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CompletedNCT04972643Updated Jul 26, 2021

The Protective Effect of Omega-3 Fatty Acid on Cognitive Function Among Patients With Mild Dementia

An interventional study of EPA and DHA in Alzheimer Disease and Dementia Disorder, sponsored by Taichung Veterans General Hospital. Completed at 1 site in Taiwan. Open to participants aged 65 Years to 105 Years. Per ClinicalTrials.gov, last updated 2021-07-26.

Sponsored by Taichung Veterans General Hospital · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Registered 5 years 4 months after the study started (first participant enrolled Sep 2012, registered Feb 2018).
Phase
Not applicable
Study type
Interventional
Enrollment
163
Allocation
Randomized
Ages
65 Years to 105 Years
Sex
All
01

Study summary

Background： Dementia is a progressive, devastating, and fatal neurodegenerative disorder. Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than 50% of patients with dementia. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the major bioactive components of n-3 polyunsaturated fatty acids (n-3 PUFAs) , might connect to the etiology of several neuropsychiatric diseases. To our knowledge, it has never been studied to look at the different effects of DHA, EPA and their combination on associated symptoms of AD.

Objectives To examine the effects of DHA, EPA and their combination on associated symptoms of AD, including cognitive function, depressive symptoms, and functional ability.

Method This is a randomized, double-blind, placebo-controlled, 24-month follow-up study, enrolling 200-400 patients with mild AD (Mini-Mental Status Examination (MMSE) 19-26 or Clinical Dementia Rating (CDR) 0.5-1). Cognitive ability is assessed by the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the MMSE. Mood status is assessed by Geriatric Depression Scale (GDS). Functional ability is assessed by the Alzheimer Disease Cooperative Study activities of daily living (ADCS-ADL) and global function by the CDR, quality of life scale (QOL-AD). Brain function is assessed by resting state brain magnetic resonance imaging (MRI).

Read the detailed description

Background Dementia is a progressive, devastating, and fatal neurodegenerative disorder (Cummings, 2004). As of 2010, there are an estimated 35.6 million people with dementia worldwide. By 2050, it is projected that this figure will have increased to over 115 million (1, 2). Therefore, dementia is not only an important medical disease but also a public health issue to demand immediate attention. A conservative estimate of economic burden from dementia (based on Alzheimer's Society's Dementia United Kindom (UK) report published in February 2007) reaches 20 billion by the year 2010, which suggests an average cost of 25,472 per person annually. It indicated a heavy social financial expense for the whole world in general. Alzheimer's disease (AD) is the most common cause of dementia, accounting for 60-80% of patients with dementia. Given that it is still lacking in effective treatments for AD, there has been growing interest in early detection and prevention for this disastrous illness. Delaying AD onset by 1 year could potentially lower its incidence by more than 9 million cases over the next 40 years (3).

