-Coon J, Purandare N, Lang IA, Ukoumunne OC, Llewellyn DJ.
Source
Peninsula Collaboration for Leadership in Applied Health Research and Care, University of Exeter Medical School, Exeter, United Kingdom.
Abstract
BACKGROUND:
Adherence to a Mediterranean diet has been associated with lower risk of various age-related diseases including dementia. Although narrative reviews have been published, no systematic review has synthesized studies on the association between Mediterranean diet adherence and cognitive function or dementia.
METHODS:
We conducted a systematic review of 11 electronic databases (including Medline) of published articles up to January Reference lists, selected journal contents, and relevant websites were also searched. Study selection, data extraction, and quality assessment were performed independently by two reviewers using predefined criteria. Studies were included if they examined the association between a Mediterranean diet adherence score and cognitive function or dementia.
RESULTS:
Twelve eligible papers (11 observational studies and one randomized controlled trial) were identified, describing seven unique cohorts. Despite methodological heterogeneity and limited statistical power in some studies, there was a reasonably consistent pattern of associations. Higher adherence to Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline, and reduced risk of Alzheimer disease in nine out of 12 studies, whereas results for mild cognitive impairment were inconsistent.
CONCLUSIONS:
Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Further studies would be useful to clarify the association with mild cognitive impairment and vascular dementia. Long-term randomized controlled trials promoting a Mediterranean diet may help establish whether improved adherence helps to prevent or delay the onset of Alzheimer disease and dementia.
Comment in
Commentary: Mediterranean diet and cognitive outcomes: epidemiological evidence suggestive, randomized trials needed. [Epidemiology. 2013]
Commentary: Mediterranean diet and cognitive function: are we approaching clarity in this area? [Epidemiology. 2013]
PMID:
[PubMed - in process]

41. Vitamin E
n = 5395, 55+ years, free of dementia, provided dietary information at baseline
mean follow-up period of 9.6 years
higher intake of vitamin E at study baseline was associated with lower long-term risk of dementia (P = .02 for trend).
Lowest tertile of vitamin E intake vs highest tertile were 25% less likely to develop dementia (HR 0.75; 95% CI )
Dietary intake of vitamin C, beta carotene, and flavonoids were not associated with dementia risk (P > .99 for trend for vitamin C and beta carotene and P = .60 for trend for flavonoids)
Devore EE et al, (2010) Dietary antioxidants and long-term risk of dementia. Arch Neurol. 67:
Arch Neurol Jul;67(7): doi: /archneurol
Dietary antioxidants and long-term risk of dementia.
Devore EE, Grodstein F, van Rooij FJ, Hofman A, Stampfer MJ, Witteman JC, Breteler MM.
Source
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Abstract
BACKGROUND:
The Rotterdam Study previously found that higher dietary intakes of vitamins E and C related to lower risk of dementia and Alzheimer disease (AD) over 6 years of follow-up.
OBJECTIVE:
To study consumption of major dietary antioxidants relative to long-term risk of dementia.
DESIGN:
Population-based prospective cohort study.
SETTING:
The Rotterdam Study in the Netherlands.
PARTICIPANTS:
A total of 5395 participants, 55 years and older, who were free of dementia and provided dietary information at study baseline.
MAIN OUTCOME MEASURES:
Incidence of dementia and AD, based on internationally accepted criteria, relative to dietary intake of vitamin E, vitamin C, beta carotene, and flavonoids.
RESULTS:
During a mean follow-up period of 9.6 years, dementia developed in 465 participants, of whom 365 were diagnosed as having AD. In multivariate models adjusted for age, education, apolipoprotein E epsilon4 genotype, total energy intake, alcohol intake, smoking habits, body mass index, and supplement use, higher intake of vitamin E at study baseline was associated with lower long-term risk of dementia (P = .02 for trend). Compared with participants in the lowest tertile of vitamin E intake, those in the highest tertile were 25% less likely to develop dementia (hazard ratio, 0.75; 95% confidence interval, with adjustment for potential confounders). Dietary intake levels of vitamin C, beta carotene, and flavonoids were not associated with dementia risk after multivariate adjustment (P > .99 for trend for vitamin C and beta carotene and P = .60 for trend for flavonoids). Results were similar when risk for AD was specifically assessed.
CONCLUSION:
Higher intake of foods rich in vitamin E may modestly reduce long-term risk of dementia and AD.

