Uric acid within the "normal" range predict 9-year cardiovascular mortality in older individuals. The InCHIANTI study.

BACKGROUND AND AIMS: Increased uric acid levels correlate with cardiovascular disease and cardiovascular/overall mortality. To identify a uric acid threshold above which cardiovascular mortality rises, we studied the relationship between uric acid concentration and overall/cardiovascular mortality. METHODS AND RESULTS: We analyzed data from the InCHIANTI study, a cohort study of Italian community-dwelling people with 9 years of follow-up. We selected a sample of 947 individuals over 64 years of age, free from cardio-cerebrovascular disease and with available uric acid measurement at baseline. The sample was divided according to plasma uric acid tertiles. The Hazard ratio (HR) for mortality was calculated by multivariate Cox proportional hazard model. Mean age of participants was 75.3 ± 7.3 years; the mean value of uric acid was 5.1 ± 1.4 mg/dl. Over 9-years of follow-up, 342 (36.1%) participants died, 143 deaths (15.1%) were due to cardiovascular disease. Subjects with higher uric acid concentrations presented a higher cardiovascular mortality [II (4.6-5.5 mg/dl) vs I (1.8-4.5 mg/dl) tertile HR: 1.98, 95%C.I. 1.22-3.23; III (≥5.6 mg/dl) vs I tertile HR: 1.87, 95%C.I. 1.13-3.09]. We found a non-linear association between uric acid concentrations and cardiovascular mortality with the lowest mortality for values of about 4.1 mg/dl and a significant risk increment for values above 4.3 mg/dl. CONCLUSION: In community-dwelling older individuals free from cardio-cerebrovascular events, the lowest 9-year cardiovascular mortality was observed for uric acid values far below current target values. If confirmed, these data might represent the background for investigating the efficacy of uric acid levels reduction in similar populations.

Lower Plasma Klotho Concentrations Are Associated with Vascular Dementia but Not Late-Onset Alzheimer's Disease.

BACKGROUND: The protein Klotho is involved in biological processes related to longevity, cardiovascular health, and cognition. Serum Klotho levels have been associated with better cognition in animal models; moreover, lower Klotho concentrations in cerebrospinal fluid from subjects with late-onset Alzheimer's disease (LOAD) have been reported. OBJECTIVE: Our study aimed to examine the possible relationship between Klotho plasma concentrations and cognitive status in the elderly. METHODS: We evaluated plasma Klotho levels in a sample of 320 elderly patients admitted to a Memory Clinic. Four groups of subjects were enrolled, including cognitively intact individuals complaining about memory loss (controls) and patients affected by LOAD, mild cognitive impairment, or vascular dementia (VD). The sample was stratified by plasma Klotho tertiles. RESULTS: Lower levels of plasma Klotho (1st tertile) were associated with older age, higher prevalence of VD, single/multiple lacunar infarcts and leukoaraiosis, coronary heart disease and stroke, and higher levels of creatinine, homocysteine, and high-sensitivity C-reactive protein. On multivariate logistic regression analysis, the risk of VD was 3- and 4-fold in subjects belonging to the 1st tertile (≤514.8 pg/mL, OR 3.54, 95% CI 1.05-11.93) and 2nd tertile (> 514.8, < 659.1 pg/mL, OR 4.28, 95% CI 1.30-14.06) compared to the 3rd tertile (≥659.1 pg/mL). A significantly increased VD risk was found for Klotho values < 680 pg/mL. CONCLUSION: In a sample of elderly individuals, we found a significant association between low plasma Klotho levels and VD, but not LOAD. This finding suggests that, although these 2 forms of dementia might overlap, some physiopathological mechanisms related to VD and LOAD remain distinct.

The relationship between hyperhomocysteinemia and neurodegeneration.

Homocysteine (Hcy) is a key junction in methionine metabolism. In inherited forms of hyperhomocysteinemia patients develop early vascular damage and cognitive decline. Hyperhomocysteinemia is a common consequence of dietary, behavioral and pathological conditions and is epidemiologically related to different diseases, among them neurodegenerative ones are receiving progressively more attention in the last years. Several detrimental mechanisms that see in Hcy a possible promoter seem to be implicated in neurodegeneration (protein structural and functional modifications, oxidative stress, cellular metabolic derangements, epigenetic modifications, pathological aggregates deposition, endothelial damage and atherothrombosis). Interventional studies exploring B group vitamins administration in terms of prevention of Hcy-related cognitive decline and cerebrovascular involvement have shown scant results. In this review, current and possible alternative/complementary approaches are discussed.

Cognitive Status According to Homocysteine and B-Group Vitamins in Elderly Adults.

