Loss of ARHGAP15 affects the directional control of migrating interneurons in the embryonic cortex and increases susceptibility to epilepsy.

GTPases of the Rho family are components of signaling pathways linking extracellular signals to the control of cytoskeleton dynamics. Among these, RAC1 plays key roles during brain development, ranging from neuronal migration to neuritogenesis, synaptogenesis, and plasticity. RAC1 activity is positively and negatively controlled by guanine nucleotide exchange factors (GEFs), guanosine nucleotide dissociation inhibitors (GDIs), and GTPase-activating proteins (GAPs), but the specific role of each regulator in vivo is poorly known. ARHGAP15 is a RAC1-specific GAP expressed during development in a fraction of migrating cortical interneurons (CINs) and in the majority of adult CINs. During development, loss of ARHGAP15 causes altered directionality of the leading process of tangentially migrating CINs, along with altered morphology in vitro. Likewise, time-lapse imaging of embryonic CINs revealed a poorly coordinated directional control during radial migration, possibly due to a hyper-exploratory behavior. In the adult cortex, the observed defects lead to subtle alteration in the distribution of CALB2-, SST-, and VIP-positive interneurons. Adult Arhgap15-knock-out mice also show reduced CINs intrinsic excitability, spontaneous subclinical seizures, and increased susceptibility to the pro-epileptic drug pilocarpine. These results indicate that ARHGAP15 imposes a fine negative regulation on RAC1 that is required for morphological maturation and directional control during CIN migration, with consequences on their laminar distribution and inhibitory function.

p140Cap Controls Female Fertility in Mice Acting via Glutamatergic Afference on Hypothalamic Gonadotropin-Releasing Hormone Neurons.

p140Cap, encoded by the gene SRCIN1 (SRC kinase signaling inhibitor 1), is an adaptor/scaffold protein highly expressed in the mouse brain, participating in several pre- and post-synaptic mechanisms. p140Cap knock-out (KO) female mice show severe hypofertility, delayed puberty onset, altered estrus cycle, reduced ovulation, and defective production of luteinizing hormone and estradiol during proestrus. We investigated the role of p140Cap in the development and maturation of the hypothalamic gonadotropic system. During embryonic development, migration of Gonadotropin-Releasing Hormone (GnRH) neurons from the nasal placode to the forebrain in p140Cap KO mice appeared normal, and young p140Cap KO animals showed a normal number of GnRH-immunoreactive (-ir) neurons. In contrast, adult p140Cap KO mice showed a significant loss of GnRH-ir neurons and a decreased density of GnRH-ir projections in the median eminence, accompanied by reduced levels of GnRH and LH mRNAs in the hypothalamus and pituitary gland, respectively. We examined the number of kisspeptin (KP) neurons in the rostral periventricular region of the third ventricle, the number of KP-ir fibers in the arcuate nucleus, and the number of KP-ir punctae on GnRH neurons but we found no significant changes. Consistently, the responsiveness to exogenous KP in vivo was unchanged, excluding a cell-autonomous defect on the GnRH neurons at the level of KP receptor or its signal transduction. Since glutamatergic signaling in the hypothalamus is critical for both puberty onset and modulation of GnRH secretion, we examined the density of glutamatergic synapses in p140Cap KO mice and observed a significant reduction in the density of VGLUT-ir punctae both in the preoptic area and on GnRH neurons. Our data suggest that the glutamatergic circuitry in the hypothalamus is altered in the absence of p140Cap and is required for female fertility.

Rho GTPases in Intellectual Disability: From Genetics to Therapeutic Opportunities.

