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En los últimos 15 años, algunos de los más grandes acuíferos cársticos italianos han sido estudiados con el fin de realizar mapas de vulnerabilidad intrínseca e integrada a la contaminación utilizando el método SINTACS. La búsqueda ha evidenciado que algunas características peculiares de los acuíferos cársticos pueden llegar a dificultar la definición de un valor fijo para los 7 parámetros SINTACS. Entre estas características, las más importantes son: el diferente nivel de heterogeneidad del sistema de drenaje, el diferente nivel de carstificación sea a nivel superficial o profundo, el espesor de la zona no saturada (a menudo de poco espesor, pero altamente carstificada). Por lo tanto para obtener una mejor conexión del mapa de la vulnerabilidad con la situación real existente en un determinado acuífero cárstico, los valores SINTACS para algunos parámetros han sido en ocasiones cambiados respecto a los valores oficiales. En este trabajo se presenta una propuesta preliminar de nueva puntuación, para obtener una mejor concordancia entre los mapas de vulnerabilidad intrínseca e integrada a la contaminación y a las condiciones hidroestructurales que pueden cambiar en los acuíferos cársticos.doi: doi en revision

Sono presentati e discussi alcuni dei principali risultati del progetto di ricerca nazionale (PRIN). Speleotemi di alcune grotte scelte dell’Italia settentrionale, centrale e meridionale sono stati studiati con diverse tecniche e datati in spettrometria di massa con il metodo U/Th. In generale, la velocità di accrescimento dopo aver raggiunto una massima velocità durante la prima parte dell’Olocene decresce sensibilmente. Si può notare come esista un’interrelazione tra temperatura media della grotta e velocità di accrescimento. I cambiamenti del δ13C mostrano un trend generalmente negativo, soprattutto durante il Tardiglaciale e la prima parte dell’Olocene. Soltanto durante gli ultimi 2 ka si nota un’inversione verso valori tendenzialmente positivi. I cambiamenti nel δ18O degli speleotemi delle grotte Savi (TS) e Frasassi (AN) mostrano un trend prevalentemente positivo durante l’Olocene (valori compresi tra -5 e -10 ‰); al contrario il trend della stalagmite delle Grotta di Carburangeli (PA) è negativo. La luminescenza eccitata da laser degli speleotemi della grotta Savi mostra i suoi massimi nella prima parte dell’Olocene, probabilmente in relazione con lo sviluppo di suoli forestali. I valori più bassi sono quelli degli ultimi 1,5 ka. Da uno sguardo d’insieme, i dati sono in accordo con le conoscenze sui cambiamenti climatici in Italia durante il Tardiglaciale e l’Olocene. Emergono tuttavia alcuni dati problematici che suggeriscono ulteriori ricerche. Some of the main result of a national research project (PRIN) are here presented and discussed. The speleothems of some selected caves of northern, central and southern Italy have been studied with different techniques and dated by U/Th mass spectrometry. In general, the growth rate shows a decrease during the middle and upper Holocene in all caves. A relationship between the annual growth rate and the cave mean annual temperatures seems evident. The δ13C changes show a generally negative trend, with a main slope during the Lateglacial and the fi rst part of Holocene. Only during the last 2 ka an inversion towards more positive values is occurring. The δ18O changes of the speleothems from Savi (TS) and Frasassi (AN) cave, show a mainly positive trend during the Holocene (range of values between -5 and -10‰); on the contrary the trend of Carburangeli cave (PA) stalagmite is negative. The laser induced luminescence of the spelothems of Savi cave shows the highest values during the fi rst part of the Holocene probably infl uenced by the soil and forest development. The lowest values are those of the last 1.5 ka. From an overall view, these data seem to fi t with the present day knowledge of the climatic and environmental changes of Italy. Nevertheless some problematic aspects arise suggesting further research work.

