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It is still unclear whether early glycemic profile after admission for acute ischemic stroke (IS) has the same prognostic significance in patients with lacunar and non-lacunar infarction. Data from 4011 IS patients admitted to a Stroke Unit (SU) were retrospectively analyzed. Lacunar IS was diagnosed by clinical criteria. A continuous indicator of early glycemic profile was calculated as the difference of fasting serum glucose (FSG) measured within 48 h after admission and random serum glucose (RSG) measured on admission. Logistic regression was used to estimate the association with a combined poor outcome defined as early neurological deterioration, severe stroke at SU discharge, or 1-month mortality. Among patients without hypoglycemia (RSG and FSG > 3.9 mmol/L), an increasing glycemic profile increased the likelihood of a poor outcome for non-lacunar (OR, 1.38, 95%CI, 1.24–1.52 in those without diabetes; 1.11, 95%CI, 1.05–1.18 in those with diabetes) but not for lacunar IS. Among patients without sustained or delayed hyperglycemia (FSG < 7.8 mmol/L), an increasing glycemic profile was unrelated to outcome for non-lacunar IS but decreased the likelihood of poor outcome for lacunar IS (OR, 0.63, 95%CI, 0.41–0.98). Early glycemic profile after acute IS has a different prognostic significance in non-lacunar and lacunar patients.

Aims We investigated age-specific rates of undiagnosed diabetes and prediabetes among patients with acute stroke. Methods We used data from 2223 patients with acute stroke consecutively admitted to an Italian Stroke Unit (SU) between 2010 and 2015. Information from medical records and glycated hemoglobin (HbA1c) measured on admission was retrospectively used to screen for diabetes and prediabetes defined according to standard criteria. Results Overall rate of diabetes undiagnosed at admission and diabetes still undiagnosed at SU discharge were 9.7% and 6.7% but age-specific prevalence peaked up to 12.0% and 9.0% after age 80. At admission, the proportion of all undiagnosed diabetes on total diabetes cases was one out of every two cases before age 60 and three out of every four cases after age 80. In these same age intervals, one out of every three diabetes cases was still undiagnosed at SU discharge. Regardless of age, about three out of ten patients with acute stroke had prediabetes. Less than 2% of these patients had a prediabetes diagnosis before or after SU admission. Conclusions In patients with acute stroke, diabetes is substantially underdiagnosed before age 60 and after age 80. Prediabetes is highly prevalent but mostly undiagnosed at all ages.

Objective To investigate whether oldest-old age (≥85y) is an independent predictor of exclusion from stroke rehabilitation. Design Retrospective cohort study. Setting Stroke unit (SU) of a tertiary hospital. Participants Elderly patients (N=1055; aged 65–74y, n=230; aged 75–84y, n=432; aged ≥85y, n=393) who, between 2009 and 2012, were admitted to the SU with acute stroke and evaluated by a multiprofessional team for access to rehabilitation. The study excluded patients for whom rehabilitation was unnecessary or inappropriate. Interventions Not applicable. Main Outcome Measures Access to an early mobilization (EM) protocol during SU stay and subsequent access to postacute rehabilitation after SU discharge. Analyses were adjusted for prestroke and stroke-related characteristics. Results 32.2% of patients were excluded from EM. Multivariable-adjusted odds ratios (ORs) of EM exclusion were 1.30 (95% confidence interval [CI], .76–2.21) for ages 75 to 84 years and 2.07 (95% CI, 1.19–3.59) for ages ≥85 years compared with ages 65 to 74 years. Of 656 patients admitted to EM and who, at SU discharge, had not yet fully recovered their prestroke functional status, 18.4% were excluded from postacute rehabilitation. For patients able to walk unassisted at SU discharge, the probability of exclusion did not change across age groups. For patients unable to walk unassisted at SU discharge, ORs of exclusion from postacute rehabilitation were 3.74 (95% CI, 1.26–11.13) for ages 75 to 84 years and 9.15 (95% CI, 3.05–27.46) for ages ≥85 years compared with ages 65 to 74 years. Conclusions Oldest-old age is an independent predictor of exclusion from stroke rehabilitation.

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: Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (Methods: We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. Results: Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had the highest admission hematoma volume (p < 0.01). Age was unrelated to all other ICH characteristics including HE. In elderly patients, multivariable adjusted risk of in-SU and 1-year mortality did not vary across age categories. Conclusions: Oldest-old subjects with acute supratentorial ICH have higher admission hematoma volume than young and young-old subjects but do not differ for other ICH characteristics. When taking into account confounding from ICH characteristics, risk of in-SU and 1-year mortality in elderly subjects with acute supratentorial ICH does not differ across age categories. Our findings question use of age as an independent criterion for stratification of mortality risk in elderly subjects with acute ICH.

