***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Chronic caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer 's disease . Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive  decline that male Wistar rats experience from young ( ≈3 months ) to middle age ( ≈10 months ) . When animals were young they were evaluated at weekly intervals in three tests : motor activity habituation in the open field ( 30-min sessions at the same time on consecutive days ) , continuous spontaneous alternation in the Y-maze ( 8 min ) , and elevated plus-maze ( 5 min ) . Afterward , rats from the same litter were r and omly assigned either to a caffeine-treated group ( n=13 ) or a control group ( n=11 ) , which received only tap water . Caffeine treatment ( 5 mg/kg/day ) began when animals were ≈4 months old , and lasted for 6 months . Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal , a time period that is far in excess for the full excretion of a caffeine dose in this species . Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining . Compared with controls , we found that middle-aged rats that had chronically consumed low doses of caffeine ( 1 ) maintained their locomotor habituation during the second consecutive day exposure to the open field ( an index of non-associative learning ) , ( 2 ) maintained their exploratory drive to complete the conventional minimum of nine arm visits required to calculate the alternation performance in the Y-maze in a greater proportion , ( 3 ) maintained their alternation percentage above chance level ( an index of working memory ) , and ( 4 ) did not increase the anxiety indexes assessed by measuring the time spent in the open arms of the elevated plus maze . In addition , morphometric analysis of hippocampal neurons revealed that dendritic branching ( 90 - 140 μm from the soma ) , length of 4th and 5th order branches , total dendritic length , and spine density in distal dendritic branches were greater in the basal but not the apical dendrites of CA1 pyramidal neurons from rats chronically treated with caffeine , in comparison with their age- and littermate-matched controls . Altogether , the present findings strengthen the epidemiological observations suggesting that prolonged caffeine intake prevents the cognitive decline associated with aging , and open the possibility that this process could be mediated by promoting the growth of dendrites and spines in neurons of the adult mammalian brain Background — Data on the association between coffee consumption and  risk of stroke  are sparse . We assessed the association between coffee consumption and the risk of stroke over 24 years of follow-up in women . Methods and Results — We analyzed data from a prospect i ve cohort of 83 076 women in the Nurses ’ Health Study without history of stroke , coronary heart disease , diabetes , or cancer at baseline .  Coffee consumption was assessed first in 1980 and then repeatedly every 2 to 4 years , with follow-up through 2004 . We documented 2280 strokes , of which 426 were hemorrhagic , 1224 were ischemic , and 630 were undetermined . In multivariable Cox regression models with adjustment for age , smoking status , body mass index , physical activity , alcohol intake , menopausal status , hormone replacement therapy , aspirin use , and dietary factors , the relative risks ( RRs ) of stroke across categories of coffee consumption ( < 1 cup per month , 1 per month to 4 per week , 5 to 7 per week , 2 to 3 per day , and ≥4 per day ) were 1 , 0.98 ( 95 % CI , 0.84 to 1.15 ) , 0.88 ( 95 % CI , 0.77 to 1.02 ) , 0.81 ( 95 % CI , 0.70 to 0.95 ) , and 0.80 ( 95 % CI , 0.64 to 0.98 ) ( P for trend=0.003 ) . After further adjustment for high blood pressure , hypercholesterolemia , and type 2 diabetes , the inverse association remained significant . The association was stronger among never and past smokers ( RR for ≥4 cups a day versus < 1 cup a month , 0.57 ; 95 % CI , 0.39 to 0.84 ) than among current smokers ( RR for ≥4 cups a day versus < 1 cup a month , 0.97 ; 95 % CI , 0.63 to 1.48 ) . Other drinks containing caffeine such as tea and caffeinated soft drinks were not associated with stroke . Decaffeinated coffee was associated with a trend toward lower risk of stroke after adjustment for caffeinated coffee consumption ( RR for ≥2 cups a day versus < 1 cup a month , 0.89 ; 95 % CI , 0.73 to 1.08 ; P for trend=0.05 ) . Conclusions — Long-term coffee consumption was not associated with an increased risk of stroke in women . In contrast , our data suggest that coffee consumption may modestly reduce risk of stroke The relationship between habitual coffee and tea consumption and cognitive performance was examined using data from a cross-sectional survey of a representative sample of 9003 British adults ( the Health and Lifestyle Survey ) . Subjects completed tests of simple reaction time , choice reaction time , incidental verbal memory , and visuo-spatial reasoning , in addition to providing self-reports of usual coffee and tea intake . After controlling extensively for potential confounding variables , a dose-response trend to improved performance with higher levels of coffee consumption was observed for all four tests ( P<0.001 in each case ) . Similar but weaker associations were found for  tea  consumption , which were significant for simple reaction time ( P=0.02 ) and visuo-spatial reasoning ( P=0.013 ) . Estimated overall caffeine consumption showed a dose-response relationship to improved cognitive performance ( P<0.001 for each cognitive test , after controlling for confounders ) . Older people appeared to be more susceptible to the performance-improving effects of caffeine than were younger . The results suggest that tolerance to the performance-enhancing effects of caffeine , if it occurs at all , is incomplete Retrospective and prospect i ve epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer 's disease ( AD ) . Underscoring this premise , our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase . Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD , we examined effects of caffeinated and decaffeinated coffee on plasma cytokines , comparing their effects to caffeine alone . In both AβPPsw+PS1 transgenic mice and non-transgenic littermates , acute i.p . treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor ( GCSF ) , IL-10 , and IL-6 . Neither caffeine solution alone ( which provided high plasma caffeine levels ) or decaffeinated coffee provided this effect , indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines . The increase in GCSF is particularly important because long-term treatment with coffee ( but not decaffeinated coffee )  enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines . Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms ( e.g. , recruitment of microglia from bone marrow , synaptogenesis , and neurogenesis ) , the same mechanisms could be complimentary to caffeine 's established ability to suppress Aβ production . We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels , result ing in multiple therapeutic actions against AD Antioxidants have been hypothesized to protect against Alzheimer 's disease , but studies conducted in late life have been inconsistent . Risk factors measured in midlife may better predict dementia in late life because they are less affected by the disease process . The authors examined the association of midlife dietary intake of antioxidants to  late-life dementia  and its subtypes . Data were obtained from the Honolulu-Asia Aging Study , a prospect i ve community-based study of Japanese-American men who were aged 45 - 68 years in 1965 - 1968 , when a 24-hour dietary recall was administered . The analysis included 2,459 men with complete dietary data who were dementia-free at the first assessment in 1991 - 1993 and were examined up to two times for dementia between 1991 and 1999 . The sample included 235 incident cases of dementia ( 102 cases of Alzheimer 's disease , 38 cases of Alzheimer 's disease with contributing cerebrovascular disease , and 44 cases of vascular dementia ) . Relative risks by quartile of intake were calculated using Cox proportional hazards models with age as the time scale , after adjustment for sociodemographic and lifestyle factors , cardiovascular risk factors , other dietary constituents , and apolipoprotein E e4 . Intakes of beta-carotene , flavonoids , and vitamins E and C were not associated with the risk of dementia or its subtypes . This analysis suggests that midlife dietary intake of antioxidants does not modify the risk of late-life dementia or its most prevalent subtypes BACKGROUND Caffeine is the world 's most widely used central nervous system stimulant , with approximately 80 % consumed in the form of coffee . However , studies that analyze prospect ively the relationship between coffee or caffeine consumption and depression risk are scarce . METHODS A total of 50,739 US women ( mean age , 63 years ) free of depressive symptoms at baseline ( in 1996 ) were prospect ively followed up through June 1 , 2006 . Consumption of caffeine  was measured from vali date d question naires completed from May 1 , 1980 , through April 1 , 2004 , and computed as cumulative mean consumption with a 2-year latency period applied . Clinical depression was defined as self-reported physician-diagnosed depression and antidepressant use . Relative risks of clinical depression were estimated using Cox proportional hazards regression models . RESULTS During 10 years of follow-up ( 1996 - 2006 ) , 2607 incident cases of depression were identified . Compared with women consuming 1 or less cup of caffeinated coffee per week , the multivariate relative risk of depression was 0.85 ( 95 % confidence interval , 0.75 - 0.95 ) for those consuming 2 to 3 cups per day and 0.80 ( 0.64 - 0.99 ; P for trend<.001 ) for those consuming 4 cups per day or more . Multivariate relative risk of depression was 0.80 ( 95 % confidence interval , 0.68 - 0.95 ; P for trend=.02 ) for women in the highest ( ≥550 mg/d ) vs lowest ( < 100 mg/d ) of the 5 caffeine consumption categories . Decaffeinated coffee was not associated with depression risk . CONCLUSIONS In this large longitudinal study , we found that depression risk decreases with increasing caffeinated coffee consumption . Further investigations are needed to confirm this finding and to determine whether usual caffeinated coffee consumption can contribute to depression prevention BACKGROUND  Coffee consumption  is associated with a decreased risk of  type 2 diabetes .  Suggested mechanisms underlying the association have included attenuation of sub clinical inflammation and a reduction in oxidative stress . OBJECTIVE The aim was to investigate the effects of daily coffee consumption on biomarkers of coffee intake , sub clinical inflammation , oxidative stress , glucose , and lipid metabolism . DESIGN Habitual coffee drinkers ( n = 47 ) refrained for 1 mo from coffee drinking ; in the second month they consumed 4 cups of filtered coffee/d and in the third month 8 cups of filtered coffee/d ( 150 mL/cup ) . Blood sample s were analyzed by gas chromatography-mass spectrometry , bead-based multiplex technology , enzyme-linked immunosorbent assay , or immunonephelometry . RESULTS Coffee consumption led to an increase in coffee-derived compounds , mainly serum caffeine , chlorogenic acid , and caffeic acid metabolites . Significant changes were also observed for serum concentrations of interleukin-18 , 8-isoprostane , and adiponectin ( medians : -8 % , -16 % , and 6 % , respectively ; consumption of 8 compared with 0 cups coffee/d ) . Serum concentrations of total cholesterol , HDL cholesterol , and apolipoprotein A-I increased significantly by 12 % , 7 % , and 4 % , respectively , whereas the ratios of LDL to HDL cholesterol and of apolipoprotein B to apolipoprotein A-I decreased significantly by 8 % and 9 % , respectively ( 8 compared with 0 cups coffee/d ) . No changes were seen for markers 
    Output:
    
Besides its short-term effect , some case-control and cross-sectional and longitudinal population -based studies evaluated the long-term effects on brain function and provided some evidence that coffee , tea , and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia .
In particular , several cross-sectional and longitudinal population -based studies suggested a protective effect of coffee , tea , and caffeine use against late-life cognitive impairment/decline , although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association , with a stronger effect among women than men .
Furthermore , for dementia and AD prevention , some studies with baseline examination in midlife pointed to a lack of association , although other case-control and longitudinal population -based studies with briefer follow-up periods supported favourable effects of coffee , tea , and caffeine consumption against AD .