Instantons and the Path to Intermittency in Turbulent Flows.

Processes leading to anomalous fluctuations in turbulent flows, referred to as intermittency, are still challenging. We consider cascade trajectories through scales as realizations of a stochastic Langevin process for which multiplicative noise is an intrinsic feature of the turbulent state. The trajectories are conditioned on their entropy exchange. Such selected trajectories concentrate around an optimal path, called instanton, which is the minimum of an effective action. The action is derived from the Langevin equation, estimated from measured data. In particular instantons with negative entropy pinpoint the trajectories responsible for the emergence of non-Gaussian statistics at small scales.

Five-year audit of adherence to an anaesthesia pre-induction checklist.

Although patient safety related to airway management has improved substantially over the last few decades, life-threatening events still occur. Technical skills, clinical expertise and human factors contribute to successful airway management. Checklists aim to improve safety by providing a structured approach to equipment, personnel and decision-making. This audit investigates adherence to our institution's airway checklist from 1 June 2016 to 31 May 2021. Inclusion criteria were procedures requiring airway management and we excluded all procedures performed solely under regional anaesthesia, sedation without airway management or paediatric and cardiovascular surgery. The primary outcome was the proportion of wholly performed pre-induction checklists. Secondary outcomes were the pattern of adherence over the 5 years well as details of airway management, including: airway management difficulties; time and location of induction; anaesthesia teams in operating theatres (including teams for different surgical specialities); non-operating theatre and emergency procedures; type of anaesthesia (general or combined); and urgency of the procedure. In total, 95,946 procedures were included. In 57.3%, anaesthesia pre-induction checklists were completed. Over the 5 years after implementation, adherence improved from 48.3% to 66.7% (p < 0.001). Anticipated and unanticipated airway management difficulties (e.g. facemask ventilation, supraglottic airway device or intubation) defined by the handling anaesthetist were encountered in 4.2% of all procedures. Completion of the checklist differed depending on the time of day (61.3% during the day vs. 35.0% during the night, p < 0.001). Completion also differed depending on location (66.8% in operating theatres vs. 41.0% for non-operating theatre anaesthesia, p < 0.001) and urgency of procedure (65.4% in non-emergencies vs. 35.4% in emergencies, p < 0.001). A mixed-effect model indicated that urgency of procedure is a strong predictor for adherence, with emergency cases having lower adherence (OR 0.58, 95%CI 0.49-0.68, p < 0.001). In conclusion, over 5 years, a significant increase in adherence to an anaesthesia pre-induction checklist was found, and areas for further improvement (e.g. emergencies, non-operating room procedures, night-time procedures) were identified.

Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients.

PURPOSE: To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naïve patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. METHODS: TTV DNA was quantified in plasma samples of 301 therapy-naïve HIV-1-infected patients and correlated to CD4+ cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4+ cell count and to the extent of CD4+ T-cell increase within the first year of cART. RESULTS: TTV DNA was detectable in 96% of the patients' plasma samples with a median TTV plasma concentration of 5.37 log10 cop/ml. The baseline CD4+ cell count was negatively correlated with TTV plasma concentration (p = 0.003). In patients with a CD4+ cell recovery < 50 cells/µl, the median TTV plasma concentration was significantly higher compared to patients with a CD4+ cell recovery of > 200 CD4+ cells/µl (5.68 log10 cop/ml versus 4.99 log10 cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4+ cell count were significantly correlated to CD4+ cell recovery (p = 0.004). For all other parameters considered, no significant correlation for CD4+ cell recovery was found. CONCLUSION: Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4+ cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4+ cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency.

Monocyte-derived dendritic cells display a highly activated phenotype and altered function in patients with familial Mediterranean fever.

