[Dislipidemia and lipid lowering drugs: from guidelines to clinical practice. An updated review of the literature.] / Dislipidemia e terapia ipolipemizzante: dalle linee guida alla pratica clinicaUna rassegna aggiornata della letteratura.

The atherosclerotic cardiovascular disease (ASCVD) represents the leading cause of death and disability not only in countries with a high degree of socio-economic development but also in low- middle-income countries. The study of atherosclerosis and the strategies to control ASCVD are evolving. All strategies emphasize the need to lower LDL cholesterol through an appropriate lifestyle and the use of lipid-lowering drugs. A therapy with statin with or without other lipid lowering drugs is recommended in secondary prevention. In primary prevention, the use of the lipid-lowering drug should instead take into account the cost-benefit ratio. Available evidence coming from clinical trials is useful to inform clinical choices but must be associated with a shared decision-making process between doctor and patient.

Familial late-onset Alzheimer's disease: description of an Italian family with four affected siblings and one case of early-onset dementia in the preceding generation.

We describe a family composed of six siblings, four of which affected by late-onset Alzheimer's disease (LOAD). We constructed the family pedigree, evaluated mutations usually associated with early-onset Alzheimer's disease (APP, PSEN1, PSEN2), and assessed polymorphisms in the apolipoprotein E (APOE) gene and in cytokine genes that we had previously found to be associated with a higher risk of LOAD (IL-10, IL-6, TNF-α). Results showed that all subjects carried one ε4 allele of the APOE gene and those with the earliest age of onset exhibited the AA (-1082) IL-10 and the CC (-174) IL-6 genotypes. The only male had a genetic profile which also included the A (-308) TNF-α allele. These data confirm the role of the APOE gene as genetic risk factor in LOAD, and suggest that the risk of developing AD may be governed by a "susceptibility profile" involving polymorphisms in inflammatory genes.

Electrocardiographic monitoring for new prescriptions of quetiapine co-prescribed with acetylcholinesterase inhibitors or memantine from 2005 to 2009. A population study on community-dwelling older people in Italy.

PURPOSE: The aims of this study are to analyse, in community-dwelling people aged 65+ living in Italy's Lombardy Region, electrocardiographic (ECG) monitoring for new users of the atypical antipsychotic quetiapine co-prescribed with acetylcholinesterase inhibitors (AChEIs) or memantine and to find independent predictors of ECG monitoring before and after the starting of this prescription. METHODS: The Lombardy Region's administrative health database was used to retrieve prescriptions of ECG exams as well as prevalence rates of subjects aged 65+ who were prescribed such psychotropic drugs from 2005 to 2009. Multivariable analyses were adjusted for age, sex, number of drugs, treatment with beta-blockers, digoxin, verapamil or diltiazem, any antiarrhythmic drug and antidepressants. RESULTS: Overall 2,623 community-dwelling older people started therapy with quetiapine, co-prescribed with AChEIs or memantine, during these 5 years. At least one ECG was performed in 714 cases (27.2 %) in the 6 months before-and in 398 cases (15.2 %) within 3 months after-the starting of this prescription. ECG monitoring was performed both before and after starting quetiapine in only 160 cases (6.1 %). At multivariable analyses, number of drugs taken, beta-blocker and antiarrhythmic drug use were found to be independent correlates of ECG monitoring whereas female sex was associated with a lower probability of receiving an ECG within 3 months after the initiation of quetiapine (odds ratio 0.78, 95 % CI 0.62-0.98). CONCLUSIONS: ECG monitoring for new prescriptions of quetiapine in older people suffering from behavioural and psychological symptoms in dementia was actually performed infrequently, independently of the age of drug users, especially in women. Our results support the need for greater awareness within the medical community of the importance of such ECG monitoring.

[Dyslipidemias and statins: from guidelines to clinical practice. An updated review of the literature]. / Dislipidemia e statine: dalle linee guida alla pratica clinica.Una rassegna aggiornata della letteratura.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability not only in countries with a high degree of socio-economic development but also in low-middle income countries. The study of atherosclerosis and the strategies to control ASCVD are in progress. All strategies emphasize the need for lowering LDL cholesterol through appropriate lifestyle and use of lipid-lowering drugs, mainly statins. The mode of approach is variable. Statin therapy is recommended in secondary prevention, whereas use in primary prevention is still a matter of debate. The guidelines provided by international panels serve as a reference in clinical practice but, as stated by the National Cholesterol Education Program (NCEP), do not replace the physician's clinical judgment.

