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Appendix: Summary of Individual Studies Linking Alzheimer’s Disease to Nutrients

EPIDEMIOLOGICAL

COMBINATION

Article N Age Sex Type of Study Genetics/Ethnicity Intervention OutcomeDietary antioxidants and long-term risk of dementia.22

5395 55+ M&F Prospective cohort

Residents of Rotterdam, Netherlands

Followed dietary intakes of Vitamin E, C, beta carotene, and flavinoids. for 6 years

Dietary intake of Vitamin C, beta carotene, and flavinoids was not associated with dementia risk. Vitamin E dietary intake may reduce long-term risk of dementia/AD.

Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in older adults.23

2969 w/o cognitive impairment

65+ M&F Prospective observational cohort

Participants were followed for 5 years and asked biennially about vitamin E, C, and multivitamin intake. They were categorized as: non-use, C alone, E alone, MVI alone, C+MVI, E+MVI, and C+E (with or without MVI).

There was no effect of supplemental use of vitamins E or C alone or in combination on risk for overall dementia or AD.

Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.24

4740 Population overlaps with reference 29 above

65+ M&F Cross-sectional and Prospective Study

Supplement intake of Vitamin E, C, or both was assessed at the beginning of the study. Dementia status was assessed at beginning of study and at 3 year follow-up.

Use of vitamin E and vitamin C supplements in combination was associated with reduced prevalence and incidence of AD. Use of either vitamin alone was not significantly associated with AD incidence.

Antioxidant vitamin intake and risk of Alzheimer disease.25

980 w/o dementia

65+ M&F Prospective Observational study*

A clinical assessment of dementia was conducted at baseline and follow-up. Semiquantitative food frequency questionnaire at baseline and follow-up was used to obtain dietary data. Followed for

Risk of AD was not associated with supplemental, dietary, or total intake of carotenes, vitamin C, or vitamin E.

1

4 years.Dietary intake of antioxidants and risk of Alzheimer disease.26

5395 w/o dementia

55+ M&F Prospective observational cohort

Rotterdam study Dementia and AD were assessed using cognitive tests and clinical examinations. Dietary intake was assessed by a checklist and interview, which utilized a semiquantitative food frequency questionnaire. Mean follow-up was 6 years.

High intake of vitamin C and vitamin E from food may be associated with a lower incidence of Alzheimer disease.

Dietary intake of antioxidant and the risk of incident Alzheimer disease in a biracial community study.27

815 w/o AD

65+ M&F Prospective observational study

Participants completed food frequency questionnaires a mean of 1.7 years after baseline. Evaluations for AD were conducted by specialists.

Intake of vitamin E from food was inversely associated with incident AD. There was no association with vitamin E supplement use. Vitamin C and beta carotene also had no statistically significant association with AD.

Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study.28

2459 w/o dementia

71-93

M Longitudinal Study

Japanese Americans

Diets were assessed using a 24-hour dietary recall. Dementia was assessed using cognitive tests and clinical diagnosis. Median follow-up was about 25 years.

There was no association between midlife dietary intake of antioxidants and the incidence of dementia and its subtypes in late life.

Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study.29

3376 65+ M&F Prospective observational study*

Compared mental states of participants over 8 years in 5 groups: 1) non-users of vitamin E, vitamin C, and NSAIDs; 2) users of NSAIDs but not vitamin E or C; 3) users of vitamin E and C but not NSAIDs; 4) users of vitamin E or C (but not both) with or without NSAIDs (Vit E or C +/- NSAIDs), and 5) users of vitamin E and C and NSAIDs.

In people with the APOE epsilon4 allele, there was an association between using antioxidant supplements in combination with NSAIDs and less cognitive decline over time.

Poor Nutrient Intakes during 1-Year

94 (36 w/ early-stage

65+ M&F Prospective observational

Participants were interviewed 4 to 5 times

Controls had higher dietary and supplemental intake of

2

Follow-Upwith Community-Dwelling Older Adults withEarly-Stage Alzheimer Dementia Compared toCognitively Intact Matched Controls.30

AD & 58 age-matched controls)

study* over 18 months, assessing diet and supplement use.

calcium, vitamin D, zinc, magnesium, iron, folate, vitamins B-6 and B-12, n-3, n-6, and dietary fiber as compared with AD patients.

