human
***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: Oxidative stress , inflammation , and increased cholesterol levels are all mechanisms that have been associated with Alzheimer ’s disease ( AD ) pathology . Several epidemiologic studies have reported a decreased risk of AD with fish consumption . This pilot study was design ed to evaluate the effects of supplementation with omega-3 fatty acids alone ( ω-3 ) or omega-3 plus alpha lipoic acid ( ω-3 + LA ) compared to placebo on oxidative stress biomarkers in AD . The primary outcome measure was peripheral F2-isoprostane levels ( oxidative stress measure ) . Secondary outcome measures included performance on : Mini-Mental State Examination ( MMSE ) , Activities of Daily Living/Instrumental Activities of Daily Living ( ADL/IADL ) , and Alzheimer Disease Assessment Scale-cognitive subscale ( ADAS-cog ) . Thirty-nine AD subjects were r and omized to one of three groups : 1 ) placebo , 2 ) ω-3 , or 3 ) ω-3 + LA for a treatment duration of 12 months . Eighty seven percent ( 34/39 ) of the subjects completed the 12-month intervention . There was no difference between groups at 12 months in peripheral F2-isoprostane levels ( p = 0.83 ) . The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog ( p = 0.98 , p = 0.86 ) and in ADL ( p = 0.15 , p = 0.82 ) . Compared to placebo , the ω-3+LA showed less decline in MMSE ( p < 0.01 ) and IADL ( p= 0.01 ) and the ω-3 group showed less decline in IADL ( p < 0.01 ) . The combination of ω-3+LA  slowed cognitive and functional decline in AD over 12 months . Because the results were generated from a small sample size , further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted 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 OBJECTIVES To study the effects of omega (Omega)-3 fatty acid ( FA ) supplements on weight and appetite in patients with mild to moderate Alzheimer 's disease ( AD ) in relation to inflammatory biomarkers and apolipoprotein E epsilon4 ( APOEepsilon4 ) . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Specialist memory clinics in the Stockholm catchment area . PARTICIPANTS Two hundred four patients ( aged 73+/-9 , 52 % women ) with mild to moderate AD . INTERVENTION Patients with AD received 1.7 g of docosahexaenoic acid ( DHA ) and 0.6 g of eicosapentaenoic acid ( EPA ) ( Omega-3/Omega-3 group ; n=89 , aged 73+/-9 , 57 % women ) or placebo 0.6 g of linoleic acid per day ( placebo/Omega-3 group ; n=85 , aged 73+/-9 , 46 % women ) for 6 months . After 6 months , all patients received DHA and EPA for another 6 months . MEASUREMENTS Anthropometry , biochemical nutritional and inflammatory markers , and appetite assessed by caregiver . RESULTS Mean weight and body mass index ( kg/m(2 ) ) at baseline were 70.0+/-11.8 kg and 24.3+/-3.0 kg/m(2 ) , respectively . At 6- and 12-month follow-up , weight had increased 0.7+/-2.5 kg ( P=.02 ) and 1.4+/-2.9 kg ( P<.001 ) in the Omega-3/Omega-3 group . In the placebo group , weight was unchanged at 6 months but had increased ( P=.01 ) at 12 months follow-up after Omega-3 supplementation was initiated . Appetite improved in the Omega-3/Omega-3 group over the treatment period ( P=.01 ) . In logistic regression analyses , not carrying the APOEepsilon4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up . CONCLUSION A DHA-enriched Omega-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD . Not carrying the APOEepsilon4 allele and high DHA were independently associated with weight gain Specialized proresolving mediators ( SPMs ) induce resolution of inflammation . SPMs are derivatives of n-3 and n-6 PUFAs and may mediate their beneficial effects . It is unknown whether supplementation with PUFAs influences the production of SPMs . Alzheimer ’s disease ( AD ) is associated with brain inflammation and reduced levels of SPMs . The OmegAD study is a r and omized , double-blind , and placebo-controlled clinical trial on AD patients , in which placebo or a supplement of 1.7 g DHA and 0.6 g EPA was taken daily for 6 months . Plasma levels of arachidonic acid decreased , and DHA and EPA levels increased after 6 months of n-3 FA treatment . Peripheral blood mononuclear cells ( P BMC s ) were obtained before and after the trial . Analysis of the culture medium of P BMC s incubated with amyloid-β 1–40 showed unchanged levels of the SPMs lipoxin A4 and