Rho-class small GTPases are implicated in basic cellular processes at nearly all brain developmental steps, from neurogenesis and migration to axon guidance and synaptic plasticity. GTPases are key signal transducing enzymes that link extracellular cues to the neuronal responses required for the construction of neuronal networks, as well as for synaptic function and plasticity. Rho GTPases are highly regulated by a complex set of activating (GEFs) and inactivating (GAPs) partners, via protein:protein interactions (PPI). Misregulated RhoA, Rac1/Rac3 and cdc42 activity has been linked with intellectual disability (ID) and other neurodevelopmental conditions that comprise ID. All genetic evidences indicate that in these disorders the RhoA pathway is hyperactive while the Rac1 and cdc42 pathways are consistently hypoactive. Adopting cultured neurons for in vitro testing and specific animal models of ID for in vivo examination, the endophenotypes associated with these conditions are emerging and include altered neuronal networking, unbalanced excitation/inhibition and altered synaptic activity and plasticity. As we approach a clearer definition of these phenotype(s) and the role of hyper- and hypo-active GTPases in the construction of neuronal networks, there is an increasing possibility that selective inhibitors and activators might be designed via PPI, or identified by screening, that counteract the misregulation of small GTPases and result in alleviation of the cognitive condition. Here we review all knowledge in support of this possibility.

Hyperactivity of Rac1-GTPase pathway impairs neuritogenesis of cortical neurons by altering actin dynamics.

The small-GTPase Rac1 is a key molecular regulator linking extracellular signals to actin cytoskeleton dynamics. Loss-of-function mutations in RAC1 and other genes of the Rac signaling pathway have been implicated in the pathogenesis of Intellectual Disability (ID). The Rac1 activity is negatively controlled by GAP proteins, however the effect of Rac1 hyperactivity on neuronal networking in vivo has been poorly studied. ArhGAP15 is a Rac-specific negative regulator, expressed in the main subtypes of pyramidal cortical neurons. In the absence of ArhGAP15, cortical pyramidal neurons show defective neuritogenesis, delayed axonal elongation, reduced dendritic branching, both in vitro and in vivo. These phenotypes are associated with altered actin dynamics at the growth cone due to increased activity of the PAK-LIMK pathway and hyperphosphorylation of ADF/cofilin. These results can be explained by shootin1 hypo-phosphorylation and uncoupling with the adhesion system. Functionally, ArhGAP15-/- mice exhibit decreased synaptic density, altered electroencephalographic rhythms and cognitive deficits. These data suggest that both hypo- and hyperactivation of the Rac pathway due to mutations in Rac1 regulators can result in conditions of ID, and that a tight regulation of Rac1 activity is required to attain the full complexity of the cortical networks.

Disruption of ArhGAP15 results in hyperactive Rac1, affects the architecture and function of hippocampal inhibitory neurons and causes cognitive deficits.

During brain development, the small GTPases Rac1/Rac3 play key roles in neuronal migration, neuritogenesis, synaptic formation and plasticity, via control of actin cytoskeleton dynamic. Their activity is positively and negatively regulated by GEFs and GAPs molecules, respectively. However their in vivo roles are poorly known. The ArhGAP15 gene, coding for a Rac-specific GAP protein, is expressed in both excitatory and inhibitory neurons of the adult hippocampus, and its loss results in the hyperactivation of Rac1/Rac3. In the CA3 and dentate gyrus (DG) regions of the ArhGAP15 mutant hippocampus the CR+, PV+ and SST+ inhibitory neurons are reduced in number, due to reduced efficiency and directionality of their migration, while pyramidal neurons are unaffected. Loss of ArhGAP15 alters neuritogenesis and the balance between excitatory and inhibitory synapses, with a net functional result consisting in increased spike frequency and bursts, accompanied by poor synchronization. Thus, the loss of ArhGAP15 mainly impacts on interneuron-dependent inhibition. Adult ArhGAP15-/- mice showed defective hippocampus-dependent functions such as working and associative memories. These findings indicate that a normal architecture and function of hippocampal inhibitory neurons is essential for higher hippocampal functions, and is exquisitely sensitive to ArhGAP15-dependent modulation of Rac1/Rac3.

Functional status and mortality in older women with gynecological cancer.