Reduced concentrations of several vitamins in normal weight patients with late-onset dementia of the Alzheimer type without vascular disease.31

38 (20 w/ DAT, 18 w/o DAT, all w/o vascular disease)

75-85

F Case-control Analysis was done using blood samples, CSF from lumbar puncture, and spinal puncture.

The DAT group had lower B12, ascorbic acid, a-tocopherol, and thiamine as compared with the control group.

Food combination and Alzheimer disease risk: a protective diet.32

2148 65+ M&F Prospective observational cohort

Followed dietary patterns of intake of saturated fatty acids, monounsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E, vitamin B12, and folate for an average of 3.96 years.

There was a lower AD risk with a higher intake of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter.

3

SELENIUM

Article N Age Sex Type of Study Genetics/Ethnicity Intervention OutcomeNutritional status of selenium in Alzheimer's disease patients.33

57 (28 w/AD & 29 control)

60-89

M&F Case-control Se intake was evaluated using food record, and measured in plasma, erythrocytes, and nails.

There was deficient Se intake in AD group.

VITAMIN K

Article N Age Sex Type of Study Genetics/Ethnicity Intervention OutcomeLow vitamin K intakes in community-dwelling elders at an early stage of Alzheimer's disease.34

62 (31 w/ early-stage AD & 31 age-and sex-matched controls)

65+ M&F Case control Compared 3 to 5 days of dietary records over 3 months and compared Vitamin K intake.

Participants w/ AD consumed significantly less Vitamin K than the healthy control group.

4

VITAMIN B

Article N Age Sex Type of Study Genetics/Ethnicity Intervention OutcomeDietary folate, vitamin B-12, vitamin B-6 and incident Alzheimer's disease: the cache county memory, health and aging study.15


Dietary data was collected using a 142-item food frequency questionnaire. Follow-up over 9 years.

There were no observed differences in risk of AD regarding intake of folate, vitamin B-12, or vitamin B-6. Also, there were no observed differences in AD risk with folate or B6 supplement.

Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline.35

3718 65+ M&F Prospective cohort study

A food frequency questionnaire was used to determine nutrient intake, and cognitive tests were used to assess cognitive change over a 6 year period.

There were inverse associations between AD and dietary intakes of totalniacin (foods and supplements), niacin from foods only, and tryptophan. Higher intake of niacin from food sources was also associated with lower cognitive decline.

Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer’s disease.36

1041 w/o AD

65+ M&F Prospective cohort study

A food frequency questionnaire was used to examine the association between risk of incident AD and dietary intakes of folate, vitamin B-12, and vitamin B-6. Participants were followed for a median of 3.9 years.

Dietary intakes of folate, vitamin B-12 or vitamin B-6 were not significantly associated with the risk of developing AD over 4 years.

Relation of higher folate intake to lower risk of Alzheimer disease in the elderly.37

965 w/o dementia

65+ M&F Prospective observational cohort study*

Information on daily dietary, supplement, and total intake of folate and vitamins B6 and B12 was estimated from a semiquantitative food frequency questionnaire.

There were no differences between people with and without incident AD in the energy-adjusted intake of vitamins B6 and B12 or in the use of supplements. People with AD had an energy-

5

adjusted total folate intake that was almost statistically significantly lower.

Vitamin B(12) and folate in relation to the development of Alzheimer’s disesase.38

370, all without dementia

75+ M&F Population-based observational study*

Participants were followed for 3 years to assess how folate and B12 levels affected development of AD and dementia.

Participants with low levels of vitamin B(12) or folate had higher risks of developing AD or dementia as compared to those with high levels of B(12) or folate.

Nutritional Status of Free-Living Alzheimer’s Patients.39

63 (22 w/ SDAT, and 41 normal)

60+ Food consumption records were kept by subjects or their caretakers for 3 days. Nutritional status was determined from non-fasting blood samples.

B12, thiamin, and folate were lower in SDAT subjects. Individuals in both groups who used multivitamins had higher biochemical values for thiamin, riboflavin, and B12.

