Omega-3 fatty acids and blood-based biomarkers in Alzheimer’s disease and mild cognitive impairment: A randomized placebo-controlled trial

Lin, Pan-Yen; Cheng, Chih‐Tao; Satyanarayanan, Senthil Kumaran; Chiu, Lu-Ting; Chien, Y.-C.; Chuu, Chih‐Pin; Lan, Tsuo-Hung; Su, Kuan‐Pin

doi:10.1016/j.bbi.2021.10.014

Cited by 50 publications

(28 citation statements)

References 73 publications

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“…For example, previous RCTs of omega-3 supplementation showed significant improvement in cognition among patients with mild cognitive impairment (MCI), but not AD [ 15 , 26 ]. One recent RCT of different components of omega-3 supplementation demonstrated no protective effect on cognition, but on some subitems of Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog), such as spoken language ability and constructional praxis [ 12 ]. Regarding dementia prevention, more consistent evidence from epidemiological studies has shown an association between higher fish or omega-3 intake and lower cognitive decline and risk of dementia [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…PUFAs have been demonstrated to ameliorate overactive immune reactions. Lin et al recently demonstrated in an RCT that EPA supplementation reduced C-C motif ligands 4 (CCL-4), one marker of chronic inflammation associated with the AD pathogenesis [ 33 ], in patients with AD, suggesting EPA is an effective low-risk dietary intervention to modulate inflammation [ 12 ]. Furthermore, n-3 PUFAs also specifically suppress the expression of proinflammatory cytokines (e.g., tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1b) or IL-6) and promote neurotrophin production (e.g., brain-derived neurotrophic Factor (BDNF)) [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, longitudinal studies have reported higher blood concentrations of PUFAs and a decreased risk of developing dementia [ 9 , 10 , 11 ]. However, in clinical aspects, several randomized controlled trials (RCTs) showed no effect of omega-3 in slowing the rate of cognitive decline among patients already diagnosed with dementia [ 12 , 13 , 14 , 15 ], although variation in the dosage, duration and particularly the DHA to EPA ratio might influence the outcomes [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Higher Serum DHA and Slower Cognitive Decline in Patients with Alzheimer’s Disease: Two-Year Follow-Up

et al. 2022

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Omega-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with slower rates of cognitive decline. We investigated the association between omega-3 PUFAs and cognitive function in patients with Alzheimer’s disease (AD) receiving acetylcholinesterase inhibitors (AChEIs). This was a prospective cohort study using registered data. Patients with AD receiving AChEIs were recruited from 1 May 2016 to 30 April 2019 and were followed up for two years. Their daily diet record and blood concentration of omega-3 PUFAs were analyzed. Multiple linear and binary logistic regression was used to determine the factors associated with cognitive decline (continuous and dichotomized cognitive change). In the research, 129 patients with AD were identified with a mean age of 76.5 ± 6.6. Patients with AD with lower baseline omega-3 PUFAs levels were associated with a higher risk of cognitive decline than those with higher levels (odds ratio [OR] = 1.067, 95% confidence interval [CI]: 1.012, 1.125; p = 0.016) after adjustment. Patients with AD with a lower baseline DHA (OR = 1.131, 95% CI: 1.020, 1.254; p = 0.020), but not EPA, were associated with a higher risk of cognitive decline. We found that higher Mini-Nutritional Assessment scores (beta = −0.383, 95% CI = −0.182–−0.048, p = 0.001) and total fat (beta = −0.248, 95% CI = −0.067–−0.003, p = 0.031) were independently associated with slow cognitive decline in patients with AD receiving AChEIs. The baseline blood levels of omega-3 PUFAs were associated with cognitive decline in patients with AD receiving AChEIs. Future randomized controlled trials are needed to clarify whether this association is causal.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Higher Serum DHA and Slower Cognitive Decline in Patients with Alzheimer’s Disease: Two-Year Follow-Up

et al. 2022

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“…In terms of clinical relevance, the lack of benefits in cognitive performance in randomized controlled trials involving DHA [31][32][33][34][35] urges to improve the design of future trials. Other study designs to elucidate causation (e.g., Mendelian Randomization) may also be valuable, though identifying a good quality genetic instrument for DHA may prove challenging [36,37].…”