New prescriptions of spironolactone associated with angiotensin-converting-enzyme inhibitors and/or angiotensin receptor blockers and their laboratory monitoring from 2001 to 2008: a population study on older people living in the community in Italy.

PURPOSE: To analyse, in older community-dwelling people living in Italy's Lombardy region, 8-year trends in new users of spironolactone co-prescribed with angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs); blood test monitoring; and independent predictors of appropriate blood test monitoring. METHODS: The region's administrative health database from 2001 to 2008 was used to retrieve yearly frequencies of subjects aged 65+ who started this co-prescription. Multivariate analyses were adjusted for age, sex, local health unit, treatment with beta-blockers, drugs for diabetes, and polypharmacy (i.e., exposure to five or more different drugs). RESULTS: Only new users of spironolactone co-prescribed with ARBs increased from 2001 to 2008 (P < 0.001). In the 6 months before starting the co-prescriptions 96 to 100% of patients measured serum creatinine (mean 99.3%), sodium (97.3%) and potassium (98.6%). Within 3 months of starting the co-prescriptions 96 to 99% of patients measured serum sodium (mean 97.3%) and potassium (98.6%), but on average only 48% of them (range 43 to 53%) measured serum creatinine, with an increase over time (odds ratio [change in regression per year] = 1.03, 95% CI 1.02-1.05, P < 0.001). At multivariate analysis polypharmacy was found to be the only independent predictor of such creatinine monitoring (P < 0.001). CONCLUSIONS: Our results support the need for greater awareness within the medical community of the potential renal toxicity of the association of spironolactone with ACE-Is and/or ARBs. Adequate short-term monitoring of serum creatinine in all older community-dwelling people who receive such co-prescription is necessary in order to ensure safe usage of these medications.

Delusion of inanimate doubles: description of a case of focal retrograde amnesia.

This paper reports the case of a patient, M.P., who developed delusion of inanimate doubles, without Capgras syndrome, after traumatic brain injury. His delusional symptoms were studied longitudinally and the cognitive impairments associated with delusion were investigated. Data suggest that M.P. did 'perceive' the actual differences between doubles and originals rather than 'confabulate' them. The cognitive profile, characterized by retrograde episodic amnesia, but neither object processing impairment nor confabulations, supports this hypothesis. The study examines the nature of object misidentification based on Ellis' and Staton's account and proposes a new account based on concurrent unbiased retrieval of semantic memory traces and biased recollection of episodic memory traces.

Frailty syndrome diagnosed according to the Study of Osteoporotic Fractures criteria and mortality in older outpatients suffering from Alzheimer's disease: a one-year prospective cohort study.

OBJECTIVE: The frailty syndrome is associated with adverse clinical outcomes independently of cognitive impairment. The recent easy-to-apply Study of Osteoporotic Fractures (SOF) criteria for frailty could be useful to diagnose such syndrome also in Alzheimer's disease (AD) patients. The aim of this study was to apply these criteria among AD outpatients in order to determine: (i) the prevalence and correlates of frailty and (ii) the one-year predictors of death in this population. METHOD: This prospective cohort study enrolled 109 community-dwelling outpatients aged 65+ (median age 84 years) consecutively diagnosed with AD at a geriatric outpatient service in Italy in 2009. At baseline, participants underwent a comprehensive geriatric assessment including the evaluation of frailty status by means of the SOF criteria. Multiple logistic regression analysis was performed to find correlates of frailty. At a one-year follow-up, data on mortality were available for 95 participants and predictors of death were evaluated by means of multiple logistic regression analysis. RESULTS: Most participants had mild (52%) or moderate (29%) dementia. Frailty status was defined for all subjects at baseline: 25 (22%) were robust, 30 (28%) pre-frail and 54 (50%) frail. Independent correlates of frailty were age and dependence in the basic activities of daily living, and in particular in dressing. One year after enrolment, frailty was an independent predictor of death (odds ratio 11.27, 95% confidence interval 1.64-77.72, p = 0.014) after correction for age, sex, dependence in the basic activities of daily living, severity of cognitive impairment and comorbidity. CONCLUSION: Frailty status was diagnosed according to the SOF criteria in all AD outpatients and it was an independent one-year predictor of death. In order to provide them with appropriate prognostic evaluation and therapeutic advice all AD outpatients, especially those with specific disabilities, could be screened by means of the SOF criteria for frailty.

