THESIS AWARD
Nutrition and brain aging: role of fatty acids with an epidemiological perspective
Cecilia SAMIERI Abstract: In the absence of identified etiologic treatment for dementia, the potential Pascale BARBERGER-GATEAU preventive role of nutrition may offer an interesting perspective. The objective of the thesis of C. Samieri was to study the association between nutrition and brain aging in Inserm, U897, 1,796 subjects, aged 65 y or older, from the Bordeaux sample of the Three-City study, Equipe Epidemiologie de la nutrition with a particular emphasis on fatty acids. Considering the multidimensional nature of et des comportements alimentaires, nutritional data, several complementary strategies were used. At the global diet level, Universite Bordeaux Segalen, dietary patterns actually observed in the population were identified by exploratory Case 11, methods. Older subjects with a ‘‘healthy’’ pattern, who consumed more than 3.5 weekly 146 rue Leo-Saignat, servings of fish in men and more than 6 daily servings of fruits and vegetables in women, F-33076 Bordeaux cedex, showed a better cognitive and psychological health. Adherence to the Mediterranean France diet, measured according to a score-based confirmatory method, was associated with
With the aging of populations, demen- diagnosed when the onset of cognitive 2010). Indeed, while dementia diag- tia and Alzheimer’s disease (AD) as its impairment is progressive and insidious nosis is made when cognitive impair- more frequent form, has become an and when no other systemic or brain ment is widespread enough to important concern worldwide (Brayne, disease may account for the progres- generate disability, the first cognitive 2007). In the absence of promising sive cognitive deficits. AD specific symptoms start more than 10 y before treatment, the prevalence of late-life brain lesions include extracellular accu- (Amieva et al., 2008), and the first dementia is expected to double every mulation of b-amyloid peptides and brain lesions leading to neurodegen- 20 y, reaching 115 millions by 2050 intracellular accumulation of hyper- eration could occur decades before the (Prince and Jackson, 2009). Therefore, phosphorylated protein Tau. New clinical manifestations (Reiman et al., finding strategies capable of reducing research criteria have been recently 2004). This long time-lag between the the burden of AD is a major societal and proposed, combining evidence of AD first lesions in the brain and the clinical public health challenge. pathology based on neuroimaging and symptoms defines a large window of There is no definite diagnostic test for biological biomarkers, and clinical signs opportunity for potential preventive dementia and AD. The diagnosis of of memory impairment of the hippo- factors, before irreversible neurode- dementia is based on clinical evidence campal type (episodic memory) (Dubois generation. of both a memory disorder and impair- et al., 2007). An important feature for the study of risk ment in at least one other cognitive AD has been recently defined as a factors of brain aging is that late-life domain, both of which interfere with complex clinico-biological entity, char- dementia is multifactorial. It results from 10.1684/ocl.2011.0397 doi: activities of daily living (American acterized by a long-term pathological AD specific lesions and other lesions also Psychiatric Association, 2000). AD is process (Dubois et al., 2010; Jack et al., found in normal aging such as vascular
To cite this article: Samieri C, Barberger-Gateau P. Nutrition and brain aging: role of fatty acids with an epidemiological perspective. OCL 2011; 18(4): 228-35. doi : 10.1684/ocl.2011.0397
228 OCL VOL. 18 N8 4 juillet-aouˆ t 2011