resolvin D1 in the group supplemented with n-3 FAs , whereas a decrease was seen in the placebo group . The changes in SPMs showed correspondence to cognitive changes . Changes in the levels of SPMs were positively correlated to changes in transthyretin . We conclude that supplementation with n-3 PUFAs for 6 months prevented a reduction in SPMs released from P BMC s of AD patients , which was associated with changes in cognitive function IMPORTANCE Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease ( AD ) , evidence is limited in mild to moderate AD . OBJECTIVE To determine if vitamin E ( alpha tocopherol ) , memantine , or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor . DESIGN , SETTING , AND PARTICIPANTS Double-blind , placebo-controlled , parallel-group , r and omized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers . INTERVENTIONS Participants received either 2000 IU/d of alpha tocopherol ( n = 152 ) , 20 mg/d of memantine ( n = 155 ) , the combination ( n = 154 ) , or placebo ( n = 152 ) . MAIN OUTCOMES AND MEASURES Alzheimer 's Disease Cooperative Study /Activities of Daily Living ( ADCS-ADL ) Inventory score ( range , 0 - 78 ) . Secondary outcomes included cognitive , neuropsychiatric , functional , and caregiver measures .  RESULTS Data from 561 participants were analyzed ( alpha tocopherol = 140 , memantine = 142 , combination = 139 , placebo = 140 ) , with 52 excluded because of a lack of any follow-up data . Over the mean ( SD ) follow-up of 2.27 ( 1.22 ) years , ADCS-ADL Inventory scores declined by 3.15 units ( 95 % CI , 0.92 to 5.39 ; adjusted P = .03 ) less in the alpha tocopherol group compared with the placebo group . In the memantine group , these scores declined 1.98 units less ( 95 % CI , -0.24 to 4.20 ; adjusted P = .40 ) than the placebo group 's decline . This change in the alpha tocopherol group translates into a delay in clinical progression of 19 % per year compared with placebo or a delay of approximately 6.2 months over the follow-up period . Caregiver time increased least in the alpha tocopherol group . All-cause mortality and safety analyses showed a difference only on the serious adverse event of " infections or infestations , " with greater frequencies in the memantine ( 31 events in 23 participants ) and combination groups ( 44 events in 31 participants ) compared with placebo ( 13 events in 11 participants ) . CONCLUSIONS AND RELEVANCE Among patients with mild to moderate AD , 2000 IU/d of alpha tocopherol compared with placebo result ed in slower functional decline . There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol . These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00235716 BACKGROUND Dietary fish or fish oil rich in n-3 fatty acids ( n-3 FAs ) , eg , docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) , ameliorate inflammatory reactions by various mechanisms . Whereas most studies have explored the effects of predominantly EPA-based n-3 FAs preparations , few have addressed the effects of n-3 FAs preparations with DHA as the main FA . OBJECTIVE The objective was to determine the effects of 6 mo of dietary supplementation with an n-3 FAs preparation rich in DHA on release of cytokines and growth factors from peripheral blood mononuclear cells ( P BMC s ) . DESIGN In a r and omized , double-blind , placebo-controlled trial , 174 Alzheimer disease ( AD ) patients received daily either 1.7 g DHA and 0.6 g EPA ( n-3 FAs group ) or placebo for 6 mo . In the present study blood sample s were obtained from the 23 first r and omized patients , and P BMC s were isolated before and after 6 mo of treatment . RESULTS Plasma concentrations of DHA and EPA were significantly increased at 6 mo in the n-3 FAs group . This group also showed significant decreases of interleukin (IL)-6 , IL-1beta , and granulocyte colony-stimulating factor secretion after stimulation of P BMC s with lipopolysaccharide . Changes in the DHA and EPA concentrations were negatively associated with changes in IL-1beta and IL-6 release for all subjects . Reductions of IL-1beta and IL-6 were also significantly correlated with each other . In contrast , this n-3 FA treatment for 6 mo did not decrease tumor necrosis factor-alpha , IotaL-8 , IL-10 , and granulocyte-macrophage colony-stimulating factor secretion . CONCLUSION AD patients treated with DHA-rich n-3 FAs