Blood thyroid function tests (TFT) are routinely used to screen for thyroid disorders in several clinical settings. TFT on hospital admission may also be useful prognostic predictors of acute IS: according to recent evidence, poststroke outcome is better in patients with lower thyroid function and worse in those with higher thyroid function. However, previous reports are few and mostly compared patients with thyroid disorders to euthyroid patients. Thyroid disorders are known risk factors for cerebrovascular disease. However, hyperthyroidism is related to cardioembolic IS whereas hypothyroidism is related to atherosclerotic risk factors. Therefore, findings from available studies of TFT might just reflect the worse prognosis of cardioembolic IS compared to other IS subtypes. Another limitation of previous studies is the lack of information for older persons, who represent three quarters of all IS patients. In this paper, we investigated whether serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) measured on Stroke Unit (SU) admission are associated with early outcomes of acute IS in 775 euthyroid patients aged ≥ 65. years (mean age 80.1 ± 8.7. years). Two composite outcomes were investigated: poor functional outcome (death during SU stay or disability at SU discharge), and unfavorable discharge setting (death during SU stay, transfer from SU to other acute hospital unit or transfer from SU to long-term care-facilities as opposed to direct discharge home). Analyses were performed using logistic regression models. Curvilinear associations were tested including TFT as polynomial terms. Models were adjusted for demographics, prestroke, and IS-related confounders. We found that lower TSH had a complex curvilinear association with poor functional outcome and that the shape of the associations changed with age. At age 65, the curve was U-shaped: outcome risk decreased with increasing TSH, reached its minimum at TSH near 3.00. mUI/L and then started to rise. Between ages 70 and 75, however, the shape of the curve straightened and, starting from age 80 took an inverted U-shape: outcome risk rose with increasing TSH, reached its maximum at TSH values that progressively shifted upward with increasing age (from 1.70. mU/L at age 80 to about 2.20. mUI/L at age 90), then started to decrease. A linear inverse association was found between FT3 and unfavorable discharge setting. Our study suggests that measurement of TFT on SU admission can provide independent prognostic information for early outcomes of acute IS in older euthyroid patients.

Three thousand two hundred and ninety-eight patients admitted to our Stroke Unit with hemorrhagic, large artery atherosclerosis, cardioembolic, small-vessel occlusion, and undetermined etiology-cryptogenic strokes were included in the study. The circadian variability in onset in each stroke subgroup and the associations with various risk factors were analyzed. In each subgroup, a significant minority of patients suffered from stroke during sleep. In the ischemic group, hypercholesterolemia, paroxysmal atrial fibrillation, and previous myocardial infarction facilitated the onset during waking. During waking, stroke onset was significantly higher in the morning compared to the afternoon both in the hemorrhagic and in the ischemic type. In hemorrhagic stroke, a previous stroke was associated with a lower early morning occurrence. In large artery atherosclerosis stroke, males were at higher risk of early morning occurrence (p<0.01). In small-vessel occlusion stroke, hypertension is significantly more present in the morning compared to the afternoon onset (p<0.005). Circadian patterns of stroke onset were observed both in hemorrhagic and in ischemic stroke, irrespective of the ischemic subgroup. In all groups, stroke was more likely to occur during waking than during sleep and, in the diurnal period, during morning than during afternoon. Moreover, sex and some clinical factors influence the diurnal pattern.

The incidence of ischemic stroke rises exponentially with age, with a steep increase in the age interval between 75 and 85 years. Thrombolytic therapy restores cerebral blood flow in patients with acute ischemic stroke of any etiology by using drugs that dissolve blood clots. Infusion for 1 h of alteplase at the dose of 0.9 mg/kg within 3 h of the start of the symptoms is associated to a 30% increase in the likelihood of gaining a favorable outcome with respect to placebo. There is strong evidence that selected patients with ischemic stroke may benefit from intravenous thrombolysis when treated within 3 h. The aim of the study was to evaluate available evidence for the efficacy and safety of thrombolytic therapy in patients with ischemic stroke aged 80 years and over. Compared to younger stroke patients treated with thrombolytic therapy, those aged 80 years and over have higher acute mortality due to symptomatic intracranial hemorrhage. However, functional outcome at six months is significantly better for over-80-year-olds than younger patients. There is a need for screening tools that take into account pre-stroke functional and cognitive status that are able to identify those over-80-year-old patients with ischemic stroke who can most benefit from thrombolytic treatment. Available evidence supports further recruitment of oldest-old patients into ongoing trials of thrombolysis.

Objectives Plasma total homocysteine (tHcy) is a risk factor for ischemic stroke (IS) but its relationship with IS outcome is uncertain. Moreover, previous studies underrepresented older IS patients, although risk of both hyperhomocysteinemia and IS increases with age. We investigated whether, in elderly patients with acute IS, tHcy measured on admission to the Stroke Unit (SU) is an independent predictor of SU discharge outcomes. Materials and Methods Data are for 644 consecutive patients aged 80.3 ± 8.7 years, admitted to an Italian SU with diagnosis of acute IS. Plasma tHcy was measured on SU admission. Investigated outcomes included mortality during SU stay and poor functional status (modified Rankin Scale score ≥3) at SU discharge for survivors. The association of plasma tHcy with the study outcomes was assessed using Odds Ratios (OR) and their corresponding 95% confidence intervals (95%CI) from logistic regression models adjusted for demographics, pre-stroke features, IS severity, and laboratory data on SU admission (serum C-reactive protein, serum albumin, and renal function). Results Median plasma tHcy was 16.7 μmol/L (interquartile range, 13.0–23.3 μmol/L). Outcome incidence was 5.3% for mortality and 49.7% for poor functional status. Plasma tHcy was unrelated to mortality in both univariate and multivariable-adjusted analyses. Conversely, plasma tHcy was associated with poor functional status of survivors in univariate analyses (P = 0.014). Multivariable-adjusted analyses showed that, compared to normal homocysteinemia (tHcy

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.

