The effect of regional transmural agreements on the information transfer of frail older patients.

INTRODUCTION: Frail older patients are at risk for many complications when admitted to the hospital. Multidisciplinary regional transmural agreements (RTA) in which guidelines were set concerning the information transfer of frail older patients might improve outcomes. We aim to investigate the effect of implementation of the RTA on the completeness of the information transfer of frail older patients when admitted to and discharged from the hospital. METHODS: This is a retrospective cohort study in which we collected data from 400 randomly selected hospitalized frail older patients (70+) before the implementation of the RTA, January through March 2021, and after, October through December 2021. The cohort was split up into four groups, which determined what correspondence would be checked (referral letter by General Practitioner (GP) and three groups of 'hospital letters': ED letter upon admittance, clinical discharge letter to the elderly care physician and clinical discharge letter to the GP. We assessed for mention of frailty, a medication list and mention of resuscitation orders. RESULTS: In the period before implementation the mean age of patients was 82.6 years (SD 7.4) and 101 were female (50.5%), after implementation mean age was 82.3 (SD 6.9) and 112 were female (56.0%). Frailty was mentioned in hospital letters in 12.7% before and 15.3% after implementation (p = 0.09). More GP referral letters were present after implementation (32.0% vs. 54.0%, p = 0.03), however frailty was mentioned only in 12.5% before and 7.4% after (p = 0.58). There was a good handover of medication lists from the hospital (89.3% before, 94% after, p = 0.20) and even better from the GP (93.8% before, 100% after, p = 0.19). Resuscitation orders were mentioned in 59.3% of letters from the hospital before implementation and 57.3% after (p = 0.77), which is higher than in the referral letters (18.8% before and 22.2% after (p = 0.91). DISCUSSION: The implementation of RTA improved the number of GP referral letters present; however, it did not lead to other significant improvements in communication between the hospital and the GP's. Frailty and resuscitation orders are still frequently not mentioned in the reports. After a successful reimplementation, the improvements of outcomes could be investigated.

Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort.

OBJECTIVE: To determine how amyloid ß 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) levels in CSF behave in a large cohort of patients with different types of dementia. METHODS: Baseline CSF was collected from 512 patients with Alzheimer disease (AD) and 272 patients with other types of dementia (OD), 135 patients with a psychiatric disorder (PSY), and 275 patients with subjective memory complaints (SMC). Aß42, t-tau, and p-tau (at amino acid 181) were measured in CSF by ELISA. Autopsy was obtained in a subgroup of 17 patients. RESULTS: A correct classification of patients with AD (92%) and patients with OD (66%) was accomplished when CSF Aß42 and p-tau were combined. Patients with progressive supranuclear palsy had normal CSF biomarker values in 90%. Patients with Creutzfeldt-Jakob disease demonstrated an extremely high CSF t-tau at a relatively normal CSF p-tau. CSF AD biomarker profile was seen in 47% of patients with dementia with Lewy bodies (DLB), 38% in corticobasal degeneration (CBD), and almost 30% in frontotemporal lobar degeneration (FTLD) and vascular dementia (VaD). PSY and SMC patients had normal CSF biomarkers in 91% and 88%. Older patients are more likely to have a CSF AD profile. Concordance between clinical and neuropathologic diagnosis was 85%. CSF markers reflected neuropathology in 94%. CONCLUSION: CSF Aß42, t-tau, and p-tau are useful in differential dementia diagnosis. However, in DLB, FTLD, VaD, and CBD, a substantial group exhibit a CSF AD biomarker profile, which requires more autopsy confirmation in the future.

Multicenter assessment of CSF-phosphorylated tau for the prediction of conversion of MCI.

BACKGROUND: The measurement of hyperphosphorylated tau (p-tau) in CSF has been proposed as a biomarker candidate for the prediction of Alzheimer disease (AD) in patients with mild cognitive impairment (MCI). However, a standard quantitative criterion of p-tau has not been evaluated. OBJECTIVE: To assess in a multicenter study the predictive accuracy of an a priori defined criterion of tau phosphorylated at threonine 231 (p-tau(231)) for the prediction of conversion from MCI to AD during a short-term observation interval. METHODS: The study included 43 MCI converters, 45 stable MCI (average follow-up interval = 1.5 years), and 57 healthy controls (at baseline only). Subjects were recruited at four international expert sites in a retrospective study design. Cox regression models stratified according to center were used to predict conversion status. Bootstrapped 95% CIs of classification accuracy were computed. RESULTS: Levels of p-tau(231) were a significant predictor of conversion (B = 0.026, p = 0.001), independent of age, gender, Mini-Mental State Examination, and ApoE genotype. For an a priori-defined cutoff point (27.32 pg/mL), sensitivity ranged between 66.7 and 100% and specificity between 66.7 and 77.8% among centers. The bootstrapped mean percentage of correctly classified cases was 79.95% (95% CI = 79.9 to 80.00%). Post hoc defined cutoff values yielded a mean bootstrapped classification accuracy of 80.45% (95% CI = 80.24 to 80.76%). CONCLUSIONS: An a priori defined cutoff value of p-tau(231) yields relatively stable results across centers, suggesting a good feasibility of a standard criterion of p-tau(231) for the prediction of Alzheimer disease.

