Age- and Sex-Different Associations between Cognitive Performance and Inflammatory Biomarkers in Community Dwelling Older Adults: towards Precision Preventive Strategies.

BACKGROUND: Studies have demonstrated associations between inflammatory biomarkers and cognitive function in people with dementia or stroke, but little is known regarding these associations in healthy middle-aged and older populations. OBJECTIVES: This study aims to examine associations between inflammatory biomarkers (both vascular and systemic) and cognitive performance in stroke- and dementia-free middle-aged and older adults without apolipoprotein E4 (ApoE ε4) allele carriers. DESIGN: A cross-sectional study. SETTING: Social Environment and Biomarkers of Aging Study (SEBAS) 2006. PARTICIPANTS: A total of 983 participants aged 53 years and older. MEASUREMENTS: Composite cognitive function assessment, including the Short Portable Mental Status Questionnaire, the Rey Auditory Verbal Learning Test, and the Wechsler Adult Intelligence Scale. Overnight venous blood sampling for 6 inflammatory biomarkers (C-reactive protein, interleukin-6, fibrinogen, homocysteine, intercellular adhesion molecule-1 and E-selectin) and ApoE genotyping. RESULTS: Among 983 participants (mean age: 65.8±9.5 years), 808 were non-ApoE e4 allele carriers and were stroke- and dementia-free. Higher log fibrinogen was associated with poorer cognitive function after adjustment for potential confounding factors in non-ApoE e4 allele carriers and stroke- and dementia-free populations (unstandardized coefficients ß= -1.553, P value= 0.003). In participants aged 65 years or older, both of elevated fibrinogen and homocysteine were associated with poorer cognitive function (ß= -2.288, P value= 0.015; ß= -1.331, P value= 0.012, respectively). Elevated log CRP was significantly associated with lower cognitive function only in women (ß= -0.514, P value= 0.024). CONCLUSION: Higher serum levels of fibrinogen were negatively associated with cognitive function, which was independent of ApoE genotyping and prior cerebrovascular events in dementia-free community-dwelling older adults. Further studies are needed to validate the roles of fibrinogen in the pathophysiology of dementia and elucidate the underlying mechanisms.

Physio-Cognitive Decline Syndrome as the Phenotype and Treatment Target of Unhealthy Aging.

In this era of unprecedented longevity, healthy aging is an important public health priority. Avoiding or shortening the period of disability or dementia before death is critical to achieving the defining objectives of healthy aging, namely to develop and maintain functional capabilities that enable wellbeing in older age. The first step is to identify people who are at risk and then to implement effective primary interventions. Geriatricians have identified a distinct clinical phenotype of concurrent physical frailty and cognitive impairment, which predicts high risk of incident dementia and disability and is potentially reversible. Differing operational definitions for this phenotype include "cognitive frailty", "motoric cognitive risk syndrome" and the recently proposed "physio-cognitive decline syndrome (PCDS)". PCDS is defined as concurrent mobility impairment no disability (MIND: slow gait or/and weak handgrip) and cognitive impairment no dementia (CIND: ≥1.5 SD below the mean for age-, sex-, and education-matched norms in any cognitive domain but without dementia). By these criteria, PCDS has a prevalence of 10-15% among community-dwelling older persons without dementia or disability, who are at increased risk for incident disability (HR 3.9, 95% CI 3.0-5.1), incident dementia (HR 3.4, 95% CI 2.4-5.0) and all-cause mortality (HR 6.7, 95% CI 1.8-26.1). Moreover, PCDS is associated with characteristic neuroanatomic changes in the cerebellum and hippocampus, and their neurocircuitry, which are distinct from neuroimaging features in normal aging and common dementia syndromes. Basic research and longitudinal clinical studies also implicate a hypothetical muscle-brain axis in the pathoetiology of PCDS. Most important, community-dwelling elders with PCDS who participated in a multidomain intervention had significant improvements in global cognitive function, and especially in the subdomains of naming and concentration. Our proposed operational definition of PCDS successfully identifies an appreciable population of at-risk older people, establishes a distinct phenotype with an apparently unique pathoetiology, and is potentially reversible. We now need further studies to elucidate the pathophysiology of PCDS, to validate neuroimaging features and muscle-secreted microRNA biomarkers, and to evaluate the effectiveness of sustained multidomain interventions.