MCI is regarded as a precursor of dementia, but not all patients with MCI actually develop dementia. As Alzheimer and vascular dementia (AD and VD, respectively) are thought to share many common etiopathogenetic mechanisms, we investigated whether the vascular risk factor atrial fibrillation affect the risk of conversion to dementia for different MCI subtypes diagnosed according to international criteria. One-hundred-eigthy elderly outpatients with MCI and 431 elderly outpatients with a normal cognition were followed-up for a mean of 3 and 4 years, respectively. The risk of conversion to dementia associated with atrial fibrillation was studied in both samples using a Cox proportional-hazards model adjusted for sociodemographic and medical variables. Overall conversion rate to dementia was 10.5 (8.0–13.8) per 100 person-years in the MCI group and 2.2 (1.5–3.1) per 100 person-years in the normal cognition group. Atrial fibrillation was significantly associated with conversion to dementia (hazard ratio = HR = 4.63, 95% confidence interval = Cl = 1.72–12.46) in the MCI group, but not in the cognitively normal group (HR = 1.10, 95% Cl = 0.40–3.03). Current diagnostic criteria for MCI subtypes define heterogeneous populations, but atrial fibrillation can be useful in identifying people with increased risk of conversion to dementia.

OBJECTIVE—Little is known about the prevalence of the metabolic syndrome among elderly people in Italy, its association with all-cause mortality, and whether measurement of serum C-reactive protein (CRP) and interleukin (IL)-6 affects this association. RESEARCH DESIGN AND METHODS—The baseline prevalence of metabolic syndrome, diagnosed according to the National Cholesterol Education Program (NCEP) criteria, and all-cause mortality at 4 years were recorded in an Italian population-based cohort (981 subjects, 55% women, aged 65–97 years). A Cox model adjusted for sociodemographic, lifestyle, and medical variables was used to investigate 1) whether metabolic syndrome was a predictor of mortality and 2) how the association was affected by baseline high CRP (>3 mg/l) and IL-6 (>1.33 pg/ml). RESULTS—Overall, metabolic syndrome prevalence was 27.2% [95% CI 24.0–30.5] and higher in women (33.3% [28.7–38.0]) than in men (19.6% [15.5–24.2]). During follow-up, 137 deaths occurred. Using the no metabolic syndrome/no high IL-6 group as the reference, mortality was not associated with the metabolic syndrome alone (multivariable-adjusted hazard ratio 1.24 [0.60–2.59]), only weakly associated with high IL-6 alone (1.66 [1.04–2.63]), but strongly associated with the concurrent presence of metabolic syndrome and high IL-6 (3.26 [2.00–5.33]). High CRP was not a mortality predictor (0.83 [0.58–1.20]) nor did it affect the association of the other variables with mortality. CONCLUSIONS—Metabolic syndrome by NCEP criteria is highly prevalent in the Italian elderly population. It is not itself associated with mortality but may improve the usefulness of IL-6 as a mortality predictor in older age.

Objectives: To determine the usefulness of physical phenotype of frailty, cognitive impairment, and serum albumin for risk stratification of elderly medical impatients. Design: Prospective, observational cohort study. Setting: A general internal medicine unit of a university hospital in Italy. Participants: Inpatients with an average age of 80.8 ± 7.5 yr (N=470). Measurements: Frailty was defined using the Study of Osteoporotic Fractures Index, a parsimonious version of the physical phenotype (two of the following markers: weight loss, inability to rise five times from a chair, and exhaustion). Two frailty markers from non-physical dimensions were also evaluated: cognitive impairment (Mini-Cog score < 3) and low serum albumin on ward admission (< 3,5 gr/dl). Logistic regression adjusted for preadmission and admission-related confounders was used to investigate whether the physical phenotype of frailty and the two non-physical markers were associated with ward length of stay and unfavorable discharge (death plus any other ward discharge disposition different from direct return home). Areas Under the receiver operating characteristic Curve (AUCs) and Likelihood Ratios (LRs) were used for evaluation of discriminatory ability and clinical usefulness of significant predictors. Results: The physical phenotype of frailty was associated with both study outcomes (p

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. Recent prospective studies reported that increased plasma homocysteine levels are an independent predictor of osteoporotic fracture in elderly persons. These studies, however, did not take into account folate and vitamin B12, which are the major nutritional determinants of homocysteinemia. Methods. Incident osteoporotic fractures were assessed in 702 Italian participants aged 65–94 years with a mean follow-up of 4 years (1999/2000–2003/2004). A multivariable logistic regression model was used to study the relation of baseline plasma homocysteine, serum folate, and serum vitamin B12 with risk of fracture. Results. After adjustment for sociodemographic and clinical confounders, the odds ratio (OR) for each increase of 1 standard deviation in log-transformed plasma homocysteine was 1.39 (95% confidence interval [CI], 1.01–1.91), but decreased to 1.22 (95% CI, 0.85–1.74) after further adjustment for serum folate and vitamin B12. The corresponding multivariable-adjusted OR for hyperhomocysteinemia (plasma total homocysteine [tHcy] . 15 lmoL) was 1.58 (95% CI, 0.71–3.53). Participants in the lowest serum folate quartile (� 9.3 nmol/L) had an increased risk of fracture than did those in higher quartiles (multivariable-adjusted OR ¼ 2.06; 95% CI. 1.02–4.18), but no dose-related protective effect for increasing serum folate levels was found (multivariable-adjusted OR ¼ 0.84 for each increase of 1 standard deviation in log-transformed serum folate, 95% CI, 0.59–1.19). No independent association was found for serum vitamin B12. Conclusions. Low serum folate is responsible for the association between homocysteine and risk of osteoporotic fracture in elderly persons.