Background and aims: The prevalence of the preclinical phase of dementia varies greatly, according to the diagnostic criteria and assessment procedures applied. The purpose of this study was to estimate the prevalence of cognitive impairment according to the Aging-Associated Cognitive Decline (AACD) diagnostic criteria in an Italian elderly population. Methods: In a multicenter community-based prospective study, 4785 Italian subjects aged 65-84 years, randomly selected from the registries of 12 Italian municipalities, were assessed by personal and informant interviews, physical and neurological examinations and an extensive neuropsychological battery. Results: Of these older subjects, 274 (9.2%) fulfilled all the AACD criteria, whereas 561 (18.8%) fulfilled only 3 of them (AACD-3). When the two groups diagnosed according to AACD criteria (AACD and AACD- 3) were merged, the prevalence was 28.0% (28.3% for men, 27.6% for women). Two other groups of subjects were also identified: a) Subjects with Objective evidence of Cognitive Decline without cognitive complaints (OCD), 508 (17.0%), i.e., subjects with documented neuropsychological deficits, although neither subjects nor informants reported cognitive complaints; and b) Subjects with Cognitive Complaints without objective demonstrable cognitive deficits (CC), 44 (1.5%), i.e., subjects and/or informants reported cognitive complaints without evidence of neuropsychological deficits. Thus, taking into account the additional OCD group, a total of 1343 persons with cognitive impairment without dementia (45.0%) was identified. Conclusions: On the basis of our results, we estimate that 45% of our population-based Italian sample aged 65-84 years had some kind of cognitive deficits without dementia.

We used the quantitative theory of solubility of karst rocks of Shopov et. al, (1989, 1991a) in dependence of the temperature and other thermodynamic parameters to make reconstructions of past carbonate denudation rates. This theory produced equations assessing the carbonate denudation rates in dependence on the temperature or on the precipitation. We estimated the averaged denudation rate in the region to 14 mm/kyr or 38 t/km2 per year. We used this estimate as starting point and substituted our proxy records of the annual temperature and the annual precipitation in the equations of dependence of karst denudation rate on precipitation and temperature. This way we reconstructed variations of the annual karst denudation rate for the last 280 years in dependence on the annual precipitation and for the last 1250 years in dependence on the temperature. Both reconstructions produce quite reasonable estimate of the variations of carbonate denudation, which is within observed variation of 8- 20 mm/kyr (86% variation). Precipitation dependence of carbonate denudation produces 79 % variation in the denudation rate in result of the reconstructed variation of 300 mm/yr from the driest to the wettest year during the last 280 years. Temperature dependence of carbonate denudation due to temperature dependence of solubility of the carbonate dioxide produce only 9.3% variation in the denudation rate in result of the reconstructed variation of 4.7 deg. C during the last 1250 years, so it is negligible in respect of the precipitation dependence.

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon 4 allele of the APOE gene.

NT-proB-type natriuretic peptide (NT-proBNP) increases with age and is associated with all-cause mortality. With this study, we assessed its possible utilization as a marker of biological age in comparison with other variables. The study included 1079 non-institutionalized elderly subjects (mean age 72.8 ± 5.5 years, 561 women). Baseline measurements were performed of serum NT-proBNP and of some laboratory variables previously utilized to estimate biological age (creatinine, albumin, C-reactive protein, cholesterol, blood glucose, leukocytes, lymphocytes, hemoglobin, mean cell volume). During 7 years of follow-up, 114 all-cause deaths occurred. The logarithm of NT-proBNP was the most age-related parameter (r = 0.35, P P for trend = 0.0002). In conclusion, NT-proBNP was the best indicator of biological age, which can be estimated by simple formulas and might be used for prognostic purposes or as a surrogate end point in epidemiological and intervention studies.

Over the past 15 years several expeditions by French, American and especially Italian cavers have unveiled over 50 caves in the Cordillera de la Sal (Atacama Desert, Northern Chile). Many of these caves contain a variety of speleothems and minerals, some of which have rarely been observed within karst systems. Most of the secondary deposits in these caves are composed of halite, but also other halide, carbonate, sulphate, nitrate, phosphate, and silicate minerals have been found. Among the sixteen cave mineral species recognized, atacamite, darapskite, blödite, leonite, anhydrite, and especially antarcticite are worth mentioning. In one of the samples an unknown Ca-Sr-bearing chloride mineral has also been discovered, but it has not been possible to carry out detailed mineralogical analyses. These often-rare minerals have formed in this region due to the very extreme hyperarid and salt-rich environment. This research reports the mineralogical results and proposes the genetical mechanisms leading to the formation of antarcticite, powdery anhydrite, and the paragenesis of the halite-darapskite-blödite. This study also shows that Atacama caves may be excellent analogues to study weathering processes and subsurface secondary minerals in hyperarid and hypersaline environments on Mars.

