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Beta-secretase (BACE1) is a key enzyme in the formation of amyloid-β; its activity/concentration is increased in brain and cerebrospinal fluid of patients with late-onset Alzheimer's disease (LOAD). Since BACE1 was found also in blood, we evaluated its potential as peripheral biomarker. To this aim, serum BACE1 activity was assessed in 115 subjects with LOAD and 151 controls. We found that BACE1 changed across groups (p < 0.001) with a 25% increase in LOAD versus controls. High levels of BACE1 (IV quartile) were independently associated with the diagnosis of LOAD (OR 2.8; 1.4-5.7). Diagnostic accuracy was 76% for LOAD. Our data suggest that increased BACE1 activity in serum may represent a potential biomarker for LOAD. Additional studies are needed to confirm the usefulness of BACE1, alone or in combination with other markers, in discriminating patients and predicting LOAD onset and progression.

The decline in basic and instrumental activities of daily living (BADLs and IADLs, respectively) is a well-established clinical hallmark of dementia. Growing evidence has shown that systemic subclinical inflammation may be related to functional impairment. We evaluated the possible association between low-grade systemic inflammation and functional disability in older individuals affected by dementia. We explored the association between high-sensitivity C-reactive protein (hs-CRP) levels and BADLs/IADLs in older individuals affected by late onset Alzheimer's disease (LOAD; n 110), "mixed" dementia (n 135), or mild cognitive impairment (MCI; n 258), and compared them with 75 normal Controls. Independent of age, gender, comorbidity, and other potential confounders, higher hs-CRP was significantly associated with poorer BADLs (loss ≥ 1 function) in people with LOAD (odds ratio [OR] 3.14, 95% confidence interval [CI], 1.33-7.33) and mixed dementia (OR 2.48, 95%CI 1.12-5.55), but not in those with MCI (OR 1.38, 95%CI 0.83-2.45) or Controls (OR 2.98, 95%CI 0.54-10.10). No association emerged between hs-CRP and IADLs in any of the sub-group. Our data suggest that systemic low-grade inflammation may contribute to functional disability in older patients with dementia.

Objective: Delirium is a frequent clinical complication in geriatric patients admitted to the hospital, because of the simultaneous presence and synergistic effect of predisposing and precipitating factors. Also anaemia is a common concern in geriatric population. The aim of this study was to investigate the association between anaemia (precipitating factor) and delirium in a sample of Italian older hospitalized patients with different degree of cognitive impairment (predisposing factor)., Design, Setting, Participants: Cross-sectional analysis of 1069 participants enrolled in the CRIME study, with assessment of hemoglobin levels at hospital admission., Measurements: Delirium was assessed using DSM-IV criteria, whereas cognitive status was categorized as dementia, cognitive impairment or normal, according to clinical history, specific treatment and MMSE score. Anaemia was defined according to sex-specific WHO criteria. The association of hemoglobin levels and delirium was investigated with multivariable logistic regression models., Results: Mean age of study participants was 81.4±7.2 years, 52.2% had prevalent anaemia, 6.1% had delirium. According to cognitive status 20.8% had dementia and 40.9% had cognitive impairment. Overall there was no association between anaemia and delirium. However, among patients with cognitive impairment (MMSE <24, no dementia) anaemia was significantly associated with the likelihood of delirium (p<0.006). Multivariate logistic regression analysis, adjusted for potential confounders, showed in these patients a graded increased risk of delirium according to anaemia severity with an almost six-fold increased risk of delirium in moderate-severe anaemia (OR 5.95, 95% CI:1.15-30.73)., Conclusion: In older patients with cognitive impairment moderate-severe anaemia is independently associated with the likelihood of delirium. Further studies should investigate if anaemia correction would translate in delirium risk reduction., Competing Interests: G. Brombo, L. Bianchi, E. Savino, S. Magon, A. Cherubini, A. Corsonello, G. Zuliani, G. Onder, and S. Volpato declare no conflict of interest.