Background and aims: Identification of patients with Mild Cognitive Impairment (MCI) is strongly recommended because of their increased risk of dementia. Two brief global cognitive instruments, the Mini Mental State Examination (MMSE) and the Clock Drawing Test (CDT), were examined as useful screening methods for MCI. Methods: The sensitivity and specificity of MMSE and CDT, scored using the Sunderland and Wolf-Klein methods, were evaluated in 113 elderly individuals with three different MCI subtypes: amnestic, multiple domain impairments, and single non-memory domain. Diagnoses were made on the basis of extensive clinical and neuropsychometric assessment. Results: Used alone, MMSE and CDT at standard cut-offs were highly specific (about 0.80) but rather insensitive (less than 0.50) to all MCI subtypes. By contrast, when used in combination, an abnormal result on either MMSE or CDT scored by the Sunderland method had a specificity of 0.69 [0.57–0.81] and a sensitivity of 0.75 [0.64–0.87] for multiple domain impairments MCI. Results were similar for MMSE in combination with CDT scored by the Wolf-Klein method (specificity 0.71 [0.59–0.83]; sensitivity 0.68 [0.56–0.80]). Conclusions: MMSE and CDT alone are not valid screening methods for MCI detection. In combination, they reach fair sensitivity and specificity for the multiple domain impairment MCI subtype. However, some theoretical concerns relating to this subtype, together with the uncertainty that still lingers about its prognostic value, caution against routine use of MMSE and CDT as MCI screening instruments.

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.

BACKGROUND Chronic low-grade inflammation, as measured with the peripheral serum marker C-reactive protein (sCRP), may be a risk factor for dementia in elderly persons. METHODS The relationship between sCRP and score on the Mini-Mental State Examination (MMSE), a commonly used screening cognitive measure, was investigated in 540 well functioning, healthy, and cognitively normal elders (age 73 +/- 6 years). Sociodemographic status, lifestyle, health status, traditional and nontraditional cardiovascular risk factors including plasma total homocysteine (tHcy), and other peripheral blood markers of vascular inflammation (leukocyte count, serum albumin, and plasma fibrinogen) were also assessed. RESULTS Risk for having sCRP in the highest decile (>0.7 mg/dl) was significantly higher in individuals with MMSE score 24-25 (odds ratio = 3.07, 95% confidence interval, 1.2-7.9) and 26-28 (odds ratio = 2.10, 95% confidence interval, 1.1-3.9) compared with those scoring above 28 (reference group). Results were unaffected by adjustment for all potential confounders. No association was found between MMSE and peripheral markers of vascular inflammation other than sCRP, but lower MMSE scores were also independently associated with hyperhomocysteinemia (plasma tHcy > 15 mmol/L). CONCLUSION In healthy, cognitively normal elderly community dwellers, increased sCRP levels are associated with concurrent cognitive impairment as measured by MMSE. The association is independent of sociodemographic status, lifestyle, health status, and traditional and nontraditional cardiovascular risk factors including hyperhomocysteinemia. Results support the hypothesis that chronic low-grade inflammation may be involved in age-related cognitive impairment.

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.

Elevated plasma total homocysteine (tHcy) concentrations are common in the elderly and have been suggested to be a risk factor for dementia.In an elderly population, we examined the relation between plasma tHcy and scores on the Mini-Mental State Examination (MMSE), a commonly used screening measure of cognitive impairment in general practice.Fasting plasma tHcy concentrations were measured in 650 healthy, cognitively normal Italian community dwellers agedor = 65 y (x +/- SD: 72.8 +/- 6.0 y). Socioeconomic status; serum folate, vitamin B-12, and creatinine; other potential dietary and lifestyle determinants of tHcy; and conventional vascular disease risk factors were also assessed.Subjects with MMSE scores of 26-28 had higher plasma tHcy concentrations (12.7 micromol/L; range: 12.2-13.2 micromol/L) than did those with scores28 (11.9 micromol/L; 11.4-12.3 micromol/L; P0.01). Subjects with scores of 24-25 had higher plasma tHcy concentrations (14.5 micro mol/L; 13.5-15.6 micromol/L) than did subjects with scores of 26-28 (P0.01) or28 (P0.001). The risk of hyperhomocysteinemia (plasma tHcy15 micromol/L) was higher in subjects with scores of 24-25 (odds ratio: 3.81; 95% CI: 1.9, 7.5) or 26-28 (odds ratio: 1.96; 95% CI: 1.3, 3.0) than in those with scores28. The results did not change after adjustment for conventional vascular risk factors and for age, medical, dietary, and lifestyle determinants of plasma tHcy.Elevated plasma tHcy has an independent, graded association with concurrent cognitive impairment as measured with the MMSE in healthy elderly community dwellers.