Dementia could be resulted from numerous risk factors and medical conditions including vascular risk factors (e.g. hypertension, diabetes, and obesity), psychosocial factors (e.g. depression), and health behaviors (e.g. physical inactivity and smoking) (4, 5). Indeed, reflecting its heterogeneity, several hypotheses have been proposed for etiology of dementia, including genetic susceptibility, vascular changes, inflammatory process, oxidative stress, and recently, n-3 polyunsaturated fatty acids (n-3 PUFAs) (Fratiglioni et al., 2008;Samieri et al., 2008;Cole and Frautschy, 2010;Mucke and Pitas, 2004;Gomez-Pinilla, 2008). PUFAs are classified into mainly n-3 (or omega-3) and n-6 (or omega-6) groups. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the major bioactive components of n-3 PUFAs, are associated with neuronal membrane stability and fluidity, neurogenesis, neuroplasticity, neurotransmission and anti-inflammation, which might connect to the etiology of several neuropsychiatric diseases including depression and dementia (Horrobin and Bennett, 1999;Su et al., 2000;Chalon, 2006;Lukiw and Bazan, 2006;Su, 2009b;Lin et al., 2010a). On the other hand, arachidonic acid (AA), the major components of n-6 PUFAs, is a precursor of eicosanoids and is important to modulate proinflammatory effects, which might also link to the pathogenesis of neuroinflammatory and neurodegenerative diseases like dementia (Sanchez-Mejia and Mucke, 2010;Lukiw and Bazan, 2010). Consistent with the theoretical relevance, evidences to link PUFAs to dementia have been reported extensively from more epidemiological studies. For example, it has been observed that regions with a high consumption of fish, which are good sources of n-3 PUFAs, appear to have a lower prevalence of dementia (Barberger-Gateau et al., 2002;Barberger-Gateau et al., 2007;Huang et al., 2005;Morris et al., 2003;Kalmijn et al., 1997) and Mild cognitive Impairment (MCI) ;(Roberts et al., 2010)). Although clinical studies until now have failed to demonstrate beneficial effects of n-3 PUFA supplementation in patients with moderate or severe AD (Freund-Levi et al., 2006a;Quinn et al., 2010a), it may benefit in patients with mild AD or MCI and those without apolipoprotein E(APOE) ε4 allele (Freund-Levi et al., 2006b;Chiu et al., 2008;Quinn et al., 2010b). In addition, the two main n-3 PUFAs have different biological effects. DHA is the main n-3 PUFAs in the brain and is important in neuroplasticity and neuroprotection. EPA, on the other hand, is very little in the brain but is important in modulate inflammation and immune function (Lin et al., 2010b;Su, 2009a). To our knowledge, it has never been studied to look at the different effects of DHA, EPA and their combination on different associated symptoms of AD. To provide more evidence for the association between n-3 PUFAs and associated symptoms of AD, including cognitive function, depression, and physical activity in AD, we propose to conduct this double-blind, placebo-controlled, 24-month research. In addition, neuroprotective effects of vitamin B, preliminary findings in recent studies have shown cognitive-protection effects of it among patients with MCI. Moreover, deficiency of vitamin B is known to cause nervousness, depression, and peripheral and central neuropathy. The importance of vitamin B in developmental processes of the brain is supported by the findings that vitamin B deficiency at certain stages of brain development interferes with brain cell proliferation, migration and maturation . Vitamin B affords survival-promoting activities on cultured brain neurons (6). This is probably the first study to evaluate the effects of vitamin B on cognitive protection among Asian patients with AD. Based on the review of the possible benefits from n-3 PUFAs supplement on cognitive function preservation after balancing for its slightest side effects, we here propose a randomized clinical trial study design to test whether Hypothesis Omega-3 PUFAs is protective against cognitive decline among people with mild AD.

Primary Aim To examine whether consumption of n-3 PUFAs protects against cognitive decline in patients with mild AD.

Secondary Aims

  1. To examine the different effects of DHA, EPA and their combination on different symptoms of AD.
  2. To examine whether consumption of n-3 PUFAs improves cognitive function in patients with mild AD.
  3. To examine whether consumption of n-3 PUFAs improves depressive symptoms in patients with mild AD.
  4. To examine whether consumption of n-3 PUFAs improves physical activity level in patients with mild AD.

Significance of Study

  1. To provide a simple way through dietary supplement of n-3 PUFAs to prevent cognitive decline and improve depressive symptoms and physical activity in patients with mild AD.
  2. No placebo-controlled studies regarding n-3 PUFAs in cognitive prevention have been conducted among Asian people.
02

Conditions studied

  • Alzheimer Disease
  • Dementia Disorder

Keywords

  • Dementia Alzheimer
03

In context

Alzheimer Disease

3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.

This study's enrollment of 163 is above the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

Taichung Veterans General Hospital is the lead sponsor of 170 studies on the registry; 37 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
65 Years to 105 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients may be included in the study if they meet the following criteria:

    1. Males and females over 65 years of age.
    2. Diagnosis of Alzheimer's Dementia disorder.
    3. Each individual must have a level of understanding sufficient to perform all tests and examinations required.
    4. Individuals must be willing to accept all laboratory examinations and MRI examination.
    5. Individuals must be willing to provide a small sample of blood for evaluation.
    6. Individuals must be willing to participate in a short 30-60 minute clinical interview.

Exclusion criteria

Exclusion Criteria:

  • Patients may be excluded from the study for any of the following reasons:

    1. Serious unstable illness such that death is anticipated within 1 year or intensive care unit hospitalization for the condition is anticipated within 6 months.
    2. Diagnosis of Vascular Dementia disorder.
    3. Uncorrected hypothyroidism or hyperthyroidism
    4. Participants will be excluded if they had evidence of epilepsy; focal brain lesion; head injury with loss of consciousness or confusion after the injury; DSMIV-TR (text revision) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, or alcohol or substance abuse; or potential bleeding tendency.
    5. History of allergy to fish or omega-3 polyunsaturated fatty acids.
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Investigator)
Enrollment
163 participants (actual)

Study arms

  • Experimental
    EPA and DHA intervention

    EPA 1000mg and DHA 1000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months.

