Getting old in the desired gender: a systematic review on aging diseases in transgender people.

INTRODUCTION: The growing demographic presence of the transgender (TGD) population has sparked an increase in clinical investigations focusing on the impacts of gender-affirming hormone therapy (GAHT) in adults with gender dysphoria. Despite this surge in studies, there remains a significant gap in the literature regarding the health status of older TGD individuals. This review aims to assess prevalent pathological conditions within the TGD population, specifically concentrating on aging-related diseases investigated to date. METHODS: A systematic search across Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science databases was conducted to identify articles reporting on the aging process in TGD individuals. Methodological quality was evaluated using Newcastle-Ottawa Scale (NOS) scores. RESULTS: Initial database searches yielded 12,688 studies, which were refined to 18 through elimination of duplicates and title/abstract review. Following a comprehensive appraisal, nine studies were included in the systematic review. These articles, published between 2017 and 2023, involved a total of 5403 participants. The evidence indicates a noteworthy percentage of the TGD population being at risk for cardiovascular diseases, experiencing depression or disability, and demonstrating hesitancy toward major recommended screening programs. CONCLUSIONS: Limited studies on older TGD individuals highlight not only an organic risk of chronic diseases but also a cognitive/psychiatric risk that should not be underestimated. Further research is imperative to deepen our understanding of the pathophysiological mechanisms involved in the health challenges faced by older TGD individuals.

Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study.

PURPOSE: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). METHODS: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). RESULTS: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. CONCLUSIONS: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

Taking care of inpatients with fragility hip fractures: the hip-padua osteosarcopenia (Hip-POS) fracture liaison service model.

PURPOSE: Osteoporotic fragility fractures (FF), particularly those affecting the hip, represent a major clinical and socio-economic concern. These fractures can lead to various adverse outcomes, which may be exacerbated by the presence of sarcopenia, especially among older and frail patients. Early identification of patients with FF is crucial for implementing effective diagnostic and therapeutic strategies to prevent subsequent fractures and their associated consequences. METHODS: The Hip-POS program, implemented at Azienda Ospedale-Università Padova, is a Fracture Liaison Service (FLS) program to evaluate patients aged > 50 years old admitted with fragility hip fractures, involving an interdisciplinary team. After the identification of patients with hip fractures in the Emergency Department, a comprehensive evaluation is conducted to identify risk factors for further fractures, and to assess the main domains of multidimensional geriatric assessment, including muscle status. Patients are then prescribed with anti-fracture therapy, finally undergoing periodic follow-up visits. RESULTS: During the first five months, a total of 250 patients were evaluated (70.4% women, median age 85 years). Following assessment by the Hip-POS team, compared to pre-hospitalization, the proportion of patients not receiving antifracture therapy decreased significantly from 60 to 21%. The prescription rates of vitamin D and calcium increased markedly from 29.6% to 81%. CONCLUSIONS: We introduced the Hip-POS program for the care of older adults with hip fractures. We aspire that our model will represent a promising approach to enhancing post-fracture care by addressing the multifactorial nature of osteoporosis and its consequences, bridging the gap in secondary fracture prevention, and improving patient outcomes.

Managing comorbid cognitive impairment and hearing loss in older adults: a UK survey of audiology and memory services.

BACKGROUND: midlife hearing loss is a potentially modifiable risk factor for dementia. Addressing comorbid hearing loss and cognitive impairment in services for older adults may offer opportunities to reduce dementia risk. OBJECTIVE: to explore current practice and views amongst UK professionals regarding hearing assessment and care in memory clinics and cognitive assessment and care in hearing aid clinics. METHODS: national survey study. Between July 2021 and March 2022, we distributed the online survey link via email and via QR codes at conferences to professionals working in National Health Service (NHS) memory services and audiologists working in NHS and private adult audiology services. We present descriptive statistics. RESULTS: 135 professionals working in NHS memory services and 156 audiologists (68% NHS, 32% private sector) responded. Of those working in memory services, 79% estimate that >25% of their patients have significant hearing difficulties; 98% think it useful to ask about hearing difficulties and 91% do so; 56% think it useful to perform a hearing test in clinic but only 4% do so. Of audiologists, 36% estimate that >25% of their older adult patients have significant memory problems; 90% think it useful to perform cognitive assessments, but only 4% do so. Main barriers cited are lack of training, time and resources. CONCLUSIONS: although professionals working in memory and audiology services felt addressing this comorbidity would be useful, current practice varies and does not generally address it. These results inform future research into operational solutions to integrating memory and audiology services.

