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Background: Alzheimer’s disease (AD) may be a vascular disorder with neurodegenerative consequences opening possibility of preventing AD by targeting vascular risk factors including homocysteine. Objective: The study aims were to assess homocysteine distribution in different forms and severity of cognitive impairment (CogI) [mild cognitive impairment (MCI), probable AD (Prob-AD), possible AD (Poss-AD), and vascular dementia (VaD)] and in NoCogI, and to estimate possible association between hyperhomocysteinemia levels with functional deficit severity and psychobehavioral complications. Methods: In total, 929 (M = 366, F = 563; mean age of 72.55±6.24 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. Homocysteine serum was set on two levels: between 0 and 10μmol/L and > 10μmol/L. For each patient, blood concentration of folate, vitamin B12, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), cholesterol, triglycerides, and glycemia were measured. Results: CogI patients demonstrated significantly a higher frequency of homocysteine > 10 (p = 0.003), than NoCogI patients. Patients with moderate and severe dementia had a higher frequency of homocysteine > 10 (p 10 (p = 0.003), than Prob-AD patients. Homocysteine > 10 frequency is directly proportional to increased neuropsychiatric symptom severity (p

The widespread use of Field Programmable Gate Array (FPGA) in the consumer electronics market makes designers integrate more and more solutions with these programmable logic devices. In this paper, the authors use a CYCLONE V 5CSEMA5FC31C6N Altera-Intel FPGA in order to implement a UART-to-Bell202 converter for the direct interfacing of an FPGA with an analogue line on the voice band, not still available for industrial and consumer electronic for communications applications. In particular, a transmitter is created with an Audio Shift Keying modulation without phase continuity, capable of converting UART signals coming from any UART transmitter (for example a personal computer, PC) into a modulated signal. The design has been performed using the Terasic DE1-SoC development board, while instrumental tests have been performed with a ZEROPLUS LAP-C logic states analyzer and a CML1102 oscilloscope..

Background: Although it is known that Alzheimer's disease (AD) is associated with the progressive accumulation of amyloid β-peptide (Aβ) in the human brain, its pathogenic role has to be completely clarified. Aβ moves from the bloodbrain barrier to the plasma and an increased Aβ production in brain could be associated with higher Aβ concentrations in blood. A recent study has evaluated Aβ40 and Aβ42 levels in human red blood cells (RBCs) with evidence of agedependent higher Aβ concentration in RBCs. Objective: The aim of the study was to investigate if erythrocyte associated Aβ (iAβ) levels could be different in subjects affected by dementia in comparison with controls and according to the patient’s cognitive impairment or different dementia subtypes. Method: To answer these questions we assessed iAβ40 and iAβ42 levels in 116 patients: 32 healthy controls, 39 with diagnosis of vascular dementia (VaD), 14 mild cognitive impairment (MCI) and 31 AD. Results: In this population we found significant differences in iAβ42 between controls and cognitive impaired patients. Moreover, iAβ42 significantly differed between dementia vs MCI. AD also showed different iAβ42 levels as compared to VaD. Conversely, no differences were found for iAβ40. All the analyses were adjusted for potential confounders like age, gender and Hb concentration. A direct correlation between increasing iAβ42 concentration and the progression of the cognitive decline using the MMSE score as continuous variable was also found. Conclusion: Our findings support the evidence that iAβ42 could be an instrument to early recognize dementia and predict cognitive impairment.

Background/Aim: The aim of the study was to evaluate the prognostic power of late-life depression (LLD) compared with amnestic mild cognitive impairment (aMCI) for the onset of Alzheimer’s disease (AD) within 4 years of follow-up. Methods: We estimated the incidence of AD in 60 patients presenting with aMCI, 115 patients suffering of LLD treated with antidepressants with good compliance, and 66 healthy control (HC) patients, followed for 4 years. Results: The risk to develop AD, within 4 years, was 68.33% for aMCI and 49.57% for LLD. In AD patients 5.60% deteriorated without depression, and 72.20% deteriorated with depression after 4 years of follow-up (p < 0.0001). No HC patients deteriorated to AD or any other dementia type. Conclusion: In our results, aMCI was the first predictive condition that increased the risk to develop AD. Depression is a potentially preventable medical condition across the lifespan and may be a modifiable risk factor.

Background Serotoninergic pathways underlying delusion symptoms in Alzheimer’s disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription. Methods We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer’s Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory. Results Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p

Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p < 0.001), and were more likely to be older (p < 0.001), have a significant clear cognitive impairment (MMSE: p < 0.001), show the presence of a depressive mood (HDRS-21: p < 0.001) and have major impairments in ADL (p < 0.001), IADL (p < 0.001), MNA (p < 0.001), and ESS (p < 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Na+: p < 0.001; K+: p < 0.001; Cl−: p < 0.001), risk of dehydration (osmolality p < 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer’s disease (AD) patients showed a major risk for current dehydration (p ≤ 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p < 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p < 0.001) and IADL (p < 0.001), but independently associated with age (r2 = 0.0046, p = 0.77), ESS (r2 = 0.0052, p = 0.54) and MNA (r2 = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65–75 years, p = 0.001; 76–85 years, p = 0.001; ≥86 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage.

