Fish consumption and cognitive decline with age in a large community study. Essential fatty acids preparation (SR-3) improves Alzheimer's patients quality of life. Early Protection Against Sudden Death by n-3 Polyunsaturated Fatty Acids After Myocardial Infarction: Time-Course Analysis of the Results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione Essential fatty acids in Alzheimer's disease. Dietary fats and the risk of incident Alzheimer disease. Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45-70 y: the OPTILIP Study. Cognitive functions are not affected by dietary fatty acids in elderly subjects in the Pro.V.A. study population Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats Effect of infarcts on dementia in the Baltimore longitudinal study of aging Influence of nutrition on cognitive function in a group of elderly, independently living people Dietary fat intake and the risk of incident dementia in the Rotterdam study Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction Docosahexaenoic acid supplementation improves the moderately severe dementia from thrombotic cerebrovascular diseases Omega-3 fatty acids and risk of cognitive impairment and dementia. Effect of fish oil on cognitive performance in older subjects Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.
BACKGROUND Dietary intake of fish and the omega-3 fatty acids have been associated with lower risk of Alzheimer disease and stroke . OBJECTIVE To examine whether intakes of fish and the omega-3 fatty acids protect against  age-related cognitive decline .  DESIGN Prospect i ve cohort study . SETTING Geographically defined Chicago , Ill , community . PARTICIPANTS Residents , 65 years and older , who participated in the Chicago Health and Aging Project . MAIN OUTCOME MEASURE Change in a global cognitive score estimated from mixed models . The global score was computed by summing scores of 4 st and ardized tests . In-home cognitive assessment  s were performed 3 times over 6 years of follow-up . RESULTS Cognitive scores declined on average at a rate of 0.04 st and ardized units per year ( SU/y ) . Fish intake was associated with a slower rate of cognitive decline in mixed models adjusted for age , sex , race , education , cognitive activity , physical activity , alcohol consumption , and total energy intake . Compared with a decline rate in score of -0.100 SU/y among persons who consumed fish less than weekly , the rate was 10 % slower ( -0.090 SU/y ) among persons who consumed 1 fish meal per week and 13 % slower ( -0.088 SU/y ) among persons who consumed 2 or more fish meals per week . The fish association was not accounted for by cardiovascular-related conditions or fruit and vegetable consumption but was modified after adjustment for intakes of saturated , polyunsaturated , and trans fats . There was little evidence that the omega-3 polyunsaturated fatty acids were associated with cognitive change . CONCLUSIONS Fish consumption may be associated with slower cognitive decline with age . Further study is needed to determine whether fat composition is the relevant dietary constituent In a number of previous reports we showed the salutary effects on rats of SR-3 , a compound comprising a 1:4 ratio of n-3 and n-6 fatty acids . Improvements were noted in learning tasks , thermoregulation , recovery from neurotoxins , and seizure protection . Because we were impressed that these effects are related to changes in membrane fluidity and neuronal functioning and because Alzheimer 's Disease is also associated with lipid defects , we undertook a short term ( 4 week ) double blind study with 100 Alzheimer patients ( 60 received SR-3 and 40 in a placebo control ) . The results indicated improvements in mood , cooperation , appetite , sleep , ability to navigate in the home , and short term memory . Overall improvement was reported for 49 patients , and in no case did a guardian report adverse effects to the compound . While not uniform or permanent , and while no mode of action for SR-3 can be precisely identified at this time , the promising results in quality of life for the patient and caregiver warrant further clinical trials and continued basic research into the neuropsychological substrate of the disease and its response to SR-3 Background —Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids ( PUFAs ) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent ( <3 months ) myocardial infa rct ion . Methods and Results —In this study , 11 323 patients were r and omly assigned to supplements of n-3 PUFAs , vitamin E ( 300 mg/d ) , both , or no treatment ( control ) on top of optimal pharmacological treatment and lifestyle advice . Intention-to-treat analysis adjusted for interaction between treatments was carried out . Early efficacy of n-3 PUFA treatment for total , cardiovascular , cardiac , coronary , and sudden death ; nonfatal myocardial infa rct ion ; total coronary heart disease ; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after r and omization up to 12 months . Survival curves for n-3 PUFA treatment diverged early after r and omization , and total mortality was significantly lowered after 3 months of treatment ( relative risk [ RR ] 0.59 ; 95 % CI 0.36 to 0.97;P = 0.037 ) . The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months ( RR 0.47 ; 95 % CI 0.219 to 0.995;P = 0.048 ) . A similarly significant , although delayed , pattern after 6 to 8 months of treatment was observed for cardiovascular , cardiac , and coronary deaths . Conclusions —The early effect of low-dose ( 1 g/d ) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug . Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes , animal models , and epidemiological and clinical studies Concentrations of essential fatty acids ( EFAs ) in plasma and red blood cell phospholipids were found to be abnormal in patients with Alzheimer 's disease . A double-blind , placebo-controlled trial of treatment with EFAs plus appropriate antioxidants was carried out in 36 patients with Alzheimer 's disease . After 20 weeks both the EFA and placebo groups had improved , but the degree of improvement was consistently greater in the EFA group BACKGROUND Few studies have investigated the effects of dietary fats on the development of Alzheimer disease . We examined the associations between intake of specific types of fat and incident Alzheimer disease in a biracial community study . METHODS We performed clinical evaluations on a stratified r and om sample of 815 community residents aged 65 years and older who were unaffected by Alzheimer disease at baseline and who completed a food-frequency question naire a mean of 2.3 years before clinical evaluation . RESULTS After a mean follow-up of 3.9 years , 131 persons developed Alzheimer disease . Intakes of saturated fat and trans-unsaturated fat were positively associated with risk of Alzheimer disease , whereas intakes of omega-6 polyunsaturated fat and monounsaturated fat were inversely associated . Persons in the upper fifth of saturated-fat intake had 2.2 times the risk of incident Alzheimer disease compared with persons in the lowest fifth in a multivariable model adjusted for age , sex , race , education , and apolipoprotein E epsilon4 allele status ( 95 % confidence interval , 1.1 - 4.7 ) . Risk also increased with consumption of trans-unsaturated fats , beginning with the second fifth of intake ( relative risk , 2.4 compared with the lowest fifth ; 95 % confidence interval , 1.1 - 5.3 ) . We observed linear inverse associations between Alzheimer disease and vegetable fat ( P = .002 ) , and , after further adjustment for other types of fat , marginally significant associations with intake of omega-6 polyunsaturated fat ( P = .10 for trend ) and monounsaturated fat ( P = .10 for trend ) . Intakes of total fat , animal fat , and dietary cholesterol were not associated with Alzheimer disease . CONCLUSION High intake of unsaturated , unhydrogenated fats may be protective against Alzheimer disease , whereas intake of saturated or trans-unsaturated ( hydrogenated ) fats may increase risk BACKGROUND Insulin resistance is associated with elevated plasma triacylglycerol , low HDL concentrations , elevated postpr and ial lipemia , and a predominance of small , dense LDLs ( sdLDLs ) . It has been hypothesized that the dietary ratio of n-6 to n-3 ( n-6:n-3 ) polyunsaturated fatty acids ( PUFAs ) may have favorable effects on these risk factors by increasing insulin sensitivity . OBJECTIVE The objective was to measure changes in insulin sensitivity , lipoprotein size , and postpr and ial lipemia after a 6-mo alteration in n-6:n-3 . DESIGN In a r and omized , parallel design in 258 subjects aged 45 - 70 y , we compared 4 diets providing 6 % of energy as PUFAs with an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1 . The diets were enriched in alpha-linolenic acid , eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , or both . Insulin sensitivity was assessed with the homeostatic model assessment of insulin resistance and the revised quantitative insulin sensitivity test . RESULTS Dietary intervention did not influence insulin sensitivity or postpr and ial lipase activities . Fasting and postpr and ial triacylglycerol concentrations were lower , and the proportion of sdLDLs decreased ( by 12.7 % ; 95 % CI : -22.9 % , 2.4 % ) , with an n-6:n-3 of approximately 3:1 , which was achieved by the addition of long-chain n-3 PUFAs ( EPA and DHA ) . CONCLUSIONS Decreasing the n-6:n-3 does not influence insulin sensitivity or lipase activities in older subjects . The reduction in plasma triacylglycerol after an increased intake of n-3 long-chain PUFAs results in favorable changes in LDL size Background and aims : Environmental , lifestyle , and dietary factors , including the type of dietary fatty acids consumed , may influence the onset of dementia . The aim of the present study was therefore to examine whether type of dietary fats consumed is associated with cognitive performance . Methods : Using gaschromatography , plasma phospholipid fatty acid composition was determined in a sample of subjects ( age ≥ 65 years ) r and omly selected from the general Pro . V.A. study population . Plasma phospholipid fatty acid composition is a reliable marker of the type of fats present in the diet . The subjects ’ cognitive capacity was tested using the Mini-Mental State Examination ( MMSE ) . Results : At multiple regression