ObjectiveThe role of diabetes as a predictor of mortality after stroke remains uncertain, and there are very few data for pre-diabetes. This study investigated the association of pre-diabetes and diabetes with 30-day and 1-year mortality after ischemic stroke (IS) and primary intracerebral hemorrhage (ICH).Research design and methodsBetween 2006 and 2013, 2076 patients with IS and 586 patients with ICH (median age 79) were admitted to hospital within 24 hours after stroke onset and were treated in a stroke unit, where they underwent measurement of glycated hemoglobin (HbA1c). Diabetes was retrospectively defined based on medical history, diagnosis during hospital stay or HbA1c ≥6.5% (48 mmol/mol). Pre-diabetes was defined as HbA1c of 5.7%–6.4% (39–47 mmol/mol). Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). HRs were used to test the association of pre-diabetes and diabetes with 30-day and 1-year mortality after stroke onset.ResultsAmong patients with IS, 830 had pre-diabetes and 632 had diabetes; 280 died within 30 days and the other 77 within 1 year. Among patients with ICH, 106 had pre-diabetes and 56 had diabetes; 150 died within 30 days and the other 92 within 1 year. In both stroke subtypes, pre-diabetes and diabetes were associated with higher 30-day mortality. In IS, however, the association was limited to patients with prestroke disability and very severe stroke. At NIHSS 25, HR was 1.58 (95% CI 1.07 to 2.35) for pre-diabetes and 1.67 (95% CI 1.14 to 2.46) for diabetes compared with normoglycemia. In ICH, the association was limited to women for pre-diabetes (HR 1.93, 95% CI 1.15 to 3.24) and to men for diabetes (HR 1.78, 95% CI 1.02 to 3.12). Prestroke glycemic status was unrelated to 1-year mortality.ConclusionsBoth pre-diabetes and diabetes predict short-term mortality after acute stroke, but the association varies depending on both prestroke and stroke-related characteristics. These findings may explain the heterogeneous results obtained by previous studies.

Background: Current data have shown that lung ultrasound (LUS) may be useful in the detection of interstitial lung disease (ILD) by the evaluation of B-lines, the sonographic marker of pulmonary interstitial syndrome. Nevertheless, no prospective study has compared LUS to chest X-ray (CXR) for ILD assessment, and there is no general agreement on the specific echographic diagnostic criteria for defining ILD. Objectives: The aims of this study were (1) to compare the accuracy of LUS and CXR in the detection of ILD using high-resolution CT (HRCT) as the gold standard and (2) to compare the accuracy of different echographic diagnostic criteria for ILD diagnosis. Methods: LUS was performed on 104 patients undergoing HRCT for suspected ILD. In 49 patients, a CXR scan performed within 3 months of HRCT was analyzed. ILD was defined as the presence of ≥5 B-lines in ≥3 chest areas. A total B-line score (TBLS) was also calculated, as in previous studies. The observers evaluating LUS and CXR were blinded to the HRCT results and clinical data. Results: On HRCT, ILD was assessed in 50 patients. CXR was specific (91%; 95% CI 80-100) but not sensitive (48%; 95% CI 28-67). Conversely, LUS showed high sensitivity (92%; 95% CI 84-99) and low specificity (79%; 95% CI 69-90). Using a TBLS, sensitivity did not change, while specificity decreased. Conclusions: LUS could be a sensitive tool for ILD detection. CXR and LUS have different but complementary features, and their combined use could reduce the need for HRCT. The use of different diagnostic criteria for defining ILD does not affect sensitivity but influences specificity.

Background Adipocyte-fatty acid binding protein (A-FABP) is an intracellular lipid transporter that mediates metabolically triggered inflammation, and it is associated with insulin resistance, atherogenic dyslipidemia, and cardiovascular risk. Aims The aim of this study was to evaluate A-FABP behavior in elderly people, and especially its association with liver steatosis at abdominal ultrasound. Method Cross-sectional study of two cohort of individuals with and without steatosis, with assessment of several clinical and laboratory variables. Prospective evaluation of liver steatosis remodeling after six years of follow-up. One hundred and fifty-six subjects aged over 65 years were enrolled. Results Serum A-FABP positively correlated with body fat percentage, total cholesterol, serum triglycerides and erythrocyte sedimentation rate. Unlike expected, high A-FABP levels were associated with absence of liver steatosis, while there was no evidence of association with steatosis grade changes after 6 years of follow-up. Conclusion Among individuals aging more than 65 years included in the study, A-FABP was inversely associated with liver steatosis. It can be argued, that still uncovered mechanisms modify A-FABP behavior in elderly people, especially its association with multifactorial diseases.