Dendritic cells (DCs) are sentinels of the immune system that bridge innate and adaptive immunity. By capturing antigens in peripheral tissue, processing and presenting them with concurrent expression of co-stimulatory molecules and cytokine secretion they control and modulate immune reactions. Through pattern recognition receptors, DCs sense molecules that are associated with infection or tissue damage, frequently resulting in the formation of inflammasomes upon intracellular stimulation. The inherited autoinflammatory familial Mediterranean fever (FMF) is associated with deregulated activity of the pyrin inflammasome leading to acute inflammatory episodes. However, differentiation and function of DCs in this disease are as yet unclear. Therefore, we first determined DC subpopulation frequency in peripheral blood of a cohort of FMF patients. Joint evaluation without classification according to specific patient characteristics, such as mutational status, did not disclose significant differences compared to healthy controls. For the further examination of phenotype and function, we used immature and mature monocyte-derived DCs (imMo-DCs, mMo-DCs) that were generated in vitro from FMF patients. Immunophenotypical analysis of imMo-DCs revealed a significantly elevated expression of CD83, CD86 and human leukocyte antigen D-related (HLA-DR) as well as a significant down-regulation of CD206, CD209 and glycoprotein NMB (GPNMB) in our FMF patient group. Furthermore, FMF imMo-DCs presented a significantly higher capacity to migrate and to stimulate the proliferation of unmatched allogeneic T cells. Finally, the transition towards a more mature, and therefore activated, phenotype was additionally reinforced by the fact that peripheral blood DC populations in FMF patients exhibited significantly increased expression of the co-stimulatory molecule CD86.

Cardiac chamber volumes and left ventricular mass in people living with HIV and matched uninfected controls.

OBJECTIVES: People living with HIV (PLWH) have increased risk of cardiovascular diseases compared with uninfected populations. We assessed structural cardiac abnormalities and their associated risk factors in well-treated PLWH and uninfected controls using multidetector computed tomography (MDCT). METHODS: People living with HIV and age- and sex-matched uninfected controls underwent MDCT to determine left atrial volume (LAV), left ventricular diastolic volume (LVDV), right ventricular diastolic volume (RVDV) and left ventricular mass (LVM). All outcomes were indexed to body surface area (BSA) (LAVi, LVDVi, RVDVi and LVMi). RESULTS: A total of 592 PLWH and 1184 uninfected controls were included in the study. PLWH had smaller mean (SD) LAVi [40 (8) vs. 41 (9) mL/m2 ; P = 0.002] and LVDVi [61 (13) vs. 65 (14) mL/m2 ; P < 0.001] but larger RVDVi [89 (18) vs. 86 (17) mL/m2 ; P < 0.001] than uninfected controls. HIV was independently associated with 7 mL (95% CI: -10 to -3) smaller LVDV, and with 12 mL (95% CI: 8-16) larger RVDV, and 4 g (95% CI: 1-6) larger LVM after adjustment for cardiovascular risk factors and BSA. Large RVDV in PLWH was not associated with obstructive lung function. CONCLUSIONS: HIV was independently associated with smaller LVDV and larger RVDV and LVM. Alterations in cardiac chamber volumes in PLWH were mainly minor. The clinical impact of these findings is uncertain, but it seems unlikely that alterations in cardiac chamber volumes explain the increased burden of cardiovascular disease previously observed in PLWH.

Indicators of active disease and steroid dependency in patients with inflammatory bowel diseases not treated with biologics in a German real-world-setting.