Frailty syndrome diagnosed according to the Study of Osteoporotic Fractures (SOF) criteria and adverse health outcomes among community-dwelling older outpatients in Italy. A one-year prospective cohort study.

The easy-to-apply SOF criteria for frailty were recently validated in studies conducted in the U.S. only. In order to determine the ability of the SOF criteria to predict adverse health outcomes at a one-year follow-up in a sample of older outpatients in Italy we carried out a prospective cohort study on 265 community-dwelling outpatients aged 65+ (mean age 81.5 years) consecutively referred to a geriatric clinic. At baseline participants underwent a comprehensive geriatric assessment (CGA) including evaluation of their frailty status according to the SOF criteria. At a one-year follow-up, between June and December 2010, we investigated nursing home placement and death in all participants as well as any fall, any admission to the emergency department (ED), any hospitalization and a greater disability among the subset of subjects still living at home. One year after the visit 231 subjects were still living at home (87.2%), 9 had been placed in a nursing home (3.4%) and 25 had died (9.4%). Frailty was associated with a greater risk of falls (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.05-3.83, p=0.035), hospitalization (OR 2.08, 95% CI 1.02-4.24, p=0.045) and death (OR 3.07, 95% 1.02-4.24, p=0.045) after correction for demographic characteristics, comorbidity including dementia and depression, socioeconomic position and severe disability. Thus, in an older outpatient population in Italy the frailty syndrome diagnosed according to the SOF criteria was an independent predictor of several adverse health outcomes.

Quality of life in older outpatients living alone in the community in Italy.

There is limited knowledge on the relationship between the living conditions of community-dwelling older people and their quality of life (QOL) considered in all its specific domains. The purpose of this study was to determine (1) which dimensions of QOL were independently associated with living alone and (2) the independent correlates of these dimensions of QOL amongst older outpatients. We conducted a cross-sectional survey of 239 community-dwelling outpatients aged 65+ (mean age 81.5 years) consecutively referred to a geriatric medicine clinic in Italy between June and November 2009 (response rate 93%). Subjects underwent a comprehensive geriatric assessment including QOL, which was evaluated by using the Older People's QOL questionnaire. In multivariate logistic regression analyses, living alone was associated with the lowest score-based tertile of two specific dimensions of QOL out of seven, namely 'social relationships and participation' [odds ratio (OR) 2.73, 95% confidence interval (CI) 1.08-6.91] and 'home and neighbourhood' (OR 4.96, 95% CI 1.75-14.07), independently of the main demographic, social, functional and clinical characteristics of the subjects. Amongst the 107 subjects living alone, independent correlates of these dimensions of QOL were depression, having no caregiver and having never been married. Depression, having no caregiver and having never been married could provide a valuable means of identifying older people living alone who are at greater risk of a poor QOL and who would most benefit from effective social and medical interventions.

Comparison of informant reports and neuropsychological assessment in mild cognitive impairment.

The aim of this retrospective study was to investigate the accuracy of informant reports on cognitive status in mild cognitive impairment (MCI) by comparing the subjective evaluation made by patients' relatives with the objective results of neuropsychological assessment. We enrolled 119 MCI outpatients and their relatives. Cognitive impairment was assessed by a battery of standardized neuropsychological tests. Informant reports on cognitive functioning were obtained by means of a structured interview. Subjective and objective evaluations of cognitive status were rated according to the same scoring system in order to enable comparison. All but one relative reported cognitive dysfunctions at the interview, but the kind of cognitive profile emerging from their reports was quite different from the one highlighted by neuropsychological assessment. A subjective evaluation of cognitive status based on informant reports could therefore be useful to identify patients with MCI but is unable to define MCI subtypes.

Older People's Quality of Life (OPQOL) scores and adverse health outcomes at a one-year follow-up. A prospective cohort study on older outpatients living in the community in Italy.