It has been suggested that the serotonin or 5-hydroxytriptamine (5-HT) transporter (5-HTT) and its gene-linked polymorphic region (5-HTTLPR) are selective serotonin reuptake inhibitor (SSRI) response modulators in late-life depression (LLD), and particularly in late-life major depressive disorder (MDD). Previous studies differed in design and results. Our study aimed to investigate the solute carrier family 6 (neurotransmitter transporter and serotonin) member 4 (SLC6A4) gene locus, encoding 5-HTT and SSRI treatment response in late-life MDD. For a prospective cohort study, we enrolled 234 patients with late-life MDD to be treated with escitalopram, sertraline, paroxetine or citalopram for 6 months. The SLC6A4 polymorphisms rs4795541 (5-HTTLPR), rs140701 and rs3813034 genotypes spanning the SLC6A4 locus were investigated in blinded fashion. No placebo group was included. We assessed responder or non-responder phenotypes according to a reduction in the 21-item version of the Hamilton Depression Rating Scale (HDRS-21) score of ⩾ 50%. At follow-up, 30% of the late-life MDD patients were non-responders to SSRI treatment. No time-course of symptoms and responses was made. A poor response was associated with a higher baseline HDRS-21 score. We observed a significant over-representation of the rs4795541-S allele in the responder patients (0.436 versus 0.321; p = 0.023). The single S-allele dose-additive effect had OR = 1.74 (95% CI 1.12–2.69) in the additive regression model. Our findings suggested a possible influence of 5-HTTLPR on the SSRI response in patients with late-life MDD, which is potentially useful in identifying the subgroups of LLD patients whom need a different pharmacological approach.

Objective To evaluate in a pilot single-blind randomized controlled clinical trial the efficacy of an integrated treatment with rivastigmine transdermal patch (RTP) and cognitive stimulation (CS) in Alzheimer's disease (AD) patients at 6-month follow-up. Methods We enrolled 90 patients with an age ≥65 years admitted to the outpatient Alzheimer's Evaluation Unit with diagnosis of AD. Patients were randomized to enter in the Group-1 (RTP + CS) or in the Group-2 (RTP). All patients at baseline and after 6 months were evaluated with the following tools: Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression (HAM-D), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory-Distress (NPI-D), and a standardized Comprehensive Geriatric Assessment, including also activities of daily living (ADL), instrumental activities of daily living (IADL), and the Mini Nutritional Assessment (MNA). Mortality risk was assessed using the Multidimensional Prognostic Index (MPI). Results At baseline no significant difference was shown between the two groups. After 6 months of follow-up, there were significant differences between Group-1 and Group-2 in: MMSE: +6.39% vs. +2.69%, CDR: +6.92% vs. +1.54%, HDRS-D = −60.7% vs. −45.8%, GDS: −60.9% vs. −7.3%, NPI: −55.2% vs. −32.7%%, NPI-D: −55.1% vs. −18.6%, ADL: +13.88% vs. +5.95%, IADL: +67.59% vs. +18.28%, MNA: +12.02% vs. +5.91%, and MPI: −29.03% vs. −12.90%. Conclusion The integrated treatment of RTP with CS in AD patients for 6 months improved significantly cognition, depressive and neuropsychiatric symptoms, functional status, and mortality risk in comparison with a group of AD patients receiving only RTP. Copyright © 2014 John Wiley & Sons, Ltd.

Objective To characterize the differences of caregiver burden in patients with Alzheimer's disease (AD) and vascular dementia (VaD) in order to improve the care counselling and management plan. Methods We included 506 patients consecutively attending the Alzheimer's Evaluation Unit of a Geriatric Unit, evaluated with Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression, and Neuropsychiatric Inventory. To all caregivers were administered the Caregiver Burden Inventory (CBI), a 24-item multidimensional questionnaire in which 5 subscales explore 5 dimensions of caregiver burden: (1) CBI-Objective; (2) CBI-Developmental; (3) CBI-Physical; (4) CBI-Social; and (5) CBI-Emotional. Results The present study included, respectively, 253 AD patients and 253 VaD patients. AD patients at baseline showed a significantly higher instruction level (p

In Alzheimer's disease (AD) patients with delusions, clinical outcomes and mortality result from a combination of psychological, biological, functional, and environmental factors. We determined the effect of delusions on mortality risk, clinical outcomes linked to comprehensive geriatric assessment (CGA), cognitive, depressive, and neuropsychiatric symptoms (NPS) in 380 consecutive AD patients with Mini-Mental State Examination, Clinical Dementia Rating scale, 15-item Geriatric Depression Scale, and Neuropsychiatric Inventory (NPI), assessing one-year mortality risk using the Multidimensional Prognostic Index (MPI). We included 121 AD patients with delusions (AD-D) and 259 AD patients without delusions (AD-noD). AD-D patients were significantly older, with higher age at onset and cognitive impairment, a more severe stage of dementia, and more depressive symptoms than AD-noD patients. Disease duration was slightly higher in AD-D patients than in those without delusions, although this difference was not statistically significant. At CGA, AD-D patients showed a higher grade of disability in basic and instrumental activities of daily living, and an increased risk of malnutrition and bedsores. The two groups of patients significantly differed in MPI score (AD-D: 0.65 versus AD-noD: 0.51, p < 0.0001) and MPI grade. AD-D patients showed also a significant higher score in NPI of the following NPS than AD-noD patients: hallucinations, agitation/aggression, depression mood, apathy, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. Therefore, AD-D patients showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and several neuropsychiatric domains than AD-noD patients, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality.