The study area of Tang sorkh Aquifer is located on the northern flank of the Derak anticline, a part of the Zagros Mountain Range, in the central-south of Iran. The study area is limited to undifferentiated non-salt Gachsaran Formation (NSGF), mainly composed of alternative layers of marl and marlstone, and gypsum. This paper is focused on the hydrogeological and hydrochemistry characteristics of the NSGF. A detailed geological cross section, perpendicular to the strike of the GF was prepared by detailed field surveying. The thickness of GF is 1,268 m, with 82 alternative units of marl, marlstone, gypsum, sandstone and limestone. The sub-aquifers are limited to four limestone, five gypsum, and one gypsum-halite units. The waters of these sub-aquifers emerge as springs or seepage into the Tang sorkh River (TR). The average discharge of springs emerging from limestone and gypsum units ranges between 0.3–8.4 and 0.5–0.75 l s−1, respectively. The source for sub-aquifers is mainly recharge from precipitation or river water. Marly layers disconnect the hydraulic connection between the sub-aquifers, directing the general flow parallel to the strikes. The lack of sinkholes and caves in the gypsum units is due to the small thickness of sub-aquifers, and consequently, low amounts of recharge water. The springs are classified into four groups based on their lithology, electrical conductivity, type of water, and trend of ion-concentration. The type of water in most of the springs is calcium-sulfate. The electrical conductivity is the main parameter to differentiate the hydrochemistry of the groups. The hydrochemistry of springs depends on the recharge from the TR, and the lithology of sub-aquifers and their adjacent units.

We studied whether increased blood homocysteine is a predictor for incident depression in a population-based cohort aged >or=65. A total of 240 men and 217 women were identified at baseline and were assessed 4 years later for depression (Geriatric Depression Scale, GDS >or=10 or use of antidepressants). Risk of incident depression was estimated for the highest gender-specific tertile of baseline plasma homocysteine compared to the other tertiles combined in a reference group. As deficiencies of B(12) and folate are the main determinant of increased blood homocysteine in old age, serum concentrations of these vitamins were also measured. In women only, the highest homocysteine tertile was associated with incident depression. However, women with combined serum B(12)/folate deficiency had the highest blood homocysteine but also a lower depression risk than vitamin-replete women. In conclusion, the data only moderately support the hypothesis that blood homocysteine is a predictor of depression.

Uncertainty about the definition of frailty is reflected by the development of many ways to identify frail people. We aimed to compare the validity of two frailty measures in participants of the Conselice Study of Brain Aging.Prospective population-based study with 4 year follow up.1,016 subjects aged 65 and over in a rural Italian population.For each participant, a Frailty Index (FI) and a Conselice Study of Brain Aging Score (CSBAS) were determined. The FI was created from 43 deficits according to a standardized methodology; 7 variables derived from a previously validated Easy Prognostic Score comprised the CSBAS.The FI had characteristic properties described in other population samples, with a gamma distribution, a 99% limit of about 0.64 and higher values in women than men. CSBAS and FI were strongly correlated with each other (r = 0.72) and both correlated with age (r = 0.32, r = 0.27, respectively). Each was independently predictive of death in a multivariate model, with greater specificity and sensitivity than age alone.Frailty can be measured by different tools and facilitates a more direct quantification of individual vulnerability than chronological age alone. Though the Frailty Index and the Conselice Study of Brain Aging Score are underpinned by different rationales, clinical utility will continue to motivate their development.

Poiano is the largest karst spring of the Emilia Romagna region (northern Italy). It drains an aquifer of unique properties composed of anhydrite with halite lenses at depth and gypsum at the surface (both with high NaCl content). Hydrogeological research has been undertaken using automatically recorded hourly data on temperature, electrical conductivity, and water level. Water feeding the Poiano spring is restricted within the gypsum/anhydrite outcrop between the Lucola, Sologno and Secchia rivers. Karstification in the Upper Secchia Valley only concerns the gypsum rocks mainly present along the border and in the shallower parts of the sulfate outcrop and does not appear to occur at depth. Data strongly support the hypothesis that the salt content in the spring water derives from active halokinetic movements. For the first time, the fundamental hydrogeological importance of the anhydrite part inside the sulfate rocks is demonstrated. If gypsum prevails over anhydrite the karst drainage network can extend deep into the rocks following a network of fractures and fissures. Instead, if in the deep parts of the aquifer anhydrite prevails over gypsum, the karst evolution cannot take place at depth and the structure of the underground drainage paths only follows near-surface paths in gypsum.