Tissue sodium content in patients with systemic lupus erythematosus: association with disease activity and markers of inflammation.

OBJECTIVES: Sodium (Na+) is stored in the skin and muscle and plays an important role in immune regulation. In animal models, increased tissue Na+ is associated with activation of the immune system, and high salt intake exacerbates autoimmune disease and worsens hypertension. However, there is no information about tissue Na+ and human autoimmune disease. We hypothesized that muscle and skin Na+ content is (a) higher in patients with systemic lupus erythematosus (SLE) than in control subjects, and (b) associated with blood pressure, disease activity, and inflammation markers (interleukin (IL)-6, IL-10 and IL-17 A) in SLE. METHODS: Lower-leg skin and muscle Na+ content was measured in 23 patients with SLE and in 28 control subjects using 23Na+ magnetic resonance imaging. Demographic and clinical information was collected from interviews and chart review, and blood pressure was measured. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Plasma inflammation markers were measured by multiplex immunoassay. RESULTS: Muscle Na+ content was higher in patients with SLE (18.8 (16.7-18.3) mmol/L) than in control subjects (15.8 (14.7-18.3) mmol/L; p < 0.001). Skin Na+ content was also higher in SLE patients than in controls, but this difference was not statistically significant. Among patients with SLE, muscle Na+ was associated with SLEDAI and higher concentrations of IL-10 after adjusting for age, race, and sex. Skin Na+ was significantly associated with systolic blood pressure, but this was attenuated after covariate adjustment. CONCLUSION: Patients with SLE had higher muscle Na+ content than control subjects. In patients with SLE, higher muscle Na+ content was associated with higher disease activity and IL-10 concentrations.

Increased blood pressure visit-to-visit variability in patients with systemic lupus erythematosus: association with inflammation and comorbidity burden.

BACKGROUND: Blood pressure visit-to-visit variability is a novel risk factor for deleterious long-term cardiac and renal outcomes in the general population. We hypothesized that patients with systemic lupus erythematosus (SLE) have greater blood pressure visit-to-visit variability than control subjects and that blood pressure visit-to-visit variability is associated with a higher comorbidity burden. METHODS: We studied 899 patients with SLE and 4172 matched controls using de-identified electronic health records from an academic medical center. We compared blood pressure visit-to-visit variability measures in patients with SLE and control subjects and examined the association between blood pressure visit-to-visit variability and patients' characteristics. RESULTS: Patients with SLE had higher systolic blood pressure visit-to-visit variability 9.7% (7.8-11.8%) than the control group 9.2% (7.4-11.2%), P < 0.001 by coefficient of variation. Additional measures of systolic blood pressure visit-to-visit variability (i.e. standard deviation, average real variation, successive variation and maximum measure-to-measure change) were also significantly higher in patients with SLE than in control subjects. In patients with SLE, blood pressure visit-to-visit variability correlated significantly with age, creatinine, CRP, triglyceride concentrations and the Charlson comorbidity score (all P < 0.05). Hydroxychloroquine use was associated with reduced blood pressure visit-to-visit variability (P < 0.001), whereas the use of antihypertensives, cyclophosphamide, mycophenolate mofetil and corticosteroids was associated with increased blood pressure visit-to-visit variability (P < 0.05). CONCLUSION: Patients with SLE had higher blood pressure visit-to-visit variability than controls, and this increased blood pressure visit-to-visit variability was associated with greater Charlson comorbidity scores, several clinical characteristics and immunosuppressant medications. In particular, hydroxychloroquine prescription was associated with lower blood pressure visit-to-visit variability.

Real-world electronic health record identifies antimalarial underprescribing in patients with lupus nephritis.