BACKGROUND: There is limited knowledge on the ability of a poor quality of life (QOL) and health-related QOL (HRQOL) to predict mortality and other adverse health events, independently of the frailty syndrome and other confounders, in older people living in the community and not selected on the basis of specific chronic conditions. Aim of this study was to evaluate the ability of the overall QOL and of the HRQOL to predict several adverse health outcomes at a one-year follow-up in an older outpatient population living in the community. METHODS: We carried out a prospective cohort study on 210 community-dwelling outpatients aged 65+ (mean age 81.2 yrs) consecutively referred to a geriatric clinic in Milan, Italy. At baseline participants underwent a comprehensive geriatric assessment including evaluation of overall QOL and HRQOL by means of the Older People's Quality of Life (OPQOL) questionnaire. At a one-year follow-up, between June and December 2010, we investigated nursing home placement and death in all 210 participants as well as any fall, any admission to the emergency department (ED), any hospitalisation and greater functional dependence among the subset of subjects still living at home. RESULTS: One year after the visit 187 subjects were still living at home (89%) while 7 had been placed in a nursing home (3.3%) and 16 had died (7.7%). At multiple logistic regression analyses the lowest score-based quartile of the OPQOL total score at baseline was independently associated with a greater risk of any fall and any ED admission. Also, the lowest score-based quartile of the health-related OPQOL sub-score was associated with a greater risk of any fall as well as of nursing home placement (odds ratio [OR] 10.03, 95% confidence interval [CI] 1.25-80.54, P = 0.030) and death (OR 4.23, 95% CI 1.06-16.81, P = 0.041). The correlation with the latter two health outcomes was found after correction for age, sex, education, income, living conditions, comorbidity, disability and the frailty syndrome. CONCLUSIONS: In an older outpatient population in Italy the OPQOL total score and its health-related sub-score were independent predictors of several adverse health outcomes at one year. Notably, poor HRQOL predicted both nursing home placement and death even after correction for the frailty syndrome. These findings support and enhance the prognostic relevance of QOL measures.

An easy intervention to improve short-term adherence to medications in community-dwelling older outpatients. A pilot non-randomised controlled trial.

BACKGROUND: Complex interventions to improve compliance to pharmacological treatment in older people have given mixed results and are not easily applicable in clinical practice. The aim of this study was to test the short-term efficacy on self-reported medication adherence of an easy intervention in which the patient or caregiver was asked to transcribe the pharmacological treatment while it was dictated to him/her by the doctor. METHODS: Pilot non-randomised controlled trial involving 108 community-dwelling outpatients aged 65+ (54 in the intervention arm, 54 controls) referred to a geriatric service from May to July 2009 and prescribed by the geriatrician a change in therapy. The intervention was applied at the end of the visit to the person managing the medications, be it the elder or his/her caregiver. Outcome of the study was the occurrence of any adherence error, assessed at a one-month follow-up by means of a semi-structured interview. RESULTS: The socio-demographic, functional and clinical characteristics of the two compared groups were similar at baseline. At a one-month follow-up 43 subjects (40%) had made at least one adherence error, whether unintentional or intentional. In the intervention group the prevalence of adherence errors was lower than in controls (20% vs 59%; adjusted odds ratio 0.16, 95% confidence interval 0.07 - 0.39; p < 0.001) after adjusting for the person managing the medications, the adherence errors at baseline and for the number of prescribed drugs. CONCLUSIONS: In an older outpatient population the intervention considered was effective in reducing the prevalence of adherence errors in the month following the visit. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000347965.

Social vulnerability, mental health and correlates of frailty in older outpatients living alone in the community in Italy.