Background: It is unclear whether high levels of blood inflammatory proteins are associated with the risk of developing depression in late life. Methods: Blood C-reactive protein, interleukin (IL)-6, α1-antichymotrypsin (ACT), intercellular adhesion molecule 1, and tumor necrosis factor α were measured in an elderly cohort (n = 968). Major depression diagnosed according to clinical criteria and relevant depressive symptoms measured by the Geriatric Depression Scale (score ≧10) were assessed at baseline and 4 year later. Results: Baseline IL-6 and ACT were increased in both prevalent major depression and relevant depressive symptoms. Baseline ACT was increased in incident major depression. All associations weakened below significance after adjustment for possible confounders and multiple comparisons. Conclusions: Blood inflammatory proteins do not predict the risk of developing depression in older age.

Background. The associations of endogenous sex hormones with risk of dementia in the elderly population are not well known. Methods. The relationship of baseline serum total estradiol (E2) and free testosterone (FT) to 4-year risk of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) was examined in a dementia-free, population-based cohort of 433 women (mean age 74 years) and 376 men (mean age 73 years). Multivariable proportional hazards regression was used to adjust for sociodemographic and lifestyle variables, body mass index, apolipoprotein E genotype, cardiovascular conditions, and homocysteinemia. Results. Dementia developed in 71 women (46 AD, 21 VaD) and 39 men (23 AD, 12 VaD). In women with high E2 (serum E2 � 10 pg/mL), the multivariable-adjusted hazard ratio (HR) for dementia was 1.75 (95% confidence interval [CI], 1.06-2.89). The corresponding multivariable-adjusted HR for AD was 1.94 (95% CI, 1.04-3.61), whereas no association was found for VaD. No association with dementia was found for serum FT in women and for either serum E2 or FT in men. Conclusion. High serum E2 is an independent predictor for dementia and AD in elderly women.

This article highlights the relationship between speleothems growing inside gypsum caves and the particular climate that existed during their development. Speleothems in gypsum caves normally consist of calcium carbonate (calcite) or calcium sulphate (gypsum) and the abundance of such deposits greatly differs from zone to zone. Observations carried out over the last 20 years in gypsum caves subjected to very different climates (Italy, Spain, New Mexico, northern Russia, Cuba, Argentina) highlight wide variation in their cave deposits. In arid or semi-arid climates, the speleothems are mainly composed of gypsum, whilst in temperate, humid or tropical regions, carbonate formations are largely predominant. In polar zones no speleothems develop. These mineralogical details could be useful paleoclimatic indicators of climate change. The interpretation proposed is based on the fact that in gypsum karst the kind of speleothems deposited is determined by competition between the two principal mechanisms that cause precipitation of calcite and gypsum. These mechanisms are completely different: calcite speleothem evolution is mainly controlled by CO2 diffusion, while gypsum deposits develop mostly due to evaporation. Therefore, the prevalence of one kind of speleothem over the other, and the relationship between the solution–precipitation processes of calcite and gypsum, may provide evidence of a specific paleoclimate. Additionally, other non-common deposits in gypsum caves like moonmilk, cave rafts and dolomite speleothems can be used as markers for the prevalence of long, dry periods in humid areas, seasonal changes in climate, or rainfall trends in some gypsum areas. Moreover, the dating of gypsum speleothems could contribute paleoclimatic data relating to dry periods when calcite speleothems are not deposited. In contrast, the dating of calcite speleothems in gypsum caves could identify former wet periods in arid zones.

Background: Age-associated changes in the pulmonary system could be detected with imaging techniques. Widespread use of lung ultrasonography (US) requires characterization of a normal pattern. Objectives: To compare US and computed tomography (CT) findings in healthy subjects undergoing both techniques (with CT as the gold standard). Methods: We prospectively selected 59 subjects undergoing chest CT and US on the same day, without a history of smoking, respiratory symptoms, or known pulmonary pathologies. There were 44 patients in group 1 (age =60 years - elderly) and 15 patients in group 2 (age =50 years - young). Lung US was performed with a convex and a linear probe, and 10 chest areas per patient were analyzed. Convex and linear probe agreement was evaluated by means of the Cohen κ statistic; Fisher's exact test was used to compare categorical variables between groups. Results: Isolated B-lines were frequent in both group 1 (54.5%) and group 2 (40.0%); the number of chest areas positive for B-lines increased with age (16.1% in group 1 vs. 5.3% in group 2, p = 0.0028). In group 2, we found that 37.5% of subjects with B-lines had at least 1 chest area with multiple B-lines, but only 2 subjects had 2 or more. Moreover, in group 1 the chest CT documented a reticular pattern (2.3%), areas of increased density (9.1%), ground glass (6.8%), cysts (2.3%), bronchiectasis (22.7%), and bronchial thickening (6.8%); in group 2, only cysts (6.7%) and bronchiectasis (6.7%) were found. Conclusions: The senile lung is characterized by mild changes on CT and US. Chest areas positive for B-lines increase with age, and focal multiple B-lines can be found. However, diffuse patterns, especially in symptomatic subjects, suggest a different diagnosis.