Antimalarials (AMs) reduce disease activity and improve survival in patients with systemic lupus erythematosus (SLE), but studies have reported low AM prescribing frequencies. Using a real-world electronic health record cohort, we examined if patient or provider characteristics impacted AM prescribing. We identified 977 SLE cases, 94% of whom were ever prescribed an AM. Older patients and patients with SLE nephritis were less likely to be on AMs. Current age (odds ratio = 0.97, p < 0.01) and nephritis (odds ratio = 0.16, p < 0.01) were both significantly associated with ever AM use after adjustment for sex and race. Of the 244 SLE nephritis cases, only 63% were currently on AMs. SLE nephritis subjects who were currently prescribed AMs were more likely to be followed by a rheumatologist than a nephrologist and less likely to have undergone dialysis or renal transplant (both p < 0.001). Non-current versus current SLE nephritis AM users had higher serum creatinine (p < 0.001), higher urine protein (p = 0.05), and lower hemoglobin levels (p < 0.01). As AMs reduce disease damage and improve survival in patients with SLE, our results demonstrate an opportunity to target future efforts to improve prescribing rates among multi-specialty providers.

The effect of genetic variation in PCSK9 on the LDL-cholesterol response to statin therapy.

Statins (HMG-CoA reductase inhibitors) lower low-density lipoprotein cholesterol (LDL-C) and prevent cardiovascular disease. However, there is wide individual variation in LDL-C response. Drugs targeting proprotein convertase subtilin/kexin type 9 (PCSK9) lower LDL-C and will be used with statins. PCSK9 mediates the degradation of LDL receptors (LDLRs). Therefore, a greater LDL-C response to statins would be expected in individuals with PCSK9 loss-of-function (LOF) variants because LDLR degradation is reduced. To examine this hypothesis, the effect of 11 PCSK9 functional variants on statin response was determined in 669 African Americans. One LOF variant, rs11591147 (p.R46L) was significantly associated with LDL-C response to statin (P=0.002). In the three carriers, there was a 55.6% greater LDL-C reduction compared with non-carriers. Another functional variant, rs28362261 (p.N425S), was marginally associated with statin response (P=0.0064).The effect of rs11591147 was present in individuals of European ancestry (N=2388, P=0.054). The therapeutic effect of statins may be modified by genetic variation in PCSK9.

Association of estimated sodium and potassium intake with blood pressure in patients with systemic lupus erythematosus.

Sodium and potassium intake are modifiable determinants of hypertension in the general population but have not been studied in patients with systemic lupus erythematosus (SLE). We examined the relationship between urinary excretion of sodium and potassium, as an estimate of intake, and blood pressure in patients with SLE. We studied 178 SLE patients and 86 controls, matched for age, sex, and race. Urine sodium (Na+) and potassium (K+) were measured by flame photometry. Blood pressure was the average of two resting measurements. The associations between systolic (SBP) and diastolic blood pressures (DBP) and estimated 24-hour urinary Na+, K+, and Na+:K+ ratio were tested. The estimated mean 24-hour urinary K+ excretion was lower, and the Na+:K+ ratio was higher in patients with SLE than controls. There were no significant differences in the estimated 24-hour urinary Na+. In patients with SLE, a higher urinary Na+:K+ ratio was associated with higher SBP (ß coefficient = 4.01, p = 0.023) and DBP (ß coefficient = 4.41, p = 0.002) after adjusting for age, sex, and race. SLE patients had significantly lower estimated 24-hour urinary K+ and higher estimated 24-hour urinary Na+: K+ ratio than controls. The urinary Na+:K+ ratio was significantly associated with SBP and DBP.

GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus.