OBJECTIVES: To determine the association between hyperhomocysteinemia and cognitive function, taking into account the effect of B group vitamin (BGV) deficiency. DESIGN: Cross-sectional. SETTING: Memory Clinic, S. Anna University Hospital, Ferrara, Italy. PARTICIPANTS: Elderly individuals (≥65) (N = 318; 44 normal cognition, 127 with cognitive impairment, 147 with dementia) divided into four groups according to plasma homocysteine (high vs normal) and BGV (normal vs deficit) levels. MEASUREMENTS: Cognitive, clinical, biochemical, functional, and neuroimaging parameters were evaluated. RESULTS: Hyperhomocysteinemia (>15 µmol/L) was associated with a higher prevalence of cognitive and functional impairment and dementia (odds ratio (OR) = 1.98, 95% confidence interval (CI) = 1.13-3.48), independent of BGV status and other confounders. Participants with hyperhomocysteinemia with normal BGV status had the worst functional status and the highest prevalence of dementia (high homocysteine/normal BGV vs normal homocysteine/normal BGV: OR = 3.20, 95% CI = 1.65-6.21). Homocysteine levels were correlated negatively with folate and vitamin B12 levels and glomerular filtration rate and positively with free thyroxine and uric acid levels (model coefficient of determination = 0.43). CONCLUSION: Hyperhomocysteinemia was associated with worse cognitive and functional status and dementia independently of BGV levels. Approximately half of participants with hyperhomocysteinemia had normal BGV levels, suggesting that other unmeasured factors might be associated with high homocysteine levels.

Subsyndromal delirium and its determinants in elderly patients hospitalized for acute medical illness.

BACKGROUND: In older individuals, acute medical illnesses and admission to hospital are often associated with a deterioration of cognitive status, also in the absence of dementia and full-blown delirium. We evaluated the prevalence of subsyndromal delirium (SSD) and its correlates in a sample of elderly medical inpatients. METHODS: From 763 consecutive inpatients, 325 participants with known dementia or delirium were excluded, whereas 438 (mean age: 80.6 years; female participants: 60.1%) were enrolled. SSD was diagnosed within 48 hour from admission, when at least two DSM-IV delirium criteria including disorientation, attention or memory deficit, altered level of consciousness, or perceptual disturbances were present. Cognitive performance was evaluated by Mini Mental Status Examination (MMSE). General, clinical, and laboratory parameters were also registered. RESULTS: One hundred and sixty-six patients (37%) had SSD. Compared with controls, SSD patients were older individuals, had less formal education, higher comorbidity, lower hemoglobin/lymphocytes counts, and higher creatinine levels. A trend toward higher prevalence of previous stroke and widowhood was observed. A MMSE score of less than 24/30 identified SSD with 88% sensitivity and 78% specificity. In SSD patients, MMSE independently correlated with years of education, high-sensitivity C reactive protein levels, and O2 arterial saturation (model adjusted r (2) = 0.30, p = .001); conversely, only years of education were associated with MMSE in controls (adjusted r (2) = 0.06, p = .01). CONCLUSIONS: Our data suggest that SSD is common in hospitalized older medical inpatients, and low MMSE score might be useful for identification of participants at risk of SSD. Current inflammatory response and reduced O2 arterial saturation were the only independent determinants of cognitive performance in SSD patients.

Prior antiplatelet drug use and short-term mortality in older patients with acute ischemic stroke (AIS).

Some studies suggest that previous treatment with antiplatelet agents (AA) might reduce ischemic stroke severity and improve outcomes in terms of clinical deficits or mortality. We evaluated the effect of the prior chronic use of AA on short-term (30 days) mortality in a sample of consecutive patients with AIS. Four hundred thirty-nine older patients (>65 years) with "major" AIS (modified Rankin scale ≥ 3) consecutively admitted to the University ward of Internal Medicine or Geriatrics were enrolled. Stroke was classified according to Oxfordshire Community Stroke Project (OCSP). Data recorded included: (1) clinical features; (2) medical history including home therapies, and vascular risk factors; (3) routine clinical chemistry analyzes (verb)/analyses (noun). Short-term (30 days) mortality was 27.6%. One hundred fifteen subjects (26.2%) were taking AA before admission. Compared with subjects not treated, subjects taking AA were characterized by higher prevalence of recurrent stroke (35% vs. 22%). In this group, a trend toward a higher prevalence of congestive heart failure (CHF), smoking, and altered levels of consciousness (ALC) was noted. Stroke type and short-term mortality (33% vs. 26.2%; odds ratio=OR=1.25; 95% confidence interval=CI=0.75-2.10, age and gender adjusted) were not different between the two groups. Adjustment for glucose, CHF, previous stroke, smoking, and ALC did not change mortality risk (OR=0.83; 95%CI=0.40-1.72). We conclude that in older patients hospitalized for "major" AIS, prior use of AA was not associated with any benefit in terms of short-term mortality both in patients with first, as well as in those with recurrent ischemic stroke.