BACKGROUND: Screening tools for the identification of vulnerable older patients with cancer are needed. Aim of this study is to measure the prognostic value of multiple screening tools for the assessment of mortality risk in oncogeriatrics. METHODS: The prognostic value of the following assessment tools was tested in 200 older women with gynecological cancer (mean age = 73.5 years) for 1-year mortality: Short Physical Performance Battery, usual gait speed, handgrip strength, Eastern Cooperative Oncology Group Performance Status scale, Karnofsky Performance Status scale, Vulnerable Elders Scale-13, activities of daily living, and instrumental activities of daily living. Cox proportional hazard models were performed to estimate the associations of the performance measures with mortality. Areas under receiver operating characteristic curves were also estimated. RESULTS: Twenty-three participants (11.5%) died during the follow-up. The Short Physical Performance Battery, usual gait speed, and instrumental activities of daily living were the only parameters significantly associated with mortality, even after adjustment for confounders. No statistically significant results were reported for other functional measures. Similar results were obtained when testing the predictive values of the performance measures at the receiver operating characteristic analyses. CONCLUSIONS: The Short Physical Performance Battery and especially the usual gait speed may represent promising tools for measuring the mortality risk of older cancer patients, thus potentially supporting clinical decisions. Further studies are needed to confirm and extend the present findings.

Vitamin D hormone: a multitude of actions potentially influencing the physical function decline in older persons.

Vitamin D, a secosteroid (pro)-hormone, has been traditionally considered as a key regulator of bone metabolism, and calcium and phosphorous homeostasis through a negative feedback with the parathyroid hormone. However, during the last 20 years, the role played by vitamin D has been largely revised by recognizing its pleiotropic action on a wide spectrum of systems, apparatuses and tissues. Thus, vitamin D has growingly been involved as a primary determinant of biological modifications and specific clinical conditions. The effect of vitamin D on skeletal muscle and related outcomes (including physical function decline and disability) is surely one of the most relevant to study in the context of global aging. In the present review, the subclinical and clinical consequences of vitamin D deficiency/insufficiency, extremely frequent conditions in older age, are described. Special focus is given to skeletal muscle and physical function. Limitations of available scientific evidence on the topic are also discussed.

Skeletal muscle and mortality results from the InCHIANTI Study.

BACKGROUND: Sarcopenia, the age-related loss of muscle mass, may not be an isolated process but is associated with an increase in fat mass. The aim of this study was to estimate the mortality risk of sarcopenia in the presence or absence of obesity. METHODS: Data are from 934 participants aged 65 years or older, enrolled in the "Invecchiare in Chianti" study, and followed for 6 years. At baseline, a peripheral quantitative computerized tomography (pQCT) scan was performed on all participants to evaluate the muscle density, and the muscular and fat cross-sectional areas of the calf. Walking speed was measured on a 7-m track. Cox proportional hazard models were performed to estimate the association of pQCT measures (per 1 standard deviation increase) with mortality. RESULTS: Unadjusted analyses showed significant associations of muscle density (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.69-0.88), muscle area (HR 0.75, 95% CI 0.66-0.86), and fat area (HR 0.82, 95% CI 0.73-0.92) with mortality. After adjustment for potential confounders, no body composition parameter was significantly associated with mortality. Walking speed (used as a reference measure to verify whether the negative results were due to peculiarities of the study sample) confirmed its well-established association with mortality risk (HR 0.73, 95% CI 0.60-0.88). These results did not change after the analyses were stratified according to sarcopenia and body mass index groups, and restricted to participants with frailty or a high inflammatory profile. CONCLUSIONS: Calf skeletal muscle and fat mass are not significant risk factors for mortality in community-dwelling older adults. Walking speed confirmed to be a powerful predictor of health-related events.

Self-assessed health status, walking speed and mortality in older Mexican-Americans.