BACKGROUND: GlycA is a novel marker of systemic inflammation detected by nuclear magnetic resonance (NMR) spectroscopy. In the general population, GlycA is correlated with inflammatory markers such as C-reactive protein (CRP) and associated with coronary heart disease and diabetes. The utility of GlycA in patients with systemic lupus erythematosus (SLE) has not been defined. Therefore, we tested the hypothesis that GlycA concentrations are elevated in patients with SLE and associated with other markers of inflammation and coronary atherosclerosis. METHODS: We compared concentrations of GlycA, detected by NMR, in 116 patients with SLE and 84 control subjects frequency-matched for age, sex, and race. SLE disease activity index (SLEDAI) and the SLE Collaborating Clinics damage index (SLICC) were calculated. Acute phase reactants, a panel of cytokines, and a lipid panel were measured. Electron beam computer tomography (EBCT) was used to quantify coronary artery calcification, a measure of coronary artery atherosclerosis. RESULTS: Patients with SLE had higher concentrations of GlycA (398 (350-445)) than control subjects (339 (299-391)) µmol/L, p < 0.001. In patients with SLE, concentrations of GlycA were significantly associated with sedimentation rate (rho = 0.43), C-reactive protein (rho = 0.59), e-selectin (rho = 0.28), intracellular adhesion molecule-1 (rho = 0.30), triglycerides (rho = 0.45), all p < 0.0023 to account for multiple comparisons, but not with creatinine, SLEDAI, SLICC, or coronary calcium scores. CONCLUSIONS: Concentrations of GlycA are higher in patients with SLE than control subjects and associated with markers of inflammation but not with SLE disease activity or chronicity scores or coronary artery calcification.

Genetic variation and coronary atherosclerosis in patients with systemic lupus erythematosus.

Coronary artery disease is the major cause of mortality in patients with systemic lupus erythematosus (SLE). Increased cardiovascular risk in SLE is not explained by traditional risk factors. We examined the hypothesis that genetic variation contributes to the presence of coronary atherosclerosis in patients with SLE. The genotypes of single-nucleotide polymorphisms (SNP) in 152 candidate genes linked with autoimmune or cardiovascular risk were determined in 125 patients with SLE. Coronary artery calcium (CAC), a measure of coronary atherosclerosis, was detected in 32 patients (26%) by electron-beam computed tomography. Polymorphism in 20 of the candidate genes (ADAM33, ADIPOQ, CCL5, CCR7, CDKN2B, CSF1, IL4, IL12A, IL23R, INS, IRF5, MIF, MS4A1, PTGS1, PTPN22, RETN, SELE, TNFSF4, TNFRSF11B, and VCAM1) were nominally associated with the presence of CAC (p-values = 0.001-0.047 after adjustment for age, sex and race). Some of these are known susceptibility genes for SLE and others have been implicated in cardiovascular disease in other populations. No association withstood false discovery rate adjustment. Replication studies in additional cohorts of patients with SLE may be informative.

A cell-permeable fusion protein for the mineralization of human dental pulp stem cells.

Human dental pulp stem cells (hDPSCs) are the only mesenchymal stem cells in pulp tissue that can differentiate into osteoblasts, odontoblasts, and adipose cells. The transcriptional co-activator with PDZ-binding motif (TAZ) protein has been reported to modulate osteogenic differentiation in mouse MSCs. Therefore, we examined whether the TAZ protein plays the same role in human pulp stem cells. In this study, TAZ was applied to cells directly with low-molecular-weight protamine (LMWP) as a cell-penetrating peptide (CPP). The LMWP-TAZ fusion proteins were expressed in an E. coli system with a pET-21b vector and efficiently transferred into hDPSCs without producing toxicity in the cells. The efficient uptake of TAZ was shown by Western blot with an anti-TAZ antibody, fluorescence-activated cell sorting, and confocal microscopy in live cells. The delivered TAZ protein increased osteogenic differentiation, as confirmed by alkaline phosphatase (ALP) staining, RT-PCR, and Western blotting. In addition, TAZ also inhibited adipogenic differentiation, regulating peroxisome proliferator-activated receptor-γ (PPAR-γ), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (aP2) mRNA levels. These in vitro studies suggest that cell-permeable TAZ may be used as a specific regulator of hard-tissue differentiation.