42. Superfoods?? Turmeric (curcumin) Berries (flavonoids, anthocyanidins)
Brassicas (sulphoraphane)
Green tea (catechins, L-theanine)
Grapes / wine (resveratrol)

43. Polyphenols Produced by plant as defence mechanism
UV radiation, browsing animals, infection
Hormetic response to stress
Not part of our biochemistry
Not used for structure or to activate enzymes
Affect quality of our biochemistry
Regulators of our microbiome

44. Polyphenols Potential role as neuroprotective agents.
Curcumin, catechins, and resveratrol (beyond their antioxidant activity) are involved in anti-amyloidogenic and anti-inflammatory mechanisms.
Correlations between neuroprotective functions and potential therapeutic value in AD.
Davinelli S et al., (2012) Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease Oxid Med Cell Longev. doi: /2012/386527
Aggarwal, Bharat B, and Kuzhuvelil B Harikumar. "Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases." The international journal of biochemistry & cell biology 41, no. 1 (2009
Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease
Sergio Davinelli, Nadia Sapere, Davide Zella, Renata Bracale, Mariano Intrieri, Giovanni Scapagnini
Oxid Med Cell Longev. 2012;

45. Polyphenols Colourful fruits, vegetables, herbs, spices, seeds, nuts
Food sources:
Colourful fruits, vegetables, herbs, spices, seeds, nuts

46. Cochrane: Exercise and dementia
...promising evidence that exercise programs can have a significant impact in improving ability to perform activities of daily living and possibly in improving cognition in people with dementia
Forbes D et al, (2013) Exercise programs for people with dementia. Cochrane Database Syst Rev 12:CD
Cochrane Database Syst Rev Dec 4;12:CD [Epub ahead of print]
Exercise programs for people with dementia.
Forbes D, Thiessen EJ, Blake CM, Forbes SC, Forbes S.
Source
Faculty of Nursing, University of Alberta, 3rd Floor, Clinical Sciences Building, Edmonton, Alberta, Canada, T6G 2G3.
Abstract
BACKGROUND:
This is an update of our previous 2008 review. Several recent trials and systematic reviews of the impact of exercise on people with dementia are reporting promising findings. OBJECTIVES: Primary: Do exercise programs for older people with dementia improve cognition, activities of daily living (ADLs), challenging behaviour, depression, and mortality in older people with dementia?Secondary: Do exercise programs for older people with dementia have an indirect impact on family caregivers' burden, quality of life, and mortality?Do exercise programs for older people with dementia reduce the use of healthcare services (e.g. visits to the emergency department) by participants and their family caregivers?
SEARCH METHODS:
We identified trials for inclusion in the review by searching ALOIS ( the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, on 4 September 2011, and again on 13 August The search terms used were: 'physical activity' OR exercise OR cycling OR swim* OR gym* OR walk* OR danc* OR yoga OR 'tai chi'.
SELECTION CRITERIA:
In this review, we included randomized controlled trials in which older people, diagnosed with dementia, were allocated either to exercise programs or to control groups (usual care or social contact/activities) with the aim of improving cognition, ADLs, behaviour, depression, and mortality. Secondary outcomes related to the family caregiver(s) and included caregiver burden, quality of life, mortality, and use of healthcare services.
DATA COLLECTION AND ANALYSIS:
Independently, at least two authors assessed the retrieved articles for inclusion, assessed methodological quality, and extracted data. Data were analysed for summary effects using RevMan 5.1 software. We calculated mean differences or standardized mean difference (SMD) for continuous data, and synthesized data for each outcome using a fixed-effect model, unless there was substantial heterogeneity between studies, when we used a random-effects model. We planned to explore heterogeneity in relation to severity and type of dementia, and type, frequency, and duration of exercise program. We also evaluated adverse events.
MAIN RESULTS:
Sixteen trials with 937 participants met the inclusion criteria. However, the required data from three trials and some of the data from a fourth trial were not published and not made available. The included trials were highly heterogeneous in terms of subtype and severity of participants' dementia, and type, duration and frequency of exercise. Only two trials included participants living at home. Our meta-analysis suggested that exercise programs might have a significant impact on improving cognitive functioning (eight trials, 329 participants; SMD 0.55, 95% confidence interval (CI) 0.02 to 1.09). However, there was substantial heterogeneity between trials (I2 value 80%), most of which we were unable to explain. We repeated the analysis omitting one trial, an outlier, that included only participants with moderate or severe dementia. This reduced the heterogeneity somewhat (I2 value 68%), and produced a result that was no longer significant (seven trials, 308 participants; SMD 0.31, 95% CI to 0.74). We found a significant effect of exercise programs on the ability of people with dementia to perform ADLs (six studies, 289 participants; SMD 0.68, 95% CI 0.08 to 1.27). However, again we observed considerable unexplained statistical heterogeneity (I2 value 77%) in this meta-analysis. This means that there is a need for caution in interpreting these findings. In further analyses, we found that the burden experienced by informal caregivers providing care in the home may be reduced when they supervise the participation of the family member with dementia in an exercise program (one study, 40 participants; MD , 95% CI to -5.87), but we found no significant effect of exercise on challenging behaviours (one study, 110 participants; MD -0.60, 95% CI to 3.02), or depression (six studies, 341 participants; MD -0.14, 95% CI to 0.07) . We could not examine the remaining outcomes, quality of life, mortality, and healthcare costs, as either the appropriate data were not reported, or we did not retrieve trials that examined these outcomes.
AUTHORS' CONCLUSIONS:
There is promising evidence that exercise programs can have a significant impact in improving ability to perform ADLs and possibly in improving cognition in people with dementia, although some caution is advised in interpreting these findings. The programs revealed no significant effect on challenging behaviours or depression. There was little or no evidence regarding the remaining outcomes of interest.