BACKGROUND AND AIMS: While a minority of inflammatory bowel disease (IBD) patients receives biologics in Germany, little is known about therapeutic needs of patients receiving non-biologic therapies. This study aimed to identify indicators of active disease/steroid dependency in patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) treated with conventional therapies and to describe health care resource use (HCRU)/cost. METHODS: CD/UC patients treated with immunosuppressants (IS) and/or systemic or locally acting oral corticosteroids (CS) were identified in German claims data (2013-2017) and followed for 12 months post-therapy start. Indicators of active disease/steroid dependency during follow-up period were (i) ≥ 2 prescriptions of CS (sensitivity ≥ 4) or (ii) ≥ 1 IBD-related surgery or (iii) > 7 days IBD-related hospitalization(s). RESULTS: Of 9871 included IBD patients (5170 CD, 4701 UC), 25.7%/19.9% (CD/UC) received ≥ 2 prescriptions of CS (sensitivity, 17.4%/15.7%) (i), 3.2% experienced IBD-related surgeries (ii), and 2.5% > 7 days of hospitalizations (iii). Altogether, 44.4% had indicators of active disease/steroid dependency (sensitivity, 23.9%). Among patients with active disease/steroid dependency, 78.0% received CS monotherapy at baseline. Of these, 89.6% received a CS monotherapy in the follow-up period, too. Proportionally, fewer patients with CS monotherapy (57.4%) than IS therapy (91.0%) visited a specialist. HCRU/cost per patient year was significantly higher in patients with than without active disease/steroid dependency. CONCLUSIONS: A substantial percentage of biologic-naïve IBD patients suffers from active disease/steroid dependency. The majority receives a monotherapy with systemic CS. Referral to gastroenterologists for treatment optimization is recommended, also because active disease/steroid dependency is associated with increased HCRU/cost.

Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration - a pilot study in vitro.

BACKGROUND: The spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field. METHODS: In this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds' morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 µm, 300 µm, 375 µm, 450 µm and 500 µm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63. RESULTS: All scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 µm and 500 µm, a preferred box size for initial osteoblast attachment could not be found. CONCLUSIONS: These well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.

Plasma levels of ß2-microglobulin are associated with atherosclerosis in patients with systemic lupus erythematosus: a cross-sectional cohort study.

Objective The objective of this paper is to examine the association between plasma levels of ß2-microglobulin (ß2MG), a protein previously associated with atherosclerosis, and the presence of carotid plaque (CP) or coronary artery calcium (CAC) in a cross-sectional cohort study of patients with systemic lupus erythematosus (SLE). Methods Patients with SLE were enrolled between June 2013 and May 2014. The presence of CP and CAC was assessed with ultrasonography and computed tomography scan, respectively. The presence of CP or CAC in the SLE patients was analyzed with respect to plasma levels of ß2MG and renal function expressed as the estimated glomerular filtration rate (eGFR). Results The study cohort consisted of 147 patients, 89% women and 95% Caucasians. The median age was 46 (range: 21-75) years with a median disease duration of 14 years. CP and CAC was observed in 29 (20%) and 57 (39%) of patients, respectively. CP or CAC was seen in 62 (42%) patients and was associated with the highest quartile of plasma ß2MG in patients with eGFR ≥ 90 ml/min/1.73 m2; OR = 18 (95% CI: 1.7-181). ß2MG adjusted for eGFR was also associated with presence of CP or CAC in the total cohort. The exclusion of 25 patients with a prior history of cardiovascular disease did not change the observed associations. Conclusion In this study, we found significant associations between imaging markers of atherosclerosis and high plasma levels of plasma ß2MG. These data suggest that ß2MG is a candidate for further study as a biomarker for atherosclerosis in SLE.

[Suicidal tendencies in adolescence : Dysfunctional familiar communication as risk factor]. / Suizidalität in der Adoleszenz : Dysfunktionale familiäre Kommunikation als Risikofaktor.

BACKGROUND: Suicide is one of the four most common causes of death in adolescence worldwide. Although it is well known that suicidal people often have insufficient communication strategies, the importance of family communication for adolescent suicidality has not yet been sufficiently explored. OBJECTIVE: The aim of this study was to provide a systematic review of family communication as a risk factor for adolescent suicidal tendencies and to develop treatment recommendations. METHODS: In this study a systematic literature search was conducted in PubMed, Embase, CENTRAL and PsychINFO. The methodological quality of the studies was evaluated and a summary prepared. RESULT: A total of 195 studies were extracted and screened for their suitability. Of these studies, 7 which examined a total of 13,107 adolescents aged 11-22 years were included in this review and critically evaluated. Of the studies evaluated six found a correlative relationship between dysfunctional parent-child communication and adolescent suicidality. Communication with the mother appears to be more essential. CONCLUSION: The results of this literature search indicate that functional communication with parents seems to be protective for suicidal adolescents. From this, recommendations can be derived for preventive measures in families with adolescents who are otherwise at increased risk of suicide. Longitudinal study designs are needed to conclusively answer the research question.