High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affair Normative Aging Study.40

321 50+ M Cross-sectional cohort study

Assessed cognitive function using various cognitive exams and assessed dietary intake using a semiquantitative food frequency questionnaire.

Low B vitamin and high homocysteine concentrations predicted cognitive decline. Folate (plasma and dietary) remained independently protective against a decline in spatial copying score. Dietary folate was protective against a decline in verbal fluency. High homocysteine concentration was associated with a decline in recall memory.

Cobalamin levels are not reduced in Alzheimer's disease: results from a population-based study.41

545 (392 non-demented, and 153 with some sort of dementia)

74+ M&F Cross-sectional study

Residents of Stockholm, Sweden

Diet was assessed by an interview with the pro-band and next-of-kin. Cognitive function was assessed by a clinical exam and laboratory tests for secondary dementias.

Serum cobalamin levels decreased in non-demented individuals with an increase of 1 year of age. There was no difference in serum cobalamin levels in demented, AD, and non-demented people,

6

except for the oldest ages were demented and AD sufferers showed higher values. Serum cobalamin levels decreased in normal aging, but not in dementia or AD.

Vitamin B(12) and folate status in relation to decline in scores or minimental state examination in the Framingham heart study42

549 74.8+4.6 M&F 8 year followup MMSE Low B(12) predicts cognitive decline and is more rapid in persons receiving folate

Status of vitamins B(12) and B(6) but not of folate, homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism are association with impaired cognition and depression in adults43

1956 Puerto Recan 45-75Others 60+

M&F Cross-sectional Puerto Rican, White and African American

MMSE B(12) and B(6) associated with impaired cognition

Vitamin B(12), cognition and brain MRI measures: A cross-sectional examination44

121 65+y M&F Prospective cohort 4-6 yr follow up. Markers of serum B(12) activity

Vitamin B(12) deficiency may affect brain by reducing brain volume

Low folate status is associated with impaired cognitive function and dementia in the Sacramento Area Latino Study on Aging.94

1789, recruited after gov’t initiated folic acid fortification

60+ M&F Cohort study Latinos in Sacramento, CA

Fasting blood was collected to assess RBC folate and plasma B-12 and homocysteine. Cognitive functions were also assessed.

RBC folate was directly associated with cognitive function scores and was inversely associated with dementia in elderly Latinos despite folic acid fortification.

CERTAIN FOODS

Article N Age Sex Type of Study Genetics/Ethnicity Intervention OutcomeOlive oil and cognition: results


Registered residents of

Assessed intake of olive oil and administered

There were lower odds of cognitive deficit in those who

7

from the three-city study.45

France cognitive tests after 4 years.

had a moderate or intensive use of olive oil. After 4 years, a significant association b/w intensive olive oil consumption and visual memory was seen.

Midlife fruit and vegetable consumption and risk of dementia in later life in Swedish twins.46

3779 65+ M&F Case-control twin study

Swedish Twins Investigators used dietary records from 30 years prior to dementia assessment.

Midlife fruit and vegetable consumption was associated with a reduced risk of dementia and AD in women, but not men. Higher fruit and vegetable consumption was protective for those who reported angina.

Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon 4.47


474 w/ APOE epsilon 4 allele, 1570 w/o it. (Not all consented to genetic testing)

Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus. Participants were followed for an average of 5.4 years.

Consumption of fatty fish was associated with a reduced risk of dementia and AD in those without the APOE epsilon 4 allele.

Fish, meat, and risk of dementia: cohort study.48

1674 68+ M&F Cohort study Southwestern France

Investigators interviewed participants regarding their meat and fish or seafood intake, categorized as daily, once a week, time to time, or never. Participants were followed at 2, 5, and 7 years and assessed for dementia.

Increased consumption of fish or seafood was significantly associated with a lower incidence of dementia.

FATS

Article N Age Sex Type of Study Genetics/Ethnicity Intervention OutcomeHigh dietary and 266 67- M&F Case-cohort Participants had plasma Plasma and dietary DHA

8

plasma levels of the omega-3 fatty acid docosahexaenoic acid are associated with decreased dementia risk: the Rancho Bernardo study.10

100 study DHA measured and neurological and neuropsychological evaluations for dementia in 1991-93. Dietary data of intakes of DHA and fish obtained in a 1988-91 visit.

were associated with reduced odds of AD and all-cause dementia. Fish intake had similar but not significant reduced odds of dementia and AD.

Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease.49

815 w/o AD

65+ M&F Prospective study

Diet was assessed by food frequency questionnaire. AD was diagnosed by clinical evaluation. Participants followed for a mean of 3.9 years.

Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease.

Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk.50

5395 55+ M&F Population-based cohort study (Rotterdam)

Dutch The type and quantity of fish consumed and omega-3 PUFAs (DHA, EPA, ALA) was assessed with an average follow up of 9.6 years.

There was no relation of total fish intake with long-term risk of dementia and AD. There was no significant difference between different types and quantities of fish consumed. Dietary intakes of omega-3 PUFAs were also not associated with dementia or AD risk.

Omega-3 fatty acids and risk of dementia: the Canadian Study of Health and Aging.51

663 65+ M&F Prospective cohort study*

Using blood samples, n-3 PUFAs, DHA, EPA, and mercury’s association with dementia and AD incidence was evaluated with a mean follow-up of 4.9 years.

There was no association between total n-3 PUFAs, DHA, or EPA and dementia or AD. However, high mercury concentration was associated with a reduced risk of dementia if coupled with high n-3 PUFA concentration.

Dietary fats and the risk of incident Alzheimer disease.52

815 w/o AD

65+ M&F Cross-sectional study

A food frequency was questionnaire used to assess diet, and AD incidence was determined by clinical evaluation. Mean follow-up was 3.9 years.

Risk of incident AD increased with high intakes of saturated and trans-unsaturated fats and decreased risk with high intakes of -6 polyunsaturated and monounsaturated fats.

9

Intake of vegetable fat and a high ratio of polyunsaturated to saturated fats were also protective. Total fat, animal fat, and dietary cholesterol had no association with AD.

Dietary fat intake and the risk of incident dementia in the Rotterdam Study.53

5386 w/o dementia

55+ M&F Population-based prospective study

Rotterdam Study Dietary intake was assessed with a semiquantitive food frequency questionnaire. Dementia findings were based on a screening test, followed by a clinical evaluation if necessary. Participants were also evaluated for vascular dementia. Follow-up period was a mean of 2.1 years.

High intakes of total fat, saturated fat, and cholesterol were related to an increased risk of dementia, and total andsaturated fat in particular were related to dementia with a vascular component. Fish consumption, an important source of n-3 polyunsaturated fatty acids, was associated with a reduced risk of dementia, and most strongly with AD.

Fat intake at midlife and risk of dementia and Alzheimer’s disease: a population-based study.54

1,449 65+ M&F Population-based prospective study

Individuals’ fat intake at midlife was assessed with a mean follow-up of 21 years.

Moderate intake of unsaturated fats at midlife was protective, while moderate intake of saturated fats may have increased the risk of dementia and AD.

Omega-3 polyunsaturated fatty acid supplements and cognitive decline: Singapore Longitudinal Aging Studies.55


Chinese Omega-3 PUFA supplement intake and MMSE assessed at baseline, and MMSE was reassessed at median of 1.5 years follow-up.

Daily omega-3 PUFA supplement intake was significantly associated with a lower risk of cognitive decline. There was no statistically significant association between fish consumption and cognitive decline.

Dietary fatty acids intakes and rate of mild cognitive impairment. The Italian Longitudinal Study on Aging.56

704 65+ M&F Population-based prospective study

Southern Italy Investigated the role of dietary fatty acids on mild cognitive impairment in 278 and 186 nondemented survey participants (704 total) with a mean follow-up of 2.6 years.

Dietary fatty acids intakes were not significantly associated with incident mild cognitive impairment.

10

Diet and risk of dementia: Does fat matter?: The Rotterdam Study.57

5,395 65+ M&F Population-based prospective cohort study

Rotterdam Study This cohort, which consisted of people with normal cognitive function, was monitored for incident dementia over a mean of 6 years to study the association between fat intake and incident dementia.

