***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: BACKGROUND Increasing evidence points toward the efficacy of nutritional modifications in delaying cognitive decline and mood/behavioral difficulties in Alzheimer 's disease ( AD ) .  Nutritional supplementation with individual agents has shown varied results suggesting the need for combinatorial intervention . OBJECTIVE We set out to determine whether nutritional intervention could positively impact cognitive performance and behavioral difficulties for individuals diagnosed with AD . METHODS A double-blind , multi-site , phase II study ( Clinical Trials.gov NCT01320527 ; Alzheimer 's Association Trialmatch ) was conducted in which 106 individuals with AD were r and omized to a nutraceutical formulation ( NF ; folate , alpha-tocopherol , B12 , S-adenosyl methioinine , N-acetyl cysteine , acetyl-L-carnitine ) or placebo for 3 or 6 months , followed by an open-label extension where participants received NF for 6 additional months . RESULTS The NF cohort improved versus the placebo cohort within 3 months ( Clox-1 p = 0.0083 , 95%CI [ 0.4481 , 2.9343 ] ; Dementia Rating Scale p = 0.0266 , 95%CI [ 0.1722 , 2.7171 ] ) . Caregivers reported non-significant improvements in Neuropsychiatric Inventory . Both cohorts improved or maintained baseline performance during open-label extensions . Activities of Daily Living did not change for either cohort . CONCLUSIONS These findings extend phase I studies where NF maintained or improved cognitive performance and mood/behavior 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 Introduction Souvenaid ® containing Fortasyn ® Connect is a medical food design ed to support synapse synthesis in persons with Alzheimer ’s disease ( AD ) .  Fortasyn Connect includes precursors ( uridine monophosphate ; choline ; phospholipids ; eicosapentaenoic acid ; docosahexaenoic acid ) and cofactors ( vitamins E , C , B12 , and B6 ; folic acid ; selenium ) for the formation of neuronal membranes . Whether Souvenaid slows cognitive decline in treated persons with mild-to-moderate AD has not been addressed . Methods In a 24-week , double-masked clinical trial at 48 clinical centers , 527 participants taking AD medications [ 52 % women , mean age 76.7 years ( St and ard Deviation , SD = 8.2 ) , and mean Mini-Mental State Examination score 19.5 ( SD = 3.1 , range 14–24 ) ] were r and omized 1:1 to daily , 125-mL ( 125 kcal ) , oral intake of the active product ( Souvenaid ) or an iso-caloric control . The primary outcome of cognition was assessed by the 11-item Alzheimer ’s Disease Assessment Scale-Cognitive Subscale ( ADAS-cog ) . Compliance was calculated from daily diary recordings of product intake . Statistical analyses were performed using mixed models for repeated measures . Results Cognitive performance as assessed by ADAS-cog showed decline over time in both control and active study groups , with no significant difference between study groups ( difference = 0.37 points , St and ard Error , SE = 0.57 , p = 0.513 ) . No group differences in adverse event rates were found and no clinical ly relevant differences in blood safety parameters were noted . Overall compliance was high ( 94.1 % [ active ] and 94.5 % [ control ] ) , which was confirmed by significant changes in blood ( nutritional ) biomarkers . Conclusions Add-on intake of Souvenaid during 24 weeks did not slow cognitive decline in persons treated for mild-to-moderate AD . Souvenaid was well tolerated in combination with st and ard care AD medications . Trial registration Dutch Trial Register number : NTR1683 OBJECTIVES Excessive shortening of the telomeric ends of chromosomes is a marker of accelerated aging . Oxidative stress and nutritional deficiency may influence this process . The aim of this study was to investigate the effect of ω-3 polyunsaturated fatty acid ( ω-3 PUFA ) supplementation on telomeric shortening in elderly individuals with mild cognitive impairment ( MCI ) . METHODS Thirty-three adults ages > 65 y with MCI were r and omized to receive a supplement rich in the long-chain ω-3 PUFAs eicosapentaenoic acid ( EPA ; 1.67 g EPA + 0.16 g docosahexaenoic acid DHA/d ; n = 12 ) or DHA ( 1.55 g DHA + 0.40 g EPA/d ; n = 12 ) , versus ω-6 PUFA linoleic acid ( LA ; 2.2 g/d ; n = 9 ) for 6 mo . RESULTS The intervention did not show an increase in telomere length with treatment and there was a trend toward telomere shortening during the intervention period . Linear mixed modeling produced a robust model although statistically underpowered . Telomere shortening was greatest in the LA group ( d = 0.21 ) than in the DHA ( d = 0.12 ) and EPA groups ( d = 0.06 ) . Increased erythrocyte DHA levels were associated with reduced telomere shortening ( r = -0.67 ; P = 0.02 ) in the DHA group . CONCLUSION Telomeric shortening may be attenuated by ω-3 PUFA supplementation , requiring further investigation in larger sample Synaptic loss is an early pathological finding in Alzheimer ’s disease ( AD ) and correlates with memory impairment . Changes in macroscopic brain activity measured with  electro- and magnetoencephalography ( EEG and MEG ) in AD indicate synaptic changes and may therefore serve as markers of intervention effects in clinical trials . EEG peak frequency and functional networks have shown , in addition to improved memory performance , to be sensitive to detect an intervention effect in mild AD patients of the medical food Souvenaid containing the specific nutrient combination Fortasyn ® Connect  , which is design ed to enhance synapse formation and function . Here , we explore the value of MEG , with higher spatial resolution than EEG , in identifying intervention effects of the nutrient combination by comparing MEG spectral measures , functional connectivity , and networks between an intervention and a control group . Quantitative markers describing spectral properties , functional connectivity , and graph theoretical aspects of MEG from the exploratory 24-week , double-blind , r and omized , controlled Souvenir II MEG sub- study ( NTR1975 , http://www.trialregister.nl ) in drug naïve patients with mild AD were compared between a test group ( n = 27 ) , receiving Souvenaid , and a control group ( n = 28 ) , receiving an isocaloric control product .  