OBJECTIVE: To determine the main social, functional and clinical characteristics of community-dwelling older outpatients living alone and to find correlates of frailty in this population. METHOD: Cross-sectional survey of 302 community-dwelling outpatients aged 65+ (median age 82 years) consecutively referred to a geriatric medicine clinic in Italy from June to November 2009. Participants underwent a comprehensive geriatric assessment including frailty status evaluated by means of the study of osteoporotic fractures (SOF) criteria. Student's t-test and the chi-squared test were used to compare subjects 'living alone' and 'not living alone' as well as 'frail' and 'not frail' subjects among the participants living alone. Multiple logistic regression analyses were performed to find independent correlates of frailty among participants living alone. RESULTS: Participants 'living alone' were 124 (41%). Compared to subjects 'not living alone' (n = 178), they were older, received less assistance from informal and formal caregivers, had poorer living and financial conditions, a better cognitive status and functional self-sufficiency but a worse emotional status. One-third of them (n = 41) were frail. Among frail elders (n = 116), subjects living alone also showed a higher prevalence of unexpected new diagnoses of dementia than those not living alone. Independent correlates of frailty among participants living alone were: having experienced a severe acute disease in the past year (odds ratio [OR] 303.9; 95% confidence interval [CI] 13-7091; p < 0.001), dependence in the bathing BADL ability (OR 62.74; 95% CI 12.17-323.32; p < 0.001), depression (OR 10.43; 95% CI 2.31-47.13; p = 0.002) and incontinence (OR 3.98; 95% CI 1.01-15.66; p = 0.048). CONCLUSION: In older outpatients living alone, including those who were frail, we found a lower availability of personal assistance, significantly more social and financial vulnerability and a higher risk of depression. In frail elders there was also a higher prevalence of underdiagnosed dementia. In order to better recognise frail subjects in this specific population, four independent correlates of frailty were identified.

Intereleukin-10 promoter polymorphism in mild cognitive impairment and in its clinical evolution.

Specific proinflammatory alleles are associated with higher risk of Alzheimer disease (AD) in different onset age. The homozygosis for the A allele of -1082 polymorphism (G/A) of interleukin-10 (IL-10) promotes a higher risk of AD and reduced IL-10 generation in peripheral cells after amyloid stimulation. In this paper we analysed genotype and allele frequencies of this polymorphism in 138 subjects with mild cognitive impairment (MCI) diagnosed, respectively, as amnestic (a-MCI) and multiple impaired cognitive domains (mcd-MCI). The genotype frequencies were similar in a-MCI and AD subjects, whereas in mcd-MCI comparable to controls (AA genotype: 50% in a-MCI, 49.2% in AD, 28.7% in mcd-MCI and 31.8% in controls). Consequently, both allele and genotype distributions were significantly different between a-MCI and mcd-MCI (allele: P = .02, genotype: P < .05). These results support the theory that polymorphisms of cytokine genes can affect neurodegeneration and its clinical progression. IL-10 may partly explain the conversion of a-MCI to AD or be a genetic marker of susceptibility.

Dimensions and correlates of quality of life according to frailty status: a cross-sectional study on community-dwelling older adults referred to an outpatient geriatric service in Italy.

BACKGROUND: There is a lack of knowledge concerning the relationship between two closely-linked multidimensional variables: frailty and quality of life (QOL). The aim of this study was to investigate dimensions and correlates of QOL associated with frailty status among community-dwelling older outpatients. METHODS: We conducted a cross-sectional survey of 239 community-dwelling outpatients aged 65+ (mean age 81.5 years) consecutively referred to a geriatric medicine clinic in Italy between June and November 2009. Participants underwent a comprehensive geriatric assessment, including assessment of their frailty status according to the Study of Osteoporotic Fractures (SOF) criteria, and QOL, which was evaluated by using the Older People's QOL (OPQOL) questionnaire. One-way ANOVA and chi-squared tests were used to find correlates of frailty, including QOL dimensions, after stratification of participants in the "robust" (n = 72), "pre-frail" (n = 89) and "frail" (n = 78) groups. Multiple linear regression analyses were performed to find correlates of QOL in the overall sample and among "frail" and "robust" participants. RESULTS: A negative trend of QOL with frailty status was found for almost all dimensions of QOL (health, independence, home and neighbourhood, psychological and emotional well-being, and leisure, activities and religion) except for social relationships and participation and financial circumstances. Independent correlates of a poor QOL in the total sample were "reduced energy level" (SOF criterion for frailty), depressive status, dependence in transferring and bathing abilities and money management (adjusted R squared 0.39); among "frail" participants the associations were with depressive status and younger age, and among "robust" participants the association was with lower body mass index. CONCLUSIONS: Five out of seven dimensions of QOL were negatively affected by frailty, but only one SOF criterion for frailty was independently related to QOL, after correction for age, functional status and depression. A more advanced age as well as a better affective status were correlates of a better QOL among frail elders. Interventions targeting the QOL in frail community-dwelling older outpatients should consider as outcomes, not only health-related QOL, but also other domains of the QOL.