Brain involvement in neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSDs) are severe inflammatory demyelinating disorders of the central nervous system. Brain involvement is increasingly recognized. OBJECTIVE: To study brain involvement in NMOSDs among Hong Kong Chinese patients. DESIGN: Retrospective study of patients with NMOSDs. SETTING: Tertiary medical center in Hong Kong. Patients  Thirty-four Hong Kong Chinese patients with NMOSDs of 2 years or longer were recruited. INTERVENTIONS: Brain and spinal cord magnetic resonance imaging was performed during NMOSD attacks and was repeated yearly for the first 3 years. MAIN OUTCOME MEASURES: We evaluated clinical features of NMOSDs associated with brain involvement and brain lesions on magnetic resonance imaging. RESULTS: Among 34 patients with NMOSDs of 2 years or longer, 20 (59%) had brain involvement. The mean age at onset among these 20 patients was 45.6 years (age range, 19-67 years); 18 were women. Eleven patients (32% of all the patients with NMOSDs) had clinical manifestation of brain involvement, 19 patients (56%) had brain abnormalities on magnetic resonance imaging consistent with inflammatory demyelination, and 2 patients (6%) fulfilled criteria for multiple sclerosis. Clinical manifestation of brain involvement included the following: trigeminal neuralgia; vomiting, vertigo, ataxia, dysphagia, and tetraparesis from lesions around the third and fourth ventricles and aqueduct; homonymous hemianopia, aphasia, hemiparesis, and cognitive impairment from extensive hemispheric white matter lesions; and ataxia, diplopia, hiccups, facial sensory loss, internuclear ophthalmoplegia, hemisensory loss, and hemiparesis from other lesions in the midbrain, pons, cerebellar peduncles, and medulla. Eight patients (24%) developed brainstem encephalitis clinically, and brainstem encephalitis was the initial clinical manifestation in 6 patients (18%). Brain abnormalities on magnetic resonance imaging were detected in brainstem in 15 patients (44%), hemispheric periventricular white matter in 7 patients (21%), deep white matter in 7 patients (21%), corpus callosum in 4 patients (12%), subcortical white matter in 3 patients (9%), thalamus in 2 patients (6%), hypothalamus in 1 patient (3%), basal ganglia in 1 patient (3%), internal capsule in 1 patient (3%), periaqueductal gray matter in 1 patient (3%), and around the third and fourth ventricles in 1 patient (3%); large confluent lesions were detected in 2 patients (6%). CONCLUSION: Brain involvement manifesting clinically as brainstem encephalitis is common among Hong Kong Chinese patients with NMOSDs.

Adipocytokines in systemic lupus erythematosus: relationship to inflammation, insulin resistance and coronary atherosclerosis.

We tested the hypothesis that concentrations of adipocytokines are altered in SLE and associated with coronary atherosclerosis, insulin resistance and inflammation. Concentrations of resistin, leptin, adiponectin and visfatin were measured in 109 patients with SLE and 78 control subjects. Coronary calcification was measured using electron beam-computed tomography, and insulin resistance was defined by the homeostasis model assessment index. Concentrations of adiponectin (28.7 +/- 17.9 vs 22.0 +/- 15.3 microg/mL, P = 0.003), leptin (41.1 +/- 49.9 vs 19.8 +/- 24.6 ng/mL, P < 0.001) and visfatin (7.5 +/- 10.5 vs 4.5 +/- 2.8 ng/mL, P < 0.001) were higher in patients with SLE than in controls. These differences remained significant after adjustment for age, race, sex and body mass index (BMI; all P values < 0.02). Concentrations of resistin (10.7 +/- 7.6 vs 9.1 +/- 5.1 ng/mL, P = 0.41) did not differ in patients and controls. In patients with SLE, leptin was positively associated with BMI (rho = 0.80, P < 0.001), insulin resistance (rho = 0.46, P < 0.001) and C-reactive protein (CRP) (rho = 0.30, P = 0.002), whereas adiponectin was negatively associated with the same factors (rho = -0.40, P < 0.001; rho = -0.38, P < 0.001; rho = -0.22, P = 0.02, respectively). None of the adipocytokines were associated with coronary atherosclerosis in SLE. In conclusion, patients with SLE have increased concentrations of adiponectin, leptin and visfatin. Lower concentrations of adiponectin and higher concentrations of leptin are associated with insulin resistance, BMI and CRP in patients with SLE.

The association of osteoprotegerin gene polymorphisms with periodontitis.