Discharge diagnosis and comorbidity profile in hospitalized older patients with dementia.

OBJECTIVES: The aim of this study was to investigate the principal discharge diagnosis and related comorbidity in hospitalized older patients affected by dementia. METHODS: Data from 51,838 consecutive computerized discharge records of the St. Anna University Hospital (Ferrara, Italy) were analyzed. Records included only subjects aged ≥60 years. Number of admissions, length of stay in hospital, primary and secondary discharge diagnosis (by ICD-9-CM code), number of procedures, and possible death were evaluated. RESULTS: Demented patients represented 8.6% of the sample (4466 individuals) and were older and more likely to be female patients compared with controls (47,372 individuals); they were characterized by higher number of admissions to hospital, instrumental clinical investigations, secondary diagnoses, and mortality rate. Among the primary diagnoses, a higher prevalence of cerebrovascular disease, pneumonia, and hip fracture was observed in demented patients. Furthermore, pulmonary embolism, renal failure, septicemia, and urinary infections were frequently reported in demented patients, but not in controls. As regards secondary diagnoses, dementia was associated with an increased risk of delirium, muscular atrophy and immobilization, dehydration, cystitis, and pressure ulcers, whereas the risk for other conditions, including cancer, was reduced. CONCLUSIONS: Among older patients, dementia was associated with higher rate of admissions to hospital and mortality. Discharge diagnoses were sensibly different according to the presence of dementia; in particular, a greater load and a different kind of comorbidity were observed in demented patients. On the whole, our data suggest that the adequate management of demented outpatients might help to reduce hospitalization.

Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer's disease or vascular dementia: a case-control study.

BACKGROUND: In central nervous system cholesterol cannot be degraded but is secreted into circulation predominantly in the form of its polar metabolite 24(S)-hydroxycholesterol (24S-OH-Chol). Some studies suggested an association between 24S-OH-Chol metabolism and different neurological diseases including dementia. A possible decrease in 24S-OH-Chol plasma levels has been reported late onset Alzheimer's disease (LOAD) and vascular dementia (VD), but results of previous studies are partially contradictory. METHODS: By high-speed liquid chromatography/tandem mass spectrometry we evaluated the plasma levels of 24S-OH-Chol in a sample of 160 older individuals: 60 patients with LOAD, 35 patients with VD, 25 subjects affected by cognitive impairment no-dementia (CIND), and 40 (144 for genetics study) cognitively normal Controls. We also investigated the possible association between PPARgamma Pro12Ala polymorphism and dementia or 24S-OH-Chol levels. RESULTS: Compared with Controls, plasma 24S-OH-Chol levels were higher in LOAD and lower in VD; a slight not-significant increase in CIND was observed (ANOVA p: 0.001). A positive correlation between 24S-OH-Chol/TC ratio and plasma C reactive protein (CRP) levels was found in the whole sample, independent of possible confounders (multiple regression p: 0.04; r2: 0.10). This correlation was strong in LOAD (r: 0.39), still present in CIND (r: 0.20), but was absent in VD patients (r: 0.08). The PPARgamma Pro12Ala polymorphism was not associated with the diagnosis of LOAD, VD, or CIND; no correlation emerged between the Ala allele and 24S-OH-Chol plasma levels. CONCLUSIONS: Our results suggest that plasma 24S-OH-Chol levels might be increased in the first stages of LOAD, and this phenomenon might be related with systemic inflammation. The finding of lower 24S-OH-Chol concentrations in VD might be related with a more advanced stage of VD compared with LOAD in our sample, and/or to different pathogenetic mechanisms and evolution of these two forms of dementia.

Temporal prediction of touch instant during observation of human and robot grasping.

The aim of the present work was to test the ability to predict the instant at which a grasping hand touches an object. Our hypothesis was that, because of the activation of the mirror-neuron system, the same predictive process necessary for action execution should be active during observation. Experimental evidence indicates, however, that not only observed actions but also observed objects automatically activate observer's motor repertoire. What happens, therefore, if the observed action is different from the one automatically evoked by the vision of the object? To answer this question we presented subjects with two different grasping actions: the one most suitable for the presented object and a less appropriate one. Subjects were required to detect the instant at which the demonstrator's hand touched the object. In a further condition, subjects were required to detect the outcome of an action performed by a robotic arm moving with constant kinematics. Results showed that while in the case of robot grasping subjects responded before the touch instant, in the case of human grasping the response followed the touch instant, but occurred much earlier than simple reaction times. This demonstrates that subjects were able to predict the outcome of the seen action. The predictive capability was specifically enhanced during observation of the "suitable" grasping. We interpret these results as an indication of the synergic contribution of both object-related (canonical) and action-related (mirror) neurons during observation of actions directed towards graspable objects.