Friction Induces Anisotropic Propulsion in Sliding Magnetic Microtriangles.

In viscous fluids, motile microentities such as bacteria or artificial swimmers often display different transport modes than macroscopic ones. A current challenge in the field aims at using friction asymmetry to steer the motion of microscopic particles. Here we show that lithographically shaped magnetic microtriangles undergo a series of complex transport modes when driven by a precessing magnetic field, including a surfing-like drift close to the bottom plane. In this regime, we exploit the triangle asymmetric shape to obtain a transversal drift which is later used to transport the microtriangle in any direction along the plane. We explain this friction-induced anisotropic sliding with a minimal numerical model capable to reproduce the experimental results. Due to the flexibility offered by soft-lithographic sculpturing, our method to guide anisotropic-shaped magnetic microcomposites can be potentially extended to many other field responsive structures operating in fluid media.

Adaption and preliminary validation of the Addenbrooke's Cognitive Examination-III as a screening test for mild cognitive impairment and dementia in hearing-impaired individuals.

BACKGROUND: A large proportion of older adults assessed for cognitive impairment likely have hearing loss, potentially affecting accuracy of cognitive performance estimations. This study aimed to develop a hearing-impaired version of the Addenbrooke's Cognitive Examination-III (HI-ACE-III) and to assess whether the HI-ACE-III can accurately distinguish people with mild cognitive impairment (MCI) and dementia from cognitively intact controls. METHODS: The HI-ACE-III was developed by converting verbal instructions into a visual, timed PowerPoint presentation. Seventy-four participants over the age of 60 years were classified into three groups: 29 had MCI, 15 had mild to moderate dementia and 30 were cognitively intact controls. Receiver operating characteristic (ROC) curves were graphed to test screening accuracy. Concurrent validity was examined through correlations between HI-ACE-III domain scores and relevant, visually presented standardized neuropsychological measures. RESULTS: ROC analysis for dementia revealed an area under the curve (AUC) of 0.99, achieving excellent sensitivity (100%) and good specificity (93.3%) at an optimum cut-off of <87. The AUC for MCI was 0.86, achieving reasonable sensitivity (75.9%) and good specificity (86.7%) at an optimum cut-off of <92. HI-ACE-III subtests shared anticipated and statistically significant correlations with established measures of cognitive functioning. Internal consistency of the HI-ACE-III was excellent as verified with Cronbach's alpha (α = 0.904). CONCLUSIONS: Preliminarily, the HI-ACE-III showed good reliability, validity and screening utility for MCI and dementia in older adults in a hearing-impairment context. The adapted HI-ACE-III may offer accurate and reliable indication of cognitive performance, supporting timely diagnosis and research examining links between hearing loss and cognitive decline.

Paneth cells promote angiogenesis and regulate portal hypertension in response to microbial signals.

