***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 Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI  cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the  Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test .  Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions OBJECTIVES Physical exercise up-regulates brain-derived neurotrophic factor ( BDNF ) in the brain and blood . However , there is yet no consensus about the adequate blood processing conditions to st and ardize its assessment . We aim ed to find a reliable blood sample processing method to determine changes in BDNF due to exercise . DESIGN AND METHODS Twelve healthy university students performed an incremental cycling test to exhaustion .  At baseline , immediately after exercise , and 30 and 60 min of recovery , venous blood was drawn and processed under different conditions , i.e. whole blood , serum coagulated for 10 min and 24 h , total plasma , and platelet-free plasma .  BDNF concentration was measured by ELISA . RESULTS Exercise increased BDNF in whole blood and in serum coagulated for 24 h when corrected by hemoconcentration . We did not find effects of exercise on BDNF in serum coagulated for 10 min or in plasma sample s. Plasma shows heterogeneous BDNF values in response to exercise that are not prevented when platelets are eliminated while homogeneous BDNF levels were found in whole blood or serum coagulated for 24 hour sample s. CONCLUSIONS In exercise studies , BDNF levels should be adjusted by hemoconcentration . Our data highlight the importance of blood sample selection since the differences between each one affect significantly the BDNF factor changes due to exercise IMPORTANCE In animal studies , brain-derived neurotrophic factor ( BDNF ) has been shown to impact neuronal survival and function and improve synaptic plasticity and long-term memory . Circulating BDNF levels increase with physical activity and caloric restriction , thus BDNF may mediate some of the observed associations between lifestyle and the risk for dementia . Some prior studies showed lower circulating BDNF in persons with Alzheimer disease ( AD ) compared with control participants ; however , it remains uncertain whether reduced levels precede dementia onset . OBJECTIVE To examine whether higher serum BDNF levels in cognitively healthy adults protect against the future risk for dementia and AD and to identify potential modifiers of this association . DESIGN , SETTING , AND PARTICIPANTS Framingham Study original and offspring participants were followed up from 1992 and 1998 , respectively , for up to 10 years . We used Cox models to relate BDNF levels to the risk for dementia and AD and adjusted for potential confounders . We also ran sensitivity analyses stratified by sex , age , and education , as well as related BDNF genetic variants to AD risk . This community-based , prospect i ve cohort study involved 2131 dementia-free participants aged 60 years and older ( mean [ SD ] age , 72 [ 7 ] years ; 56 % women ) . MAIN OUTCOMES AND MEASURES Ten-year incidence of dementia and AD . RESULTS During follow-up , 140 participants developed dementia  , 117 of whom had AD . Controlling for age and sex , each st and ard-deviation increment in BDNF was associated with a 33 % lower risk for dementia and AD ( P = .006 and P = .01 , respectively ) and these associations persisted after additional adjustments . Compared with the bottom quintile , BDNF levels in the top quintile were associated with less than half the risk for dementia and AD ( hazard ratio , 0.49 ; 95 % CI , 0.28 - 0.85 ; P = .01 ; and hazard ratio , 0.46 ; 95 % CI , 0.24 - 0.86 ; P = .02 , respectively ) . These associations were apparent only among women , persons aged 80 years and older , and those with college degrees ( hazard ratios for AD : 0.65 , [ 95 % CI , 0.50 - 0.85 ] , P = .001 ; 0.63 [ 95 % CI , 0.47 - 0.85 ] , P = .002 ; and 0.27 [ 95 % CI , 0.11 - 0.65 ] , P = .003 , respectively ) . Brain-derived neurotrophic factor genetic variants were not associated with AD risk . CONCLUSIONS AND RELEVANCE Higher serum BDNF levels may protect against future occurrence of dementia and AD . Our findings suggest a role for BDNF in the biology and possibly in the prevention of dementia and AD , especially in select subgroups of women and older and more highly educated persons Brain-derived neurotrophic factor ( BDNF ) is a key mediator of neuronal plasticity in the adult . BDNF is known to be stored in human platelets and to circulate in plasma , but the regulation and function of BDNF in peripheral blood is still poorly understood . In this prospect i ve study , we have examined 140 healthy , non-allergic adults ( 20 - 60 years old ) to eluci date the impact of age and physical parameters on BDNF levels in human platelets and plasma . There was a wide concentration range of BDNF in serum ( median : 22.6 ng/ml ) , platelets ( median : 92.7 pg/10(6 ) platelets ) and plasma ( median : 92.5 pg/ml ) . BDNF levels in plasma decreased significantly with increasing age or weight , whereas platelet levels did not . When matched for weight , there were no significant gender differences regarding BDNF plasma levels . However , women displayed significantly lower platelet BDNF levels than men . In addition , platelet BDNF levels changed during the menstrual cycle . In conclusion , we demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF levels in peripheral blood Alzheimer ’s disease ( AD ) can be treated with inhibitors of the enzyme acetylcholinesterase ( AChE ) . Recent pre- clinical and clinical studies gave evidence that AChE-inhibitors have neuroprotective effects and thereby a disease-modifying potential . The mechanism of this action is still discussed . In an animal model oral administration of an AChE-inhibitor lead to an increase of brain derived neurotrophic factor ( BDNF ) in hippocampus and cortex . Recent studies have found a decrease of BDNF in the serum and brain of AD patients with potentially consecutive lack of neurotrophic support and contribution to progressive neurodegeneration . BDNF serum concentrations were assessed by ELISA in 19 AD patients and 20 age-matched healthy controls at baseline and in the AD patients after 15 months of treatment with donepezil 10 mg per day  ( one patient received just 5 mg ) . Before treatment with donepezil we found in AD significantly decreased BDNF serum concentrations ( 19.2 ± 3.7 ng/ml ) as compared to healthy controls ( 23.2 ± 6.0 ng/ml , P = 0.015 ) . After 15 months of treatment the BDNF serum concentration increased significantly in the AD patients ( 23.6 ± 7.0 ng/ml , P = 0.001 ) showing no more difference to the healthy controls ( P = 0.882 ) . The results of the present study confirm data of prior investigations that a down-regulation of BDNF in serum and brain of AD patients seems to begin with the first clinical symptoms and to be persistent . A treatment with the AChE-inhibitor donepezil is accompanied with an increase of BDNF serum concentration in AD patients reaching the level of healthy controls . Thus , up-regulation of BDNF might be part of a neuroprotective effect of AChE-inhibitors . The molecular mechanism of this potentially disease-modifying mechanism of action of donepezil should be clarified BACKGROUND A large proportion of patients with amnestic mild cognitive impairment ( MCI )  progress to Alzheimer 's disease ( AD ) , but the rate of conversion is highly variable , depending on selection and inclusion criteria . In the present prospect i ve study , amnestic MCI criteria were applied in order to enrich the study population with prodromal AD patients . METHODS A composite CERAD word list learning z-score of -1 was applied as a cut-off for memory performance at baseline . Competing causes of memory impairment other than prodromal AD were actively excluded . A cohort of 88 amnestic MCI patients was included ; 75 were available for follow-up . RESULTS After a mean delay of 19 months , 44 % were found to have converted to AD , corresponding to an annualized conversion rate of 28 % . The rate of new diagnoses other than stable MCI or AD was 6 % . Baseline neuropsychological variables were not instrumental to predict progression . CONCLUSION Amnestic MCI patients , as identified by the present set of criteria , carry a high risk of median-term progression to AD BACKGROUND Recent reports have suggested a role for brain-derived neurotrophic factor ( BDNF ) in psychiatric disorders . Decreased serum BDNF levels have been reported in major depression , but the cause of this decrease has not yet been investigated . The goal of this study was to assess blood BDNF and a platelet activation index , PF4 . METHODS Forty-three drug-free patients ( 27 female , 16 male ) diagnosed with major depression and 35 healthy control subjects ( 18 female , 17 male ) were assessed for plasma , serum , and blood BDNF content . Brain-derived neurotrophic factor and PF4 were assayed with enzyme-linked immunosorbent assay methods , and severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale . RESULTS Serum and plasma BDNF levels were decreased in depressed patients compared with control subjects . In whole blood , BDNF levels were unaltered in the depressed subjects compared with control subjects . The serum/blood BDNF ratio was lower in patients with major depression . Increased plasma but not serum PF4 levels were observed in depressed subjects compared with control subjects . CONCLUSIONS Our results suggest that an alteration of serum or plasma BDNF is not due to the change in blood BDNF but rather is probably related to mechanisms of BDNF release . Secretion of BDNF seems to be independent of platelet reactivity ; other mechanisms are therefore probably involved and need to be eluci date Pre clinical and clinical studies gave evidence that lithium could be useful in the treatment of Alzheimer 's disease ( AD ) . In experimental investigations , lithium induces brain-derived neurotrophic factor ( BDNF ) . Recent studies have found a decrease of BDNF in the serum and brains of AD patients with potentially consecutive lack of neurotrophic support . We assessed the influence of a lithium treatment on BDNF serum concentration in a subset of a greater sample recruited for a r and omized , single-blinded , placebo-controlled , parallel-group multicenter 10-week study , investigating the efficacy of lithium treatment in AD patients . In AD patients treated with lithium , a significant increase of BDNF serum levels , and additionally a significant decrease of ADAS-Cog sum scores in comparison to placebo-treated patients , were found . Diminution of cognitive impairment was inversely correlated with lithium serum concentration . Upregulation of BDNF might be part of a neuroprotective effect of lithium in AD patients . The results of the present investigation encourage performing studies with longer treatment phases to observe potential positive long-term effects of lithium in AD patients 
    Output:
    
There were no differences in blood BDNF levels among AD or MCI patients vs. controls by subgroup analyses according to age , sex , and drug use .
In conclusion , this meta- analysis shows that peripheral blood BDNF levels seem to be increased in early AD and decreased in AD patients with low MMSE scores respectively compared with their age- and sex-matched healthy referents .