Recent advances in our understanding of the neurobiology of Alzheimers disease (AD) have led to the development of putative disease-modifying treatments. The most revolutionary of these approaches consists in the removal of brain β-amyloid (Aβ) via anti-Aβ antibodies. Brain imaging and neuropathological studies have shown the ability of both active and passive anti-Aβ immunotherapies of clearing Aβ deposits from the brain of the AD patients. An active anti-Aβ vaccine preparation, AN1792, has been used in AD patients with some clues of clinical efficacy but causing meningoencephalitis in about 6% of patients and it has been abandoned. Several second-generation active Aβ vaccines and passive Aβ immunotherapies have been developed and are under clinical investigation with the aim of accelerating Aβ clearance from the brain of the AD patients. The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients. However, the preliminary cognitive efficacy of bapineuzumab appears uncertain. The occurrence of vasogenic edema, especially in apolipoprotein E 4 carriers, may limit its clinical use and have led to abandon the highest dose of the drug (2 mg/kg). The results of four ongoing large Phase III trials on bapineuzumab will tell us if passive anti-Aβ immunization is able to alter the course if this devastating disease.

At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important for the development of age-related cognitive decline (ARCD), mild cognitive impairment (MCI), and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). Among vascular-related factors, metabolic syndrome (MetS) has been associated with the reduced risk of predementia syndromes (ARCD and MCI), overall dementia, and VaD, but contrasting findings also exist on the possible role of MetS in AD. In the next future, trials could then be undertaken to determine if modifications of these risks including inflammation, another factor probably related to MetS, could lower risk of developing cognitive decline. If MetS is associated with increased risk of developing cognitive impairment, then early identification and treatment of these individuals at risk might offer new avenues for disease course modification. Future research aimed at identifying mechanisms that underlie comorbid associations will not only provide important insights into the causes and interdependencies of predementia and dementia syndromes, but will also inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor management could be decisive in delaying the onset of dementia syndromes or in preventing the progression of predementia syndromes.

Aim of this study was to evaluate the usefulness of a Multidimensional Prognostic Index (MPI) based on a Comprehensive Geriatric Assessment (CGA) for predicting mortality risk in older patients with dementia. The present was a retrospective study with a year of follow-up that included 262 patients aged 65 years and older with a diagnosis of dementia. A standardized CGA that included information on clinical, cognitive, functional, and nutritional aspects, as well as comorbidity, medications, and social support network, was used to calculate MPI. The predictive value of the MPI for all-cause mortality over 1 month, 6 months, and 12 months of follow-up was evaluated. Higher MPI values were significantly associated with higher mortality at 1 month (MPI-1, low risk = 0%, MPI-2, moderate risk = 5.2%, MPI-3, severe risk = 13.7%; p < 0.002), 6-months (MPI-1 = 2.7%, MPI-2 = 11.2%, MPI-3 = 28.8%; p < 0.001), and 12-months (MPI-1 = 2.7%, MPI-2 = 18.2%, MPI-3 = 35.6%; p < 0.001) of follow-up. The discrimination of the MPI was also good, with areas under the ROC curves of 0.77 (sensitivity = 82.9%, specificity = 66.0%, with a cut off value > 0.16) at 12-months of follow up. In conclusion, the MPI, calculated from information collected in a standardized CGA, accurately stratified hospitalized elderly patients with dementia into groups at varying risk of short- and long-term mortality.

The promoter region of the serotonin transporter gene (SLC6A4) shows a 22-bp tandem repeat polymorphism, indicated as polymorphism C, that has been associated to depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding its association with Alzheimer's disease (AD). No data were reported regarding its association with questionable dementia (QD). In this study we investigate for polymorphism C in the SLC6A4 gene 302 elderly subjects with a clinical diagnosis of AD (n=105), QD (n=88) and no cognitive impairment (n=114) attending a geriatric ward. A community-dwelling sample of 390 healthy subjects was also included in the analysis. A significant higher prevalence of the C16/C16 genotype in AD than in QD was observed (37.14% vs. 3%; p=0.041, OR 2.001, 95%CI 1.018-4.024), while no differences in the C16/C14 and C14/C14 genotypes as well as in the estimated allele frequencies were found. No further differences among the three groups of subjects were found, also when they were compared with the community-dwelling sample. These findings suggest that SLC6A4 gene variation may have only a minor role, if any, in AD or QD.

Background: The glutamatergic neurotransmitter systems play a crucial role in memory formation and information processing. Alterations in this system contribute to the manifestation of symptoms in Alzheimer’s disease (AD). Glutamate transmits signals via the N-methyl-D-aspartate receptors (NMDARs). Aims: The potential involvement of polymorphisms in the GRIN2B gene, encoding subunit 2B of the NMDA receptor, in the risk for AD was evaluated. Methods: We investigated the 3 single-nucleotide polymorphisms (SNPs) rs1019385, rs1806201 and rs890, i.e. the G–200→T transversion in the 5′UTR, the A2664→G transition in exon 13 and the G5072→T transition in the 3′UTR of the GRIN2B gene, in 222 Caucasian AD patients and 170 healthy Caucasian age-matched controls. Results: No differences were found in the overall distribution of the single-nucleotide polymorphism genotypes between AD patients and healthy controls, even when the analysis was adjusted for sex, age and APOE. As expected from genotype frequencies, no differences were found in the distribution of the estimated allele and haplotype frequencies between AD patients and healthy controls. Conclusion: In this study no significant association between polymorphisms in the GRIN2B gene and AD was observed. Further investigations of polymorphisms in the gene encoding the NMDA receptor 2B subunit in AD patients with different genetic setting are needed to clarify their role in the pathogenesis of AD.