The groups were unbalanced at screening with respect to Mini-Mental State Examination . Peak frequencies of MEG were compared with EEG peak frequencies , recorded in the same patients at similar time points , were compared with respect to sensitivity to intervention effects . No consistent statistically significant intervention effects were detected . In addition , we found no difference in sensitivity between MEG and EEG peak frequency . This exploratory study could not unequivocally establish the value of MEG in detecting interventional effects on brain activity , possibly due to small sample size and unbalanced study groups . We found no indication that the difference could be attributed to a lack of sensitivity of MEG  compared with  EEG . MEG in r and omized controlled trials is feasible but its value to disclose intervention effects of Souvenaid in mild AD patients needs to be studied further Background : High levels of xanthophyll carotenoids lutein ( L ) and zeaxanthin ( Z ) in the central nervous system have been previously correlated with improved cognitive function in community-dwelling older adults . In this study , we tested the effects of supplementing L and Z on older men and women with a range of baseline cognitive abilities . Objective : The purpose of this study was to determine whether or not supplementation with L+Z could improve cognitive function in community-dwelling , older adults . Design : Double-masked , r and omized , placebo-controlled trial . A total of 62 older adults were r and omized into groups receiving either 12 mg L+Z or a visually identical placebo .  Data from 51 participants ( M = 73.7 years ) were available for analysis . Retinal L+Z levels ( macular pigment optical density , MPOD ) were measured psychophysically using heterochromatic flicker photometry as a biomarker of cortical L+Z levels . Cognitive function was measured using the CNS Vital Signs computerized test platform . Results : Participants receiving the active L+Z supplement had statistically significant increases in MPOD ( p < 0.03 ) and improvements in complex attention ( p < 0.02 ) and cognitive flexibility domains ( p < 0.04 ) , relative to participants taking the placebo . A trend was also seen for the executive function domain ( p = 0.073 ) . In male participants only , supplementation yielded improved composite memory ( p = 0.04 ) . Conclusions : Supplementation with L+Z improved cognitive function in community-dwelling , older men and women Background Plasmalogens ( Pls ) reportedly decreased in postmortem brain and in the blood of patients with Alzheimer 's disease ( AD ) . Recently we showed that intraperitoneal administration of Pls improved cognitive function in experimental animals . In the present trial , we tested the efficacy of oral administration of scallop-derived purified Pls with respect to cognitive function and blood Pls changes in patients with mild AD and mild cognitive impairment ( MCI ) . Methods The study was a multicenter , r and omized , double-blind , placebo-controlled trial of 24 weeks . Participants were 328 patients aged 60 to 85 years who had 20 to 27 points in Mini Mental State Examination-Japanese ( MMSE-J ) score and five or less points in Geriatric Depression Scale-Short Version-Japanese ( GDS-S-J ) . They were r and omized to receive either 1 mg/day of Pls purified from scallop or placebo . The patients and study physicians were masked to the assignment . The primary outcome was MMSE-J. The secondary outcomes included Wechsler Memory Scale-Revised ( WMS-R ) , GDS-S-J and concentration of phosphatidyl ethanolamine plasmalogens ( PlsPE ) in erythrocyte membrane and plasma . This trial is registered with the University Hospital Medical Information Network , number UMIN000014945 . Findings Of 328 patients enrolled , 276 patients completed the trial ( 140 in the treatment group and 136 in the placebo group ) . In an intention-to-treat analysis including both mild AD ( 20 ≤ MMSE-J ≤ 23 ) and MCI ( 24 ≤ MMSE-J ≤ 27 ) , no significant difference was shown between the treatment and placebo groups in the primary and secondary outcomes , with no severe adverse events in either group . In mild AD patients , WMS-R improved significantly in the treatment group , and the between group difference was nearly significant ( P = 0.067 ) . In a subgroup analysis of mild AD patients , WMS-R significantly improved among females and those aged below 77 years in the treatment group , and the between-group differences were statistically significant in females ( P = 0.017 ) and in those aged below 77 years ( P = 0.029 ) . Patients with mild AD showed a significantly greater decrease in plasma PlsPE in the placebo group than in the treatment group . Interpret 
    Output:
    
In the present systematic review , from the 32 included RCTs published in the last four years ( 2014–2017 ) in patients aged 60 years and older with different late‐life cognitive disorders , nutritional intervention through medical food/nutraceutical supplementation and multidomain approach  improved magnetic resonance imaging findings and other cognitive‐related biomarkers , but without clear effect on cognition in mild Alzheimer 's disease ( AD ) and mild cognitive impairment ( MCI ) .
Antioxidant‐rich foods ( nuts , grapes , cherries ) and fatty acid supplementation , mainly n‐3 polyunsaturated fatty acids ( PUFA ) , improved specific cognitive domains and cognitive‐related outcomes in MCI , mild‐to‐moderate dementia , and AD .
Antioxidant vitamin and trace element supplementations  improved only cognitive‐related outcomes and biomarkers , high‐dose B vitamin supplementation in AD and MCI patients improved cognitive outcomes in the subjects with a high baseline plasma n‐3 PUFA , while folic acid supplementation had positive impact on specific cognitive domains in those with high homocysteine