Article disponible sur le site http://www.ocl-journal.org ou http://dx.doi.org/10.1051/ocl.2011.0397 lesions, inflammation and oxidative In addition, other foods and nutrients, association between plasma fatty acids stress, both balanced by compensatory such as fruits and vegetables rich in and future dementia risk and cognitive mechanisms. Accordingly, a life-course antioxidant compounds and folates, decline, taking into account the potential etiologic model of dementia has been were evoked as potential preventive modifying role of depressive symptoms proposed, in which genetic risk factors factors in brain aging (Feart et al., and the ApoE4 allele. may interact with environmental factors 2010). More generally, nutrients and to modulate the risk of dementia and AD foods are consumed in combination, so The Three-City cohort (Fotuhi et al., 2009). Age is the strongest they could exert additive or synergistic known risk factor for AD, followed by effects on brain aging, which may not study genetic susceptibility, conferred by the be captured in single-nutrient based e e Cohort studies offer a unique opportu- 4 allele of the ApoE (ApoE 4) gene, studies (Moeller et al., 2007). Dietary nity to assess risk factors of dementia and which increases the risk of AD by 3 times patterns, which represent a combina- AD early in the course of the disease, in Causasian heterozygotes and by 15 tion of foods, may be better associated before the clinical phase associated times in homozygotes (Farrer et al., to disease risk than single foods or with widespread and irreversible brain 1997). Moreover, novel susceptibility nutrients. damage. These analyses were conducted genes for AD have been recently Dietary patterns have been classified into within the Bordeaux sample of the identified (Sleegers et al., 2010). Among two main categories (Moeller et al., 3C study, a prospective cohort study of environmental risk factors, vascular risk 2007). Aprioridietary patterns are de- vascular risk factors for dementia which factors such as hypertension, diabetes, fined by scores, computed according to started in 1999-2000 and included high blood cholesterol or obesity at previous hypotheses on the beneficial or 9,294 community dwellers in Bordeaux midlife, have been associated with deleterious effects of nutritional factors (n = 2,104), Dijon (n = 4,931) and Mont- higher risk of dementia or higher cog- on health. A priori dietary patterns are pellier (n = 2,259), France (Three-City nitive decline, leading to progressive therefore classified under the category of Study Group, 2003). Baseline data col- evidence that cardiovascular diseases confirmatory methods. In contrast, a lection included socio-demographic and and dementia shared numerous com- posteriori dietary patterns are defined lifestyle characteristics, symptoms mon risk factors (Reitz et al., 2011). either by scores derived from principal and complaints, main chronic condi- Nutritional factors, capable of modulat- component analysis, or by specific clus- tions, neuropsychological testing, phys- ing vascular risk factors and probably ters derived from cluster analysis, both ical examination and blood sampling, having a direct impact on brain func- strategies being undertaken without any enabling to perform ApoE genotyping. tion, have emerged as interesting can- prior hypothesis on the diet-disease Four follow-up examinations were per- didates for prevention, especially long- relationship. Thus, a posteriori dietary formed 2, 4, 7 and 10 y after baseline. chain omega-3 polyunsaturated fatty patterns fit to the definition of explora- acids (n-3 PUFA). At each visit, cognitive performance was tory methods. assessed by trained psychologists using Indeed, long-chain n-3 PUFA may exert Considering the multidimensional a battery of neuropsychological tests, beneficial effects against brain aging, nature of nutritional data, an accurate including: the Mini Mental State Exami- explained by their major structural and study of the relationship between nutri- nation (MMSE), assessing global cogni- functional role in neurone membranes, tion and brain aging must therefore tive function; the Isaac’s Set test (IST), vascular and anti-inflammatory proper- include two complementary approaches assessing verbal fluency; the Benton ties as well as their potential ability to to estimate nutritional exposure: a Visual Retention Test (BVRT), assessing modulate neuro-inflammation and the whole-diet approach (e.g global level) working memory; Trails Making tests expression of neuronal-plasticity related and a nutrient-based approach. The part A (TMT-A) and B (TMT-B), assessing genes (see for review (Cunnane et al., main objective of the thesis of C. Samieri executive functioning; and the Free and 2009)). Several longitudinal epidemio- summarized in this report was to study, Cued Selective Reminding Test (FCSRT), logical studies suggested