Background: Polymorphism in the apolipoprotein E (APOE) gene is the major genetic risk factor associated with late-onset Alzheimer’s Disease (AD). However, it is still unclear if a relationship exists between the APOE Ε4 allele and vascular dementia (VaD) in elderly subjects. Objectives: To evaluate the prevalence of APOE alleles in elderly patients with VaD compared to AD patients and to control subjects with no cognitive impairment (NoCI). Patients and Methods: We evaluated 396 consecutive patients aged ≧65 years with definite or suspected cognitive impairment with a clinical (Mini-Mental State Examination, Clinical Dementia Rating, Geriatric Depression Scale), functional (Activities of Daily Living, Instrumental Activities of Daily Living), comorbidity (Cumulative Illness Rating Scale) and instrumental (CT scan, NMR) assessment. Diagnosis of dementia was made according to NINCDS-ADRDA and NINDS-AIREN Work Group and the DSM-IV. APOE genotypes were analyzed by a recently described method resulting in positive/negative chain reaction products for each APOE genotype. Statistical analysis was carried out using the Pearson χ2, the Kruskal-Wallis test and the ANOVA post hoc comparisons. Results: A total of 287 elderly patients (males = 138, females = 149, mean age = 77.8 ± 6.9 years, range = 65–98) with diagnoses of VaD (n = 97), AD (n = 82) or NoCI (n = 108) were included in the study. A significantly higher APOE Ε4 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects, while no differences were found between VaD patients and subjects with NoCI (AD = 24.3%, VaD = 10.3, NoCI = 8.7, p < 0.05). Furthermore, a significantly lower APOE Ε3 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects but not between VaD and NoCI patients (AD = 71.3%, VaD = 80.9, NoCI = 83.4, p < 0.05). No significant differences were observed in the APOE Ε2 allele (VaD = 8.8%, AD = 4.4, NoCI = 7.9, p = n.s.) among the 3 groups. Conclusions: In this population, the frequency of the APOE Ε4 allele is lower in VaD than in AD.

OBJECTIVES: To compare symptoms and other clinical characteristics of reflux esophagitis in patients of different ages. DESIGN: Observational cross-sectional study of consecutive patients. SETTING: Geriatric Unit, Casa Sollievo della Sofferenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico. PARTICIPANTS: Eight hundred forty patients with endoscopically diagnosed erosive esophagitis divided into four groups according to age (young (

The prevalence of gastroesophageal reflux disease (GERD) increases with age, and older people are more likely to develop severe disease. Studies of elderly patients with GERD indicate differences in presentation and diagnosis, compared with GERD in younger adults. Indeed, an older patient with GERD may present with atypical symptoms such as dysphagia, vomiting, weight loss, anaemia and anorexia, and less frequently with typical symptoms such as heartburn or acid regurgitation. These findings are attributed to pathophysiological changes in esophageal function that occur with age. Therefore, GERD in elderly patients is more likely to be poorly diagnosed or undiagnosed. Although few studies have concentrated specifically on elderly patients, the proton pump inhibitors (PPIs) have been shown to be more effective than histamine receptor antagonists for healing reflux esophagitis and for preventing its recurrence when they are given as maintenance therapy. In addition, the PPIs seem to be safe both in short- and in long-term therapy of elderly patients with GERD.

Summary Background : Although administration of gastroprotective drugs may reduce the risk of peptic ulcers associated with the chronic use of non-steroidal anti-inflammatory drugs or aspirin, no consensus exists as to whether this co-therapy is effective for short-term prevention, particularly in old age. Aim : To evaluate the risk of peptic ulcer associated with acute and chronic non-steroidal anti-inflammatory drugs or aspirin therapy in elderly subjects, and the influence of antisecretory treatment on this risk. Methods : The study included 676 elderly non-steroidal anti-inflammatory drugs or aspirin users and 2435 non-users who consecutively underwent upper gastrointestinal endoscopy. The use of non-steroidal anti-inflammatory drugs and/or aspirin as well as antisecretory drugs (H2-blockers and proton-pump inhibitors) was evaluated by a structured interview. Diagnosis of gastric and duodenal ulcer as well as Helicobacter pylori infection were carried out by endoscopy and histological examination of the gastric mucosa. Results : About 47.3% of patients were acute and 52.7% chronic users of non-steroidal anti-inflammatory drugs or aspirin. The risk of peptic ulcer, adjusted for age, gender, H. pylori infection and antisecretory drug use was higher in acute (gastric ulcer: odds ratio, OR =4.47, 95% CI: 3.19–6.26 and duodenal ulcer: OR =2.39, 95% CI: 1.73–3.31) than chronic users (gastric ulcer: OR = 2.80, 95% CI: 1.97–3.99 and duodenal ulcer: OR = 1.68, 95% CI: 1.22–2.33). Proton-pump inhibitor treatment was associated with a reduced risk of peptic ulcer in both acute (OR = 0.70, 95% CI: 0.24–2.04) and chronic (OR = 0.32, 95% CI: 0.15–0.67) non-steroidal anti-inflammatory drugs/aspirin users. Conversely, concomitant treatment with H2-blockers was associated with a significantly higher risk of peptic ulcer both in acute (OR = 10.9, 95% CI: 3.87–30.9) and chronic (OR = 6.26, 95% CI: 2.56–15.3) non-steroidal anti-inflammatory drugs/aspirin users than non-users. Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users. Conclusions : These findings suggest that proton-pump inhibitor co-treatment is advisable in symptomatic elderly patients who need to be treated with non-steroidal anti-inflammatory drugs and/or aspirin for a short period of time.