Longitudinal changes of CSF biomarkers in memory clinic patients.

OBJECTIVE: In Alzheimer disease (AD), longitudinal changes of beta-amyloid(1-42) (Abeta(1-42)), tau, and phosphorylated tau at threonine 181 (ptau-181) in CSF have been reported in small studies only. We evaluated the natural course of CSF biomarkers in patients with AD, subjective complaints, and mild cognitive impairment (MCI). METHODS: One hundred five patients (50 AD, 38 MCI, 17 subjective complaints) underwent two lumbar punctures, with a mean interval of 21 +/- 9 months. CSF levels of Abeta(1-42), tau, and ptau-181 were measured. RESULTS: CSF Abeta(1-42) and tau levels showed main effects for both diagnosis and time (all p < 0.05), with average increases of 47 +/- 72 and 49 +/- 143 pg/mL. The interaction terms were not significant, which implies a similar time effect for all diagnostic groups. CSF ptau-181 levels showed a main effect for diagnosis (p = 0.01) but not for time (p = 0.27, increase of 1.0 +/- 12 pg/mL). CONCLUSION: Levels of CSF beta-amyloid(1-42) and tau but not phosphorylated tau at threonine 181 increased over time in this memory clinic patient cohort with comparable change in all diagnostic groups. The cross-sectional difference between diagnostic groups, however, exceeded by far the longitudinal changes within individuals, suggesting that these biomarkers are not sensitive as markers of disease progression.

Amyloid beta(1-42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease.

OBJECTIVE: To determine the diagnostic value of CSF amyloid beta(1-42) (Abeta42), CSF total tau, and CSF tau phosphorylated at threonine-181 (Ptau-181) in early-onset Alzheimer disease (EAD) vs frontotemporal lobar degeneration (FTLD). METHODS: Levels of Abeta42, total tau, and Ptau-181 in CSF were measured using commercially available ELISA in 47 EAD patients, 28 FTLD patients, and 21 nondemented control subjects. RESULTS: CSF Abeta42 was significantly lower and CSF total tau and CSF Ptau-181 significantly higher in EAD patients than FTLD patients and control subjects. There was an increase in diagnostic accuracy for CSF Ptau-181 vs CSF total tau (p = 0.067). Combining low CSF Abeta42 and high CSF Ptau-181 allowed EAD patients to be distinguished from FTLD patients with a sensitivity of 72% and a specificity of 93%. Logistic regression analysis with CSF Abeta42 and CSF Ptau-181 as independent continuous variables resulted in correct classification of 46 of 47 (98%) EAD patients and 23 of 28 (82%) FTLD patients. The diagnostic accuracy for EAD was independent of gender, disease duration, and disease severity. CONCLUSION: The combination of CSF Abeta42 and CSF Ptau-181 may help in differentiating EAD from FTLD.

Activation of the contact system of coagulation does not contribute to the hemostatic imbalance in hypertriglyceridemia.

In vitro, triglyceride-rich lipoproteins may act as a surface to initiate the contact system of coagulation. Therefore, we studied the activation of factor XII (FXII), prekallikrein, and FXI and the generation of thrombin in 52 hypertriglyceridemic patients before and after 12 weeks of triglyceride-lowering treatment with gemfibrozil or n-3 polyunsaturated fatty acids. Thrombin generation was assessed by measuring the levels of prothrombin fragment F1+2 and thrombin-antithrombin (TAT) complexes. Contact activation was assessed by measuring FXIIa, kallikrein, and FXIa in complex with their major inhibitor, C1 inhibitor, and FXIa was also determined as part of a complex with alpha(1)-antitrypsin. Triglyceride and cholesterol levels decreased equally in both treatment groups. In the gemfibrozil group, there was a significant decrease in F1+2, while TAT complexes did not change. FXIIa- and kallikrein-C1 inhibitor complexes were elevated in 13% and 9% of the patients before treatment, respectively, and no changes were observed on triglyceride-lowering therapy. Also, no significant changes in regard to FXIa-C1 inhibitor and FXIa-alpha(1)-antitrypsin complexes were seen. FXIa-alpha(1)-antitrypsin complexes were present in 70% of the patients before therapy and were positively correlated with the level of TAT complexes. In conclusion, we did not detect an effect on activation markers of the contact coagulation system in hypertriglyceridemic patients after triglyceride-lowering therapy. Therefore, contact activation is not likely to contribute to the hypercoagulability seen in these patients.