a protective with an epidemiological perspective (e.g. assessing episodic memory. Diagnosis association between fish consumption, at the population level), the relationship of dementia was based on a three-step the main source of long-chain n-3 PUFA between nutrition and brain aging in procedure. All potential prevalent and in humans, or eicosapentaenoic acid 1,796 subjects, aged 65 y or older, from incident cases of dementia were inves- (EPA) and docosahexaenoic acid (DHA) the Bordeaux sample of the three-City tigated and reviewed by an indepen- consumption and cognitive decline or (3C) study. A particular interest was dent committee of neurologists to dementia risk. However, fewer studies given to n-3 PUFA. Thus, the first aim obtain a consensus on the diagnosis have assessed the exposition to long- of the thesis was, using a whole-diet and aetiology according to the chain n-3 PUFA by measuring blood approach, to identify dietary patterns by criteria of the Diagnostic and Statisti- circulating levels, which enable to take exploratory analysis and to relate them to cal Manual of Mental Disorders, into account inter-individual variations cognitive performances and depressive fourth edition (American Psychiatric in biodisponibility. Finally, intervention symptoms in older subjects. Moreover, Association, 1994). At baseline, the studies yielded mixed and mostly nega- adherence to a Mediterranean-type diet intensity of depressive symptoms was tive results (Cunnane et al., 2009). was assessed by an aprioriscore and was assessed using the Center for Epidemio- Thus, more research was needed to related to future cognitive decline and logic Studies Depression (CESD) scale, understand how long-chain n-3 PUFA dementia risk. The second aim was, using and high depressive symptoms were would be biologically related to brain a nutrient-based approach focused on defined as a CESD score of 17 or more in aging. long-chain n-3 PUFA, to study the men and 23 or more in women.
OCL VOL. 18 N8 4 juillet-aouˆ t 2011 229 Proportions of fatty acids were meas- compared to ‘‘healthy’’ eaters. Overall, role of the MeDi already suggested in ured at baseline in total plasma in 1,518 this work suggested a potential protec- the prevention of other chronic diseases. subjects, and an extensive dietary sur- tive role for a ‘‘healthy’’ pattern against Such a preventive role may rely on vey, including a food frequency ques- brain aging, although the cross-sec- additional or synergistic action of several tionnaire and a 24 h dietary recall, was tional nature of the design prevented nutrients, according to biological mecha- administered at the 2 y visit. to infer any causality in the observed nisms which remain to be determined. associations. Moreover, these findings Dietary patterns and identified clusters of subjects with a particular food behaviour associated Long-chain n-3 PUFA and brain aging with poorer cognitive and psychological health, which may be targeted for brain aging A posteriori dietary patterns and nutrition policies in order to prevent Long-chain n-3 PUFA EPA and DHA may brain aging brain aging. be key nutrients involved in the beneficial Actual dietary patterns as observed in a role of the MeDi against cognitive decline population of older subjects were iden- Adherence to a Mediterranean (Feart et al., 2011) (see article by tified by exploratory statistical methods diet, cognitive decline and risk of Barberger-Gateau et al. in this volume). (Samieri et al., 2008). Among 647 men dementia The second part of the thesis was there- and 1,033 women from the Bordeaux fore targeted at the nutrient biomarker The Mediterranean diet (MeDi) is the sample of the 3C study, cluster analysis level, and consisted in assessing the traditional diet of the Greek and South- was used on weekly servings of specific relationship between long-chain n-3 Italian populations and is mainly fea- food groups to divide the subjects into PUFA measured in plasma and brain tured by an important consumption of homogeneous non-overlapping sub- aging. plant foods, fish, monounsaturated fats groups with a similar pattern of mean from olive oil as the main fat source, a The potential confounding or modifying food intake. In order to stabilize the final moderate consumption of alcohol in the effect of depressive