BACKGROUND: It has been demonstrated that genetic variation accounts for approximately half of the variance in periodontitis. The reported association of polymorphisms in the osteoprotegerin (OPG) gene with osteoporosis suggests that the OPG gene may also influence the genetic risk for periodontitis. SUBJECTS AND METHODS: We investigated the distribution of OPG gene polymorphisms in 49 patients with aggressive (n = 14) or chronic (n = 35) periodontitis and 49 control subjects without periodontitis, using polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR-single strand conformation polymorphism followed by direct sequencing. RESULTS: A total of seven known polymorphisms and one new mutation, G373A, were identified. The T950 and G1181 alleles were more common in patients with periodontitis (P = 0.028 and P = 0.047, respectively) than in control subjects. Especially, G1181 allele was associated with patients with aggressive periodontitis. CONCLUSION: The TG haplotype of T950C and G1181C polymorphisms in the OPG gene may be useful genetic markers for the prediction of periodontitis. Further studies in a larger population are required to determine whether these alleles directly contribute to periodontitis susceptibility.

Changing patterns of medication use in patients with rheumatoid arthritis in a Medicaid population.

OBJECTIVE: To examine changes in patterns of medication utilization in patients with RA. METHODS: Data from Tennessee Medicaid (TennCare) databases (1995-2004) were used to identify adults with both a diagnosis of RA and at least one DMARD prescription each year. Annual age-specific utilization of DMARDs, glucocorticoids, NSAIDs and narcotics was measured on the last day of each year to determine the point prevalence of use of these agents. RESULTS: Records from 23 342 patients with treated RA were analysed. Most patients were females (78%) and white (74%). The median age was 57 yrs (interquartile range: 48-65). The proportion of patients who had a current DMARD prescription on the index date increased from 62% in 1995 to 71% in 2004 (P < 0.001). MTX was the most commonly used DMARD. By the end of 2004, 22% of patients had a current prescription for a biologic, and etanercept represented 51% of all biologic therapies. During the study period, the overall utilization of glucocorticoids decreased from 46% to 38% (P < 0.001), whereas NSAID utilization increased from 33% to 38% (P < 0.001), and use of narcotics increased from 38% to 55% (P < 0.001). A secondary analysis that identified RA patients based on diagnosis codes alone, showed similar patterns, but lower DMARD utilization which increased from 33% to 52% overall and from 0% to 16% for biologics. CONCLUSIONS: The utilization of DMARDs increased in TennCare patients with RA, and by 2004, use of biologics was substantial. Although glucocorticoid utilization decreased, use of both NSAIDs and narcotics increased.

Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms.

Oxidative stress may play a role in the pathogenesis of systemic lupus erythematosus (SLE). We examined the hypothesis that oxidative stress was associated with indices of lupus disease activity and severity of symptoms. Urinary F2 isoprostane excretion, a validated marker of oxidative stress, was measured in 95 patients with SLE and 103 healthy controls. Outcome measures included SLEDAI and SLICC scores, the modified health assessment questionnaire, the fatigue severity scale (FSS), and visual analogue scales (VAS) for fatigue, pain and overall disease activity. F2 isoprostane excretion was compared in patients and controls, and its relationship with clinical variables in SLE examined. F2 isoprostane excretion did not differ significantly among patients with lupus (2.7 +/- 2.3 ng/mg Cr) and control subjects (2.2 +/- 1.4 ng/mg Cr) (P = 0.70). In patients with lupus, F2 isoprostane concentrations were independently associated with higher patient reported disease activity (VAS) (OR = 1.52, P = 0.01), fatigue (FSS, OR = 1.52, P = 0.03) and lower quality of life (OR = 0.73, P = 0.05), but not with objective markers or inflammation or disease activity. In conclusion, F2 isoprostane excretion is associated with patient-reported symptoms in SLE but not with measures of inflammation, SLEDAI or SLICC. Oxidative stress may contribute to debilitating symptoms such as fatigue in SLE.

A 2-year open-label study of galantamine therapy in Chinese Alzheimer's disease patients in Hong Kong.