supplementation increased their plasma concentrations of DHA ( and EPA ) , which were associated with reduced release of IL-1beta , IL-6 , and granulocyte colony-stimulating factor from P BMC s. This trial was registered at clinical trials.gov as NCT00211159 Background Dietary fish oil , rich in n-3 fatty acids ( n-3 FAs ) , e.g. docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) , regulate inflammatory reactions by various mechanisms , e.g. gene activation . However , the effects of long-term treatment with DHA and EPA in humans , using genome wide techniques , are poorly described . Hence , our aim was to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global gene expression in peripheral blood mononuclear cells . Methods and Findings In the present study , blood sample s were obtained from a subgroup of 16 patients originating from the r and omized double-blind , placebo-controlled OmegAD study , where 174 Alzheimer disease ( AD ) patients received daily either 1.7 g of DHA and 0.6 g EPA or placebo for 6 months . In blood sample s obtained from 11 patients receiving n-3 FA and five placebo  , expressions of approximately 8000 genes were assessed by gene array . Significant changes were confirmed by real-time PCR . At 6 months , the n-3 FAs group displayed significant rises of DHA and EPA plasma concentrations , as well as up- and down-regulation of nine and ten genes , respectively , was noticed . Many of these genes are involved in inflammation regulation and neurodegeneration , e.g. CD63 , MAN2A1 , CASP4 , LOC399491 , NAIP , and SORL1 and in ubiqutination processes , e.g. ANAPC5 and UBE2V1 . Down-regulations of ANAPC5 and RHOB correlated to increases of plasma DHA and EPA levels . Conclusions We suggest that 6 months of dietary n-3 FA supplementation affected expression of genes that might influence inflammatory processes and could be of significance for AD . Trial Registration Clinical Trials.gov OBJECTIVE To report the psychometric properties of an alternative instrument to the cognitive subscale of the Alzheimer 's Disease Assessment Scale , a neuropsychological test battery 
    Output:
    
agent
***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: Oxidative stress , inflammation , and increased cholesterol levels are all mechanisms that have been associated with Alzheimer ’s disease ( AD ) pathology . Several epidemiologic studies have reported a decreased risk of AD with fish consumption . This pilot study was design ed to evaluate the effects of supplementation with omega-3 fatty acids alone ( ω-3 ) or omega-3 plus alpha lipoic acid ( ω-3 + LA ) compared to placebo on oxidative stress biomarkers in AD . The primary outcome measure was peripheral F2-isoprostane levels ( oxidative stress measure ) . Secondary outcome measures included performance on : Mini-Mental State Examination ( MMSE ) , Activities of Daily Living/Instrumental Activities of Daily Living ( ADL/IADL ) , and Alzheimer Disease Assessment Scale-cognitive subscale ( ADAS-cog ) . Thirty-nine AD subjects were r and omized to one of three groups : 1 ) placebo , 2 ) ω-3 , or 3 ) ω-3 + LA for a treatment duration of 12 months . Eighty seven percent ( 34/39 ) of the subjects completed the 12-month intervention . There was no difference between groups at 12 months in peripheral F2-isoprostane levels ( p = 0.83 ) . The ω-3 + LA and ω-3 were not significantly different than the placebo group in ADAS-cog ( p = 0.98 , p = 0.86 ) and in ADL ( p = 0.15 , p = 0.82 ) . Compared to placebo , the ω-3+LA showed less decline in MMSE ( p < 0.01 ) and IADL ( p= 0.01 ) and the ω-3 group showed less decline in IADL ( p < 0.01 ) . The combination of ω-3+LA  slowed cognitive and functional decline in AD over 12 months . Because the results were generated from a small sample size , further evaluation of the combination of omega-3 fatty acids plus alpha-lipoic acid as a potential treatment in AD is warranted 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 OBJECTIVES To study the effects of omega (Omega)-3 fatty acid ( FA ) supplements on weight and appetite in patients with mild to moderate Alzheimer 's disease ( AD ) in relation to inflammatory biomarkers and apolipoprotein E epsilon4 ( APOEepsilon4 ) . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Specialist memory clinics in the Stockholm catchment area . PARTICIPANTS Two hundred four patients ( aged 73+/-9 , 52 % women ) with mild to moderate AD . INTERVENTION Patients with AD received 1.7 g of docosahexaenoic acid ( DHA ) and 0.6 g of eicosapentaenoic acid ( EPA ) ( Omega-3/Omega-3 group ; n=89 , aged 73+/-9 , 57 % women ) or placebo 0.6 g of linoleic acid per day ( placebo/Omega-3 group ; n=85 , aged 73+/-9 , 46 % women ) for 6 months . After 6 months , all patients received DHA and EPA for another 6 months . MEASUREMENTS Anthropometry , biochemical nutritional and inflammatory markers , and appetite assessed by caregiver . RESULTS Mean weight and body mass index ( kg/m(2 ) ) at baseline were 70.0+/-11.8 kg and 24.3+/-3.0 kg/m(2 ) , respectively . At 6- and 12-month follow-up , weight had increased 0.7+/-2.5 kg ( P=.02 ) and 1.4+/-2.9 kg ( P<.001 ) in the Omega-3/Omega-3 group . In the placebo group , weight was unchanged at 6 months but had increased ( P=.01 ) at 12 months follow-up after Omega-3 supplementation was initiated . Appetite improved in the Omega-3/Omega-3 group over the treatment period ( P=.01 ) . In logistic regression analyses , not carrying the APOEepsilon4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up . CONCLUSION A DHA-enriched Omega-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD . Not carrying the APOEepsilon4 allele and high DHA were independently associated with weight gain Specialized proresolving mediators ( SPMs ) induce resolution of inflammation . SPMs are derivatives of n-3 and n-6 PUFAs and may mediate their beneficial effects . It is unknown whether supplementation with PUFAs influences the production of SPMs . Alzheimer ’s disease ( AD ) is associated with brain inflammation and reduced levels of SPMs . The OmegAD study is a r and omized , double-blind , and placebo-controlled clinical trial on AD patients , in which placebo or a supplement of 1.7 g DHA and 0.6 g EPA was taken daily for 6 months . Plasma levels of arachidonic acid decreased , and DHA and EPA levels increased after 6 months of n-3 FA treatment . Peripheral blood mononuclear cells ( P BMC s ) were obtained before and after the trial . Analysis of the culture medium of P BMC s incubated with amyloid-β 1–40 showed unchanged levels of the SPMs lipoxin A4 and resolvin D1 in the group supplemented with n-3 FAs , whereas a decrease was seen in the placebo group . The changes in SPMs showed correspondence to cognitive changes . Changes in the levels of SPMs were positively correlated to changes in transthyretin . We conclude that supplementation with n-3 PUFAs for 6 months prevented a reduction in SPMs released from P BMC s of AD patients , which was associated with changes in cognitive function IMPORTANCE Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease ( AD ) , evidence is limited in mild to moderate AD . OBJECTIVE To determine if vitamin E ( alpha tocopherol ) , memantine , or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor . DESIGN , SETTING , AND PARTICIPANTS Double-blind , placebo-controlled , parallel-group , r and omized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers . INTERVENTIONS Participants received either 2000 IU/d of alpha tocopherol ( n = 152 ) , 20 mg/d of memantine ( n = 155 ) , the combination ( n = 154 ) , or placebo ( n = 152 ) . MAIN OUTCOMES AND MEASURES Alzheimer 's Disease Cooperative Study /Activities of Daily Living ( ADCS-ADL ) Inventory score ( range , 0 - 78 ) . Secondary outcomes included cognitive , neuropsychiatric , functional , and caregiver measures .  RESULTS Data from 561 participants were analyzed ( alpha tocopherol = 140 , memantine = 142 , combination = 139 , placebo = 140 ) , with 52 excluded because of a lack of any follow-up data . Over the mean ( SD ) follow-up of 2.27 ( 1.22 ) years , ADCS-ADL Inventory scores declined by 3.15 units ( 95 % CI , 0.92 to 5.39 ; adjusted P = .03 ) less in the alpha tocopherol group compared with the placebo group . In the memantine group , these scores declined 1.98 units less ( 95 % CI , -0.24 to 4.20 ; adjusted P = .40 ) than the placebo group 's decline . This change in the alpha tocopherol group translates into a delay in clinical progression of 19 % per year compared with placebo or a delay of approximately 6.2 months over the follow-up period . Caregiver time increased least in the alpha tocopherol group . All-cause mortality and safety analyses showed a difference