status in this relation- partition, a mixed clustering method was form of wine, and a low consumption of ship was examined. Indeed, depressive applied. Five dietary clusters were iden- meat and dairy products. Adherence to status was associated with blood levels of tified in each gender (figures 1 and 2).In the MeDi has been previously associ- long-chain n-3 PUFA in several studies both male and female, the first cluster ated with a reduced risk for several (Lin et al., 2010), and, notably, with was characterized by a lower mean chronic diseases (Sofi et al., 2010). plasma EPA levels in the 3C study (Feart number of weekly servings that the et al., 2008). However, since the overall population for all food groups We investigated the relationship between observed associations were all cross- and a lower total energy intake. It was adherence to the MeDi and cognitive sectional, no causal relationship could thus labelled ‘‘small eaters’’. The second decline and dementia risk in the 3C be inferred from these studies: lower cluster, labelled ‘‘biscuits and snacking’’, study (Feart et al., 2009). Among 1,410 exposure to long-chain n-3 PUFA could was characterized by a high consump- participants from the Bordeaux sample of cause depressive symptoms, or, alter- tion of biscuits and cakes and included a the 3C study, a score of adherence to natively, depression could change diet- high proportion of individual consuming the MeDi was constructed at the first ary habits and therefore lower fish frequent snacks. The third cluster was a follow-up, as originally described by consumption, leading to lower blood ‘‘healthy’’ dietary pattern, mainly charac- Trichopoulou et al. (Trichopoulou et al., levels of long-chain n-3 PUFA. Moreover, terized by a high consumption of fish 1995) (see paper by Barberger-Gateau several studies suggested that depression in men and of fruits and vegetables in et al.inthisvolume). could be a potential risk factor for women. The fourth cluster was charac- Higher MeDi score was significantly dementia (Panza et al., 2010). Thus, terized by a greater consumption of associated with lower decline to MMSE one could expect that a positive associ- ‘‘charcuterie, meat and alcohol’’ in performances over 5 y of follow-up (b = – ation between blood levels of long-chain men and ‘‘charcuterie and starchy 0.006, P = 0.04 for 1 point-increase of n-3 PUFA and depressive status ex- foods’’ in women. Finally, the fifth cluster MeDi score), after adjustment for numer- plained the potential association bet- included frequent ‘‘pasta eaters’’ in men ous potential confounders (age, sex, ween these fatty acids and dementia risk and frequent ‘‘pizzas and sandwiches’’ education, marital status energy intake, or cognitive decline (e.g confounding eaters in women (Samieri et al., 2008). physical activity, depressive symptoms, effect of depression). Otherwise, the Older subjects from the ‘‘healthy’’ medication use, ApoE4 genotype, cardio- presence of high depressive symptoms pattern, who consumed more than vascular risk factors and stroke). No could enhance the effect of long-chain 3.5 weekly servings of fish in men and association was found between MeDi n-3 PUFA on cognition (e.g modifying more than 6 daily servings of fruits and score and the risk for incident dementia. effect of depression, detected as an vegetables in women, showed higher However, due to a relatively small interaction in epidemiological studies). global cognitive performances as asse- number of incident dementia cases ssed by the score to the MMSE. (n = 99), the power to detect such Plasma long-chain n-3 PUFA and Moreover, women from the ‘‘healthy association was limited in this study. risk of dementia pattern’’ had lower depressive symp- Suggesting that higher adherence to the toms as assessed by the CESD. Women MeDi lower decline to global cognitive First, the relationship between plasma in the ‘‘biscuits and snacking’’ cluster performances, this result extended to fatty acids and dementia risk over 4 y had greater risk of poor perceived health the field of AD the potential beneficial of follow-up was studied, taking into
230 OCL VOL. 18 N8 4 juillet-aouˆ t 2011 "Small eaters" "Biscuits, snacking" "Healthy" Food groups(n=203) Food groups(n=58) Food groups (n=157)