To evaluate whether performance in the clock-drawing test (CDT) is associated with sociodemographic status and risk factors for cognitive impairment, we examined 744 Italian community dwellers aged ≧65 (73 ± 6) years scoring ≧24 on the MMSE. CDT was scored by two different methods, the Sunderland and the Wolf-Klein methods. Sociodemographic, lifestyle, clinical and biochemical variables were also recorded. For both scoring methods, lower CDT scores were associated with age, poor education, increased serum C-reactive protein and history of cancer. Associations of lower CDT scores with increased serum glucose and history of cerebrovascular disease were also found for the method with the highest sensitivity to cognitive impairment. This study shows that in elderly community dwellers, CDT may be not totally free from sociodemographic biases, and that it is associated with risk factors for cognitive impairment and frailty.

Physical activity has been reported to affect endocrine function in elderly men.To establish an association between regular moderate physical activity and endogenous anabolic hormone levels in healthy aging men.Twenty four middle-aged (57.4+/-4.7 years) and 24 elderly (68.3+/-2.6 years) physically active men who in the past 10 years had been regularly bicycling during leisure time were compared with 24 middle-aged (57.9+/-4.0 years) and 24 elderly (67.2+/-1.7 years) sedentary men. Groups did not differ for body composition.Serum dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I (IGF-1), free testosterone (FT), and thyroid hormone levels were assessed.In general, elderly men had lower IGF-1 (P0.001), DHEAS (P=0.013), and triodothyronine levels (P0.001) than their middle-aged counterparts. Independently of age, however, physically active men had on average higher IGF-1 (P=0.031), DHEAS (P=0.001), and triodothyronine serum levels (P0.001) than sedentary men. FT and thyroid stimulating hormone (TSH) serum concentrations did not differ across age groups, but physically active men had lower TSH values than sedentary men (P=0.021).Our results suggest that, in aging men, regular moderate physical activity is associated with higher levels of IGF-1 and DHEAS levels and with thyroid function alterations.

Trace elements such as zinc (Zn) and selenium (Se) play an important role in maintaining the metabolic homeostasis in elderly people and the risk of deficiency seems to increase in proportion to the age. Zn and Se concentrations, as indices of the micronutrient status in healthy subjects over 90 years, are scarcely analyzed and could represent a model for studying the physiology of successful aging. Our aim was to investigate Zn and Se concentrations in the healthy persons over the age of 90 years. One hundred and fifty two subjects volunteered for the study. They were divided into two groups: 90 non-institutionalized nonagenarians/centenarians (91-110 years) (group A) and 62 elderly subjects (60-90 years) used for comparison (group B). Serum concentrations of Zn and Se were determined, respectively, by flame atomic absorption spectrophotometry (FAAS) and electrothermal atomic absorption spectrophotometry (ETAAS). The effect of age and sex on ion concentrations was investigated. Mean values+/-standard deviation of Zn and Se concentrations in the group A were 11.97+/-2.00 and 0.87+/-0.28 micromol/l, respectively. A significant decrease of Se and Zn values was demonstrated in group A, when compared with group B, in both males and females. However, 84.4% of the 'healthy' nonagenarians/centerians had both Zn and Se concentrations equal to or greater than the lowest values of the elderly group and only 3.3% of cases showed both Zn and Se deficiencies. Consequently, a prospective and follow-up evaluation of Zn and Se could be proposed as a good index for a correct monitoring of the micronutrient deficiencies, that could represent an early sign of disease.

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. Bone loss in elderly men is associated with changes in body composition and reduced secretion of endogenous anabolizing hormones. The independent influences of body composition and endocrine factors on male bone metabolism, however, are unclear. Methods. Bone mass density (BMD) (bone mass content [BMC, g]/projected bone area [BA, cm 2 ]) at different skeletal sites, skeletal muscle, and body fat mass were measured by dual-energy X-ray absorptiometry in 129 men aged 20 to 95 years. Free testosterone, 17- b -estradiol, dehydroepiandrosterone-sulfate, and insulin-like growth factor 1 (IGF-1) serum concentrations were measured. Because BMD may fail to control for differences in skeletal size, the associations of bone mass with body composition and hormones were studied by comparing BMD regression models incorporating age and knee height only with BMC regression models also incorporating BA. Results. Skeletal muscle had close associations ( p at least , .01) with BMD and BMC at almost all skeletal sites, but the strength of these associations was generally reduced in BMC with respect to BMD models. Weak associations ( p , .05) were found in both models for fatness with femoral bone and for 17- b -estradiol with total body and femoral bone. The association of 17- b -estradiol with spinal bone was significant ( p , .05) in the BMD but not in the BMC model. No association of BMC or BMD with androgens and IGF-1 reached significancy. Conclusions. Skeletal muscle may be more important than fatness and anabolizing hormones in preserving bone mass in elderly men. In contrast to traditional belief, estrogens may be more important than androgens and IGF-1 in male bone metabolism.