Serum interleukin-6 (sIL6) is an acknowledged predictor of all-cause mortality in older age. A common G/C polymorphism has been identified at position −174 of the IL6 gene promoter (IL6−174G>C), but its associations with sIL6 and mortality are still unclear. Data from a population-based elderly cohort (n = 824) were used to study the associations of baseline sIL6 with the IL6−174 C-allele (C+) carrier status and all-cause mortality at 4 years, in the presence and absence of preexisting major diseases (PMD). Analyses were adjusted for socio-demographic factors and body-mass-index. Three-hundred-eighty-eight participants (47.1%) had PMD. Compared to the bottom sIL6 quartile, mortality increased both in presence [Hazard Ratio (HR) = 3.04; 95% confidence interval (CI): 1.48–6.25] and absence of PMD [HR = 3.91; 95%CI: 1.42–10.72] for the third higher sIL6 quartile, but only in presence of PMD for the top sIL6 quartile [HR = 2.30; 95%CI: 1.09–4.83]. In absence of PMD, C+ carrier status did not affect both sIL6 and mortality. In presence of PMD, C+ carrier status was associated with increased baseline sIL6 [odds ratio 2.01; 95%CI: 1.25–3.22, for all sIL6 quartiles above the bottom] but not with increased mortality risk. A survival advantage was even found for C+ carriers with PMD and sIL6 in the top quartile [HR = 0.31, 95%CI: 0.13–0.76]. In conclusion, although associated with increased sIL6 levels in presence of major diseases, the IL6−174 C-allele does not seem to have direct detrimental effects on survival in older age.

Background: In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitiveimpairmentanddementia.Incidencestudiesofthisissuearefew and have produced conflicting results. Objective: We investigated the relation between high plasma tHcy concentrations and risk of dementia and Alzheimer disease (AD) in an elderly population. Design: A dementia-free cohort of 816 subjects (434 women and 382 men; mean age: 74 y) from an Italian population-based study constituted our study sample. The relation of baseline plasma tHcy to the risk of newly diagnosed dementia and AD on follow-up was examined. A proportional hazards regression model was used to adjust for age, sex, education, apolipoprotein E genotype, vascular risk factors, and serum concentrations of folate and vitamin B-12. Results: Over an average follow-up of 4 y, dementia developed in 112 subjects, including 70 who received a diagnosis of AD. In the subjects with hyperhomocysteinemia (plasma tHcy 15 mol/L), the hazard ratio for dementia was 2.08 (95% CI: 1.31, 3.30; P 0.002). The corresponding hazard ratio for AD was 2.11 (95% CI: 1.19, 3.76; P 0.011). Independently of hyperhomocysteinemia and other confounders, low folate concentrations (11.8 nmol/L) were also associated with an increased risk of both dementia (1.87; 95% CI: 1.21, 2.89; P 0.005) and AD (1.98; 95% CI: 1.15, 3.40; P 0.014), whereas the association was not significant for vitamin B-12.

The cross-sectional association of functional impairment with several peripheral blood inflammatory markers (increased C-reactive protein (CRP), fibrinogen and leucocyte count, decreased cholesterol and albumin) was studied in 739 elderly community-dwellers. Functional measures included Tinetti test for gait and balance, and basic and Instrumental Activities of Daily Living. When considering each marker individually, only increased CRP was inversely associated with all functional measures independently of demographics, lifestyle, and comorbidity (P0.05). When considering the sum of positive markers, having more than one marker was also inversely associated with all functional measures (P0.05), but no clear gradient of impairment was found across increasing numbers of markers. When considering specific combinations of markers, having both increased CRP and at least another positive marker had a stronger association with functional impairment (P0.01 for all measures) than increased CRP alone (P0.05), or other positive markers alone or in combination (P0.05). In conclusion, in elderly individuals, peripheral blood markers of inflammation are associated with functional impairment independently of potential confounders. A specific combination of CRP with other markers provides a better correlate of functional impairment than both individual markers or a simple count of positive markers.