There was no association between high total fat, saturated fat, trans fat, and cholesterol, or low MUFA and PUFA intake and dementia.

VITAMIN E

Article N Age Sex Type of Study Genetics/Ethnicity Intervention OutcomeRelation of the tocopherol forms to incident Alzheimer disease and to cognitive change.58


Dietary intake was assessed using food frequency questionnaire, and cognitive state was assessed using cognitive tests and clinical evaluations. Participants were followed for 6 years.

Various tocopherol forms rather than alphatocopherol alone may be important in vitamin E’s protective association with Alzheimer disease.

ALUMINUM

Article N Age Sex Type of Study Genetics/Ethnicity Intervention OutcomeA preliminary study of dietary aluminum intake and risk of Alzheimer’s disease.59

46 (23 w/ AD, and 23 paired controls)

64+ M&F Matched case-control

Carers of AD patients and next-of-kin of controls recalled dietary intake for the 5 years preceding onset of AD (and the same time period for control group).

Intake of pancakes, waffles, biscuits, muffins, cornbread and/or corn tortillas differed significantly between cases and controls. Adjusted odds ratios were also elevated for grain product desserts, American cheese, chocolate pudding or beverages, salt and chewing gum. However, the odds ratio was not elevated for tea consumption. Dietary intake of aluminum may affect the risk of developing AD.

11

*To maintain consistency, the types of studies reported in the tables have been adjusted from how they were reported in the articles.Interventional

INTERVENTIONAL

MIXED FORMULAS

Article Title N Age Sex Type of Study

Genetics/Ethnicity

Intervention Outcome Label

A vitamin/ nutriceutical formulation improves memory and cognitive performance in community-dwelling adults without dementia.60

115 18-86

M&F Randomized control trial

Participants were given placebo or formula of folic acid, B12, Vitamin E, S-adenosylmethionine, N-acetyl cysteine and Acetyl-L-carnitine.

There was better cognitive performance with formula versus placebo, and performance declined when formula was withdrawn. Less improvement was seen in those 74+. Cognitive performance assessed w/ California Verbal Learning Test II and the Trail-Making Test.

B

Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer's disease: a placebo-controlled pilot study.61

12 w/ moderate to late-stage AD

M&F Randomized control trial

Participants were given a nutriceutical formula of folic acid (400 mg), vitamin B12 (6 mg), vitamin E (as alphatocopherol;30 IU), SAM (400 mg), NAC (600 mg), and ALCAR (500 mg). Or, they were given placebo for 9 months.

Participants given formula had a delay in decline.

B

Effect of vitamin and trace-element supplementation on cognitive function in elderly subjects.62

86 65+ M&F Randomized, double-blind, placebo-controlled trial

Participants received a supplement of trace elements and vitamins or a placebo daily for 12 months.

The supplemented group showed a significant improvement in all cognitive tests except long-term memory recall. There was no significant correlation between individual nutrient levels and performance on various cognitive function tests.

A

12

Efficacy of a medical food in mild Alzheimer’s disease: A randomized, controlled trial.63

225 w/ probable AD

50+ M&F Randomized, double-blind, controlled trial

Participants were randomly assigned to have 125 mL of the Souvenaid nutrient drink each day or a control drink for 12 weeks.

Participants with mild AD assigned to the Souvenaid drink had an improvement in delayed verbal recall score. Participants with very mild AD had an improvement in delayed and immediate verbal recall.

A

Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women.64

49 60-80

F Randomized, double-blind, placebo- controlled trial

Women were randomized to receive 800 mg/day DHA, 12 mg/day lutein, combination of DHA and lutein, or placebo for 4 months. Participants took cognitive tests and reported their moods at randomization and upon completion of the trial.

Verbal fluency scores improved significantly in the DHA, lutein, and combined treatment groups. The lutein and combination groups showed the most significant change. Mood was not affected by supplementation.

A

Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over: a randomized controlled trial.65

910 65+ M&F Randomized, double-blind, placebo-controlled trial

Participants were randomly assigned to active treatment of one tablet containing 11 vitamins and 5 minerals or a matching placebo tablet taken daily for 12 months. Immediate memory and executive functioning studies were conducted before and after the intervention period.

