***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: Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia . However , previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline . Herein , we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline . We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium . The Vantaa 85 + study examined 553 individuals ( 92 % of those eligible ) aged ≥85 years at baseline , 3 , 5 , 8 and 10 years .  Brain autopsy was performed in 52 % . Fixed and r and om-effects regression models were used to assess associations between ( i ) delirium and incident dementia and ( ii ) decline in Mini-Mental State Examination scores in the whole group . The relationship between dementia and common neuropathological markers ( Alzheimer-type , infa rcts and Lewy-body ) was modelled , stratified by history of delirium . Delirium increased the risk of incident dementia ( odds ratio 8.7 , 95 % confidence interval 2.1–35 ) . Delirium was also associated with worsening dementia severity ( odds ratio 3.1 , 95 % confidence interval 1.5–6.3 ) as well as deterioration in global function score ( odds ratio 2.8 , 95 % confidence interval 1.4–5.5 ) . In the whole study population , delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year ( 95 % confidence interval 0.11–1.89 ) than those with no history of delirium . In individuals with dementia and no history of delirium ( n = 232 ) , all pathologies were significantly associated with dementia . However , in individuals with delirium and dementia ( n = 58 ) , no relationship between dementia and these markers was found . For example , higher Braak stage was associated with dementia when no history of delirium ( odds ratio 2.0 , 95 % confidence interval 1.1–3.5 , P = 0.02 ) , but in those with a history of delirium , there was no significant relationship ( odds ratio 1.2 , 95 % confidence interval 0.2–6.7 , P = 0.85 ) . This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid , apolipoprotein ε status , presence of infa rcts , α-synucleinopathy and neuronal loss in substantia nigra . These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old . However , in this study , the relationship did not appear to be mediated by classical neuropathologies associated with dementia Background The inflammatory cell product neopterin is elevated in serum before and during delirium . This suggests a role for disordered cell-mediated immunity or oxidative stress . Cerebrospinal fluid ( CSF ) neopterin levels reflect brain neopterin levels more closely than serum levels . Here we hypothesized that CSF neopterin levels would be higher in delirium . Methods In this prospect i ve cohort study , 139 elderly patients with acute hip fracture were recruited in Oslo and Edinburgh . Delirium was diagnosed with the confusion assessment method performed daily pre-operatively and on the first 5 days post-operatively . Paired CSF and blood sample s were collected at the onset of spinal anaesthesia . Neopterin levels were measured using high-performance liquid chromatography . Results Sixty-four ( 46 % ) of 139 hip fracture patients developed delirium perioperatively . CSF neopterin levels were higher in delirium compared to controls ( median 29.6 vs 24.7 nmol/mL , p = 0.003 ) , with highest levels in patients who developed delirium post-operatively . Serum neopterin levels were also higher in delirium ( median 37.0 vs 27.1 nmol/mL , p = 0.003 ) . CSF neopterin remained significantly associated with delirium after controlling for relevant risk factors . Higher neopterin levels were associated with poorer outcomes ( death or new institutionalization ) 1 year after surgery ( p = 0.02 for CSF and p = 0.03 for serum ) . Conclusions This study is the first to examine neopterin in CSF from patients with delirium . Our findings suggest potential roles for activation of cell-mediated immune responses or oxidative stress in the delirium process . High levels of serum or CSF neopterin in hip fracture patients may also be useful in predicting poor outcomes Background To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and /or monoamine metabolites in cerebrospinal fluid ( CSF ) and serum . Methods In this prospect i ve cohort study , 77 patients admitted with an acute hip fracture to Oslo University Hospital , Norway , were studied . The concentrations of amino acids in CSF and serum were determined by high performance liquid chromatography . The patients were assessed daily for delirium by the  Confusion Assessment Method  ( pre-operatively and post-operative day 1–5 ( all ) or until discharge ( delirious patients ) ) . Pre-fracture dementia status was decided by an expert panel . Serum was collected pre-operatively and CSF immediately before spinal anesthesia . Results Fifty-three ( 71 % ) hip fracture patients developed delirium . In hip fracture patients without dementia ( n = 39 ) , those with delirium had significantly higher CSF levels of tryptophan ( 40 % higher ) , tyrosine ( 60 % higher ) , phenylalanine ( 59 % higher ) and the monoamine metabolite 5-hydroxyindoleacetate ( 23 % higher ) compared to those without delirium . The same amino acids were also higher in CSF in delirious patients with dementia ( n = 38 ) . The correlations between serum and CSF amino acid levels were poor . Conclusion Higher CSF levels of monoamine precursors in hip fracture patients with delirium suggest a higher monoaminergic activity in the central nervous system during delirium in this patient group BACKGROUND Delirium is a risk factor for dementia in cognitively intact patients . Whether an episode of delirium accelerates cognitive decline in patients with known dementia , is less explored . METHODS This is a prospect i ve follow-up study of 287 hip fracture patients with pre-fracture cognitive impairment . During the hospitalization , the patients were screened daily for delirium using the Confusion Assessment Method . Pre-fracture cognitive impairment was defined as a score of 3.44 or higher on the pre-fracture Informant Question naire on Cognitive Decline in the Elderly Short Form ( IQCODE-SF ) . At follow-up after 4 - 6 months , the caregivers rated cognitive changes emerging after the fracture using the IQCODE-SF , and the patients were tested with the  Mini Mental State Examination ( MMSE ) .  