Raw vegetables Raw vegetables Raw vegetables Cooked vegetables Cooked vegetables Cooked vegetables Pasta Pasta Pasta Rice Rice Rice Potatoes Potatoes Potatoes Pulses Pulses Pulses Fruits Fruits Fruits Eggs Eggs Eggs Poultry Poultry Poultry Meat Meat Meat Fish Fish Fish Pizza, sandwich Pizza, sandwich Pizza, sandwich Charcuterie Charcuterie Charcuterie Biscuits, cakes Biscuits, cakes Biscuits, cakes Sweets, chocolate Sweets, chocolate Sweets, chocolate Dairy products Dairy products Dairy products Cereals Cereals Cereals Alcohol Alcohol Alcohol Coffe Coffe Coffe Tea Tea Tea
-1,0 -0,50,0 0,5 1,0 1,5 2,0 -1,0 -0,50,0 0,5 1,0 1,5 2,0 -1,0 -0,50,0 0,5 1,0 1,5 2,0 difference from overall mean intake difference from overall mean intake difference from overall mean intake
(food group mean - overall mean) / overall SD (food group mean - overall mean) / overall SD (food group mean - overall mean) / overall SD
"Charcuterie, meat, alcohol" "Pasta eaters" Food groups (n=95) Food groups (n=136)
Raw vegetables Raw vegetables Cooked vegetables Cooked vegetables Pasta Pasta Rice Rice Potatoes Potatoes Pulses Pulses Fruits Fruits Eggs Eggs Poultry Poultry Meat Meat Fish Fish Pizza, sandwich Pizza, sandwich Charcuterie Charcuterie Biscuits, cakes Biscuits, cakes Sweets, chocolate Sweets, chocolate Dairy products Dairy products Cereals Cereals Alcohol Alcohol Coffe Coffe Tea Tea
-1,0 -0,50,0 0,5 1,0 1,5 2,0 -1,0 -0,50,0 0,5 1,0 1,5 2,0 difference from overall mean intake difference from overall mean intake
(food group mean - overall mean) / overall SD (food group mean - overall mean) / overall SD
Figure 1. Dietary patterns among elderly men living in Bordeaux, France, the Three-City study, 2001-2002 (N = 647), published in (Samieri et al., 2008). account depressive status as a potential dementia cases were diagnosed over 4 plasma DHA proportion = 2.20% in confounder (Samieri et al., 2008). y. Baseline plasma EPA and DHA were future demented vs. 2.41% in controls, Among the 1,214 subjects from the lower in future dementia cases com- P = 0.04). Each increase of 1 standard Bordeaux sample of the 3C study who pared to controls (mean plasma EPA deviation (SD) (= 0.5%, corresponding had plasma fatty acid measurement and proportion in future demented = 0.83% to approximately 0.5 weekly portion of were non-demented at baseline, 65 vs. 0.83% in controls, P = 0.03; mean fish) of plasma EPA at baseline was
OCL VOL. 18 N8 4 juillet-aouˆ t 2011 231 "Small eaters" "Biscuits, snacking" "Healthy" Food groups (n=334) Food groups (n=162) Food groups (n=267)
Raw vegetables Raw vegetables Raw vegetables Cooked vegetables Cooked vegetables Cooked vegetables Pasta Pasta Pasta Rice Rice Rice Potatoes Potatoes Potatoes Pulses Pulses Pulses Fruits Fruits Fruits Eggs Eggs Eggs Poultry Poultry Poultry Meat Meat Meat Fish Fish Fish Pizza, sandwich Pizza, sandwich Pizza, sandwich Charcuterie Charcuterie Charcuterie Biscuits, cakes Biscuits, cakes Biscuits, cakes Sweets, chocolate Sweets, chocolate Sweets, chocolate Dairy products Dairy products Dairy products Cereals Cereals Cereals Alcohol Alcohol Alcohol Coffe Coffe Coffe Tea Tea Tea
-1,0 -0,50,0 0,5 1,0 1,5 2,0 -1,0 -0,50,0 0,5 1,0 1,5 2,0 -1,0 -0,50,0 0,5 1,0 1,5 2,0 difference from overall mean intake difference from overall mean intake difference from overall mean intake
(food group mean - overall mean) / overall SD (food group mean - overall mean) / overall SD (food group mean - overall mean) / overall SD
"Charcuterie, starchy foods" "Pizza, sandwich" Food groups (n=266) Food groups (n=48)
Raw vegetables Raw vegetables Cooked vegetables Cooked vegetables Pasta Pasta Rice Rice Potatoes Potatoes Pulses Pulses Fruits Fruits Eggs Eggs Poultry Poultry Meat Meat Fish Fish Pizza, sandwich Pizza, sandwich Charcuterie Charcuterie Biscuits, cakes Biscuits, cakes Sweets, chocolate Sweets, chocolate Dairy products Dairy products Cereals Cereals Alcohol Alcohol Coffe Coffe Tea Tea
-1,0 -0,50,0 0,5 1,0 1,5 2,0 -1,0 -0,50,0 0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 difference from overall mean intake difference from overall mean intake
(food group mean - overall mean) / overall SD (food group mean - overall mean) / overall SD
Figure 2. Dietary patterns among elderly women living in Bordeaux, France, the Three-City study, 2001-2002 (N = 1,077), published in (Samieri et al., 2008).