BACKGROUND: Self-assessed health status (SAHS) and physical performance measures (in particular, walking speed) are strong predictors of health-related events. Nevertheless, the possible interaction between them in predicting major outcomes has not been clearly explored. OBJECTIVE: The aim of the study is to evaluate the predictive and additive value for mortality of a SAHS measure and a walking speed test. METHODS: Data are from 2,139 Mexican-Americans aged >or=65 years enrolled in the Hispanic Established Populations for Epidemiologic Studies of the Elderly, and followed for 5.8 years. At the baseline visit, participants were asked to answer to the question 'How is your health in general?' presented as a four-level Likert item (i.e., poor, fair, good, excellent). They were also asked to 'walk down and back as fast as it felt safe and comfortable' along an 8-ft track. Cox proportional hazard models, receiver operating characteristic (ROC) curve, and specificity/sensitivity analyses were performed to evaluate the predictive value of SAHS and walking speed for mortality. RESULTS: The mean age of the sample was 72.1 years. Participants reporting 'poor' SAHS were more likely to die compared to those with 'excellent' SAHS, even after adjustment for potential confounders (HR 1.52, 95% CI 1.10-2.10). Similar results were obtained for participants with slow walking speed (<0.29 m/s; HR 1.68, 95% CI 1.27-2.24; reference group: walking speed >or=0.81 m/s). A statistically significant, but weak, correlation between SAHS and walking speed was observed (Pearson's r=0.069, p=0.001). No significant differences in areas under curves from ROC analyses were reported for the prediction of mortality when the SAHS and walking speed were tested (alone or in combination). Both tests presented high specificity (>or=80%) for the prediction of mortality. CONCLUSION: SAHS and walking speed are not only significant and independent predictors of mortality in older Mexican-Americans, but also present a similar predictive value. The additive prognostic value of the two measures is limited.

Physical function and self-rated health status as predictors of mortality: results from longitudinal analysis in the ilSIRENTE study.

BACKGROUND: Physical function measures have been shown to predict negative health-related events in older persons, including mortality. These markers of functioning may interact with the self-rated health (SRH) in the prediction of events. Aim of the present study is to compare the predictive value for mortality of measures of physical function and SRH status, and test their possible interactions. METHODS: Data are from 335 older persons aged >or= 80 years (mean age 85.6 years) enrolled in the "Invecchiamento e Longevità nel Sirente" (ilSIRENTE) study. The predictive values for mortality of 4-meter walk test, Short Physical Performance Battery (SPPB), hand grip strength, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and a SRH scale were compared using proportional hazard models. Kaplan-Meier survival curves for mortality and Receiver Operating Characteristic (ROC) curve analyses were also computed to estimate the predictive value of the independent variables of interest for mortality (alone and in combination). RESULTS: During the 24-month follow-up (mean 1.8 years), 71 (21.2%) events occurred in the study sample. All the tested variables were able to significantly predict mortality. No significant interaction was reported between physical function measures and SRH. The SPPB score was the strongest predictor of overall mortality after adjustment for potential confounders (per SD increase; HR 0.64; 95%CI 0.48-0.86). A similar predictive value was showed by the SRH (per SD increase; HR 0.76; 95%CI 0.59-0.97). The chair stand test was the SPPB subtask showing the highest prognostic value. CONCLUSION: All the tested measures are able to predict mortality with different extents, but strongest results were obtained from the SPPB and the SRH. The chair stand test may be as useful as the complete SPPB in estimating the mortality risk.

Physical function, physical activity and recent falls. Results from the "Invecchiamento e Longevità nel Sirente (ilSIRENTE)" Study.

BACKGROUND AND AIMS: A fall is a common and traumatic event in the life of older persons. This study aims: 1) to explore the relationship between recent falls and measures of physical function in elders, and 2) to examine the role played by habitual physical activity in the relationship between recent falls and physical function. METHODS: We used baseline data from 361 community-dwelling persons aged > or = 80 years (mean age 85.9 yrs) enrolled in the "Invecchiamento e Longevità nel Sirente (ilSIRENTE)" study. Physical performance was assessed using the Short Physical Performance Battery (SPPB) and usual gait speed. Muscle strength was measured by hand grip strength. Functional status was assessed by the Basic (ADL) and Instrumental Activities of Daily Living (IADL) scales. Self-reported recent falls over the previous three months were recorded. Analyses of covariance were performed to evaluate the relationship between recent fall events and physical function measures. RESULTS: Fifty participants (13.9%) reported at least one recent fall. Physically active participants had fewer falls and significantly higher physical function compared with sedentary subjects, regardless of recent falls. Significant interactions for physical activity were found in the relationships of usual gait speed and SPPB with recent fall history (p for interaction terms <0.01). A difference in usual gait speed and SPPB according to history of recent falls was found only in physically active subjects. CONCLUSIONS: Physical performance measures are negatively associated with recent falls in physically active, but not sedentary, participants. Physical activity is associated with better physical function, independently of recent fall history.