47. Alcohol
A J-shaped relationship may exist between alcohol consumption and cognitive decline in MCI patients
Xu G et al., (2009) Alcohol consumption and transition of mild cognitive impairment to dementia. Psychiatry Clin Neurosci. 63:43-9
In MCI pts, up to 1 drink/day of alcohol or wine may decrease the rate of progression to dementia. Solfrizzi V et al., (2007) Alcohol consumption, mild cognitive impairment, and progression to dementia.; Italian Longitudinal Study on Aging Working Group. Neurology 68:
Some evidence to suggest that limited alcohol intake in earlier adult life may be protective against incident dementia later
Peters R et al., (2008) Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age and Ageing 37:  
Xu G, Liu X, Yin Q, Zhu W, Zhang R, Fan X (2009) Alcohol consumption and transition of mild cognitive impairment to dementia. Psychiatry Clin Neurosci. 63:43-9
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
AIM: Mild cognitive impairment (MCI) is a prodrome for dementia. Alcohol drinking patterns may affect cognitive functions and the effects may accumulate to a significant level at an advanced age. This study investigated the relationship between alcohol consumption and risks for dementia in a cohort of elderly patients with MCI. METHODS: Patients with suspected cognitive impairment were screened. One hundred and seventy-six patients who met the MCI criteria were enrolled. Lifetime and daily alcohol consumptions were assessed at baseline using a self-report questionnaire answered by patients and their caregivers. Patients were classified according to alcohol consumptions as abstainers, light-moderate and heavy drinkers. Global cognitive functions were assessed periodically with Mini-Mental State Examination (MMSE). Enrolled patients were followed for 2 years. RESULTS: Of the 176 patients diagnosed as having MCI, 15 (8.5%) died, 13 (7.4%) were lost to follow up, and 66 (37.5%) developed dementia during follow up. Light-moderate alcohol drinkers had better MMSE performance than abstainers (P < 0.05) and heavy drinkers (P < 0.01) 2 years after MCI diagnosis. Patients who consumed a total of <or=300 kg alcohol prior to MCI diagnosis had less cognitive decline than patients who consumed no (P < 0.05) or >300 kg alcohol (P < 0.01). Heavy drinkers had a higher risk for dementia than abstainers (P < 0.05) and light-moderate drinkers (P < 0.05) 2 years after MCI diagnosis. CONCLUSIONS: A J-shaped relationship may exist between alcohol consumption and cognitive decline in MCI patients. Light-moderate alcohol drinking may be associated with decreased risks for dementia in elderly patients with MCI.
Solfrizzi V, D'Introno A, Colacicco AM, Capurso C, Del Parigi A, Baldassarre G, Scapicchio P, Scafato E, Amodio M, Capurso A, Panza F (2007) Neurology 68:
Alcohol consumption, mild cognitive impairment, and progression to dementia.; Italian Longitudinal Study on Aging Working Group.
Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Policlinico, Bari, Italy.
OBJECTIVE: To estimate the impact of alcohol consumption on the incidence of mild cognitive impairment and its progression to dementia. METHODS: We evaluated the incidence of mild cognitive impairment in 1,445 non-cognitively impaired individuals and its progression to dementia in 121 patients with mild cognitive impairment, aged 65 to 84 years, participating in the Italian Longitudinal Study on Aging, with a 3.5-year follow-up. The level of alcohol consumption was ascertained in the year before the survey. Dementia and mild cognitive impairment were classified using