Literature data consistently show different prevalence estimates of dementia when different classification systems are used in the same population. Very few data are available for the oldest old of the elderly. We investigated the occurrence of dementia among 34 nonagenarians and centenarians according to four classification systems: the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, third edition revised (DSM-III-R) and fourth edition (DSM-IV), the World Health Organization’s International Classification of Diseases, 10th revision (ICD-10), and the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). Cognitive functioning, work, social function and independence in activities of daily living were evaluated by using an extensive neuropsychological examination. The prevalence (95% CI) of dementia was the following: 47.1% (95% CI 30.3–63.8) with the DSM-III-R criteria, 41.2% (95% CI 24.6–57.7) with the DSM-IV criteria, 29.4% (95% CI 14.1–44.7) with the ICD-10 criteria and 38.2% (95% CI 21.9–54.6) with the CAMDEX. The factors that best predicted disagreement between DSM-III-R and DSM-IV were calculation impairment and the presence or absence of personality changes. DSM-III-R and ICD-10 were differentiated by the weight given to executive functions that all have to be impaired according to ICD-10, whereas progressive deterioration differentiated CAMDEX from DSM-III-R. It should be noted that although the DSM-III-R diagnoses differ by a factor of 1.6 times from the ICD-10 and 1.2 times from the CAMDEX diagnoses, we are speaking about dementia, which is very frequent in nonagenarians and centenarians. Moreover, with regard to public health, an estimation of the number of subjects who will lose their autonomy is rather more useful and informative than simple prevalence figures of dementia by itself. In this light, classification systems, such as the ICD-10, that do not include impairment of social function as a criterion for assessing dementia become less adequate.

The possible involvement of oxidative damage and antioxidant protection has been suggested in the pathogenesis of dementia, a cognitive disorder whose prevalence increase with aging. In this study we investigated the relationship between dementia and plasma status of antioxidants and oxidative products in oldest-old subjects. Plasma levels of thiobarbituric acid-reactive substances (TBARS), vitamin A, vitamin E, coenzyme Q10 (CoQ10), and serum levels of selenium (Se) and zinc (Zn) were determined in 30 demented patients aged 90 to 107 years in comparison with 32 normal individuals aged 90 to 103 years. Dementia was diagnosed according to DSM-IV criteria. TBARS, vitamin A, vitamin E and CoQ10 were measured by HPLC method. Zn and Se were measured by absorption spectrometry. Vitamins were expressed as lipid-adjusted concentrations. Demented men had higher plasma TBARS (p = 0.037) and lower plasma lipid-adjusted vitamin E (p = 0.043) than normal men, whereas no difference was found for the remaining variables. No difference was found between demented and normal women for the variables of interest. In oldest-old men, but not in women, dementia seems to be associated with an enhanced lipid peroxidation and a reduced vitamin E reserve. It remains to be resolved, however, as to whether this enhanced oxidative stress is a cause or a result of lowered antioxidants.

Background: Cognitive assessment is thought to increase the ability of the physical phenotype of frailty to identify older persons at a higher risk for adverse outcomes. Objective: Data from a cohort of dementia-free community dwellers were used to investigate whether the clock drawing test (CDT), a quick and easy cognitive screening test, is associated with adverse health outcomes independently of the physical phenotype of frailty. Methods: This was a prospective population-based cohort study of 766 dementia-free Italian community dwellers aged 65 years or older. Baseline assessment included the physical phenotype of frailty, 3 different CDT protocols [Sunderland, Shulman, and the clock drawing interpretation scale (CDIS)], and several health confounders. Hazard ratios (HR) and odds ratio (OR) along with their corresponding 95% confidence intervals (CI) from models adjusted for frailty and sociodemographic and health confounders were used to estimate the independent association of the CDT with the 7-year risk of all-cause mortality and the 3-year risk of new and worsening disability, hospitalization, and fractures. Results: After adjustment for confounders, the Sunderland CDT was significantly associated with all-cause mortality independently of the physical phenotype of frailty (HR = 1.44, 95% CI 1.03-2.01, p = 0.031). However, compared to all nonfrail participants with a normal Sunderland CDT, the HR was 1.57 (95% CI 1.09-2.26, p = 0.016) for those with impairment on the Sunderland CDT only, 2.48 (95% CI 1.46-4.20, p = 0.001) for those with frailty only, and 2.52 (95% CI 1.34-4.77, p = 0.004) for those with both frailty and impairment on the Sunderland CDT. Mortality was unrelated to the CDIS CDT (p = 0.359) and the Shulman CDT (p = 0.281). No statistically significant relationship was found between nonlethal outcomes and any CDT protocol, although trends were found for an association of both the Sunderland CDT (p = 0.118) and the CDIS CDT with worsening disability (p = 0.154). Conclusions: In older persons, depending on the scoring system, the CDT may predict the mortality risk independently of the physical phenotype of frailty. However, combining the two measurements does not improve their individual prognostic abilities.