[Informal care for dementia according to type of service]. / Informelle Pflege bei Demenz nach Leistungsarten.

BACKGROUND: Dementia is a major challenge for society and its impact will grow in the future. Informal care is an essential part of dementia care. Previous studies considered informal care as a whole and not by its components. OBJECTIVE: We aimed to assess the degree of association between specific informal care services and dementia. MATERIAL AND METHODS: This analysis is based on data from the seventh wave of the AgeCoDe/AgeQualiDe study. Dementia was diagnosed based on the DSM-IV criteria. Severity of dementia was assessed and categorized by means of the Clinical Dementia Rating and eight individual informal care services were considered. Logistic regression models were used to assess associations. RESULTS: Of the 864 participants 18% suffered from dementia (very mild: 4%; mild: 6%; moderate: 5%; severe: 3%). All informal care services were significantly associated with dementia, with an emphasis on "supervision", "regulation of financial matters" and "assistance in the intake of medication". Considering different degrees of dementia severity, similar results arose from the analyses. All three aforementioned services showed a pronounced association with all degrees of dementia severity, except for supervision and very mild dementia. CONCLUSION: The provision of all types of informal care services is associated with dementia. The association is pronounced for services that can be more easily integrated into the daily routines of the informal caregiver. Policy makers who plan to integrate informal care into the general care arrangements for dementia should consider this.

[Longitudinal Predictors of the Need for Care]. / Einflussfaktoren auf die Pflegebedürftigkeit im Längsschnitt.

Background: Little is known about the longitudinal predictors of the need for care in old age. However, the knowledge of these factors is important for developing strategies for prevention or delay the need for care. Thus, we aimed at investigating the factors affecting the need for care in old age. Methods: In this population-based prospective cohort study (AgeCoDe, with n=3 217 individuals aged 75 years and above at baseline), the need for care was observed over 4.5 years. The need for care was quantified by the care level defined by the German Law (§ 15 SGB XI). Longitudinal predictors (sociodemographic variables, impairment in mobility/hearing/vision, dementia and depression) of the need for care were examined by using Random Effects Logit regressions. Results: Longitudinal regression analysis revealed that the probability of the need for care significantly increased with the occurrence of dementia (OR: 48.2), mobility impairments (aggravated walking, OR: 26.4; disability of walking, OR: 747.9) and age (e. g. 90 years and above vs.<80 years, OR: 32.3). The influence of family status, living conditions, visual impairment and depression on need for care was markedly smaller, and the effect of hearing impairments did not achieve statistical significance. Conclusion: In order to prevent or delay the need for care in old age, treatments should aim at preserving mobility and cognition. Due to demographic ageing, developing such programs is of major importance for health policy.

(1) H MRS in the human spinal cord at 7 T using a dielectric waveguide transmitter, RF shimming and a high density receive array.