BACKGROUND & AIMS: Paneth cells (PCs) synthesize and secrete antimicrobial peptides that are key mediators of host-microbe interactions, establishing a balance between intestinal microflora and enteric pathogens. We observed that their number increases in experimental portal hypertension and aimed to investigate the mechanisms by which these cells can contribute to the regulation of portal pressure. METHODS: We first treated Math1Lox/LoxVilcreERT2 mice with tamoxifen to induce the complete depletion of intestinal PCs. Subsequently, we performed partial portal vein or bile duct ligation. We then studied the effects of these interventions on hemodynamic parameters, proliferation of blood vessels and the expression of genes regulating angiogenesis. Intestinal organoids were cultured and exposed to different microbial products to study the composition of their secreted products (by proteomics) and their effects on the proliferation and tube formation of endothelial cells (ECs). In vivo confocal laser endomicroscopy was used to confirm the findings on blood vessel proliferation. RESULTS: Portal hypertension was significantly attenuated in PC-depleted mice compared to control mice and was associated with a decrease in portosystemic shunts. Depletion of PCs also resulted in a significantly decreased density of blood vessels in the intestinal wall and mesentery. Furthermore, we observed reduced expression of intestinal genes regulating angiogenesis in Paneth cell depleted mice using arrays and next generation sequencing. Tube formation and wound healing responses were significantly decreased in ECs treated with conditioned media from PC-depleted intestinal organoids exposed to intestinal microbiota-derived products. Proteomic analysis of conditioned media in the presence of PCs revealed an increase in factors regulating angiogenesis and additional metabolic processes. In vivo endomicroscopy showed decreased vascular proliferation in the absence of PCs. CONCLUSIONS: These results suggest that in response to intestinal flora and microbiota-derived factors, PCs secrete not only antimicrobial peptides, but also pro-angiogenic signaling molecules, thereby promoting intestinal and mesenteric angiogenesis and regulating portal hypertension. LAY SUMMARY: Paneth cells are present in the lining of the small intestine. They prevent the passage of bacteria from the intestine into the blood circulation by secreting substances to fight bacteria. In this paper, we discovered that these substances not only act against bacteria, but also increase the quantity of blood vessels in the intestine and blood pressure in the portal vein. This is important, because high blood pressure in the portal vein may result in several complications which could be targeted with novel approaches.

Hearing-impaired population performance and the effect of hearing interventions on Montreal Cognitive Assessment (MoCA): Systematic review and meta-analysis.

BACKGROUND: Older adults are at high risk of developing age-related hearing loss (HL) and/or cognitive impairment. However, cognitive screening tools rely on oral administration of instructions and stimuli that may be impacted by HL. This systematic review aims to investigate (a) whether people with HL perform worse than those without HL on the Montreal Cognitive Assessment (MoCA), a widely used screening tool for cognitive impairment, and what the effect size of that difference is (b) whether HL treatment mitigates the impact of HL. METHOD: We conducted a systematic review and meta-analysis including studies that reported mean MoCA scores and SDs for individuals with HL. RESULTS: People with HL performed significantly worse on the MoCA (4 studies, N = 533) with a pooled mean difference of -1.66 points (95% confidence interval CI -2.74 to -0.58). There was no significant difference in MoCA score between the pre- vs post-hearing intervention (3 studies, N = 75). However, sensitivity analysis in the cochlear implant studies (2 studies, N = 33) showed improvement of the MoCA score by 1.73 (95% CI 0.18 to 3.28). CONCLUSION: People with HL score significantly lower than individuals with normal hearing on the standard orally administered MoCA. Clinicians should consider listening conditions when administering the MoCA and report the hearing status of the tested individuals, if known, taking this into account in interpretation or make note of any hearing difficulty during consultations which may warrant onward referral. Cochlear implants may improve the MoCA score of individuals with HL, and more evidence is required on other treatments. J Am Geriatr Soc 68:-, 2020.

The impact of sleep disturbances on care home residents with dementia: the SIESTA qualitative study.

OBJECTIVES: Nearly 40% of care home residents who are living with dementia also have symptoms of disturbed sleep. However, the impact of these disturbances is relatively unknown and is needed to indicate whether interventions are warranted; therefore, we aimed to investigate the impact. DESIGN: One-to-one semi-structured interviews. SETTINGS: Four UK care homes. PARTICIPANTS: We interviewed 18 nurses and care assistants about residents with sleep disturbances. MEASUREMENTS: We used a topic guide to explore staff experience of sleep disturbance in residents with dementia. The interviews were audio recorded and transcribed and then analyzed thematically by two researchers independently. RESULTS: Staff described that sleep disturbances in most, but not all, residents impacted negatively on the resident, other residents, staff, and relatives. Residents became more irritable or agitated if they had slept badly. They slept in the daytime after a bad night, which then increased their chances of being awake the following night. For some, being sleepy in the day led to falls, missing medication, drinks, and meals. Staff perceived hypnotics as having low efficacy, but increasing the risk of falls and drowsiness. Other residents were disturbed by noise, and staff described stress when several residents had sleep disturbance. Some of the strategies reported by staff to deal with sleep disturbances such as feeding or providing caffeinated tea at night might be counterproductive. CONCLUSIONS: Sleep disturbances in care home residents living with dementia negatively affect their physical and psychological well-being. These disturbances also disturb other residents and increase stress in staff.