associated with a 30% lower dementia baseline depressive status as assessed risk. In contrast, plasma DHA was not risk after adjustment for age, gender, by CESD did not change the magnitude associated with dementia risk in multi- education, ApoE4 allele, diabetes, of this association, suggesting that variate models (table 1). This result plasma triglycerides and plasma vitamin depressive status and EPA status were suggested a specific preventive role for E (table 1). Further adjustment for independent predictors of dementia EPA in dementia which may have been
232 OCL VOL. 18 N8 4 juillet-aouˆ t 2011 Table 1. Associations between plasma EPA and DHA proportions and 4-y incident dementia in the Bordeaux sample of the Three-City study (N=1,214), 1999-2004, published in (Samieri et al., 2008)
Risk of dementia Model 11 Model 22 Plasma fatty acids HR 95% CI P HR 95% CI P EPA for 1 SD of plasma proportion 0.69 0.48, 0.98 0.04 0.69 0.48, 0.98 0.04 Depressive status - - - 2.16 1.08, 4.34 0.03 DHA for 1 SD of plasma proportion 0.84 0.63, 1.11 0.21 0.83 0.62, 1.10 0.19 Depressive status - - - 2.22 1.10, 4.46 0.03 1 Cox proportional hazard models with delayed entry taking age as a time scale and adjusted for education (in four levels), ApoE4 allele, diabetes, plasma triacylglycerides, plasma vitamin E. 2 Model 1 + depressive status. Abbreviations: EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; HR: Hazard Ratio; SD: Standard Deviation.
12 12 BVRT ApoE4 -, dep - ApoE4 +, dep - score
10 10 1.3 pt
8 8
β=0.001 (P=0.93) β=0.077 (P=0.003)
6 6 0123456789 0123456789
12 12 ApoE4 -, dep + ApoE4 +, dep +
10 10 2.1 pts 3.4 pts 8 8 β=0.096 (P=0.04) β=0.172 (P<0.001)
6 6 0123456789 0123456789
EPA=0.4%
EPA=1%
EPA=1.6%
Figure 3. Evolution of predicted mean BVRT score for three typical levels of plasma EPA proportion according to depressive symptoms and ApoE4 carrier status, estimated in a multivariate linear mixed model in participants from the Bordeaux Sample of the Three-City Study non demented at baseline (1999-2006) (N=1,130), published in (Samieri, Feart et al., 2010). ApoE4 carriers (at least one -e4 allele) were noted as ApoE4 + and ApoE4 non carriers as ApoE4. Participants with high depressive symptoms were noted as dep + and those with low depressive symptoms as dep –. Predicted mean evolution of cognitive scores over time were represented for men with average age (74 y), body mass index (26.4 kg/m2), number of drugs regularly consumed (4), plasma vitamin E (15.8 mmol/L) and triglycerides (1.3 mmol/L), and who had a low level of education, were married, non-smokers, who did not consume alcohol or use antidepressants, who had no history of cardiovascular disease, no diabetes and no recent weight loss >3 kg. The three typical values of plasma EPA were chosen as: overall mean – 1 SD; overall mean; overall mean + 1 SD. In each group, Beta coefficients and their p-value were given for EPA x Time term (corresponding to the variation in slope associated with each increase of 1 standard deviation of plasma EPA). Abbreviations: BVRT: Benton Visual Retention Test; EPA: eicosapentaenoic acid.