Multimodal MRI is the state of the art method for clinical diagnostics and therapy monitoring of the spinal cord, with MRS being an emerging modality that has the potential to detect relevant changes of the spinal cord tissue at an earlier stage and to enhance specificity. Methodological challenges related to the small dimensions and deep location of the human spinal cord inside the human body, field fluctuations due to respiratory motion, susceptibility differences to adjacent tissue such as vertebras and pulsatile flow of the cerebrospinal fluid hinder the clinical application of (1) H MRS to the human spinal cord. Complementary to previous studies that partly addressed these problems, this work aims at enhancing the signal-to-noise ratio (SNR) of (1) H MRS in the human spinal cord. To this end a flexible tight fit high density receiver array and ultra-high field strength (7 T) were combined. A dielectric waveguide and dipole antenna transmission coil allowed for dual channel RF shimming, focusing the RF field in the spinal cord, and an inner-volume saturated semi-LASER sequence was used for robust localization in the presence of B1 (+) inhomogeneity. Herein we report the first 7 T spinal cord (1) H MR spectra, which were obtained in seven independent measurements of 128 averages each in three healthy volunteers. The spectra exhibit high quality (full width at half maximum 0.09 ppm, SNR 7.6) and absence of artifacts and allow for reliable quantification of N-acetyl aspartate (NAA) (NAA/Cr (creatine) 1.31 ± 0.20; Cramér-Rao lower bound (CRLB) 5), total choline containing compounds (Cho) (Cho/Cr 0.32 ± 0.07; CRLB 7), Cr (CRLB 5) and myo-inositol (mI) (mI/Cr 1.08 ± 0.22; CRLB 6) in 7.5 min in the human cervical spinal cord. Thus metabolic information from the spinal cord can be obtained in clinically feasible scan times at 7 T, and its benefit for clinical decision making in spinal cord disorders will be investigated in the future using the presented methodology. Copyright © 2016 John Wiley & Sons, Ltd.

[Hospital financing in 2016. Relevant changes for rheumatology]. / Krankenhausfinanzierung 2016. Relevantes für die internistische Rheumatologie.

Hospital financing 2016 will be influenced by the prospects of the approaching considerable changes. It is assumed that the following years will lead to a considerable reallocation of financial resources between hospitals. While not directly targeted by new regulations, reallocations always also affect specialties like rheumatology. Compared to the alterations in the legislative framework the financial effects of the yearly adaptation of the German diagnosis-related groups system are subordinate. Only by comprehensive consideration of current and expected changes a forward-looking and sustainable strategy can be developed. The following article presents the relevant changes and discusses the consequences for hospitals specialized in rheumatology.

Mortality in incident dementia - results from the German Study on Aging, Cognition, and Dementia in Primary Care Patients.

OBJECTIVE: Dementia is known to increase mortality, but the relative loss of life years and contributing factors are not well established. Thus, we aimed to investigate mortality in incident dementia from disease onset. METHOD: Data were derived from the prospective longitudinal German AgeCoDe study. We used proportional hazards models to assess the impact of sociodemographic and health characteristics on mortality after dementia onset, Kaplan-Meier method for median survival times. RESULTS: Of 3214 subjects at risk, 523 (16.3%) developed incident dementia during a 9-year follow-up period. Median survival time after onset was 3.2 years (95% CI = 2.8-3.7) at a mean age of 85.0 (SD = 4.0) years (≥2.6 life years lost compared with the general German population). Survival was shorter in older age, males other dementias than Alzheimer's, and in the absence of subjective memory complaints (SMC). CONCLUSION: Our findings emphasize that dementia substantially shortens life expectancy. Future studies should further investigate the potential impact of SMC on mortality in dementia.

[Hindfoot fusion for Charcot osteoarthropathy with a curved retrograde nail]. / Rückfußarthrodese beim Charcot-Fuß mit retrogradem Nagel.

BACKGROUND: Charcot osteoarthropathy of the hindfoot with considerable dislocation and instability represents a therapeutic dilemma. The treatment goal is a plantigrade, stable foot that is free of infection and ulceration with the ability to ambulate in special footwear. MATERIALS AND METHODS: Over a period of 6 years, we performed 23 hindfoot fusions in 21 patients with manifest Charcot arthropathy with the help of a curved retrograde nail (HAN). All patients suffered from insulin-dependent diabetes mellitus with polyneuropathy; 12 patients had additional peripheral vasculopathy. An average of 3.5 previous surgeries had been performed prior to hindfoot fusion. RESULTS: Complete tibiotalocalcaneal fusion was obtained in 16 of 21 patients (76 %). Of these 21 patients, 18 (86 %) were followed clinically and radiologically for an average of 2 years. Overall, 16 patients (89 %) reported a substantial subjective improvement compared to the preoperative state. Hardware failure occurred in 7 cases (30 %) that could be brought to consolidation with exchange of the locking bolts or the complete nail. In 5 cases (22 %), a postoperative hematoma had to be removed and in 8 cases (35 %) wound edge necrosis was treated with local wound care. In 2 cases (9 %), a secondary or reactivated osteitis occurred that finally required below knee amputation. CONCLUSION: Tibiotalocalcaneal fusion with a curved retrograde intramedullary nail (HAN) is an effective treatment option in highly unstable and deforming Charcot osteoarthropathy of the hindfoot. It is an alternative to external or other internal fixation methods and helps to avoid below knee amputation in more than 90 % of cases.