One-year caloric restriction and 12-week exercise training intervention in obese adults with type 2 diabetes: emphasis on metabolic control and resting metabolic rate.

PURPOSE: The effect of combined lifestyle interventions (LSI) including dietary and physical activity on metabolic health, energy metabolism and VO2max in diabetic patients has provided mixed results. We evaluated the impact of 1-year caloric restriction (CR), and 12-week supervised structured exercise training (SSET) on metabolic health, RMR and VO2max in obese adults with type 2 diabetes. METHODS: After 1-month education for LSI, 33 participants had anthropometric, biochemical and metabolic assessments. They then started CR based on RMR, and 3-month SSET during the months 1-3 (Early-SSET) or 4-6 (Late-SSET). Reassessments were planned after 3, 6 and 12 months. Using a per-protocol analysis, we evaluated parameter changes from baseline and their associations for the 23 participants (11 Early-SSET, 12 Late-SSET) who completed the study. RMR was adjusted (adjRMR) for age, sex, fat-free mass (FFM) and fat mass (FM). RESULTS: Compared with baseline, after 6 months we found significant increases in VO2max (+ 14%) and HDL-cholesterol (+ 13%), and reduction in body mass index (- 3%), FM (- 8%) and glycated hemoglobin (HbA1c, - 7%). Training-related caloric expenditure negatively correlated with changes in body weight (p < 0.001), FM (p < 0.001) and HbA1c (p = 0.006). These results were confirmed at the 12-month follow-up. Pooling together all follow-up data, adjRMR changes correlated with changes in glycemia (r = 0.29, p = 0.02), total-cholesterol (r = 0.29, p = 0.02) and VO2max (r = - 0.26,p = 0.02). No significant differences emerged between the Early- and Late-SSET groups. CONCLUSIONS: Combined intervention with SSET and CR improved metabolic control. Changes in metabolic health and fitness correlated with changes of adjRMR, which was reduced improving fitness, glycemia and cholesterolemia. CLINICAL TRIAL REGISTRY: Trial registration number: NCT03785379. URL of registration: http://clinicaltrials.gov .

Effects of acetyl-L-carnitine in diabetic neuropathy and other geriatric disorders.

A long history of diabetes mellitus and increasing age are associated with the onset of diabetic neuropathy, a painful and highly disabling complication with a prevalence peaking at 50% among elderly diabetic patients. Acetyl-L-carnitine (ALC) is a molecule derived from the acetylation of carnitine in the mitochondria that has an essential role in energy production. It has recently been proposed as a therapy to improve the symptoms of diabetic neuropathy. ALC is widely distributed in mammalian tissues, including the brain, blood-brain barrier, brain neurons, and astrocytes. Aside from its metabolic activity, ALC has demonstrated cytoprotective, antioxidant, and antiapoptotic effects in the nervous system. It exerts an analgesic action by reducing the concentration of glutamate in the synapses. It facilitates nerve regeneration and damage repair after primary trauma: its positive effects on metabolism promote the synthesis, fluidity, and functionality of neuronal membranes, increase protein synthesis, and improve the axonal transport of neurofilament proteins and tubulin. It also amplifies nerve growth factor responsiveness, an effect that is believed to enhance overall neurite growth. ALC has been proposed for the treatment of various neurological and psychiatric diseases, such as mood disorders and depression, dementias, Alzheimer's disease, and Parkinson's disease, because synaptic energy states and mitochondrial dysfunction are core factors in their pathogenesis.

Influence of number of drugs on olfaction in the elderly.

