***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: [11C]Pittsburgh compound B ( [11C]PIB ) and [18F]‐2‐fluoro‐2‐deoxy‐D‐glucose ( [18F]FDG ) PET  measure fibrillar amyloid‐β load and glucose metabolism , respectively . We evaluated the impact of these tracers on the diagnostic process in a memory clinic population 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 Purpose [11C]PIB and [18F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer ’s disease ( AD ) . [18F]FDG is a glucose analogue and its uptake reflects metabolic activity . The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment ( MCI ) and in healthy controls . Methods Longitudinal , paired , dynamic [11C]PIB and [18F]FDDNP ( 90 min each ) and static [18F]FDG ( 15 min ) PET scans were obtained in 11 controls , 12 MCI patients and 8 AD patients . The mean interval between baseline and follow-up was 2.5 years ( range 2.0–4.0 years ) . Parametric [11C]PIB and [18F]FDDNP images of binding potential ( BPND ) and [18F]FDG st and ardized uptake value ratio ( SUVr ) images were generated . Results A significant increase in global cortical [11C]PIB BPND was found in MCI patients , but no changes were observed in AD patients or controls . Subsequent regional analysis revealed that this increase in [11C]PIB BPND in MCI patients was most prominent in the lateral temporal lobe ( p < 0.05 ) . For [18F]FDDNP , no changes in global BPND were found . [18F]FDG uptake was reduced at follow-up in the AD group only , especially in frontal , parietal and lateral temporal lobes ( all p < 0.01 ) . Changes in global [11C]PIB binding ( ρ = −0.42 , p < 0.05 ) and posterior cingulate [18F]FDG uptake ( ρ = 0.54 , p < 0.01 ) were correlated with changes in Mini-Mental-State Examination score over time across groups , whilst changes in [18F]FDDNP binding ( ρ = −0.18 , p = 0.35 ) were not . Conclusion [11C]PIB and [18F]FDG track molecular changes in different stages of AD . We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients . [18F]FDDNP seems to be less useful for examining disease progression Objective : To investigate the 10-year risk of dementia in subjects with mild cognitive impairment ( MCI ) ages 40 to 85 years . Methods : We selected subjects from a memory clinic if they met one of the following definitions of MCI : cognitive complaints ( n = 181 ) , aging-associated cognitive decline ( AACD ) ( n = 163 ) , mild functional impairment ( n = 86 ) , or amnestic MCI ( n = 64 ) . Subjects were reassessed after 2 , 5 , and 10 years . The risk of dementia was calculated with Kaplan-Meier statistics . Analyses were conducted in the entire sample and in subgroups of subjects aged 40 to 54 years , 55 to 69 years , and 70 to 85 years . Results : The 10-year risk of dementia was 0.27 ( 95 % CI 0.20 to 0.34 ) in subjects with cognitive complaints , 0.28 ( 95 % CI 0.21 to 0.35 ) in subjects with AACD , 0.44 ( 95 % CI 0.32 to 0.56 ) in subjects with mild functional impairment , and 0.48 ( 95 % CI 0.35 to 0.61 ) in subjects with amnestic MCI . Ninety-one percent of the demented subjects had probable AD . The risk of dementia increased with increasing age for all MCI definitions ( p < 0.001 ) . Depending on the MCI definition used , the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years , from 0.37 to 0.52 in subjects aged 55 to 69 years , and from 0.77 to 1.0 in subjects aged 70 to 85 years . Conclusions : The majority of subjects with MCI  do not progress to dementia at the long term . Age strongly influences the dementia risk . MCI often represents the predementia stage of a neurodegenerative disorder in elderly subjects but rarely in younger subjects CONTEXT Small single-center studies have shown that cerebrospinal fluid ( CSF ) biomarkers may be useful to identify incipient Alzheimer disease ( AD ) in patients with mild cognitive impairment ( MCI ) , but large-scale multicenter studies have not been conducted . OBJECTIVE To determine the diagnostic accuracy of CSF beta-amyloid(1 - 42 ) ( Abeta42 ) , total tau protein ( T-tau ) , and tau phosphorylated at position threonine 181 ( P-tau ) for predicting incipient AD in patients with MCI . DESIGN , SETTING , AND PARTICIPANTS The study had 2 parts : a cross-sectional study involving patients with AD and controls to identify cut points , followed by a prospect i ve cohort study involving patients with MCI  , conducted 1990 - 2007 . A total of 750 individuals with MCI , 529 with AD , and 304 controls were recruited by 12 centers in Europe and the United States . Individuals with MCI  were followed up for at least 2 years or until symptoms had progressed to clinical dementia . MAIN OUTCOME MEASURES Sensitivity , specificity , positive and negative likelihood ratios ( LRs ) of CSF Abeta42 , T-tau , and P-tau for identifying incipient AD . RESULTS During follow-up , 271 participants with MCI were diagnosed with AD and 59 with other dementias . The Abeta42 assay in particular had considerable intersite variability . Patients who developed AD had lower median Abeta42 ( 356 ; range , 96 - 1075 ng/L ) and higher P-tau ( 81 ; range , 15 - 183 ng/L ) and T-tau ( 582 ; range , 83 - 2174 ng/L ) levels than MCI patients who did not develop AD during follow-up ( 579 ; range , 121 - 1420 ng/L for Abeta42 ; 53 ; range , 15 - 163 ng/L for P-tau ; and 294 ; range , 31 - 2483 ng/L for T-tau , P < .001 ) . The area under the receiver operating characteristic curve was 0.78 ( 95 % confidence interval [ CI ] , 0.75 - 0.82 ) for Abeta42 , 0.76 ( 95 % CI , 0.72 - 0.80 ) for P-tau , and 0.79 ( 95 % CI , 0.76 - 0.83 ) for T-tau . Cut-offs with sensitivity set to 85 % were defined in the AD and control groups and tested in the MCI group , where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83 % ( 95 % CI , 78%-88 % ) , specificity 72 % ( 95 % CI , 68%-76 % ) , positive LR , 3.0 ( 95 % CI , 2.5 - 3.4 ) , and negative LR , 0.24 ( 95 % CI , 0.21 - 0.28 ) . The positive predictive value was 62 % and the negative predictive value was 88 % . CONCLUSIONS This multicenter study found that CSF Abeta42 , T-tau , and P-tau identify incipient AD with good accuracy , but less accurately than reported from single-center studies . Intersite assay variability highlights a need for st and ardization of analytical techniques and clinical procedures Abstract OBJECTIVES To determine the 2-year outcome from 16 different current classifications of mild cognitive impairment ( MCI ) in a population -based sample . DESIGN Prospect i ve cohort study : baseline and 2-year follow-up phases . SETTING Large-scale multicenter study , United Kingdom . PARTICIPANTS : Thirteen thous and four individuals aged 65 and older from the Medical Research Council Cognitive Function and Ageing Study . From this , a sub sample of 2,640 individuals was selected and completed a more-detailed cognitive assessment  . Individuals who underwent further assessment were asked to complete annual or 2-year follow-ups . MEASUREMENTS Information on sociodemographic status , general health , cognitive impairment and functional ability were collected using a structured interview . Individuals were classified according to 16 different definitions of MCI . These were applied retrospectively . RESULTS The dominant outcome across definitions was an impairment that was not classifiable or reversion to normality . Progression to dementia was variable and generally poor . Overall progression was highest in classifications in which impairment extended to memory and nonmemory domains . Predictability was age dependent in some but not all classifications . CONCLUSION Current classifications of MCI have variable outcomes in population -based sample s. Progression to dementia is relatively rare and is dependent on age and definition . Selection criteria developed for the clinic are based on a " high risk " approach that leads to exclusion of a large percentage of the impaired population who are neither normal nor demented and for whom no intervention options are currently available . A refined definition of this construct is urgently needed if MCI is to be used to predict dementia in population -based studies UNLABELLED Patients with mild cognitive impairment ( MCI ) represent a risk population for progressing to dementia of the Alzheimer type ( DAT ) . However , clinical criteria do not ensure reliable individual prognosis in these patients . The objective of this longitudinal , prospect i ve study was to examine the value of (18)F-FDG PET of cerebral glucose metabolism and of genetic susceptibility , as defined by an APOEepsilon4-positive genotype , with regard to the early diagnosis of DAT in patients with MCI . METHODS In 30 patients with the diagnosis of MCI ( 16 female , 14 male ; age , 70 + /- 8 y ) , baseline and follow-up examinations ( mean observation period , 16 mo ) were performed . In all patients , the APOE genotype was assessed and cerebral glucose metabolism was evaluated at baseline using cranial (18)F-FDG PET . Individual PET data were screened for findings suggestive of Alzheimer 's disease ( AD ) , with the help of an automated computer program . After stereotactical normalization of the PET images , this program performs an observer-independent statistical comparison with an age-matched reference data base ( n = 22 ) . RESULTS In 43 % of all MCI subjects , a  PET scan suggestive of AD pathology according to our predefined criteria was observed at baseline ( PET+ ) ; 57 % of all MCI patients were carriers of the APOE epsilon4 allele ( e4 + ) . In 40 % of all patients , progression of symptoms within the observation period justified the clinical diagnosis of probable DAT at the time of follow-up reevaluation . Statistical evaluation revealed the best results for 
    Output:
    
Conclusion : Systematic and comprehensive assessment of studies of 18FDG-PET for prediction of conversion from MCI to AD dementia reveals many studies have method ological limitations according to Cochrane diagnostic test accuracy gold st and ards , and shows accuracy remains highly variable , including in the most recent studies .