Associations between Serum Omega-3 Fatty Acid Levels and Cognitive Functions among Community-Dwelling Octogenarians in Okinawa, Japan: The KOCOA Study

Nishihira, Junko; Tokashiki, Takashi; Higashiuesato, Yasushi; Willcox, D. Craig; Mattek, Nora; Shinto, Lynne; Ohya, Yusuke; Dodge, Hiroko H.

doi:10.3233/jad-150910

Cited by 28 publications

(19 citation statements)

References 61 publications

(52 reference statements)

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“…We cannot explain this finding, which contrasts the general scientific opinion promoting that the content of omega-3 PUFA in the human brain generally increases with age over the first 2 decades and then levels off [41] or even drops [3,12]. However, previous research on cardiovascular patients has shown that a higher omega-3 index was associated with longer survival [42].…”

Section: Discussioncontrasting

confidence: 52%

“…In a cross-sectional study in dementia-free Framingham study participants (n = 1,575, mean age: 67 years, SD ±9), low levels of EPA and DHA in erythrocytes were associated with small brain volumes and a vascular pattern of cognitive impairment [11]. Another cross-sectional study from Japan including 158 non-demented participants (mean age: 84.1 years, SD ±3.4) showed that higher global cognitive function was significantly associated with higher levels of serum EPA and DHA+EPA after controlling for confounders [12]. Nonetheless, there is conflicting evidence from population-based studies of the relationship between blood (plasma or erythrocyte) omega-3 PUFA composition and some form of cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, population-based studies on the relationship between blood (plasma or erythrocyte) omega-3 PUFA composition and some form of cognitive impairment yielded inconclusive results [10], either showing a strong relationship between DHA and/or EPA and a vascular pattern of cognitive impairment [11], global cognitive function [12], and major aspects of cognitive performance [13] or failing to show significant associations [13]. In some studies, the association attenuated after adjustment for confounders [14].…”

Section: Introductionmentioning

confidence: 99%

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Cognitive Impairment Is Associated with a Low Omega-3 Index in the Elderly: Results from the KORA-Age Study

Lukaschek

Schacky

Kruse

et al. 2016

Dement Geriatr Cogn Disord

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Background: Omega-3 polyunsaturated fatty acids (PUFA) may affect the risk of cognitive decline in older adults. Methods: Cross-sectional analysis was conducted among 720 (50.4% women) participants aged 68-92 years (mean age: 77.6, SD ±6.2) of the population-based KORA-Age study. Eicosapentaenoic acid and docosahexaenoic acid (omega-3 index) were measured in erythrocytes as a percentage of total fatty acids. The categories low (<5.7), intermediate (5.7-6.8), and high (>6.8) levels of the omega-3 index were built using tertiles. The association between cognitive status and omega-3 levels was assessed by logistic regression analyses with adjustments for important concurrent risk factors of cognitive decline. Results: In the sex- and age-adjusted model (model 1), subjects with a low omega-3 index were at a significantly higher risk for cognitive impairment (OR: 1.77, 95% CI: 1.15-2.73, p = 0.009). This association remained stable after further adjusting for educational level (model 2; OR: 1.75, 95% CI: 1.13-2.71, p = 0.01) and metabolic risk factors (model 3; OR: 1.77, 95% CI: 1.14-2.75, p = 0.01). After further controlling for affective disorders (model 4), the association did not attenuate (OR: 1.77, 95% CI: 1.14-2.76, p = 0.01). Conclusion: A robust association was found between low omega-3 levels and cognitive impairment in an elderly population. Further research is needed to understand the link between omega-3 PUFA and cognitive functioning.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cognitive Impairment Is Associated with a Low Omega-3 Index in the Elderly: Results from the KORA-Age Study