only on the serious adverse event of " infections or infestations , " with greater frequencies in the memantine ( 31 events in 23 participants ) and combination groups ( 44 events in 31 participants ) compared with placebo ( 13 events in 11 participants ) . CONCLUSIONS AND RELEVANCE Among patients with mild to moderate AD , 2000 IU/d of alpha tocopherol compared with placebo result ed in slower functional decline . There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol . These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00235716 BACKGROUND Dietary fish or fish oil rich in n-3 fatty acids ( n-3 FAs ) , eg , docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) , ameliorate inflammatory reactions by various mechanisms . Whereas most studies have explored the effects of predominantly EPA-based n-3 FAs preparations , few have addressed the effects of n-3 FAs preparations with DHA as the main FA . OBJECTIVE The objective was to determine the effects of 6 mo of dietary supplementation with an n-3 FAs preparation rich in DHA on release of cytokines and growth factors from peripheral blood mononuclear cells ( P BMC s ) . DESIGN In a r and omized , double-blind , placebo-controlled trial , 174 Alzheimer disease ( AD ) patients received daily either 1.7 g DHA and 0.6 g EPA ( n-3 FAs group ) or placebo for 6 mo . In the present study blood sample s were obtained from the 23 first r and omized patients , and P BMC s were isolated before and after 6 mo of treatment . RESULTS Plasma concentrations of DHA and EPA were significantly increased at 6 mo in the n-3 FAs group . This group also showed significant decreases of interleukin (IL)-6 , IL-1beta , and granulocyte colony-stimulating factor secretion after stimulation of P BMC s with lipopolysaccharide . Changes in the DHA and EPA concentrations were negatively associated with changes in IL-1beta and IL-6 release for all subjects . Reductions of IL-1beta and IL-6 were also significantly correlated with each other . In contrast , this n-3 FA treatment for 6 mo did not decrease tumor necrosis factor-alpha , IotaL-8 , IL-10 , and granulocyte-macrophage colony-stimulating factor secretion . CONCLUSION AD patients treated with DHA-rich n-3 FAs supplementation increased their plasma concentrations of DHA ( and EPA ) , which were associated with reduced release of IL-1beta , IL-6 , and granulocyte colony-stimulating factor from P BMC s. This trial was registered at clinical trials.gov as NCT00211159 Background Dietary fish oil , rich in n-3 fatty acids ( n-3 FAs ) , e.g. docosahexaenoic acid ( DHA ) and eicosapentaenoic acid ( EPA ) , regulate inflammatory reactions by various mechanisms , e.g. gene activation . However , the effects of long-term treatment with DHA and EPA in humans , using genome wide techniques , are poorly described . Hence , our aim was to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global gene expression in peripheral blood mononuclear cells . Methods and Findings In the present study , blood sample s were obtained from a subgroup of 16 patients originating from the r and omized double-blind , placebo-controlled OmegAD study , where 174 Alzheimer disease ( AD ) patients received daily either 1.7 g of DHA and 0.6 g EPA or placebo for 6 months . In blood sample s obtained from 11 patients receiving n-3 FA and five placebo  , expressions of approximately 8000 genes were assessed by gene array . Significant changes were confirmed by real-time PCR . At 6 months , the n-3 FAs group displayed significant rises of DHA and EPA plasma concentrations , as well as up- and down-regulation of nine and ten genes , respectively , was noticed . Many of these genes are involved in inflammation regulation and neurodegeneration , e.g. CD63 , MAN2A1 , CASP4 , LOC399491 , NAIP , and SORL1 and in ubiqutination processes , e.g. ANAPC5 and UBE2V1 . Down-regulations of ANAPC5 and RHOB correlated to increases of plasma DHA and EPA levels . Conclusions We suggest that 6 months of dietary n-3 FA supplementation affected expression of genes that might influence inflammatory processes and could be of significance for AD . Trial Registration Clinical Trials.gov OBJECTIVE To report the psychometric properties of an alternative instrument to the cognitive subscale of the Alzheimer 's Disease Assessment Scale , a neuropsychological test battery 
    Output:
    