There was no significant beneficial effect of daily multivitamin and multimineral supplements on immediate memory and executive functioning.

A

Effects of a multivitamin, mineral, and herbal supplement on cognition and blood biomarkers in older men: A randomized placebo-controlled trial66

900 50-74

M Placebo controlled double blind

Multivitamins, minerals, herbal for 8 weeks

Effect only on contextual recognition memory

A

Cognitive function after supplementation

1748 45-80

M&F Randomized France Block randomization with stratification by sex, age, prior cardiovascular disease and

No overall effects.Small effect on temporal orientation task in

A

13

with B vitamins and long chain Omega-3 fatty acids: Ancillary findings from the SU.FOL.OM3 randomized trial67

city of residence to (1) folate, B6, B12; (2) EPA and DHA; (3) combination; or (4) placebo

persons with stroke

VITAMIN B

Article N Age Sex Type of Study

Genetics/Ethnicity


Vitamins B(12), B(6), and folic acid for cognition in older men.68

299, hyperten-sive

75+ M Randomized, double-blind controlled trial

Participants were randomized into 2 groups. The vitamin group received a capsule of 400 μg B12, 2 mg folic acid, and 25 mg B6 to take once each day. The control group received an identical placebo. Everyone was assessed at 6 month intervals for 2 years regarding dementia and cognitive impairment. A secondary aim of the study was to determine via telephone interview if supplementation with vitamins decreased the risk of cognitive impairment and dementia over 8 years.

Use of vitamins B6, B12, and folate for 2 years did not change the rate of cognitive decline among men with hypertension aged 75 years or older. 2 years of B-vitamin supplementation did not seem to benefit these men in terms of mortality or a later diagnosis of dementia.

A

Folic acid supplementation in dementia: a preliminary report.69

7 70+ M&F

Double-blind, placebo-controlled study

For 10 weeks, 4 participants were given 10 mg/day of folic acid, and 3 participants were given placebo.

There were no significant differences between the control and folic acid groups regarding language, memory, speed, or concentration.

A

High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a

340 w/ probable AD

50+ M&F

Randomized, double-blind, controlled trial

202 participants were given 5 mg folic acid, 1 mg vitamin B12, and 25 mg vitamin B6/day. 138 control participants were given

Vitamin B supplements did not slow cognitive decline in people with mild to moderate AD.

A

14

randomized controlled trial.70

identical placebo.This was done for 18 months.

The group given supplements had more adverse events involving depression.

A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease.71

57 w/ probable AD

70+ M&F

Randomized, double-blind, placebo controlled trial

Participants were treated with cholinesterase inhibitor with either folic acid or placebo for 6 months.

There was a significant difference in the change from baseline in combined Instrumental Activities of Daily Living and Social Behavior scores, but no change in MMSEScores. Response to ChI in AD patients may be improved w/ folic acid use.

A

Efficacy of multivitamin supplementation containing vitamins B(6) and B(12) and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer’s disease: A 26-week, randomized, double-blind, placebo-controlled study in taiwanese patients72

89 >50 M&F

Randomized double-blind placebo controlled

B(6), B(12) and folic acid for 26 weeks

No significant effects on cognition or ADL function

A

Oral folic acid and vitamin B(12) supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms—the Beyond Ageing Project: A randomized controlled trial73

900 60-74

M&F

Randomized, double-blind placebo conrolled

Folic acid and B(12) for 24 months

Improvement in cognitive functioning, particularly in immediate and delayed memory performance.

A

15

OMEGA-3 STUDIES


Genetics/Ethnicity


Reduced prostaglandin F2 alpha release from blood mononuclear leukocytes after oral supplementation of omega3 fatty acids: the OmegAD study.74

25 w/ AD 57-82

M&F

Randomized control trial

Patients were given 1.7 g DHA plus 0.6 g EPA (both omega-3) or placebo for 6 months.

PGF-2alpha release from LPS-(not PHA-) stimulated PBMC diminished in omega-3 group (reduced inflammatory reactions).