To evaluate in a pilot single-blind randomized controlled clinical trial the efficacy of an integrated treatment with rivastigmine transdermal patch (RTP) and cognitive stimulation (CS) in Alzheimer's disease (AD) patients at 6-month follow-up.We enrolled 90 patients with an age ≥65 years admitted to the outpatient Alzheimer's Evaluation Unit with diagnosis of AD. Patients were randomized to enter in the Group-1 (RTP + CS) or in the Group-2 (RTP). All patients at baseline and after 6 months were evaluated with the following tools: Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression (HAM-D), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory-Distress (NPI-D), and a standardized Comprehensive Geriatric Assessment, including also activities of daily living (ADL), instrumental activities of daily living (IADL), and the Mini Nutritional Assessment (MNA). Mortality risk was assessed using the Multidimensional Prognostic Index (MPI).At baseline no significant difference was shown between the two groups. After 6 months of follow-up, there were significant differences between Group-1 and Group-2 in: MMSE: +6.39% vs. +2.69%, CDR: +6.92% vs. +1.54%, HDRS-D = -60.7% vs. -45.8%, GDS: -60.9% vs. -7.3%, NPI: -55.2% vs. -32.7%%, NPI-D: -55.1% vs. -18.6%, ADL: +13.88% vs. +5.95%, IADL: +67.59% vs. +18.28%, MNA: +12.02% vs. +5.91%, and MPI: -29.03% vs. -12.90%.The integrated treatment of RTP with CS in AD patients for 6 months improved significantly cognition, depressive and neuropsychiatric symptoms, functional status, and mortality risk in comparison with a group of AD patients receiving only RTP.

To characterize the differences of caregiver burden in patients with Alzheimer's disease (AD) and vascular dementia (VaD) in order to improve the care counselling and management plan.We included 506 patients consecutively attending the Alzheimer's Evaluation Unit of a Geriatric Unit, evaluated with Mini Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hamilton Rating Scale for Depression, and Neuropsychiatric Inventory. To all caregivers were administered the Caregiver Burden Inventory (CBI), a 24-item multidimensional questionnaire in which 5 subscales explore 5 dimensions of caregiver burden: (1) CBI-Objective; (2) CBI-Developmental; (3) CBI-Physical; (4) CBI-Social; and (5) CBI-Emotional.The present study included, respectively, 253 AD patients and 253 VaD patients. AD patients at baseline showed a significantly higher instruction level (p .0001), higher grade of cognitive impairment (MMSE, p .0001), and increased severity stage of dementia (CDR, p .0001) than VaD patients. AD caregivers, mainly females (p = 0.010), devoted significantly more length of time care (in months, p = 0.010) and time of daily care (in hours, p = 0.011) and showed a significantly higher burden level in CBI-Objective (p = 0.047), CBI-Physical (p .0001), CBI-Social (p = 0.003), CBI-Emotional (p .0001), and CBI-total score (p .0001), than VaD caregivers. In both caregiver groups, a higher presence of spouses and sons (p .0001) compared to other relatives was observed. AD caregiver burden showed a significant association with sex of caregivers and length of time care in months.AD caregivers showed a higher burden level than VaD caregivers, and this appeared to be associated with sex and length of time care.

Nephrologists worldwide are gradually coping with el- derly patients. This is because of the burden of chronic disease in the aging population and specifically chron- ic kidney disease (CKD). CKD in the elderly rarely oc- curs in isolation from other chronic conditions and can often be a marker of these conditions themselves. Geriatricians usually take care of chronic conditions and are trained to perform comprehensive geriatric assessment, a tool to estimate frailty, that is the risk of adverse outcome, disability, and death in the clini- cal setting of elderly inpatients. Unfortunately, they are not used to a CHD invasive and non-invasive approach and so there is no doubt about the need for a co-man- aged care model for these patients. However, where and how this model must be realized is still question- able. New hospital care models are patient-centered and encompass the concepts of departments to em- brace the differentiated levels of care approach. Ac- cording to this model the hospital is subdivided into three different standards of care: 1-high; 2 -intermedi- ate; 3- low and this organization avoids inpatients be- ing transferred frequently to different units, receiving specific care easily obtained by moving and changing the medical staff in charge of the patient. The lean care approach integrates the principles of the Toyota Pro- ducing System (TPS), a leading system of the industrial world, into intensity-based hospital care, thereby max- imizing quality processes and promoting co-managed care as in the nephro-geriatric clinical setting.