The aging process and potential interventions to extend life expectancy.

Aging is commonly defined as the accumulation of diverse deleterious changes occurring in cells and tissues with advancing age that are responsible for the increased risk of disease and death. The major theories of aging are all specific of a particular cause of aging, providing useful and important insights for the understanding of age-related physiological changes. However, a global view of them is needed when debating of a process which is still obscure in some of its aspects. In this context, the search for a single cause of aging has recently been replaced by the view of aging as an extremely complex, multifactorial process. Therefore, the different theories of aging should not be considered as mutually exclusive, but complementary of others in the explanation of some or all the features of the normal aging process. To date, no convincing evidence showing the administration of existing "anti-aging" remedies can slow aging or increase longevity in humans is available. Nevertheless, several studies on animal models have shown that aging rates and life expectancy can be modified. The present review provides an overlook of the most commonly accepted theories of aging, providing current evidence of those interventions aimed at modifying the aging process.

Depression and physical function: results from the aging and longevity study in the Sirente geographic area (ilSIRENTE Study).

Depression in older persons represents a major issue because of its relevant prevalence and the associated higher risk of adverse health-related events. The aim of this study was to evaluate the relationship of depressive symptoms with measures of physical performance, muscle strength, and functional status. Data are from baseline evaluation of the ilSIRENTE Study (n = 364). Physical performance was assessed using the Short Physical Performance Battery and the 4-meter walking test. Muscle strength was measured by hand-grip strength. Functional performance was assessed using Basic and Instrumental Activities of Daily Living. Depression was defined by analyzing the different depressive manifestations included in the Minimum Data Set for Home Care Form: verbal expression of sad and/or anxious mood and demonstrated signs of mental distress. Analyses of covariance and linear regressions were performed to evaluate the relationship between depression and physical function. Participants with depression showed significantly worse results in all of the physical function tests. Subjects with depression presented significantly lower adjusted mean results for the 4-meter walking test (0.41 m/s; SE, 0.03) and the Short Physical Performance Battery score (5.68; SE, 0.38) compared with those without depression (0.50 m/s; SE, 0.01 and 6.93; SE, 0.21; all P < .01, respectively). Participants with depressed mood also presented a higher number of impaired instrumental activities of daily living (3.69; SE, 0.25) compared with participants with less than 3 depressive symptoms (2.85; SE, 0.14; P = .005). No significant difference was reported for the hand-grip strength and the Basic Activities of Daily Living scale. In conclusion, physical performance and functional status measures are significantly and negatively influenced by the presence of depression in community-dwelling older persons aged 80 years and older.

Anemia and cognitive performance in hospitalized older patients: results from the GIFA study.

BACKGROUND: Anemia represents a major risk factor for adverse health-related events in older persons. The aim of this study was to evaluate the association between hemoglobin levels/anemia and cognitive function in hospitalized older persons. METHOD: Data are from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study. Hemoglobin levels (in g/dL) were measured upon admission to hospital; anemia was defined according to the WHO criteria. Cognitive performance was assessed by the Abbreviated Mental Test (AMT) on admission; an AMT score <7 defined cognitive impairment. Logistic regressions and analyses of covariance were performed to evaluate the relationship between cognitive status and hemoglobin levels/anemia. RESULTS: Mean age of the sample (n = 13,301) was 72.0 years. Participants with cognitive impairment presented a higher prevalence of anemia (47%) compared to those without cognitive impairment (35%, p < 0.001). Adjusted logistic regressions showed that hemoglobin levels/anemia were significantly associated with cognitive impairment (OR = 0.96, 95%CI = 0.94-0.99, p = 0.004, and OR = 1.32, 95%CI = 1.18-1.48, p < 0.001, respectively). Patients with anemia and cognitive impairment at the hospital admission presented a higher number of impaired Activities of Daily Living compared to those with only one or none of the studied conditions (p for trend < 0.001). CONCLUSION: Low hemoglobin levels and anemia are independently associated with cognitive performance in older persons admitted to acute care units.

Effects of an occupational therapy program on functional outcomes in older stroke patients.

