***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: Of 57 individuals diagnosed with Alzheimer 's disease ( AD ) in a phase III study , 13 ( 23 % ) had amyloid-β ( Aβ ) levels  on postmortem histopathology that did not explain the dementia . Based on postmortem histopathology , a wide range of different non-AD conditions was identified , including frontotemporal dementia , hippocampal sclerosis , and dementia with Lewy bodies . Of the histopathologically Aβ negative scored cases ante-mortem Florbetaben PET scans were classified as negative for Aβ in 11 patients based on visual analysis and in all 12 quantifiable cases based on composite st and ardized uptake value ratios . Thus , florbetaben PET can assist physicians in the differential diagnosis of neurodegenerative disorders by reliably excluding Aβ pathology 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 Evaluation of brain β‐amyloid by positron emission tomography ( PET ) imaging can assist in the diagnosis of Alzheimer disease ( AD ) and other dementias 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 Background We assessed the clinical utility of β-amyloid ( Aβ ) imaging with 18F-florbetaben ( FBB ) in mild cognitive impairment ( MCI ) by evaluating its prognostic accuracy for progression to Alzheimer 's disease ( AD ) , comparing semiquantitative with visual scan assessment , and exploring the relationships among Aβ , hippocampal volume ( HV ) and memory over time . Methods 45 MCI underwent FBB positron emission tomography , MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years . Positive FBB ( FBB+ ) , defined by a cortical to cerebellar cortex st and ardised uptake value ratio ( SUVR ) ≥1.45 , was compared with visual assessment by five readers . Amnestic MCI ( aMCI ) was defined by a composite episodic memory ( EM ) Z-score of < −1.5 . Results At baseline , 24 ( 53 % ) MCI were FBB+ . Majority reads agreed with SUVR classification ( κ 0.96 ) . In 2 years , 18 ( 75 % ) FBB+ progressed to AD compared with 2 ( 9.5 % ) FBB− , yielding a predictive accuracy of 83 % ( 95 % CI 61 % to 94 % ) . Four FBB− developed non-AD dementia . Predictive accuracies of HV ( 58 % ( 95 % CI 42 % to 73 % ) ) and aMCI status ( 73 % ( 95 % CI 58 % to 81 % ) ) were lower . Combinations did not improve accuracy . By 4 years , 21 ( 87.5 % ) FBB+ had AD whereas 5 ( 24 % ) FBB− had non-AD dementia yielding a predictive accuracy of 94 % ( 95 % CI 74 % to 99 % ) . While the strong baseline association between FBB SUVR and EM declined over 2 years , the association between EM and HV became stronger . FBB SUVR increased 2.2%/year in FBB+ with no change in FBB−. Conclusions 18F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD . As neurodegeneration progresses , and in contrast with the early stages of the disease , hippocampal atrophy and not Aβ , seems to drive memory decline . Trial registration number NCT01138111 Assessment of disease biomarkers , particularly the in vivo assessment of amyloid-β ( Aβ ) burden with positron emission tomography ( PET ) , is gradually becoming central to the diagnosis of mild cognitive impairment ( MCI ) due to Alzheimer 's disease ( AD ) . However , the incorporation of biomarker evidence to the diagnostic process is currently restricted mainly to research setting s. The identification of memory measures that are associated with Aβ is of clinical relevance as this may enhance the confidence in making a diagnosis of MCI due to AD in clinical setting s. Forty one persons with amnestic MCI underwent Aβ imaging with (18)F-Florbetaben PET , magnetic resonance imaging , and a comprehensive neuropsychological assessment .  All measures of episodic memory were significantly correlated with Aβ burden , but regression analyses revealed a strong and selective association between story recall and Aβ over and beyond the effects of age , education , global cognition , hippocampal volume , or other memory tests . Analyses of sensitivity and specificity of memory measures to detect high versus low Aβ scans suggested that word-list recall performed better when high sensitivity was preferred , whereas story recall performed better when high specificity was preferred . In conclusion , a measure of story recall may increase the confidence in making a diagnosis of MCI due to AD in clinical setting A retrospective clinico-pathological study of a consecutive  autopsy series of 1050 elderly demented individuals ( mean age 83.4 + /- 6.0 years ; MMSE < 20 ) was performed . Clinical diagnoses were probable or possible Alzheimer disease ( 62.9 % ) , nonspecific degenerative dementia ( 10.4 % ) , vascular dementia ( 10 % ) , Parkinson disease with dementia ( 9.5 % ) , 1.5 % mixed dementia , and 5.7 % other disorders . At autopsy , 86 % revealed Alzheimer-related pathology , but only 42.8 % showed " pure " Alzheimer disease , with additional cerebrovascular lesions in 22.6 % and Lewy body pathology in 10.8 % , while among 660 cases of clinical ly suspected Alzheimer disease , Alzheimer pathology was seen in 93 % , only 44.7 % in " pure " form , and additional vascular lesions and Lewy bodies in 27.7 and 10 % , respectively . The non-Alzheimer cases included Huntington and Creutzfeldt-Jakob disease , frontotemporal dementias , and others . These and other recent data indicate that in patients with the clinical diagnosis of Alzheimer disease its combination with cerebro 
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Although we were able to calculate one estimation of DTA in , especially , the prediction of progression from MCI to ADD at four years follow-up , the small number of participants implies imprecision of sensitivity and specificity estimates .