Objective Polymorphism C in the solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) gene has been variously associated with major depressive disorder (MDD). To the best of our knowledge, no data were reported regarding a role of SLC6A4 in late-life MDD. The aim of this study was to explore the possible involvement of the SLC6A4 locus in patients with late-life MDD by means of a haplotype-tagged approach. Design Case-control study. Setting Older patients attending a geriatric unit. Participants A total of 218 patients with late-life MDD (61 men and 157 women) age 65 to 92 years (76.29 ± 6.53 years) and 363 depression-free healthy subjects (156 men and 207 women) age 41 to 65 years (48.33 ± 5.94 years). Measurements Genotyping and haplotype estimation of the three markers rs4795541, rs140701, and rs3813034 spanning a 39-kb block the SLC6A4 locus. Diagnoses of late-life MDD, mild cognitive impairment, Alzheimer disease, vascular dementia, and other dementing diseases were made using current clinical criteria. Results No significant differences were observed in allele or genotype distribution for the three SLC6A4 markers across the study groups. Because the comparison group could not be matched for age, a sensitivity analysis for the misclassification of controls was performed according to different scenarios. For each simulated scenario, the same nonsignificant result was observed. However, the results are limited to late-life MDD that is specifically not associated with cognitive impairment, and there was limited power for detecting very small effect sizes. Conclusions Our findings suggested that the SLC6A4 locus play a minor role, if any, in the pathogenesis of late-life MDD. Also, tempering our conclusions, we were unable to account for population stratification, recurrence or chronicity of depression, nor the influence of coexisting medical, cognitive, and psychosocial stressors.

Background Neuropsychiatric symptoms (NPS) are a common feature of Alzheimer's disease (AD), resulting in particular AD endophenotypes. The common AD genetic risk factor apolipoprotein E (APOE) has been suggested underlying these AD endophenotypes. Methods APOE genotyping, a comprehensive geriatric assessment (CGA), and Neuropsychiatric Inventory were performed on 322 consecutive older patients. Patients were divided into three groups: AD with NPS (N = 93), AD without NPS (N = 108), and, as a control group, patients with no cognitive impairment (NoCI: N = 121). Patients with NPS were further sub-divided in four groups according to the European Alzheimer's Disease Consortium (EADC) classification of neuropsychiatric syndromes in AD: hyperactive, psychotic, affective, and apathetic. Results AD patients with NPS showed a significantly higher grade of cognitive impairment, more severity stage of dementia, more disability in the activities of daily living (ADL), and the instrumental ADL than AD patients without NPS. As expected, an higher frequency of APOE e3/e4 genotype was observed in patients with AD, both with and without NPS, than patients with NoCI. No difference in the distribution of APOE genotypes was found between AD patients with vs. without NPS. However, in AD patients APOE e4-carriers, there was an increased risk of affective [odds ratio (OR): 2.34, 95% confidence interval (CI): 1.19–4.58) and apathetic (OR: 2.24,95%CI: 1.19–4.22) syndromes. Conclusions These findings did not suggest a significant association between APOE polymorphism and presence of NPS in AD patients. In AD patients with NPS, however, APOE e4-carrier status was associated with an increased risk of affective and apathetic syndromes. Copyright © 2010 John Wiley & Sons, Ltd.

Objective Cytochrome P450 (CYP) 2D6 enzyme is the major responsible for the metabolism of donepezil, an inhibitor of acetyl cholinesterase currently used for the symptomatic treatment of mild-to-moderate Alzheimer's disease (AD). Functional polymorphisms in the CYP2D6 gene may affect enzyme activity and thus, the metabolism of donepezil. The aim of this study was to evaluate the effect of 16 functional polymorphisms in the CYP2D6 gene on the clinical response to donepezil treatment in patients with mild-to-moderate AD. Methods In this multicenter prospective cohort study we evaluated 57 unrelated Caucasians clinically diagnosed as AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association Work Group criteria. Patients were treated with donepezil (5-10 mg/daily) for 6 months. The response to donepezil treatment was evaluated at 6-month follow-up according to the National Institute for Health and Clinical Excellence requirements. The identification of 16 clinically relevant CYP2D6 gene variants was performed by a high-throughput genetic analysis. Results Thirty-eight of 57 patients (67%) were responders and 19 patients (33%) were nonresponders to donepezil treatment. A significantly higher frequency of gene variants conferring decreased or absent enzyme activity was observed in responder than in nonresponder patients (73.68% vs. 36.84%; P=0.005). The presence of gene variants conferring decreased or absent activity of the CYP2D6 enzyme was significantly associated with a clinical response to donepezil treatment (odds ratio=6.286; 95% confidence interval=1.828-21.667). Conclusions Functional polymorphisms in the CYP2D6 gene can influence the clinical efficacy of donepezil. The analysis of CYP2D6 genotypes may be useful in identifying subgroups of AD patients with different clinical response to donepezil treatment.

Background: Genotypes of the solute carrier family 6 (neurotransmitter transporter, serotonin) member 4 (SLC6A4) have been variously associated with depression, obsessive-compulsive disorder, memory impairment, and anxiety. Less clear are data regarding their association with severe dementia, in particular with vascular dementia (VaD). Aims: To evaluate the possible involvement of different SLC6A4 genotypes/haplotypes in VaD. Methods: The analysis of the 3 markers rs3813034, rs140701 and rs4795541 spanning the SLC6A4 locus was made in 541 consecutive patients clinically diagnosed as having VaD (n = 372) or no cognitive impairment (n = 169) attending a geriatric ward. A community-dwelling sample of 353 healthy subjects, as a reference for the genetic frequencies in the recruitment area, was also included in the study. All patients and subjects were free from any symptoms of depression, obsessive-compulsive disorder and anxiety. A complete neuroimaging documentation was available for all patients. Results: No important differences were observed in genotype distribution across the study groups. Similarly, no important differences were observed in haplotype distribution when a 3-point analysis was made. Conclusion: Our findings suggest that polymorphism C in the promoter region of the SLC6A4 gene plays a minor role, if any, in the pathogenesis of VaD.