Several micronutrients are involved in thyroid hormone metabolism, but it is unclear whether their marginal deficits may contribute to the alterations in thyroid function observed in extreme aging. The relationships among blood concentrations of thyroid hormones and selenium, zinc, retinol, and α-tocopherol were studied in 44 healthy Northern Italian oldest-old subjects (age range, 90–107 yr), selected by the criteria of the SENIEUR protocol. Control groups included 44 healthy adult (age range, 20–65 yr) and 44 SENIEUR elderly (age range, 65–89 yr) subjects. Oldest-old subjects had higher TSH (P < 0.01) and lower free T3 (FT3)/freeT4 (FT4) ratio, zinc, and selenium serum values (P < 0.001) than adult and elderly control subjects. No significant difference was found for plasma retinol and α-tocopherol values. The associations between micronutrients and thyroid hormones were evaluated by multivariate analysis. In oldest-old subjects, plasma retinol was negatively associated with FT4 (P = 0.019) and TSH serum levels (P = 0.040), whereas serum zinc was positively associated with serum FT3 (P = 0.010) and FT3/FT4 ratio (P = 0.011). In younger subjects, no significant association was found among thyroid variables and micronutrients. In conclusion, blood levels of specific micronutrients are associated with serum iodothyronine levels in extreme aging.

Summary As in the literature data about the relationships between dementia and nutritional indices in oldest-old people are scarce, we evaluated the nutritional and cognitive status of 27 non-hospitalized, over 90-year-old women living in Bologna. Among them, 15 subjects were demented according to the guidelines of the American Psychiatric Association (DSM-III-R). Body mass index (BMI) was calculated as weight/height (kg/m). Fat mass percentage (FM%) was calculated from anthropometric measurements according to the Durnin-Womersley' formula. Serum albumin, vitamin D (1,25(OH) 2 D), and insulin-like-growth factor 1 (IGF-1) were also measured. No difference between demented and non demented people was found for BMI and serum albumin, whereas demented women had smaller values of FM%, 1,25(OH) 2 D and IGF-1. As demented women were also significantly older and less literate than normal women, the statistical significance of these differences was retested by ANOVA variance analysis adjusting for age and years of education. FM% (p = 0.017), 1,25(OH) 2 D (p = 0.004) and IGF-1 (p = 0.004) were all confirmed being significantly reduced in demented women. The conclusions are: (i) demented over 90-year-old women have an increased risk of mal-nutrition; (ii) although usually used in clinical routine, BMI and serum albumin seem to be less sensible nutritional indicators than the less commonly evaluated skinfold thicknesses, vitamin D and IGF-1.

Summary Animal and human studies suggest that the adrenal androgen dehydroepiandrosterone sulphate (DHEAS) may be related to cognitive function. Aim of this study was to explore the relationships between circulating serum levels of DHEAS and cognitive function in a sample of over 90-year-olds. Thirty-four subjects (7 males, 27 females) aged 91–104 years were recruited in long-stay elderly facilities or at home in Bologna. Each subject received a semi-structured interview assessing medical history in order to exclude as much as possible the influence of medical conditions, pharmacological treatments and nutritional status on DHEAS levels. The diagnosis of dementia was made for 18 subjects according to the guidelines of the American Psychiatric Association. No differences were found between DHEAS concentrations of demented and non-demented subjects (sex and age-adjusted ANOVA F = 2.003, p = 0.168). No significant correlations were found between DHEAS and a number or cognitive testing scores, when adjusting for sex and age. In conclusion, our data do not suggest a causal role of DHEAS in senile dementia. The low DHEAS levels observed by some authors in patients with organic brain syndromes could be an artifact deriving from infectious or debilitating conditions.

Summary Starting from a previous investigation on the diagnosis of dementia based on the guidelines of the American Psychiatric Association in the oldest old patients, the present work focuses on the suicidal thoughts expressed as the Montgomery-Asberg depression rating scale (MADRS), item 10 score in the two subgroups of 18 demented and 16 non-demented subjects aged 91–104 years. We have not found any differences regarding depression or suicidal thoughts between the two subgroups. Our results are discussed and support the trends of recent literature, accessed through the Medline database.

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.

Male aging is associated with alterations in plasma levels of antioxidants such as Coenzyme Q(10) (CoQ(10)) , and with a decrease of the fat-free body mass (FFM). In order to reveal, whether these changes can affect CoQ(10) metabolism, 73 non-obese, healthy males were studied, in age range 22-100 years, divided in 4 age groups: 20-55 (n = 23); 56-70 (n = 20); 71-90 (n = 8) and 91-100 (n =22). Serum CoQ(10) was measured by HPLC technique. Body composition was assessed by multifrequency bioimpedance analysis. Subjects aged 91-100 years displayed lower serum CoQ(10) levels and FFM than the other age-groups (p

Vitamin K antagonists, such as warfarin, used in oral anticoagulation therapy currently represent the standard drugs for the primary and secondary prevention of stroke in non-valvular atrial fibrillation (AF), with a relative risk reduction close to 70%. Newer oral anticoagulants, such as direct thrombin inhibitors (i.e., dabigatran) and direct factor Xa inhibitors (i.e., apixaban and rivaroxaban) have been recently compared with warfarin in large randomized trials for stroke prevention in AF. The new oral anticoagulants showed, compared with warfarin, no statistically significant difference in the rate of stroke or systemic embolism in secondary prevention (patients with previous transient ischemic attack or stroke) subgroups. With regard to safety, the risk of intracranial bleeding was reduced with new anticoagulants compared with warfarin. Indirect treatment comparisons of clinical trials on secondary prevention cohorts showed no significant difference in efficacy among apixaban, rivaroxaban, and dabigatran; but dabigatran 110 mg was associated with less intracranial bleedings than rivaroxaban.