analysis , the MMSE score variance was correlated with age and education level in 30 % of cases , whereas the other variables considered ( including type of fatty acids consumed ) had an almost negligible effect . Conclusions : In free-living elderly subjects , moderate to severe cognitive impairment is not associated with dietary fatty acids BACKGROUND Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids , for example , docosahexaenoic acid and eicosapentaenoic acid , may prevent Alzheimer disease ( AD ) . OBJECTIVE To determine effects of dietary omega-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD . DESIGN R and omized , double-blind , placebo-controlled clinical trial . PARTICIPANTS Two hundred four patients with AD ( age range [ mean + /- SD ] , 74 + /- 9 years ) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination ( MMSE ) score of 15 points or more were r and omized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid ( omega-3 fatty acid-treated group ) or placebo  for 6 months , after which all received omega-3 fatty acid supplementation for 6 months more . MAIN OUTCOME MEASURES The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale . The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale ; safety and tolerability of omega-3 fatty acid supplementation ; and blood pressure determinations . RESULTS One hundred seventy-four patients fulfilled the trial . At baseline , mean values for the Clinical Dementia Rating Scale , MMSE , and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 r and omized groups were similar . At 6 months , the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups . However , in a subgroup ( n = 32 ) with very mild cognitive dysfunction ( MMSE > 27 points ) , a significant ( P<.05 ) reduction in MMSE decline rate was observed in the omega-3 fatty acid-treated group compared with the placebo group . A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving omega-3 fatty acid supplementation . The omega-3 fatty acid treatment was safe and well tolerated . CONCLUSIONS Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale . However , positive effects were observed in a small group of patients with very mild AD ( MMSE > 27 points ) BACKGROUND Docosahexaenoic acid ( DHA ) is an abundant fatty acid in the brain . In the diet , DHA is found mostly in fatty fish . The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia . OBJECTIVE To determine whether plasma phosphatidylcholine ( PC ) DHA content is associated with the risk of developing dementia . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve follow-up study in 899 men and women who were free of dementia at baseline , had a median age of 76.0 years , and were followed up for a mean of 9.1 years for the development of all-cause dementia and Alzheimer disease . MAIN OUTCOME MEASURES Plasma PC fatty acid levels were measured at baseline . Cox proportional regression analysis was used to assess relative risks of all-cause dementia and Alzheimer disease according to baseline plasma levels . RESULTS Ninety-nine new cases of dementia ( including 71 of Alzheimer disease ) occurred during the follow-up . After adjustment for age , sex , apolipoprotein E epsilon4 allele , plasma homocysteine concentration , and education level , subjects in the upper quartile of baseline plasma PC DHA levels , compared with subjects in the lower 3 quartiles , had a relative risk of 0.53 of developing all-cause dementia ( 95 % confidence interval , 0.29 - 0.97 ; P=.04 ) and 0.61 of developing Alzheimer disease ( 95 % confidence interval , 0.31 - 1.18 ; P=.14 ) . Subjects in the upper quartile of plasma PC DHA levels had a mean DHA intake of 0.18 g/d and a mean fish intake of 3.0 servings per week ( P<.001 ) in a subset of 488 participants . We found no other significant associations . CONCLUSION The top quartile of plasma PC DHA level was associated with a significant 47 % reduction in the risk of developing all-cause dementia in the Framingham Heart Study Wistar rats were fed a fish oil-deficient diet through three generations . The young ( five-week-old ) male rats of the third generation were r and omly divided into two groups . Over 10 weeks , one group was perorally administered docosahexaenoic acid dissolved in 5 % gum Arabic solution at 300 mg/kg/day ; the other group received a similar volume of vehicle alone . Five weeks after starting the administration , the rats were tested for learning ability related to two types of memory , reference memory and working memory , with the partially ( four of eight ) baited eight-arm radial maze . Reference memory is information that should be retained until the next trial . Working memory is information that disappears in a short time . Entries into unbaited arms and repeated entries into visited arms were defined as reference memory errors and working memory errors , respectively . Docosahexaenoic acid administration over 10 weeks significantly reduced the number of reference memory errors , without affecting the number of working memory errors , and significantly increased the docosahexaenoic acid content and the docosahexaenoic acid/arachidonic acid ratio in both the hippocampus and the cerebral cortex . In addition , the ratio demonstrated a significantly negative correlation with the number of reference memory errors . These results suggest that chronic administration of docosahexaenoic acid is conducive to the improvement of reference memory-related learning ability , and that the docosahexaenoic acid/arachidonic acid ratio in the hippocampus or the cerebral cortex , or both , may be an indicator of learning ability To define the magnitude and mechanism of the effect of brain infa rcts on the odds of dementia  in a prospect i ve study Objective : To study the differences in cognitive status with respect to food habits and energy and nutrient intake in a group of non institutionalised , elderly people . Design : Prospect i ve study . Setting : The study subjects were independently living , elderly people who spent some of their time at day centres in the Comunidad de Madrid ( the Madrid region ) . The study centres were selected by the Madrid City Hall . Subjects : The study included 168 elderly people aged 65–90 y. All accepted the invitation to participate , met all inclusion criteria , and were free of significant cognitive impairment . Interventions :  Dietary intake was monitored using a ‘ food record ’ for 7 consecutive days including a Sunday . In addition , the ‘ precise individual weighing ’ method was used for 5 days in order to monitor the meals taken by the subjects at the centres ' canteens .  Cognitive capacity was measured using Folstein 's mini-mental state examination ( MMSE ) , vali date d for the Spanish population . Results : Subjects with an adequate cognitive capacity ( MMSE≥28 ) showed a greater intake of total foods , fish , and alcoholic drinks , but took less foods from the ‘ various ’ group ( chocolates , cakes , etc ) . These subjects had a more adequate intake of fatty acids and cholesterol , and a greater intake of vitamins implicated in correct brain function ( thiamine , folic acid , vitamin C ) . Conclusions : Subjects with satisfactory intellectual function generally had a better diet . This shows the importance of correct nutrition in its maintenance A high intake of saturated fat and cholesterol and a low intake of polyunsaturated fatty acids have been related to an increased risk of cardiovascular disease . Cardiovascular disease has been associated with dementia . We investigated the association between fat intake and incident dementia among participants , age 55 years or older , from the population ‐based prospect i ve Rotterdam Study .  Food intake of 5,386 nondemented participants was assessed at baseline with a semiquantitative food‐frequency question naire . At baseline and after an average of 2.1 years of follow‐up , we screened for dementia with a three‐step protocol that included a clinical examination . The risk of dementia at follow‐up ( RR [ 95 % CI ] ) was assessed with logistic regression . After adjustment for age , sex , education , and energy intake , high intakes of the following nutrients were associated with an increased risk of dementia : total fat ( RR = 2.4 [ 1.1–5.2 ] ) , saturated fat ( RR = 1.9 [ 0.9–4.0 ] ) , and cholesterol ( RR = 1.7 [ 0.9–3.2 ] ) . Dementia with a vascular component was most strongly related to total fat and saturated fat . Fish consumption , an important source of n‐3 polyunsaturated fatty acids , was inversely related to incident dementia ( RR = 0.4 [ 0.2–0.9 ] ) , and in particular to Alzheimer 's disease ( RR = 0.3 [ 0.1–0.9 ] ) . This study suggests that a  high saturated fat and cholesterol intake increases the risk of dementia , whereas fish consumption may decrease this risk Age-dependent increase of peroxidation of membrane fatty acids such as arachidonic acid ( ARA ) and docosahexaenoic acid ( DHA ) in neurons was reported to cause a decline of the hippocampal long-term potentiation ( LTP ) and cognitive dysfunction in rodents . Although supplementation of ARA and DHA can improve LTP and cognitive function in rodents , their effects in humans are unknown . The present work was undertaken to study whether ARA and DHA have beneficial effects in human amnesic patients . The subjects were 21 mild cognitive dysfunction ( 12 MCI-A with supplementation and 9 MIC-P with placebo ) , 10 organic brain lesions ( organic ) , and 8 Alzheimer 's disease ( AD ) . The cognitive functions were evaluated using Japanese version of repeatable battery for assessment of neuropsychological status ( RBANS ) at two time points : before and 90 days after the supplementation of 240 mg/day ARA and DHA , or 240 mg/day of olive oil , respectively . MCI-A group showed a significant improvement of the immediate memory and attention score . In addition , organic group showed a significant improvement of immediate and delayed memories . However , there were no significant improvements of each score in AD and MCI-P groups . It is suggested from these data that ARA and DHA supplementation can improve the cognitive dysfunction due to organic brain damages or aging T. Terano a , * , S. Fujishiro b , T. Ban c , K. Yamamoto d , T. Tanaka e , Y. Noguchi e , Y. Tamura ~ , K. Yazawa g and T. Hirayama h aDepartment of Internal Medicine , Chiba Municipal Hospital Chiba 260 , bKyoundou Hospital , Tokyo , ~Kuniyoshi Hospital , Chiba , dKimitsu Central Hospital , Chiba , e2nd Department Internal Medicine , Chiba University , Chiba , ~Kyoundou Hiratsuka Hospital , Kanagawa , gSagami Chemical Research Center , Kanagawa , and hHirayama Hospital , Chiba , It has been suggested that the dietary intake of omega-3 polyunsaturated fatty acids could be inversely related to the risk of dementia and cognitive decline .  