current clinical criteria. RESULTS: Patients with mild cognitive impairment who were moderate drinkers, i.e., those who consumed less than 1 drink/day (approximately 15 g of alcohol), had a lower rate of progression to dementia than abstainers (hazard ratio [HR] 0.15; 95% CI 0.03 to 0.78). Furthermore, moderate drinkers with mild cognitive impairment who consumed less than 1 drink/day of wine showed a significantly lower rate of progression to dementia than abstainers (HR 0.15; 95% CI 0.03 to 0.77). Finally, there was no significant association between higher levels of drinking (> or =1 drink/day) and rate of progression to dementia in patients with mild cognitive impairment vs abstainers. No significant associations were found between any levels of drinking and the incidence of mild cognitive impairment in non-cognitively impaired individuals vs abstainers. CONCLUSIONS: In patients with mild cognitive impairment, up to 1 drink/day of alcohol or wine may decrease the rate of progression to dementia.
Peters R, Peters J, Warner J, Beckett N, Bulpitt C. (2008) Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age and Ageing 37:
Imperial College, London, UK.
BACKGROUND: dementia and cognitive decline have been linked to cardiovascular risk. Alcohol has known negative effects in large quantities but may be protective for the cardiovascular system in smaller amounts. Effect of alcohol intake may be greater in the elderly and may impact on cognition. METHODS: to evaluate the evidence for any relationship between incident cognitive decline or dementia in the elderly and alcohol consumption, a systematic review and meta-analyses were carried out. Criteria for inclusion were longitudinal studies of subjects aged >or=65, with primary outcomes of incident dementia/cognitive decline. RESULTS: 23 studies were identified (20 epidemiological cohort, three retrospective matched case-control nested in a cohort). Meta-analyses suggest that small amounts of alcohol may be protective against dementia (random effects model, risk ratio [RR] 0.63; 95% CI ) and Alzheimer's disease (RR 0.57; ) but not for vascular dementia (RR 0.82; ) or cognitive decline (RR 0.89; ) However, studies varied, with differing lengths of follow up, measurement of alcohol intake, inclusion of true abstainers and assessment of potential confounders. CONCLUSIONS: because of the heterogeneity in the data these findings should be interpreted with caution. However, there is some evidence to suggest that limited alcohol intake in earlier adult life may be protective against incident dementia later.

48. Drug-nutrient interactions
Effect
PPI
H-2 receptor antagonists
↓ B12, minerals
Metformin
↓ B12
Statins
↓ Co-enzyme Q10

49. Advice for the patient Do: Don’t: Eat low-carb Mediterranean style
↑ vegetables, fresh fruit, seeds, nuts, legumes, cereals, oils, fish, eggs
X trans fats, refined carbs, sugar
Engage in physical, mental and social activity
Consider supplementing fish oil, multi / B-complex, vitamin D
Drink water
Eat BAD
British Average Diet
Eat sugar or refined carbohydrates
Drink juice
Smoke
Over consume alcohol or caffeine
Be chronically stressed

50. What can you do? Test homocysteine Test B12 Test red cell folate
B vitamin supplementation to bring down to 8µmol/l
Test B12
B12 supplementation (100µg/day) to maintain in top half of range
Test red cell folate
Folate supplementation to maintain in range
Test vitamin D3
D3 supplementation to maintain above 125 nmol/l

51. e deborah@thinkingnutrition.co.uk w www.thinkingnutrition.co.uk
Deborah Colson MSc DipION e w
@thinkinutrition 