BACKGROUND: The etiology of age-related olfactory loss is still unclear, but it has been claimed that polypharmacotherapy may contribute to olfactory dysfunction, particularly in the elderly, who are more likely to need multiple drugs. The present pilot study investigated the relationship between smell and the number and type of drugs taken in a group of elderly. METHODOLOGY: 50 elderly volunteers (over 64 years old) who were healthy from the sinonasal standpoint (SNOT-22 under 1) and had no cognitive impairments [Mini Mental State Examination (MMSE over 18) were administered the Screening 12 test and tested on their n-butanol olfactory threshold. Their olfactory performance was then connected with the number and type of drugs participants used. RESULTS: The mean age of the included volunteers was 74 plus/minus 7 years. No association emerged between odor identification and number of drugs taken. The number of drugs taken correlated directly with a worse olfactory threshold and with a worse MMSE score, meaning a worse cognitive status. Odor identification significantly worsened with age. Comparing those volunteers taking only one drug known to not influence olfaction with another sub-group of volunteers taking five or more drugs, it was evident that subjects taking only one drug scored significantly better in olfactory threshold test and MMSE, and marginally better in olfactory identification test. For what concerns the difference between male and female volunteers, no difference in olfactory test result was shown, both for threshold and identification. Univariate analysis showed a direct correlation between the consumption of calcium channel blockers, beta-blockers, acetylsalicylic acid and olfactory threshold, meaning a worse sense of smell. Acetylsalicylic acid also correlated inversely with odor identification, meaning again a worse sense of smell, and so did potassium-sparing diuretics. Multivariate analysis showed that MMSE scores correlated with a better sense of smell, that is a lower olfactory threshold, and that beta-blockers and acetylsalicylic acid negatively affected olfactory threshold, meaning a worse sense of smell. Acetylsalicylic acid also correlated inversely with odor identification, meaning again a worse sense of smell. CONCLUSIONS: The number of drugs taken demonstrated to be significantly correlated with a worse olfactory threshold and worse MMSE. Larger studies on elderly volunteers are needed to confirm these preliminary findings.

Prognostic impact and implications of extracapsular lymph node involvement in colorectal cancer: a systematic review with meta-analysis.

BACKGROUND: The extranodal extension (ENE) of nodal metastasis (i.e. the extension of tumor cells through the nodal capsule into the perinodal adipose tissue) has recently emerged as an important prognostic factor in different types of malignancies. However, the tumor-node-metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a systematic review and meta-analysis to determine the prognostic role of ENE in patients with lymph node-positive colorectal cancer. MATERIALS AND METHODS: Two independent authors searched PubMed and SCOPUS until 7 January 2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with colorectal cancer, comparing participants with the presence of ENE (ENE+) versus only intranodal extension (ENE-) were eligible. Data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) together with 95% confidence intervals (CIs) for time-dependent risk related to ENE+, adjusted for potential confounders. RESULTS: Thirteen studies including 1336 patients were identified with a median follow-up of 4.7 years. ENE was associated with a higher T stage and tumor grading. In addition, ENE was associated with a significantly increased risk of all-cause mortality (RR = 1.75; 95% CI 1.42-2.16, P < 0.0001, I(2) = 60%; HR = 1.69, 95% CI 1.32-2.17, P < 0.0001, I(2) = 46%) and of recurrence of disease (RR = 2.07, 95% CI 1.65-2.61, P < 0.0001, I(2) = 47%; HR = 2.31, 95% CI 1.54-3.44, P < 0.0001, I(2) = 48%). CONCLUSIONS: Based of these results, in colorectal cancer, ENE should be considered from the gross sampling to the pathology report, as well as in future oncologic staging systems.

Nephrolithiasis, bone mineral density, osteoporosis, and fractures: a systematic review and comparative meta-analysis.