[Hospital financing in 2015. Relevant changes for rheumatology]. / Krankenhausfinanzierung 2015. Relevantes für die internistische Rheumatologie.

The announced major reforms will most probably not have an impact on hospital financing before 2016. Nevertheless, the numerous minor changes in the legislative framework and the new version of the German diagnosis-related groups (G-DRG) system can be important for hospitals specialized in rheumatology. The following article presents the relevant changes and discusses the consequences for hospitals specialized in rheumatology.

ABO-compatible retransplantation after ABO-incompatible infant heart transplantation: absence of donor specific isohemagglutinins.

Implementation of ABO-incompatible (ABOi) pediatric heart transplantation has contributed to significant reduction in the mortality of infants on the waiting list, without increasing the risk of rejection. This has been attributed to the immature and therefore not fully competent immune system in this population group, which results in lower production of isohemagglutinins compared to older children and adults. Serial evaluations of isohemagglutinin titers in infants revealed cases with absence of donor specific anti-blood group antibodies. However, it is currently unknown whether continuous exposure to donor antigens is necessary to prevent formation of donor specific isohemagglutinins (DSI) in recipients. We are reporting a case of an infant who underwent ABOi heart transplantation, with no evidence of DSI even 4 years after ABO-compatible retransplantation. Hence, temporary exposure to donor antigens in infants may contribute to permanent absence of donor specific anti-blood group antibodies, suggesting the possibility of induced permanent B cell tolerance.

Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: analysis of gene-environment interaction for the risk of dementia and Alzheimer's disease dementia.

BACKGROUND: As physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimer's disease (AD) dementia, we tested for such a gene-environment interaction in a sample of general practice patients aged ⩾75 years. METHOD: Data were derived from follow-up waves I-IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan-Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene-environment interaction by calculating three indices of additive interaction. RESULTS: Among the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk. CONCLUSIONS: Physical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.

A hierarchy of predictors for dementia-free survival in old-age: results of the AgeCoDe study.

OBJECTIVE: Progression from cognitive impairment (CI) to dementia is predicted by several factors, but their relative importance and interaction are unclear. METHOD: We investigated numerous such factors in the AgeCoDe study, a longitudinal study of general practice patients aged 75+. We used recursive partitioning analysis (RPA) to identify hierarchical patterns of baseline covariates that predicted dementia-free survival. RESULTS: Among 784 non-demented patients with CI, 157 (20.0%) developed dementia over a follow-up interval of 4.5 years. RPA showed that more severe cognitive compromise, revealed by a Mini-Mental State Examination (MMSE) score < 27.47, was the strongest predictor of imminent dementia. Dementia-free survival time was shortest (mean 2.4 years) in such low-scoring patients who also had impaired instrumental activities of daily living (iADL) and subjective memory impairment with related worry (SMI-w). Patients with identical characteristics but without SMI-w had an estimated mean dementia-free survival time of 3.8 years, which was still shorter than in patients who had subthreshold MMSE scores but intact iADL (4.2-5.2 years). CONCLUSION: Hierarchical patterns of readily available covariates can predict dementia-free survival in older general practice patients with CI. Although less widely appreciated than other variables, iADL impairment appears to be an especially noteworthy predictor of progression to dementia.