Objective: To evaluate the influence of the single nucleotide polymorphism rs1080985 in the cytochrome P450 2D6 ( CYP2D6 ) gene on the efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). Methods: This was a multicenter, prospective cohort study of 127 white patients with AD according to the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association Work Group criteria. Patients were treated with donepezil 5–10 mg/daily for 6 months. Cognitive and functional statuses were evaluated at baseline and at 6-month follow-up. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Compliance and drug-related adverse events were also evaluated. The analyses identifying the CYP2D6 and APOE polymorphisms were performed in blinded fashion. Results: At 6-month follow-up, 69 of 115 patients (60%) were responders and 46 patients (40%) were nonresponders to donepezil treatment. A significantly higher frequency of patients with the G allele of rs1080985 was found in nonresponders than in responders (58.7% vs 34.8%, p = 0.013). Logistic regression analysis adjusted for age, sex, Mini-Mental State Examination score at baseline, and APOE demonstrated that patients with the G allele had a significantly higher risk of poor response to donepezil treatment (odds ratio 3.431, 95% confidence interval 1.490–7.901). Conclusions: The single nucleotide polymorphism rs1080985 in the CYP2D6 gene may influence the clinical efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). The analysis of CYP2D6 genotypes may be useful in identifying subgroups of patients with AD who have different clinical responses to donepezil.

Our objective was to construct and validate a Multidimensional Prognostic Index (MPI) for 1-year mortality from a Comprehensive Geriatric Assessment (CGA) routinely carried out in elderly patients in a geriatric acute ward. The CGA included clinical, cognitive, functional, nutritional, and social parameters and was carried out using six standardized scales and information on medications and social support network, for a total of 63 items in eight domains. A MPI was developed from CGA data by aggregating the total scores of the eight domains and expressing it as a score from 0 to 1. Three grades of MPI were identified: low risk, 0.0-0.33; moderate risk, 0.34-0.66; and severe risk, 0.67-1.0. Using the proportional hazard models, we studied the predictive value of the MPI for all causes of mortality over a 12-month follow-up period. MPI was then validated in a different cohort of consecutively hospitalized patients. The development cohort included 838 and the validation cohort 857 elderly hospitalized patients. Of the patients in the two cohorts, 53.3 and 54.9% were classified in the low-risk group, respectively (MPI mean value, 0.18 +/- 0.09 and 0.18 +/- 0.09); 31.2 and 30.6% in the moderate-risk group (0.48 +/- 0.09 and 0.49 +/- 0.09); 15.4 and 14.2% in the severe-risk group (0.77 +/- 0.08 and 0.75 +/- 0.07). In both cohorts, higher MPI scores were significantly associated with older age (p = 0.0001), female sex (p = 0.0001), lower educational level (p = 0.0001), and higher mortality (p = 0.0001). In both cohorts, a close agreement was found between the estimated mortality and the observed mortality after both 6 months and 1 year of follow-up. The discrimination of the MPI was also good, with a ROC area of 0.751 (95%CI, 0.70-0.80) at 6 months and 0.751 (95%CI, 0.71-0.80) at 1 year of follow-up. We conclude that this MPI, calculated from information collected in a standardized CGA, accurately stratifies hospitalized elderly patients into groups at varying risk of mortality.

To compare symptoms and other clinical characteristics of reflux esophagitis in patients of different ages.Observational cross-sectional study of consecutive patients.Geriatric Unit, Casa Sollievo della Sofferenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico.Eight hundred forty patients with endoscopically diagnosed erosive esophagitis divided into four groups according to age (young (50, mean 36.7, n=114), adult (50-69, mean 59.1, n=126), elderly (70-84, mean 77.3, n=425), and very elderly (or=85, mean 88.4, n=175)).Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptom Rating Scale questionnaire. Other symptoms were recorded when present as an indication for endoscopy. Severity of esophagitis, presence of Helicobacter pylori infection, presence and size of hiatus hernia, Barrett's esophagus, antrum or corpus gastric atrophy, and nonsteroidal antiinflammatory drug (NSAID) use were also evaluated.Elderly and very elderly patients had a significantly lower prevalence of typical gastroesophageal reflux disease symptoms (heartburn or acid regurgitation (P.001) and epigastric pain (P.001)) than young and adult patients. Conversely, the prevalence of other symptoms (anorexia (P.001), weight loss (P.007), anemia (P.001), vomiting (P.001), and dysphagia (P.001)) significantly increased with age. The prevalence of severe esophagitis (P.001), hiatus hernia (P.005), the size of hiatus hernia (P.001), antrum and corpus gastric atrophy (P.05) and NSAID use (P.005) also significantly increased with age. Multivariate analysis demonstrated that older age (65-84, odds ratio (OR)=2.66, 95% confidence interval (CI)=1.38-5.12;or=85, OR=4.57, 95% CI=2.15-9.71), hiatus hernia larger than 3 cm in diameter (OR=2.38, 95% CI=1.41-4.01), and male sex (OR=2.83, 95% CI=1.72-4.64) are independent risk factors for severe esophagitis, whereas H. pylori infection, gastric atrophy, NSAID use, and the presence of hiatus hernia were not.Elderly patients with reflux esophagitis had less-typical and more-nonspecific symptoms than young or adult patients. Old age, male sex, and hiatus hernia size greater than 3 cm are significantly associated with severe esophagitis. Clinicians caring for older patients should be aware of the nonspecific presentation and potential severity of reflux esophagitis in this population.