There was no long-term clinical study on galantamine in Alzheimer's disease (AD) in the Asian population. The objectives of this study were to evaluate the efficacy of galantamine on cognitive function, daily functioning, behavioural symptoms and its safety in Chinese AD patients. This was a 2-year open-label clinical trial. The inclusion criteria were patients with probable AD by the NINCDS-ADRDA criteria. A historical control group (n = 19) of AD patients with no galantamine or other cholinesterase inhibitor therapy was employed. In the galantamine group, 33 and 32 subjects had completed a 1-year and 2-year follow up, respectively. Within the galantamine group and at a 6-month follow up, the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog score) showed an improvement of 2.9 +/- 1.18 (p = 0.019, paired t-test) but remained the same at 1 and 2 years. The Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) deteriorated by 4.31 +/- 2.06 (p = 0.044, paired t-test) at 6 months but showed no significant decline at 1 and 2 years vs. baseline. The Neuropsychiatric Inventory (NPI) score also showed a significant deterioration of 5 +/- 1.99 (p = 0.017, paired t-test) at 6 months, 8.06 +/- 1.97 (p < 0.001, paired t-test) at 1 year and 7.31 +/- 1.76 at 2 years. Comparison between the two groups showed a statistically significant improvement in the 1-year ADAS-cog score but decline in the NPI score in the galantamine vs. control groups. Adverse effects were commonly mild. In Chinese mild-moderate AD patients, galantamine showed beneficial effects mainly on the cognitive function.

Cardiovascular risk scores and the presence of subclinical coronary artery atherosclerosis in women with systemic lupus erythematosus.

The Framingham risk score is widely used to identify patients at increased cardiovascular risk, and women with systemic lupus erythematosus (SLE) have a marked increased prevalence of cardiovascular events. Thus, we examined the hypothesis that cardiovascular risk scores would identify women with SLE who had asymptomatic coronary atherosclerosis. Ninety-three women with SLE and 65 control subjects were studied. The Framingham score and a score for younger populations developed from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study were compared in both groups. Coronary atherosclerosis was ascertained by electron beam computed tomography. There were no significant differences in the median (interquartile range) Framingham [5 (2-10) compared to 7 (0-10), P = 0.88] and PDAY [15 (14-18) compared to 16 (13-18), P = 0.99] scores in patients with SLE and controls, respectively. Coronary atherosclerosis was associated with higher Framingham [12 (3-15) compared to 4 (1-8), P = 0.008] and PDAY [17 (15-19 compared to 15 (12-18), P = 0.03)] scores in patients with SLE; however, 99% of patients were classified as low-risk with a 10-year predicted risk of 1% (<1-3%). Our data indicate that cardiovascular risk scores are not adequate for risk stratification in women with SLE. Measurement of coronary calcification may add information to identify asymptomatic women with lupus who might benefit from aggressive preventive measures.

Work disability in early rheumatoid arthritis: higher rates but better clinical status in Finland compared with the US.

OBJECTIVE: To analyse and compare work disability attributed to rheumatoid arthritis in two cohorts of patients with early disease: one in the US and the other in Finland. PATIENTS AND METHODS: Two cohorts of patients who were working and aged <65 years at the time of their first symptom of rheumatoid arthritis were studied: 269 patients in Nashville, TN, USA (median age 46 years, 72.5% females), and 364 patients from Jyväskylä, Finland, (median age 47.1 years, 70.9% females). The cohorts were analysed and compared for measures of clinical status and work disability status over a median (interquartile range) of 38.9 months in Nashville and 48.4 months in Jyväskylä. RESULTS: The probability of working at 36 months was 0.89 (0.84-0.92) for patients from Nashville and 0.84 (0.80-0.88) for patients from Jyväskylä (p = 0.02). These rates were lower than in earlier decades. Patients from Jyväskylä had significantly higher rates of work disability (p = 0.02) than those from Nashville, but better scores for self-report physical function (p<0.001), pain (p<0.001) and global status (p<0.001) at last observation. The likelihood of being disabled from work was 2.6-fold higher in Jyväskylä compared to Nashville (95% confidence interval 1.44 to 4.59, p = 0.001), after adjustment for demographic and disease-specific variables. CONCLUSION: Rates of work disability in both early rheumatoid arthritis cohorts were improved from earlier decades, but differed significantly in two different social systems. Higher work disability rates with better clinical status was seen in the Finnish early rheumatoid arthritis cohort than in the US cohort.