Our meta-analysis demonstrates that people with nephrolithiasis have decreased bone mineral density, an increased odds of osteoporosis, and potentially an elevated risk of fractures. INTRODUCTION: People with nephrolithiasis might be at risk of reduced bone mineral density (BMD) and fractures, but the data is equivocal. We conducted a meta-analysis to investigate if patients with nephrolithiasis have worse bone health outcomes (BMD), osteoporosis, and fractures versus healthy controls (HCs). METHODS: Two investigators searched major databases for articles reporting BMD (expressed as g/cm2 or a T- or Z-score), osteoporosis or fractures in a sample of people with nephrolithiasis, and HCs. Standardized mean differences (SMDs), 95 % confidence intervals (CIs) were calculated for BMD parameters; in addition odds (ORs) for case-control and adjusted hazard ratios (HRs) in longitudinal studies for categorical variables were calculated. RESULTS: From 1816 initial hits, 28 studies were included. A meta-analysis of case-control studies including 1595 patients with nephrolithiasis (mean age 41.1 years) versus 3402 HCs (mean age 40.2 years) was conducted. Patients with nephrolithiasis showed significant lower T-scores values for the spine (seven studies; SMD = -0.69; 95 % CI = -0.86 to -0.52; I 2 = 0 %), total hip (seven studies; SMD = -0.82; 95 % CI = -1.11 to -0.52; I 2 = 72 %), and femoral neck (six studies; SMD = -0.67; 95 % CI = --1.00 to -0.34; I 2 = 69 %). A meta-analysis of the case-controlled studies suggests that people with nephrolithiasis are at increased risk of fractures (OR = 1.15, 95 % CI = 1.12-1.17, p < 0.0001, studies = 4), while the risk of fractures in two longitudinal studies demonstrated trend level significance (HR = 1.31, 95 % CI = 0.95-1.62). People with nephrolithiasis were four times more likely to have osteoporosis than HCs (OR = 4.12, p < 0.0001). CONCLUSIONS: Nephrolithiasis is associated with lower BMD, an increased risk of osteoporosis, and possibly, fractures. Future screening/preventative interventions targeting bone health might be indicated.

Baseline characteristics and treatment-emergent risk factors associated with cerebrovascular event and death with risperidone in dementia patients.

BACKGROUND: Use of antipsychotics to treat behavioural symptoms of dementia has been associated with increased risks of mortality and stroke. Little is known about individual patient characteristics that might be associated with bad or good outcomes. AIMS: We examined the risperidone clinical trial data to look for individual patient characteristics associated with these adverse outcomes. METHOD: Data from all double-blind randomised controlled trials of risperidone in dementia patients (risperidone n = 1009, placebo n = 712) were included. Associations between characteristics and outcome were analysed based on crude incidences and exposure-adjusted incidence rates, and by time-to-event analyses using Cox proportional hazards regression. Interactions between treatment (risperidone or placebo) and characteristic were analysed with a Cox proportional hazards regression model with main effects for treatment and characteristic in addition to the interaction term. RESULTS: Baseline complications of depression (treatment by risk factor interaction on cerebrovascular adverse event (CVAE) hazard ratio (HR): P = 0.025) and delusions (P = 0.043) were associated with a lower relative risk of CVAE in risperidone-treated patients (HR = 1.47 and 0.54, respectively) compared to not having the complication (HR = 5.88 and 4.16). For mortality, the only significant baseline predictor in patients treated with risperidone was depression, which was associated with a lower relative risk (P<0.001). The relative risk of mortality was increased in risperidone patients treated with anti-inflammatory medications (P = 0.021). CONCLUSIONS: Only anti-inflammatory medications increased mortality risk with risperidone. The reduced risks of CVAE in patients with comorbid depression and delusions, and of mortality with depression, may have clinical implications when weighing the benefits and risks of treatment with risperidone in patients with dementia.

Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer's disease.

