***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: Objective : To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease ( AD ) . Methods : From the prospect i ve , longitudinal BioFINDER study , we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years ( MCI-AD ) . β-Amyloid ( Aβ ) deposition in 9 brain regions was examined with [18F]-flutemetamol PET . CSF was analyzed with INNOTEST and EUROIMMUN ELISAs . The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer 's Disease Neuroimaging Initiative study . Results : The best CSF measures for identifying MCI-AD were Aβ42/total tau ( t-tau ) and Aβ42/hyperphosphorylated tau ( p-tau ) ( area under the curve [ AUC ] 0.93–0.94 ) . The best PET measures performed similarly ( AUC 0.92–0.93 ; anterior cingulate , posterior cingulate/precuneus , and global neocortical uptake ) . CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 ( AUC difference 0.03–0.12 , p < 0.05 ) . Using nonoptimized cutoffs , CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers ( sensitivity 97 % , specificity 83 % ) . The combination of CSF and PET was not better than using either biomarker separately . Conclusions : Amyloid PET and CSF biomarkers can identify early AD with high accuracy . There were no differences between the best CSF and PET measures and no improvement when combining them . Regional PET measures were not better than assessing the global Aβ deposition . The results were replicated in an independent cohort using another CSF assay and PET tracer . The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability , costs , and doctor/patient preferences since both have equally high diagnostic accuracy . Classification of evidence : This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately BACKGROUND Brain amyloid deposition is one of the key pathological hallmarks underlying the cognitive changes associated with Alzheimer 's disease . Growing interest has been given to the earliest clinical manifestations of amyloid plaques . However , the relationship between amyloid status and activities of everyday function remains largely unknown . In the present study , we examined the relationship between instrumental activities of daily living performance ( using the ADL-PI score ) and amyloid status in older adults . METHODS Cross-sectional analyses of data from the Multidomain Alzheimer Preventive Trial ( MAPT ) were performed . Volunteers underwent a brain 18F-AV45 positron emission tomography examination . Bivariate analysis and regression models were conducted to study the relationships between brain amyloid deposition and the total ADL-PI score . RESULTS We included 271 participants ( women = 60 % ; age = 76±4 years ) .  Amyloid positron emission tomography  was positive ( st and ard uptake value ≥1.17 ) for 103 participants ( 38 % ) . The ADL-PI score was lower in amyloid positive participants than in their amyloid negative counterparts ( 38.8 vs 40.3 , p = .007 ) . This association was also confirmed in regression models adjusted for age , gender , and familial history of Alzheimer 's disease ( odds ratio = 0.94 ; 95 % confidence interval 0.89 - 0.99 ; p = .02 ) . This finding was consistent in cognitively normal individuals and in those with mild cognitive impairment , using the clinical dementia rating scale . CONCLUSIONS This study highlighted an association between early functional limitations and brain  amyloid deposition in elderly subjects . These symptoms could be the clinical manifestations of amyloid plaques even in the absence of overt dementia . Further prospect i ve studies are warranted for examining the evolution of ADL-PI score over the course of Alzheimer 's disease BACKGROUND Alzheimer 's disease ( AD ) pathology is common in patients with amnestic mild cognitive impairment ( aMCI ) without dementia , but the prevalence of AD pathology in patients with subjective cognitive impairment ( SCI ) and non-amnestic mild cognitive impairment ( naMCI ) is unknown . AD is characterised by decreased CSF concentrations of Abeta(42 ) and increased concentrations of tau . We investigated the prevalence of a CSF AD profile in patients with SCI , naMCI , or aMCI and the association of this profile with cognitive outcome in each group . METHODS Patients with SCI , naMCI , aMCI , and neurologically healthy controls were recruited from 20 memory clinics across Europe , between January , 2003 , and June , 2005 , into this prospect i ve cohort study . A CSF AD profile was defined as an abnormal ratio of Abeta(42):tau . Patients were assessed annually up to 3 years . Outcome measures were changes in memory , overall cognition , mini-mental state examination ( MMSE ) score , daily function , and progression to AD-type dementia . FINDINGS The CSF AD profile was more common in patients with SCI ( 31 of 60 [ 52 % ] ) , naMCI ( 25 of 37 [ 68 % ] ) , and aMCI ( 56 of 71 [ 79 % ] ) than in healthy controls ( 28 of 89 [ 31 % ] ) . The profile was associated with cognitive decline in patients with naMCI ( memory , MMSE , and daily function ) and in patients with aMCI ( MMSE and daily function ) . In patients with aMCI , a CSF AD profile was predictive of AD-type dementia ( OR 26.8 , 95 % CI 1.6 - 456.4 ) . INTERPRETATION AD is a common cause of SCI , naMCI , and aMCI and is associated with cognitive decline in patients with naMCI or aMCI . Patients with SCI might be in the early stages of AD , and cognitive decline might become apparent only after longer follow-up . FUNDING European Commission ; Ana Aslan International Foundation OBJECTIVE In the course of performing systematic review s on the prevalence of low back and neck pain , we required a tool to assess the risk of study bias . Our objectives were to ( 1 ) modify an existing checklist and ( 2 ) test the final tool for interrater agreement . STUDY DESIGN AND SETTING The final tool consists of 10 items addressing four domains of bias plus a summary risk of bias assessment . Two research ers tested the interrater agreement of the tool by independently assessing 54 r and omly selected studies .  