We measured calcium regulating hormones and bone mineral density (BMD) in 66 men (aged 24-88 years). Vitamin D (1,25(OH)2D) does not vary with age, parathyroid hormone (PTH) increases after the age of 65 (p < 0.01) together with a parallel increase in urinary (r = 0.46, p < 0.05) and nephrogenic cAMP (r = 0.63, p < 0.01), while BMD decreases with age (r = -0.52, p < 0.01). The finding of age-associated decreases in bone mass even in the presence of constant serum levels of 1,25(OH)2D within the normal range suggests that there is an onset of tissue resistance to vitamin D in the aetiopathogenesis of osteopenia in elderly men.

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.

Mild cognitive impairment (MCI) is regarded as a precursor to dementia, but not all patients with MCI actually develop dementia. As Alzheimer and vascular dementia are thought to share many common etiopathogenetic mechanisms, we investigated whether the vascular risk factor atrial fibrillation affects the risk of conversion to dementia for different MCI subtypes diagnosed according to international criteria.One hundred and eighty elderly outpatients with MCI and 431 elderly outpatients with a normal cognition were followed up for a mean of 3 and 4 years, respectively. The risk of conversion to dementia associated with atrial fibrillation was studied in both samples using a Cox proportional hazards model adjusted for socio-demographic and medical variables.Overall conversion rate to dementia was 10.5 (8.0-13.8 per 100 person-years) in the MCI group and 2.2 (1.5-3.1 per 100 person-years) in the normal cognition group. Atrial fibrillation was significantly associated with conversion to dementia [hazard ratio (HR): 4.63; 95% confidence interval: 1.72-12.46] in the MCI group but not in the cognitively normal group (HR: 1.10; 95% confidence interval: 0.40-3.03).Current diagnostic criteria for MCI subtypes define heterogeneous populations, but atrial fibrillation can be useful in identifying people with increased risk of conversion to dementia.

Incidence studies of blood inflammatory markers as predictors of dementia in older age are few and did not take into account hyperhomocysteinemia, although this condition is associated with both inflammation and increased risk of dementia. We investigated the relationships of baseline serum C-reactive protein (CRP), serum interleukin 6 (IL6), plasma alpha-1-antichymotrypsin, and hyperhomocysteinemia (defined as plasma total homocysteine>15 micromol/L) with risk of incident Alzheimer's disease (AD) and vascular dementia (VaD) in a dementia-free Italian population-based elderly cohort (n=804, 53.2% women, mean age 74 years) with 4 years of follow-up. No inflammatory marker, alone or in combination, predicted AD risk whereas the combination of high CRP and high IL6 was associated with risk of VaD (HR, 2.56; 95%CI, 1.21-5.50) independently of socio-demographic confounders, traditional risk factors and hyperhomocysteinemia. By contrast, in the same model, hyperhomocysteinemia was independently associated with AD (HR, 1.91; 95%CI, 1.02-3.56) but not VaD risk. Blood inflammatory markers are associated with increased VaD risk but do not predict AD, which seems selectively associated with hyperhomocysteinemia.

Little is known about the prevalence of the metabolic syndrome among elderly people in Italy, its association with all-cause mortality, and whether measurement of serum C-reactive protein (CRP) and interleukin (IL)-6 affects this association.The baseline prevalence of metabolic syndrome, diagnosed according to the National Cholesterol Education Program (NCEP) criteria, and all-cause mortality at 4 years were recorded in an Italian population-based cohort (981 subjects, 55% women, aged 65-97 years). A Cox model adjusted for sociodemographic, lifestyle, and medical variables was used to investigate 1) whether metabolic syndrome was a predictor of mortality and 2) how the association was affected by baseline high CRP (3 mg/l) and IL-6 (1.33 pg/ml).Overall, metabolic syndrome prevalence was 27.2% [95% CI 24.0-30.5] and higher in women (33.3% [28.7-38.0]) than in men (19.6% [15.5-24.2]). During follow-up, 137 deaths occurred. Using the no metabolic syndrome/no high IL-6 group as the reference, mortality was not associated with the metabolic syndrome alone (multivariable-adjusted hazard ratio 1.24 [0.60-2.59]), only weakly associated with high IL-6 alone (1.66 [1.04-2.63]), but strongly associated with the concurrent presence of metabolic syndrome and high IL-6 (3.26 [2.00-5.33]). High CRP was not a mortality predictor (0.83 [0.58-1.20]) nor did it affect the association of the other variables with mortality.Metabolic syndrome by NCEP criteria is highly prevalent in the Italian elderly population. It is not itself associated with mortality but may improve the usefulness of IL-6 as a mortality predictor in older age.