PURPOSE: The purpose of the study is to evaluate whether donepezil (D) plasma concentrations and activity of CYP2D6 and CYP3A4 are associated with the therapeutic response of patients with mild to moderate Alzheimer's disease (AD). METHODS: This study comprised 54 patients affected by probable AD in therapy with D 10 mg/daily for at least 3 months. Plasma concentrations of D and its three main metabolites (6DD, 5DD, DNox) were assayed with a novel high performance liquid chromatography (HPLC) technique. Cognitive progression was assessed at baseline and at 9 months of follow-up with the mini mental state examination (MMSE). The activities of the two cytochromes involved in D metabolism-CYP2D6 and CYP3A4-were evaluated according to their metabolic ratios in plasma or urine, after test doses of probe drugs (dextromethorphan and omeprazole). RESULTS: A significant correlation was found between plasma levels of D and variations in MMSE scores after 9 months of therapy (r (2) = 0.14; p = 0.006). Neither the concentrations of D metabolites nor the metabolic ratios of CYP2D6 and CYP3A4 showed any correlations with cognitive variations. Low CYP2D6 activity and advanced age were associated with high D concentrations. Patients who were treated with CYP2D6 and P-glycoprotein (P-gp) inhibitors also had higher D plasma levels (mean difference = 19.6 ng/mL; p = 0.01) than those who were not. CONCLUSIONS: D plasma concentrations, but not cytochrome phenotyping, are associated with cognitive outcomes in AD patients.

High serum uric acid levels increase the risk of metabolic syndrome in elderly women: The PRO.V.A study.

BACKGROUND AND AIMS: Serum uric acid (SUA) is the end-product of purine metabolism in humans, and its levels often increase in subjects with metabolic syndrome (MetS). Despite several studies demonstrating a relationship between increased SUA levels and the prevalence of MetS, prospective data on SUA as a predictor of the incidence of MetS in the elderly are limited. Our aim was to conduct a prospective study on the association between SUA concentrations and the onset of MetS in an elderly Italian cohort. METHODS AND RESULTS: This is a cohort study (Progetto Veneto Anziani; Pro.V.A.) involving community-dwelling subjects aged ≥65 years and followed up for a mean 4.4 years. We included 1128 participants (aged 74.7 ± 7.1 years) without MetS at the baseline. Gender-specific SUA groups according to the standard deviation (SD) from the mean were considered, taking the incidence of MetS as the main outcome. The mean SUA level was significantly higher in men than in women (5.4 ± 1.2 vs. 4.5 ± 1.2 mg/dl; p < 0.0001). Over the 4.4-year follow-up, 496 individuals developed MetS. After adjusting for potential confounders, Cox's regression analysis revealed no relationship between higher baseline SUA concentrations and the incidence of MetS in men or in the sample as whole, while women with SUA levels more than 1 SD above the mean (≥5.7 mg/dl) carried a 58% higher risk (95%CI: 1.03-2.40; p = 0.03) of being newly diagnosed with MetS during the follow-up. CONCLUSION: High SUA levels significantly and independently predicted MetS in older women, but not in men, over a 4.4-year follow-up.

The Association Between Bone Mineral Density and Airflow Limitation in a Cohort of Fit Elderly Women.

PURPOSE: As studies examining the association between bone mineral density (BMD) and airflow limitation (AL) have produced conflicting results, the current one set out to analyze if and to what degree there are any correlations between these variables in a population of fit elderly women. METHODS: One hundred and twenty-one non-smoking, fit and healthy women (age ≥ 65 years) underwent anthropometric assessment, laboratory testing (serum 25-hydroxy vitamin D, parathormone, and cytokine levels), pulmonary function testing (PFT), and dual-energy X-ray absorptiometry to evaluate BMD values of the lumbar and femoral regions. RESULTS: A significant positive association was found between FEV1/FVC ratio (Tiffeneau index), a sensitive index of AL, and lumbar and femoral BMD; a 10 % increase in the FEV1/FVC ratio resulted in a significant increase of 0.025 g/cm2 in the total hip (p = 0.05), 0.027 g/cm2 in the femoral neck (p = 0.02), 0.028 g/cm2 in the femoral trochanter (p = 0.01), and 0.047 g/cm2 in the lumbar (p = 0.03) BMDs. Binary logistic analyses demonstrated more than a threefold higher risk of low BMD values for the lowest FEV1/FVC quartile in the lumbar (OR 4.62, 95 % CI 1.48-14.40, p = 0.008), total hip (OR 4.09, 95 % CI 1.28-13.05, p = 0.02 for the second quartile), and femoral trochanter regions (OR 3.90, 95 % CI 1.25-12.20, p = 0.02 for the third quartile). CONCLUSIONS: AL was associated with a higher risk of reduced BMD in healthy, fit elderly women.