BACKGROUND: During the last decade, occupational therapy has gained increasing importance as component of the rehabilitation programs in disabled patients. OBJECTIVE: To evaluate the efficacy of occupational therapy programs in patients with a recent stroke. METHODS: We selected all patients with a primary diagnosis of ischemic stroke (n = 50) consecutively admitted to the two post-acute Geriatric Rehabilitation Units (CEMI 2 and 3) of the 'A. Gemelli' Hospital--Catholic University of Sacred Heart, Rome, Italy. Patients in the unit CEMI 3 (intervention group) received 8 weeks (3 h per day) of a combined rehabilitation program based on occupational therapy and physiotherapy. Patients admitted to the control unit (CEMI 2) received no input from the occupational therapist. RESULTS: Overall, patients had a moderate-to-severe impairment in basic activities of daily living; the mean ADL score was 30.8 (SD +/- 7.8) in the intervention group and 30.7 (SD +/- 6.1) in the control group (p = 0.9). After 8 weeks of treatment the mean ADL score in the intervention group was 13.2 (SD +/- 9.9) compared to 20.3 (SD +/- 11.5) in the control group (p = 0.02). Differences between the intervention and control groups were statistically significant for transfers (+2.8 vs. +1.6 points on the ADL scale, p = 0.006), locomotion (+3.4 vs. +1.7 points on the ADL scale, p = 0.01), dressing (+3.0 vs. +1.8 points on the ADL scale, p = 0.01) and self-care (+3.4 vs. +1.8 points on the ADL scale, p = 0.005). CONCLUSION: Our results show that patients with stroke who received occupational therapy had a greater level of independence in activities of daily living over a period of 8 weeks than patients who did not.

Association between daily pain and physical function among old-old adults living in the community: results from the ilSIRENTE study.

Little is known about the impact of pain on physical function among old-old subjects. The aim of the present cross-sectional study was to assess the association of daily pain with muscle strength and physical performance in a population of subjects aged 80 or older living in the community. We used data from baseline evaluation of the ilSIRENTE Study. Muscle strength was measured by hand grip strength. Physical performance was assessed using the physical performance battery score, which is based on three timed tests: 4-m walking speed, balance, and chair stand tests. Daily pain was defined as any type of pain or discomfort in any part of the body manifested every day over the 7 days preceding the assessment. Mean age of 273 participants was 85.1 (SD 4.6) years, 181 (66.3%) were women and 150 (54.9%) reported daily pain. After adjustment for potential confounders, participants with daily pain had lower grip strength and physical performance battery score (indicating worse performance) than other participants (hand grip strength: daily pain 31.5 kg, SE 1.4, no daily pain 35.0, SE 1.1, p = 0.02; physical performance battery score: daily pain 6.5, SE 0.3, no daily pain 7.2, SE 0.3, p = 0.05). Both hand grip strength and physical performance battery score progressively declined as pain severity increased. In conclusion, the present study shows that among old-old subjects living in the community, daily pain is highly prevalent and that this condition is associated with impaired muscle strength and physical performance.

Comorbidity and physical function: results from the aging and longevity study in the Sirente geographic area (ilSIRENTE study).

BACKGROUND: Physical function measures have gained increased importance in the evaluation of older persons. The presence of comorbidity is a major and growing issue in geriatrics. OBJECTIVE: To evaluate the relationship between comorbidity and physical function in community-dwelling older persons. METHODS: Data are from baseline evaluation of the ilSIRENTE study (n = 364). Physical performance was assessed using the Short Physical Performance Battery (SPPB) and the 4-meter walking test. Muscle strength was measured by hand-grip strength. Functional performance was assessed using Basic and Instrumental Activities of Daily Living (ADLs and IADLs, respectively). Comorbidity was defined as >or=3 clinical conditions. Analyses of covariance and linear regressions were performed to evaluate the relationship between comorbidity and physical function. RESULTS: The mean age of participants was 85.9 (SD = 4.9) years. About one third (37.4%) of participants reported >or=3 clinical conditions. Participants with comorbidity had significantly worse results in all the physical function tests. Participants with comorbidity had significantly lower adjusted results for the 4-meter walking test (0.444 m/s) and the SPPB score (6.131) compared to those without comorbidity (0.531 m/s and 7.221; all p = 0.001, respectively). Participants with comorbidity were more IADL-impaired (3.152) than participants without comorbidity (2.767; p = 0.04). No significant association of ADLs and hand-grip strength with comorbidity was reported. Similar strengths of association for the 4-meter walking test (per SD increase, beta = -0.280; p = 0.001) and the SPPB (per SD increase, beta = -0.285; p = 0.001) with comorbidity were reported. CONCLUSIONS: Physical function measures, especially walking speed and SPPB, are associated with comorbidity. Physical performance measures may improve the clinical evaluation of older persons.