Risk of incident dementia from any cause and Alzheimer's disease (AD) in relation to the IL-1beta-511 (C--T) and IL-6-174 (G--C) polymorphisms was investigated in an Italian elderly cohort (n=791) with 4 years of follow-up. Analyses were adjusted for socio-demographic confounders (age, gender, education), presence of the Apolipoprotein E-epsilon4 allele, and plasma total homocysteine (tHcy), a newly proposed AD risk factor. No significant association was found for the IL-1beta-511 and IL-6-174 polymorphisms with either dementia or AD. However, in the baseline dementia-free cohort considered as a whole, independently of other confounders, IL-1beta-511 T/T homozygotes had lower plasma tHcy than both heterozygotes (P=0.036) and wild-types (P=0.004). These data do not support the hypothesis that the IL-1-beta-511 and IL-6-174 polymorphisms affect dementia or AD risk. The relationship between the AD risk factor plasma tHcy and the IL-1beta-511 polymorphism was never reported before and might explain previous cross-sectional reports of an association between this polymorphism and AD.

Mild cognitive impairment (MCI) is regarded as a precursor to dementia, but not all patients with MCI develop dementia. We followed up 165 elderly outpatients with MCI for a mean of 3 years. The aims were (1) to investigate the risk of conversion to dementia for different MCI subtypes diagnosed according to standardized criteria (amnestic; impairment of memory plus other cognitive domains; nonamnestic); (2) to assess whether the risk of conversion was affected by several established and emerging vascular risk factors. Forty-eight subjects (29%) converted to dementia, and the risk of conversion was doubled for amnestic MCI with respect to the other subtypes. Independently of MCI subtype, risk of conversion was associated with atrial fibrillation and low serum folate levels. Our results show that current diagnostic criteria for MCI define heterogeneous populations, but some potentially treatable vascular risk factors may be of help in predicting conversion to dementia.

Objective: To estimate age- and sex-specific incidence of dementia, Alzheimer disease (AD), and vascular dementia (VaD) in the Conselice Study of Brain Aging, an Italian prospective population-based study, and to assess whether poor education is a risk factor for dementia. Methods: In 1999 to 2000, the baseline study identified a dementia-free cohort of 937 subjects aged 65 years and older who were reexamined in 2003 to 2004 using a two-phase procedure. Results: Information was obtained for 91% of the subjects at risk; 115 incident cases of dementia were identified. Incidence rates per 1,000 person-years were 37.8 (95% CI = 30.0 to 47.7) for dementia, 23.8 (95% CI = 17.3 to 31.7) for AD, and 11.0 (95% CI = 7.2 to 16.9) for VaD. This translates into more than 400,000 new cases of dementia expected per year in Italy. Increasing age was an independent risk factor for both AD and VaD. Poor education was an independent risk factor for AD but not VaD. Sex did not affect dementia risk. Conclusions: In this Italian population-based cohort, incidence of dementia increased with age, and Alzheimer disease (AD) was the most frequent type of dementia. Poor education was associated with a higher risk of AD. Our incidence rates are higher than previously reported in Italy, and provide new estimates for projection of future burden of disease in Italy.

SUMMARY Hyperhomocysteinemia is a risk factor for dementia but only scanty data exist about its relationship to specific cognitive abilities during normal aging. We recruited 62 healthy and cognitively normal subjects of age 65-91 years from the Conselice Study of brain aging. The following neuropsychological tests were applied (i) The mental deterioration battery (MDB) consisting of 7 parts: the Rey’s 15 words immediate and delayed recall, word fluency, sentence construction, Raven’s progressive matrices ‘47, immediate visual memory, freehand copying of drawings and copying drawings with landmarks. (ii) The Prose memory test. (iii) The Corsi block-tapping task. (iv) The mini mental state examination (MMSE) scores. We measured plasma total homocysteine (tHcy), serum folate, vitamin B12 and plasma vitamin B6. Multivariate-adjusted linear regression analysis showed statistically significant negative association of plasma tHcy with scores at MMSE (b= -0.01 2, p < 0.001) and word fluency (b = -0.009, p = 0.021). A non-significant trend towards a negative association was also found for sentence construction (b = -0.006, p = 0.076). One can conclude that in healthy elderly subjects, increased plasma tHcy is correlated to poorer performance at a specific measure of language abilities being compromised in both vascular and Alzheimer’s dementia. The study suggests that plasma tHcy could be an early marker of cognitive impairment.

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.

Increased levels of plasma total homocysteine (tHcy) may play a role in both cardiovascular diseases (CVD) and old-age dementias via enhancement of vascular inflammation. However, the association between plasma tHcy and serum C-reactive protein (sCRP), taken as a marker of low-grade inflammation, is still uncertain. We investigated this association in normal aging, CVD, and dementia, and examined whether it was modified by the presence of two major comorbid diseases of older age: chronic obstructive pulmonary disease (CPOD) and peptic ulcer (PU). Six hundred-twenty-seven individuals agedor = 65 yr (74+/-7 yr) were selected for this study: 373 healthy controls; 160 patients with CVD but no evidence of comorbid diseases (CVD+/comorbidity-); 46 patients with CVD and concurrent CPOD and/or PU (CVD+/comorbidity+); and 48 patients with dementia. A positive association between plasma tHcy and serum CRP, independent of several confounders (socio-demographic status, known tHcy and sCRP determinants, inflammation markers, traditional vascular risk factors), was found for CVD+/comorbidity+ (p=0.001; not affected by dementia type) and dementia (p=0.001; not affected by dementia type), but not for CVD+/comorbidity- and controls. The results suggest that the association between plasma tHcy and sCRP is more an aspecific reflection of poor health than a specific correlate of vascular inflammation.