    Dietary Supplement: EPA · Dietary Supplement: DHA

  • Experimental
    EPA intervention

    EPA 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months.

    Dietary Supplement: EPA

  • Experimental
    DHA intervention

    DHA 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months.

    Dietary Supplement: DHA

  • Placebo comparator
    Placebo

    Placebo 2000mg capsule twice a day, the total exposure to the intervention for each subject is 24 months.

    Dietary Supplement: Placebo

Interventions

  • Dietary supplementEPA

    EPA 2000mg Soft capsules

  • Dietary supplementDHA

    DHA 2000mg Soft capsules

  • Dietary supplementPlacebo

    Placebo Soft capsules

06

What researchers measure

Primary outcomes

  1. Aspartate Aminotransferase (AST)

    Time frame: Day 0

  2. Aspartate Aminotransferase (AST)

    Time frame: Day 24 month

  3. Alanine Aminotransferase (ALT)

    Time frame: Day 0

  4. Alanine Aminotransferase (ALT)

    Time frame: Day 24 month

  5. Albumin level

    Time frame: Day 0

  6. Albumin level

    Time frame: Day 24 month

  7. Fasting blood glucose

    Time frame: Day 0

  8. Fasting blood glucose

    Time frame: Day 24 month

  9. Blood Urea Nitrogen (BUN)

    Time frame: Day 0

  10. Blood Urea Nitrogen (BUN)

    Time frame: Day 24 month

  11. Creatinine level

    Time frame: Day 0

  12. Creatinine level

    Time frame: Day 24 month

  13. Sodium (Na)

    Time frame: Day 0

  14. Sodium (Na)

    Time frame: Day 24 month

  15. Potassium (K)

    Time frame: Day 0

  16. Potassium (K)

    Time frame: Day 24 month

  17. Calcium (Ca)

    Time frame: Day 0

  18. Calcium (Ca)

    Time frame: Day 24 month

  19. Magnesium (Mg)

    Time frame: Day 0

  20. Magnesium (Mg)

    Time frame: Day 24 month

  21. Triiodothyronine (T3)

    Time frame: Day 0

  22. Triiodothyronine (T3)

    Time frame: Day 24 month

  23. Free tetraiodothyronine (free T4)

    Time frame: Day 0

  24. Free tetraiodothyronine (free T4)

    Time frame: Day 24 month

  25. Thyroxin stimulating hormone (TSH)

    Time frame: Day 0

  26. Thyroxin stimulating hormone (TSH)

    Time frame: Day 24 month

  27. Triglycerides

    Time frame: Day 0

  28. Triglycerides

    Time frame: Day 24 month

  29. Total cholesterol

    Time frame: Day 0

  30. Total cholesterol

    Time frame: Day 24 month

  31. High density lipoprotein cholesterol (HDL)

    Time frame: Day 0

  32. High density lipoprotein cholesterol (HDL)

    Time frame: Day 24 month

  33. Low density lipoprotein cholesterol (LDL)

    Time frame: Day 0

  34. Low density lipoprotein cholesterol (LDL)

    Time frame: Day 24 month

  35. Vitamine B12 level

    Time frame: Day 0

  36. Vitamine B12 level

    Time frame: Day 24 month

  37. Folic acid

    Time frame: Day 0

  38. Folic acid

    Time frame: Day 24 month

  39. Rapid plasma reagin for Syphilis test (RPR)

    Time frame: Day 0

  40. Rapid plasma reagin for Syphilis test (RPR)

    Time frame: Day 24 month

  41. Mini Mental Status Evaluation (MMSE) total score

    Minimu:0, Maximum: 30, Higher scores mean a better outcome.

    Time frame: Day 0

  42. Mini Mental Status Evaluation (MMSE) total score

    Minimu:0, Maximum: 30, Higher scores mean a better outcome.

    Time frame: Day 24 month

  43. Clinical Dementia Rating Scale (CDR) total score

    Minimu:0, Maximum: 3, Higher scores mean a worse outcome.

    Time frame: Day 0

  44. Clinical Dementia Rating Scale (CDR) total score

    Minimu:0, Maximum: 3, Higher scores mean a worse outcome.