This analysis examined the association between plasma concentration of omega-3 polyunsaturated fatty acids and prevalence and incidence of cognitive impairment and dementia . Data are reported on subjects 65 years or older who had a complete clinical evaluation at the first two waves ( 1991 - 1992 and 1996 - 1997 ) of the Canadian Study of Health and Aging . Main outcome measures were cognitive impairment and dementia by mean relative plasma concentrations of fatty acids in the phospholipid fraction at baseline . Results were adjusted for age , sex , education , smoking , alcohol intake , body mass index , history of cardiovascular disease , and apolipoprotein E e4 genotype . In the cross-sectional analysis , no significant difference in omega-3 polyunsaturated fatty acid concentrations was observed between controls and both prevalent cases of cognitive impairment and dementia . In the prospect i ve analysis , a higher eicosapentaenoic acid ( p < 0.01 ) concentration was found in cognitively impaired cases compared to controls while higher docosahexaenoic acid ( p < 0.07 ) , omega-3 ( p < 0.04 ) and total polyunsaturated fatty acid ( p < 0.03 ) concentrations were found in dementia cases . These findings do not support the hypothesis that omega-3 polyunsaturated fatty acids play a protective role in cognitive function and dementia Background : High intake of n-3 polyunsaturated fatty acids may protect against age-related cognitive decline . However , results from epidemiologic studies are inconclusive , and results from r and omized trials in elderly subjects without dementia are lacking . Objective : To investigate the effect of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) supplementation on cognitive performance . Methods : Double-blind , placebo-controlled trial involving 302 cognitively healthy ( Mini-Mental State Examination score > 21 ) individuals aged 65 years or older . Participants were r and omly assigned to 1,800 mg/d EPA – DHA , 400 mg/d EPA – DHA , or placebo capsules for 26 weeks . Cognitive performance was assessed using an extensive neuropsychological test battery that included the cognitive domains of attention , sensorimotor speed , memory , and executive function . Results : The mean age of the participants was 70 years , and 55 % were male .  Plasma concentrations of EPA – DHA  increased by 238 % in the high-dose and 51 % in the low-dose fish oil group compared with placebo , reflecting excellent compliance . Baseline scores on the cognitive tests were comparable in the three groups . Overall , there were no significant differential changes in any of the cognitive domains for either low-dose or high-dose fish oil supplementation compared with placebo . Conclusions : In this r and omized , double-blind , placebo-controlled trial , we observed no overall effect of 26 weeks of eicosapentaenoic acid and docosahexaenoic acid supplementation on cognitive performance Since the first AHA Science Advisory “ Fish Consumption , Fish Oil , Lipids , and Coronary Heart Disease,”1 important new findings , including evidence from r and omized controlled trials ( RCTs ) , have been reported about the beneficial effects of omega-3 ( or n-3 ) fatty acids on cardiovascular disease ( CVD ) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function ( including antiarrhythmic effects ) , hemodynamics ( cardiac mechanics ) , and arterial endothelial function have helped clarify potential mechanisms of action . The present Statement will address distinctions between plant-derived ( α-linolenic acid , C18:3n-3 ) and marine-derived ( eicosapentaenoic acid , C20:5n-3 [ EPA ] and docosahexaenoic acid , C22:6n-3 [ DHA ] ) omega-3 fatty acids . ( Unless otherwise noted , the term omega-3 fatty acids will refer to the latter . ) Evidence from epidemiological studies and RCTs will be review ed , and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid ( plant- and marine-derived ) supplementation . This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration ( FDA ) about the presence of environmental contaminants in certain species of fish . # # # Coronary Heart Disease As review ed by Stone,1 three prospect i ve epidemiological studies within population s reported that men who ate at least some fish weekly had a lower coronary heart disease ( CHD ) mortality rate than that of men who ate none.3–6 ⇓ ⇓ ⇓ More recent evidence that fish consumption favorably affects CHD mortality , especially nonsudden death from myocardial infa rct ion ( MI ) , has been reported in a 30-year follow-up of the Chicago Western Electric Study .7 Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of nonsudden death from MI of 0.33 . In an
Long-chain omega-3 fatty acids could have neuroprotective properties against  dementia  , which is becoming a major global public health issue .