Section: Discussionmentioning

confidence: 99%

Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study

et al. 2022

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Docosahexaenoic acid (DHA) might help prevent Alzheimer’s disease (AD). Red blood cell (RBC) status of DHA is an objective measure of long-term dietary DHA intake. In this prospective observational study conducted within the Framingham Offspring Cohort (1490 dementia-free participants aged ≥65 years old), we examined the association of RBC DHA with incident AD, testing for an interaction with APOE-ε4 carriership. During the follow-up (median, 7.2 years), 131 cases of AD were documented. In fully adjusted models, risk for incident AD in the highest RBC DHA quintile (Q5) was 49% lower compared with the lowest quintile (Q1) (Hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.27, 0.96). An increase in RBC DHA from Q1 to Q5 was predicted to provide an estimated 4.7 additional years of life free of AD. We observed an interaction DHA × APOE-ε4 carriership for AD. Borderline statistical significance for a lower risk of AD was observed per standard deviation increase in RBC DHA (HR: 0.71, 95% CI: 0.51, 1.00, p = 0.053) in APOE-ε4 carriers, but not in non-carriers (HR: 0.85, 95% CI: 0.65, 1.11, p = 0.240). These findings add to the increasing body of literature suggesting a robust association worth exploring dietary DHA as one strategy to prevent or delay AD.

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“…The consumption of drinks enriched with ϖ-3 fatty acids and antioxidants (pomegranate and chokeberry) increased RvD1 biosynthesis and Aβ phagocytosis in macrophages from AD patients [ 100 ]. However, the relation between ϖ-3 fatty acid consumption and beneficial effects against AD is unclear, considering the negligible results observed (i.e., improving dementia or cognitive impairment) in clinical trials [ 101 , 102 ].…”

Section: Modifiable Proinflammatory Lipid Mediators In Admentioning

confidence: 99%

Modifiable Innate Biology within the Gut–Brain Axis for Alzheimer’s Disease

et al. 2022

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Alzheimer’s disease (AD) is a prototypical inflammation-associated loss of cognitive function, with approximately 90% of the AD burden associated with invading myeloid cells controlling the function of the resident microglia. This indicates that the immune microenvironment has a pivotal role in the pathogenesis of the disease. Multiple peripheral stimuli, conditioned by complex and varied interactions between signals that stem at the intestinal level and neuroimmune processes, are involved in the progression and severity of AD. Conceivably, the targeting of critical innate immune signals and cells is achievable, influencing immune and metabolic health within the gut–brain axis. Considerable progress has been made, modulating many different metabolic and immune alterations that can drive AD development. However, non-pharmacological strategies targeting immunometabolic processes affecting neuroinflammation in AD treatment remain general and, at this point, are applied to all patients regardless of disease features. Despite these possibilities, improved knowledge of the relative contribution of the different innate immune cells and molecules comprising the chronically inflamed brain network to AD pathogenesis, and elucidation of the network hierarchy, are needed for planning potent preventive and/or therapeutic interventions. Moreover, an integrative perspective addressing transdisciplinary fields can significantly contribute to molecular pathological epidemiology, improving the health and quality of life of AD patients. This review is intended to gather modifiable immunometabolic processes based on their importance in the prevention and management of AD.

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Omega-3 fatty acids and blood-based biomarkers in Alzheimer’s disease and mild cognitive impairment: A randomized placebo-controlled trial

Cited by 50 publications

References 73 publications

Higher Serum DHA and Slower Cognitive Decline in Patients with Alzheimer’s Disease: Two-Year Follow-Up

Higher Serum DHA and Slower Cognitive Decline in Patients with Alzheimer’s Disease: Two-Year Follow-Up

Red Blood Cell DHA Is Inversely Associated with Risk of Incident Alzheimer’s Disease and All-Cause Dementia: Framingham Offspring Study

Modifiable Innate Biology within the Gut–Brain Axis for Alzheimer’s Disease

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