    Time frame: Day 24 month

  45. Hachinski ischemic score total score

    Minimu:0, Maximum: 18, Higher scores mean a worse vascular outcome.

    Time frame: Day 0

  46. Hachinski ischemic score total score

    Minimu:0, Maximum: 18, Higher scores mean a worse vascular outcome.

    Time frame: Day 24 month

  47. Alzheimer's Disease Assessment Scale-cognitive section (ADAS-Cog) total score

    Minimu:0, Maximum: 70, Higher scores mean a worse outcome.

    Time frame: Day 0

  48. Alzheimer's Disease Assessment Scale-cognitive section (ADAS-Cog) total score

    Minimu:0, Maximum: 70, Higher scores mean a worse outcome.

    Time frame: Day 24 month

  49. Alzheimer's Disease Assessment Scale-activities of daily living section (ADCS-ADL) total score

    Minimu:0, Maximum: 54, Higher scores mean a better outcome.

    Time frame: Day 0

  50. Alzheimer's Disease Assessment Scale-activities of daily living section (ADCS-ADL) total score

    Minimu:0, Maximum: 54, Higher scores mean a better outcome.

    Time frame: Day 24 month

  51. Geriatric Depression Scale (GDS) total score

    Minimu:0, Maximum: 15, Higher scores mean a worse outcome.

    Time frame: Day 0

  52. Geriatric Depression Scale (GDS) total score

    Minimu:0, Maximum: 15, Higher scores mean a worse outcome.

    Time frame: Day 24 month

  53. Quality of Life- Alzheimer Dementia (QOL-AD) total score

    Minimu:13, Maximum: 52, Higher scores mean a better outcome.

    Time frame: Day 0

  54. Quality of Life- Alzheimer Dementia (QOL-AD) total score

    Minimu:13, Maximum: 52, Higher scores mean a better outcome.

    Time frame: Day 24 month

  55. MRI examination 1

    Total brain volume: MRI examination will be performed on the 1.5 Telsla machine (GE, USA)

    Time frame: Day 0

  56. MRI examination 2

    Total brain volume: MRI examination will be performed on the 1.5 Telsla machine (GE, USA)

    Time frame: Day 24 months

07

Study locations

1 site
  • Taichung Veterans General Hospital
    Taichung, No.450,Sec.1,Dongda Rd.,Xitun Dist. 40764, Taiwan
08

References and documents

Publications

  • Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M; Alzheimer's Disease International. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005 Dec 17;366(9503):2112-7. doi: 10.1016/S0140-6736(05)67889-0. PubMed 16360788 ↗
  • World Alzheimer Report 2010. Alzheimer's Disease International, 2010.
  • Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement. 2007 Jul;3(3):186-91. doi: 10.1016/j.jalz.2007.04.381. PubMed 19595937 ↗
  • Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly ES Jr, Cox NJ, Dunbar-Jacob JM, Granieri EC, Hunt G, McGarry K, Patel D, Potosky AL, Sanders-Bush E, Silberberg D, Trevisan M. National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline. Ann Intern Med. 2010 Aug 3;153(3):176-81. doi: 10.7326/0003-4819-153-3-201008030-00260. Epub 2010 Jun 14. PubMed 20547888 ↗
  • Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011 Sep;10(9):819-28. doi: 10.1016/S1474-4422(11)70072-2. Epub 2011 Jul 19. PubMed 21775213 ↗
  • Wang XD, Kashii S, Zhao L, Tonchev AB, Katsuki H, Akaike A, Honda Y, Yamashita J, Yamashima T. Vitamin B6 protects primate retinal neurons from ischemic injury. Brain Res. 2002 Jun 14;940(1-2):36-43. doi: 10.1016/s0006-8993(02)02587-8. PubMed 12020872 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 26, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04972643
Lead sponsor
Taichung Veterans General Hospital
Responsible party
Tsuo-Hung Lan (Department of Psychiatry, Taichung Veterans General Hospital, Taichung Veterans General Hospital) — Principal investigator
First posted
Jul 22, 2021
Start date
Sep 23, 2012
Primary completion
May 12, 2018
Completion
Sep 23, 2018
Last update
Jul 26, 2021

Study contacts

Tsuo-Hung Lan, MD, PhD.
principal investigator · National Yang Ming Chiao Tung University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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