Background The population longitudinal study named “The Conselice Study” has been the focus of the present investigation. 65 years old or older participants of this population study on brain aging were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 46 genetic, phenotypic, clinical and nutritional factors on incident cognitive decline and incident dementia cases were investigated. Results A new statistical approach, called the Auto Contractive Map (AutoCM) was applied to find relationship between variables and a possible hierarchy in the relevance of each variable with incident dementia. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Moreover, few variables resulted to be aggregation points in the variable connectivity map related to cognitive decline and dementia. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. A risk map for age associated cognitive decline and dementia has been constructed and will be presented and discussed. Conclusion This map of variables may be use to identify subjects with increased risk of developing cognitive decline end/or dementia and provide pivotal information for early intervention protocols for prevention of dementia.

Data mining of a large data base from the population longitudinal study named "The Conselice Study" has been the focus of the present investigation. Initially, 65 years old or older participants were interviewed, underwent medical and cognitive examination, and were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 35 genetic and/or phenotypic factors with incident cognitive decline and dementia were investigated. The new mathematical approach, called the Auto Contractive Map (AutoCM), was able to show the differential importance of each variables. This new variable processing created a semantic connectivity map that: (a) preserved non-linear associations; (b) showed connection schemes; (c) captured the complex dynamics of adaptive interactions. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Few variables resulted to be aggregation points and were considered as major biological hubs. Three hubs were identified in the hydroxyl-methyl-gutaryl-CoA reductase (HMGCR) enzyme, plasma cholesterol levels and age. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. This data analysis method was compared with another mathematical model called mutual information relevance network and results are presented and discussed.

Among the age-related diseases, the development of cognitive impairments, in particular dementia, is the most devastating for the individual and has great social and healthcare costs. Accurate information is needed about the prevalence and incidence of cognitive disorders and the physiology of the aging brain. In particular, only scarce data are available about the relationship between aging, cognitive status and nutritional factors. In order to address these issues, we planned the Conselice Study, a longitudinal study of physiological and pathological brain aging. The center involved in the study was the municipality of Conselice, (Province of Ravenna), in the Northern-Italian Region Emilia-Romagna. A total of 1,016 subjects aged 65 years and over was enrolled at baseline. Information about cognitive status at 4-years of follow-up was collected from 940 of them. These data have been used to estimate prevalence and incidence of dementia in the elderly Italian population and to investigate the possible role of homocysteine as a predictor of dementia.

Hyperhomocysteinemia may be a risk factor for cognitive impairment. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine (Hcy) metabolism. Both the MTHFR 677C--T and the 1298A--C polymorphisms are associated with mild hyperhomocysteinemia, particularly in conditions of low folate status. The prevalence of these MTHFR polymorphisms and their relationships with plasma total Hcy (tHcy), serum folate and cognitive function was evaluated in 194 elderly Italian individuals: 122 healthy controls (73.8 +/- 7.1 years of age), 24 cognitively- impaired- not-demented individuals (78.6 +/- 9.3 years), and 48 subjects with Alzheimer dementia (AD = 26), vascular dementia (VD =22; 85.5 +/- 7.0 years). Twenty-one percent of all subjects were homozygous for 677C--T and 7 % for 1298A--C polymorphism. No significant relationship was found betweenMTHFR polymorphisms and age, cognitive status and type of dementia. Plasma tHcy did not differ significantly by MTHFR genotypes, but, subjects of all genotypes with low serum folate (12 nmole/l) had higher plasma tHcy (p0.001), than subjects with high serum folate (= 12 nmole/l). The study suggests that 677C--T and 1298A--C polymorphisms are common in the Northern Italian population, but do not significantly affect plasma tHcy levels of elderly individuals, even under conditions of low folate status. The lack of association of age and cognitive function with MTHFR genotypes argues against a negative selection for these polymorphisms.