OCL VOL. 18 N8 4 juillet-aouˆ t 2011 233 underestimated in previous studies, gene interaction which deserves further Cunnane SC, Plourde M, et al. Fish, docosa- possibly involving anti-inflammatory, research. In older depressed subjects, hexaenoic acid and Alzheimer’s disease. Prog vascular or energy metabolic pathways EPA, but not DHA, may slow down Lipid Res 2009; 48: 239-56. (Freeman et al., 2006; Freemantle et al., cognitive decline, possibly through an Dubois B, Feldman HH, et al. Revising the 2006). anti-depressant effect. definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 2010; 9: 1118-27. Plasma long-chain n-3 PUFA and Conclusion Dubois B, Feldman HH, et al. Research criteria cognitive decline for the diagnosis of Alzheimer’s disease: Overall, the results from this thesis revising the NINCDS-ADRDA criteria. Lancet Secondly, the associations between suggest that cognitive performances Neurol 2007; 6: 734-46. plasma EPA and DHA and cognitive and depressive symptoms, which are Farrer LA, Cupples LA, et al. Effects of age, decline to several cognitive domains two major features of brain aging, may sex, and ethnicity on the association between were examined, taking into account vary according to habitual dietary habits apolipoprotein E genotype and Alzheimer ApoEe4 allele and depression as poten- of subjects, and may be improved in disease. A meta-analysis. APOE and Alz- tial modifying factors (Samieri et al., higher fish and fruits and vegetables heimer Disease Meta Analysis Consortium. Jama 1997; 278: 1349-56. 2010). The study included 1,228 sub- consumers. Moreover, we brought jects from the Bordeaux sample of the some evidence that higher adherence Feart C, Peuchant E, et al. Plasma eicosapen- 3C study with plasma fatty acid mea- to the MeDi may contribute to slowing taenoic acid is inversely associated with severity surements who were non-demented at down age-related global cognitive of depressive symptomatology in the elderly: baseline and who had been evaluated at decline. While one of the key nutrients data from the Bordeaux sample of the least once for cognition over 7 y of for the prevention of cognitive decline Three-City Study. Am J Clin Nutr 2008; 87: 1156-62. follow-up. Baseline plasma EPA, but not may be long-chain n-3 PUFA, our results DHA, was lower in subjects with high emphasize the role of EPA. We showed Feart C, Samieri C, et al. Diet and Alzheimer’s depressive symptoms (mean plasma that increase of 1 SD of plasma EPA disease: new evidence from epidemiological EPA in subjects with high depressive (corresponding to increase of 0.5 fish studies. In: New research on Nutrition in the symptoms = 0.89% vs. 1.02% in those weekly servings) was associated with a prevention of Alzheimer’s disease. Ramassa- with low depressive symptoms, P < 0.05; 30%-decreased dementia risk over 4 y. my&Bastianetto, Research Signpost/Trans- mean plasma DHA in subjects with We also evidenced new and puzzling world Research Network, Trivandrum, high depressive symptoms = 2.40% vs. interactions with the ApoE4 genotype 2010. 2.39% in those with low depressive and depressive symptomatology on Feart C, Samieri C, et al. Adherence to symptoms). cognitive decline that will deserve a Mediterranean diet, cognitive decline, further research. and risk of dementia. Jama 2009; 302: When examining the association 638-48. between plasma long-chain n-3 PUFA Taken altogether, these results suggest that slowing down cognitive decline Feart C, Torres MJ, et al. 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