A sub-group of the patients had a pre-fracture MMSE score  which was used to calculate the yearly decline on the MMSE in patients with and without delirium . RESULTS 201 of the 287 patients developed delirium in the acute phase . In linear regression analysis , delirium was a significant and independent predictor of a more prominent cognitive decline at follow-up measured by the IQCODE-SF question naire ( p=0.002 ) . Among patients having a pre-fracture MMSE score , the patients developing delirium had a median ( IQR ) yearly decline of 2.4 points ( 1.1 - 3.9 ) , compared to 1.0 points ( 0 - 1.9 ) in the group without delirium ( p=0.001 , Mann-Whitney test ) . CONCLUSIONS Hip fracture patients with pre-fracture dementia run a higher risk of developing delirium . Delirium superimposed on dementia is a significant predictor of an accelerated further cognitive decline Importance Delirium is associated with  accelerated cognitive decline .  The pathologic substrates of this association are not yet known , that is , whether they are the same as those associated with dementia , are independent , or are interrelated . Objective To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia . Design , Setting , and Participants Harmonized data from 987 individual brain donors from 3 observational cohort studies with population -based sampling ( Vantaa 85 + , Cambridge City Over-75s Cohort , Cognitive Function and Ageing Study ) performed from January 1 , 1985 , through December 31 , 2011 , with a median follow-up of 5.2 years until death , were used in this study . Neuropathologic assessment s were performed with investigators masked to clinical data . Data analysis was performed from January 1 , 2012 , through December 31 , 2013 . Clinical characteristics of brain donors were not different from the rest of the cohort . Outcome ascertainment was complete given that the participants were brain donors . Exposures Delirium ( never vs ever ) and pathologic burden of neurofibrillary tangles , amyloid plaques , vascular lesions , and Lewy bodies . Effects modeled using r and om-effects linear regression and interactions between delirium and pathologic burden were assessed . Outcomes Change in Mini-Mental State Examination ( MMSE ) scores during the 6 years before death . Results There were 987 participants ( 290 from Vantaa 85 + , 241 from the Cambridge City Over-75s Cohort , and 456 from the Cognitive Function and Ageing Study ) with neuropathologic data ; mean ( SD ) age at death was 90 ( 6.4 ) years , including 682 women ( 69 % ) .  The mean MMSE score 6 years before death was 24.7 points . The 279 individuals with delirium ( 75 % women ) had worse initial scores ( −2.8 points ; 95 % CI , −4.5 to −1.0 ; P < .001 ) . Cognitive decline attributable to delirium was −0.37 MMSE points per year ( 95 % CI , −0.60 to −0.13 ; P < .001 ) . Decline attributable to the pathologic processes of dementia was −0.39 MMSE points per year ( 95 % CI , −0.57 to −0.22 ; P < .001 ) . However , the combination of delirium and the pathologic processes of dementia result ed in the greatest decline , in which the interaction contributed an additional −0.16 MMSE points per year ( 95 % CI , −0.29 to −0.03 ; P = .01 ) . The multiplicative nature of these variables result ed in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age- , sex- , and educational level – matched controls . Conclusions and Relevance Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself . These findings suggest that additional unmeasured pathologic processes specifically relate to delirium . Age-related cognitive decline has many contributors , and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia OBJECTIVES To examine whether anticholinergic activity ( AA ) in cerebrospinal fluid ( CSF ) and serum is associated with risk of delirium in individuals with hip fracture . DESIGN Prospect i ve cohort study . SETTING Two university hospitals in Oslo , Norway , and Edinburgh , UK . PARTICIPANTS Individuals admitted with acute hip fracture ( N = 151 ) . MEASUREMENTS Participants were assessed daily for delirium using the Confusion Assessment Method ( preoperatively and postoperative days 1 - 5 ( all ) or until discharge ( participants with delirium ) ) . Prefracture cognitive function was assessed using the Informant Question naire on Cognitive Decline in the Elderly ( IQCODE ) . Serum was collected preoperatively and CSF at the onset of spinal anesthesia .  AA in serum ( SAA ) and CSF sample s was determined according to a muscarinic radio receptor bioassay . The association between AA measures and delirium was evaluated using logistic multivariate analyses . RESULTS Fifty-two ( 54 % ) of the participants in Oslo and 20 ( 39 % ) in Edinburgh developed delirium . There was no statistically significant difference in AA between participants with and without delirium in Oslo ( serum : 7.02 vs 6.08 pmol/mL , P = .54 ; CSF : 0.39 vs 0.48 pmol/mL , P = .26 ) or in Edinburgh ( serum : 1.35 vs 1.62 pmol/mL , P = .76 ; CSF : 0.36 vs 0.31 pmol/mL , P = .93 ) . Nor was there any difference in SAA ( Oslo , P = .74 ; Edinburgh , P = .51 ) or CSF AA ( Oslo , P = .21 ; Edinburgh , P = .93 ) when participants were subdivided into prevalent , incident , subsyndromal , and never 
    Output:
    
Nevertheless , the overall interpretation of the literature supports the vulnerable brain concept , that is , that biomarker evidence of , for example , Alzheimer 's disease pathology and /or neuroinflammation , is associated with delirium