The ilSIRENTE study: a prospective cohort study on persons aged 80 years and older living in a mountain community of Central Italy.

BACKGROUND AND AIMS: "Invecchiamento e Longevità nel Sirente" (Aging and Longevity in the Sirente geographic area, ilSIRENTE) aims at investigating the socio-demographic, functional, clinical and biological characteristics of all subjects aged 80 years and older residing in a well-defined mountain area of Central Italy. METHODS: Data are from the baseline evaluation of the ilSIRENTE prospective cohort study. A list of all persons living in the Sirente area was obtained from the Registry Offices of the 13 municipalities involved in the study. Data collection started in December 2003 and was completed in September 2004. Among the 429 residents older than 80 years eligible for the study, 364 accepted to participate (response rate 84%). Participants were assessed by trained staff who collected information on socio-demographic factors, clinical conditions, medication use, physical performance and muscle strength. All participants were also evaluated using the Minimum Data Set for Home Care (MDS-HC) form and a slightly modified version of the "Invecchiare in CHIANTI" study. RESULTS: The mean age of participants was 85.6 +/- 4.8 years (range 80-102 years), with over 20% of participants aged 90 years or older. More than 65% of participants were women. Most participants (70%) were independent or required limited assistance in performing basic activities of daily living (ADL), whereas 30% of participants were independent in instrumental activities of daily living (IADL). Cognitive function (assessed by the Cognitive Performance Score) was normal in 80% of the sample. Higher degrees of disabilities (defined as the sum of dependencies in ADLs and IADLs) were associated with worse physical performance and lower muscle strength. CONCLUSIONS: Data on the socio-demographic characteristics and health status of very old people living in the Sirente mountain community are discussed and compared with findings from other epidemiological studies.

Indwelling urethral catheter and mortality in frail elderly women living in community.

AIM: Urinary incontinence is one of the most common, disruptive and often disabling conditions affecting frail older people living in community. The aims of present study were to describe the prevalence of bladder catheter in a population of older women living in community and to examine the relationship between urinary catheter and mortality. METHODS: This was an observational cohort study. We analyzed data from the Italian Silver Network Home Care project that collected data on patients admitted to Home Care programs. A total of twelve Home Health Agencies participated in such project evaluating the implementation of the Minimum Data Set for Home Care (MDS-HC) instrument. A total of 1,004 women were enrolled in the present study. The main outcome measures were prevalence of bladder catheter and 1-year survival according to catheterization. RESULTS: The prevalence of incontinent patients with bladder catheter was 38.1%. Incontinent patients with indwelling bladder catheter did not show significant difference for age and comorbidity while they showed a significant higher level of physical and functional impairment, as expressed by higher score in activities of daily living (ADL) scale (6.5 +/- 1.3 vs. 5.5 +/- 2.2, P < 0.001) and higher prevalence of sensory impairment, pressure ulcers (44% vs. 12%, P < 0.001), and urinary tract infections (21% vs. 10%, P < 0.001). After adjusting for age and for all the variables significantly different between catheterized and not-catheterized subjects at baseline, subjects with indwelling bladder catheter were more likely to die compared to those without catheter (RR, 1.44; 95% CI 1.01-2.07). CONCLUSIONS: Catheterization has an important prognostic implication for frail old women living in the community, independent of age and other clinical and functional variables. A failure in decreasing the unnecessary bladder catheter use and the duration of catheterization among frail incontinent women should be considered an indicator of poor quality of care.