Lukaschek

Schacky

Kruse

et al. 2016

Dement Geriatr Cogn Disord

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“…Cell membrane fluidity also influences the processing of APP and cellular phagocytosis, both of which might affect Aβ generation and clearance. A high dietary intake of polyunsaturated fatty acids such as docosahexaenoic acid, which maintain membrane fluidity, have a beneficial effect on cognition in patients with AD 91,92 . The study of membrane fluidity in AD might provide insights into the alteration of membrane-dependent biological functions related to Aβ, such as phagocytosis, endocytosis, macropinocytosis and autophagy.…”

mentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

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The global burden of Alzheimer disease (AD), already the most common type of dementia, is expected to increase still further owing to population ageing. AD not only causes severe distress for patients and caregivers, but also results in a large economic burden on society. Current major challenges in AD include the lack of reliable biomarkers for its early diagnosis, as well as the lack of effective preventive strategies and treatments 1,2 . Thus, increased understanding of the molecular patho genesis of AD could lead to the development of improved diagnostic and therapeutic strategies.AD is conventionally regarded as a CNS disorder. However, increasing experimental, epidemiological and clinical evidence has suggested that manifestations of AD extend beyond the brain. These systemic alterations might not be simply secondary effects of the cerebral degeneration seen in AD, but could reflect under lying processes linked to progression of the disease. AD pathogenesis is complex, involving abnormal amyloid-β (Aβ) metabolism, tau hyperphosphorylation, oxidative stress, reactive glial and microglial changes, and other pathological events. Given that Aβ is a major hallmark of AD and a fertile area of research in this disease, this Review focuses on the systemic role of Aβ in AD. We discuss the communication between peripheral and central pools of Aβ, and describe interactions between systemic abnormalities and AD pathogenesis in the brain. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we suggest that interactions between the brain and the periphery might have a crucial role in the development and progression of AD. Aβ biogenesis and catabolismA steady accrual of data from laboratories and clinics is providing increasing support for the concept that an imbalance between the production and clearance of Aβ is a very early (and often initiating) factor in AD 3 . Normal metabolism of Aβ and maintenance of the homeostatic balance between Aβ production and clearance is, therefore, essential to maintain brain health. In fact, physiological metabolism of Aβ occurs not only in the brain but also in the periphery, and communication between these regions is possible (FIG. 1). Central and peripheral production of AβAβ is derived from the proteolytic cleavage of amyloid precursor protein (APP), which is expressed not only in brain cells, including neurons, astrocytes and microglia, but also in peripheral organs and tissues, such as the Abstract | Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becom...

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“…In the cross-sectional study using the data from the Keys to Optimal Cognitive Aging (KOCOA) study, an ongoing cohort of relatively healthy volunteers aged over 80 years old, living in Okinawa, Japan, higher serum EPA and DHA + EPA levels were independently associated with better scores on global cognitive function among the oldest old, free from dementia [15]. In the retrospective cohort study, an association between red blood cell (RBC) DHA + EPA levels and age-associated cognitive decline was not observed in a cohort of older, dementia-free women [16].…”

Section: The Observational Studies Which Investigated the Associationmentioning

confidence: 99%

Effects of N-3 Polyunsaturated Fatty Acids on Dementia

Yanai

2017

J Clin Med Res

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N-3 polyunsaturated fatty acids (PUFAs) including α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory effects and neuronal protective functions and may benefit prevention of dementia; however, the epidemiological evidence is very limited. Therefore, the literature about the association between n-3 PUFA and dementia was searched, by using Pubmed. In the analyses of observational studies, n-3 PUFA has been reported to be beneficially associated with dementia in 17 studies; however, the beneficial association between n-3 PUFA and dementia was denied by three studies. In the analyses of intervention studies, n-3 PUFA supplementation was beneficially associated with dementia in eight studies; however, five studies reported the negligible effect of n-3 PUFA for dementia. N-3 PUFA may improve Alzheimer’s disease by increasing clearance of amyloid-β peptide, neurotrophic and neuroprotective factors, and by anti-inflammatory effects. In conclusion, patients with mild memory and/or cognitive impairment can be treated by a long-term and higher intake of n-3 PUFA.

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Associations between Serum Omega-3 Fatty Acid Levels and Cognitive Functions among Community-Dwelling Octogenarians in Okinawa, Japan: The KOCOA Study

Cited by 28 publications

References 61 publications

Cognitive Impairment Is Associated with a Low Omega-3 Index in the Elderly: Results from the KORA-Age Study

Cognitive Impairment Is Associated with a Low Omega-3 Index in the Elderly: Results from the KORA-Age Study

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

Effects of N-3 Polyunsaturated Fatty Acids on Dementia

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