The prevalence of Alzheimer's disease (AD) and AD-related dementias (ADRD) in acute ward— hospitalized elderly patients is not well known, owing principally to misclassification and undercoding of AD and ADRD on hospital discharge abstract forms (DAFs). The aims of this study were to evaluate the prevalence of AD and ADRD, as evaluated by the DAF, in elderly patients hospitalized in acute wards, and to compare clinical severity, length of stay, comorbidity, and number of diagnostic procedures in patients with AD versus ADRD to explain the different reimbursement costs of DRG12 (AD) versus DRG429 (ADRD). From the inpatient DAF database of the Casa Sollievo della Sofferenza Hospital, the DAFs of patients aged 65 years or over discharged from January 1, 2001, to March 31, 2003, with principal or secondary diagnoses of AD (ICD9-CM code 331) or ADRD (ICD9-CM codes from 290.0 to 290.43) were extracted and grouped by APR-grouper version 12. Age, gender, length of stay, principal and secondary diagnoses and procedures, and APR-DRG severity index (SI) and mortality risk (MR) were evaluated in these patients. Senile dementia was reported in 294 patients (0.58 percent, N = 50,253). In 123 patients (41.8 percent) dementia was the principal diagnosis, whereas in 171 patients (58.2 percent) dementia was reported on the DAF as a secondary diagnosis. Of the 123 patients with a principal diagnosis of dementia, 35 patients were included in the DRG-12 (AD) and 88 patients were included in the DRG-429 (ADRD). No differences were found in mean age, length of stay, comorbidity, or number of diagnostic procedures, as well as in the APR-DRG SI and APR-DRG MR between AD and ADRD patients. Conversely, reimbursement amounts were established as 4,033 for DRG-12 (AD) and 2,952 for DRG-429 (ADRD). AD and ADRD are undercoded in elderly hospitalized patients. The limits of the ICD9-CM classification system and the influence of reimbursement amounts may influence the coding reports by physicians.

Background and aims: Although the administration of gastroprotective drugs may reduce the risk of gastrointestinal (GI) bleeding due to intake of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin during chronic treatment, no consensus exists as to whether such co-therapy is effective in short-term prevention, particularly in old age. The aim of our study was to evaluate the risk of bleeding associated with acute and chronic NSAID or aspirin therapy in elderly subjects, and the influence of gastroprotective treatment on such a risk. Methods: The study included 467 elderly NSAID or aspirin users and 1784 non-users, who consecutively underwent upper GI endoscopy. The use of NSAIDs and/or aspirin as well as gastroprotective drugs (misoprostol, H2-blockers, proton pump inhibitors) was evaluated during a structured interview. Upper GI tract bleeding was diagnosed on the basis of symptoms and endoscopic signs of recent hemorrhage. Results: 54.2% of patients were acute and 45.8% chronic users of NSAIDs or aspirin. The risk of bleeding was higher in acute [odds ratio (OR) 4.14, 95% CI 2.97-5.78] than chronic users (OR 1.71, 95% CI 1.1-2.67). The risk of bleeding, adjusted for age, gender, Helicobacter (H) pylori infection, and gastroprotective drug use were 7.87 (CI 4.90-12.60) in acute users and 3.97 (95% CI 2.27-6.96) in chronic users of NSAIDs and/or aspirin. The risk of bleeding was significantly associated with acute but not chronic use of regular-dose aspirin (OR 5.53, 95% CI 2.29-13.3), diclofenac (OR 4.44, 95% CI 2.21-8.93), ketorolac (OR 4.81, 95% CI 2.13-10.9), naproxen (OR 14.9, 95% CI 4.23-52.4) or nimesulide (OR 4.06, 95% CI 1.2-13.8). Piroxicam increased the risk of bleeding in both acute (OR 5.36, 95% CI 1.94-14.8) and chronic therapy (OR 5.53, 95% CI 1.23-24.9). In acute users, concomitant therapy with proton pump inhibitors reduced the risk of bleeding compared with non-users (OR 1.05, 95% CI 0.19-5.65), whereas co-treatment with H2-blockers was associated with a significantly higher risk of bleeding than in non-users (OR 3.40, 95% CI 1.28-9.02). Chronic users of NSAIDs or aspirin co-treated with proton pump inhibitors had a lower risk of bleeding (OR 1.12, 95% CI 0.21-6.07) than those treated with misoprostol (OR 1.91, 95% CI 0.33-10.9) or H2 blockers (OR 2.26, 95% CI 0.81-6.36). Conclusions: The risk of upper GI bleeding is significantly higher in elderly acute vs chronic users of NSAIDs or regular-dose aspirin. In acute NSAID or aspirin users, co-treatment with proton pump inhibitors, but not with H2-blockers, may reduce the risk of bleeding compared with non-users.