B

Effects of docosahexaenoic acid–rich n–3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the OmegAD study.75

21 w/ AD 57-82

F Randomized double-blind placebo controlled trial

Patients were treated daily with either 1.7 g DHA plus 0.6 g EPA or isocaloric placebo oil for 6 months.

There was a significant decline of released IL-1β, IL-6, and G-CSF, but not of TNF-α, IL-8, -10, and GM-CSF at 6 months. However, the G-CSF response was not significantly different statistically compared with the response of the placebo group.

A

Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease: the OmegAD study.76

35 62+ M&F

Randomized control trial

Patients were given 2.3 g omega-3 FAs or placebo for 6 months.

There was no significant treatment effect of omega-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE.

B

Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild

50 with MCI

>65 M&F

Randomized, Double-blind

EPA (1.67g) and DHA (1.55g) or linoleic acid (22g)

No effect on cognitive. Possible improvement in depression

A

16

cognitive impairment: A 6-month randomised controlled trial77

Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms.78

204 w/ AD

65+ M&F

Randomized double-blind placebo controlled trial

Patients were given either 430mg DHA and 150 mg EPA/day or isocaloric placebo and assessed at 6 and 12 months.

Supplementation with omega3 in patients with mild to moderate AD did not result in marked effects on neuropsychiatric symptoms except for possible positive effects on depressive symptoms in non-APOEomega4 carriers and agitation symptoms in APOEomega4 carriers.

A

Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial.79

174 w/ AD

65+ M&F

Randomized, double-blind, placebo-controlled clinical trial.

Patients were randomized to daily intake of 1.7g of docosahexaenoic acid and 0.6g of eicosapentaenoic acid or placebo for 6 months, after which all received omega-3 fatty acid supplementation for 6 months more.

Omega-3 in patients with mild to moderate AD did not delay the rate of cognitive decline. There were positive effects, however, in patients who had very mild AD.

A

Docosahexanoic acid supplementation and cognitive decline in Alzheimer disease: A randomized trial80

402 w/ probable AD

76 M&F

Randomized double-blind

AlgalDHA 2g/d or placebo for 18 months.

No beneficial effect A

Effects of n-3 fatty acids on cognitive decline: A randomized, double-blind, placebo-controlled trial in stable myocardial infarction patients81

2911 60-80

M&F

Randomized, double-blind

40ng EPA/DHA or 2g/d ALA or both

No effect A

17

VITAMIN E


Genetics/Ethnicity


Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer's disease.82

20 w/ AD 56+ M&F

Controlled clinical trial

10 people were supplemented with 400 IU vitamin E and 1000 mg vitamin C per day for 1 month, and a second group of 10 people was supplemented for 1 month with 400 IU/d vitamin E alone.

Supplementation of AD patients with 400 IU vitamin E and 1000 mg vitamin C each day for one month significantly increased the concentrations of both vitamins in the CSF and plasma. Lipoproteins in the CSF and plasma were significantly less susceptible to in vitro oxidation in this group. In AD patients only given 400 IU of vitamin E each day for a month, CSF and plasma vitamin E concentrations significantly increased, but lipoprotein oxidatibility was not decreased.

C

Vitamin E paradox in Alzheimer’s disease: it does not prevent loss of cognition and may even be detrimental.83

57 w/ AD Prospective, double-blind, placebo-controlled study

In Valencia, Spain

Participants were randomly assigned to receive 800 IU vitamin E/ day of placebo for 6 months. They were compared to 18 age-matched controls.

In those who responded to vitamin E, GSSG levels were lower and cognitive test scores were maintained. In non-respondents, cognition decreased. Vitamin E lowered oxidative stress in some AD patients but not in others.

A

FOODS

Article N Age Sex Type of Study Genetics/Ethnicity


Blueberry supplementation

9 w/ memory

71+ M&F Controlled clinical trial

Participants consumed between 444 and 621 mL/day

Participants had improved paired

C

18

improves memory in older adults.84

decline of wild blueberry juice, depending on body weight. This was done for 12 weeks.

associate learning, word list recall, and lower depressive symptoms.

A label of “A” denotes double-blind studies, “B” denotes single-blind studies, and “C” denotes open label studies.

19

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