Interrater agreement overall and for each individual item was assessed using the proportion of agreement and Kappa statistic . RESULTS Raters found the tool easy to use , and there was high interrater agreement : overall agreement was 91 % and the Kappa statistic was 0.82 ( 95 % confidence interval : 0.76 , 0.86 ) . Agreement was almost perfect for the individual items on the tool and moderate for the summary assessment . CONCLUSION We have addressed a research gap by modifying and testing a tool to assess risk of study bias . Further research may be useful for assessing the applicability of the tool across different conditions Our objectives were ( 1 ) to test the association between the report of subjective cognitive decline ( SCD ) and prospect i ve objective cognitive performance in high age individuals and ( 2 ) to study the course of longitudinal cognitive performance before and after the first report of SCD The objective is to evaluate the prognosis of subjective cognitive complaints ( SCC ) patients during 4-year follow-up . A prospect i ve study on 92 SCC patients investigating their cognitive , affective and behavioural aspects . SCC patients were classified as having no objective cognitive impairment ( NOCI ) , mild cognitive impairment ( MCI ) , or subtypes of MCI . Results : 43 patients were found to have NOCI and 49 MCI . During the follow-up , 45.5 % of NOCI patients remained unchanged , 13.9 % were diagnosed as MCI and only one progressed to dementia . Of the MCI patients , 32.3 % remained stable , 18.4 % became demented and 4 % reverted to NOCI . Visual attention , behavioural memory , long-term verbal memory , apathy and caregiver distress , provided independent predictors of progression to dementia BACKGROUND Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer 's disease .  Florbetaben ( ¹⁸F ) is a promising ¹⁸F-labelled amyloid-β-targeted PET tracer in clinical development . We aim ed to assess the sensitivity and specificity of florbetaben ( ¹⁸F ) PET in discriminating between patients with probable Alzheimer 's disease and elderly healthy controls . METHODS We did a multicentre , open-label , non-r and omised phase 2 study in 18 centres in Australia , Germany , Switzerl and , and the USA . Imaging with florbetaben ( ¹⁸F ) PET was done on patients with probable Alzheimer 's disease ( age 55 years or older , mini-mental state examination [ MMSE ] score=18 - 26 , clinical dementia rating [CDR]=0·5 - 2·0 ) and age-matched healthy controls ( MMSE ≥ 28 , CDR=0 ) . Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90 - 110 min post-injection . PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings , and quantitatively by use of pre-established brain volumes of interest to obtain st and ard uptake value ratios ( SUVRs ) , taking the cerebellar cortex as the reference region . This study is registered with Clinical Trials.gov , number NCT00750282 . FINDINGS 81 participants with probable Alzheimer 's disease and 69 healthy controls were assessed . Independent visual assessment of the PET scans showed a sensitivity of 80 % ( 95 % CI 71 - 89 ) and a specificity of 91 % ( 84 - 98 ) for discriminating participants with Alzheimer 's disease from healthy controls . The SUVRs in all neocortical grey-matter regions in participants with Alzheimer 's disease were significantly higher ( p < 0·0001 ) compared with the healthy controls , with the posterior cingulate being the best discriminator . Linear discriminant analysis of regional SUVRs yielded a sensitivity of 85 % and a specificity of 91 % . Regional SUVRs also correlated well with scores of cognitive impairment such as the MMSE and the word-list memory and word-list recall scores ( r -0·27 to -0·33 , p ≤ 0·021 ) . APOE ɛ4 was more common in participants with positive PET images compared with those with negative scans ( 65%vs 22 % [ p=0·027 ] in patients with Alzheimer 's disease ; 50%vs 16 % [ p = 0·074 ] in healthy controls ) . No safety concerns were noted . INTERPRETATION We provide verification of the efficacy , safety , and biological relevance of florbetaben ( ¹⁸F ) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia . FUNDING Bayer Schering Pharma AG BACKGROUND There is very limited data on the prevalence of abnormal cerebrospinal fluid ( CSF ) biomarkers of Alzheimer 's disease ( AD ) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline ( SCD ) . OBJECTIVE To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment ( MCI ) from the same cohort . METHODS We analyzed prospect i ve data from memory clinic patients of the German Competence Network Dementia cohort with a baseline diagnosis of SCD ( n = 82 ) or MCI ( n = 134 ) , distinguished by actuarial neuropsychological MCI criteria ( " Jak-Bondi criteria ") . Risk of clinical progression during 3-year follow-up was evaluated with Cox-Proportional-Hazard models . RESULTS Prevalence of abnormal values in CSF markers of tau-mediated neurodegeneration ( 67.8 % versus 46.3 % ) but not of amyloid deposition ( 40.3 % versus 35.4 % ) was significantly higher in MCI compared to SCD . The rate of incident AD dementia ( 26.1 % versus 12.2 % ) was also significantly higher in MCI . In SCD , additional 22 % progressed to MCI during follow-up . Combined amyloid/tau abnormality was the strongest predictor of clinical progression in both groups . CONCLUSION High prevalence of biomarker abnormality and clinical progression , together with the predictive value of CSF biomarkers , in memory clinic patients with SCD support the validity and usefulness of this condition as a " pre-MCI " at risk stage of AD 
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Conclusion Available data consistently show that risk of progression increases across the pre clinical AD stages , where Stage 3 shows a risk of progression comparable to MCI due to AD .
The possibility to define , in the clinical routine , a patient as “ pre-MCI due to AD ” could offer these subjects the opportunity to use disease-modifying drugs at best