A narrative review on the potential of tomato and lycopene for the prevention of Alzheimer's disease and other dementias.

Oxidative stress is a major factor in aging and is implicated in the pathogenesis of tumors, diabetes mellitus, cardiovascular and neurodegenerative diseases, including Alzheimer Disease (AD). Bioactive constituents of tomato as polyphenols and carotenoids, among which lycopene (LYC) are effective in reducing markers of oxidative stress, and appear to have a protective modulator role on the pathogenetic mechanisms, cognitive symptoms and behavioral manifestations of these diseases in cell cultures and animal models. Epidemiological evidence indicates a consistent association between the intake of tomatoes and reduced cardiovascular and neoplastic risk. LYC deficiency is common in elders and AD patients and it is strongly predictive of mortality and poor cardiovascular (CV) outcomes. Dietary intake of tomatoes seems to be more effective than tomato/LYC supplementation. Limited evidence from human intervention trials suggests that increasing tomato intake, besides improving CV markers, enhances cognitive performances. In this narrative review, we analyze the existing evidence on the beneficial effects of tomatoes on AD-related processes or risk factors. Results support the development of promising nutritional strategies to increase the levels of tomato consumption for the prevention or treatment of AD and other dementias. Extensive well-structured research, however, is mandatory to confirm the neuroprotective effects of tomato/LYC in humans.

Dementia Research Fit for the Planet: Reflections on Population Studies of Dementia for Researchers and Policy Makers Alike.

In recent years, a rapidly increasing collection of investigative methods in addition to changes in diagnostic criteria for dementia have followed "high-tech" trends in medicine, with the aim to better define the dementia syndrome and its biological substrates, mainly in order to predict risk prior to clinical expression. These approaches are not without challenge. A set of guidelines have been developed by a group of European experts in population-based cohort research through a series of workshops, funded by the Joint Program for Neurodegenerative Disorders (JPND). The aims of the guidelines are to assist policy makers and researchers to understand (1) What population studies for ageing populations should encompass and (2) How to interpret the findings from population studies. Such studies are essential to provide evidence relevant to the understanding of healthy and frail brain ageing, including the dementia syndrome for contemporary and future societies by drawing on the past.

Exploring the relationship between Nutrition, gUT microbiota, and BRain AgINg in community-dwelling seniors: the Italian NutBrain population-based cohort study protocol.

BACKGROUND: Epidemiological evidence suggests that healthy diet is associated with a slowdown of cognitive decline leading to dementia, but the underlying mechanisms are still partially unexplored. Diet is the main determinant of gut microbiota composition, which in turn impacts on brain structures and functions, however to date no studies on this topic are available. The goal of the present paper is to describe the design and methodology of the NutBrain Study aimed at investigating the association of dietary habits with cognitive function and their role in modulating the gut microbiota composition, and brain measures as well. METHODS/DESIGN: This is a population-based cohort study of community-dwelling adults aged 65 years or more living in Northern Milan, Italy. At the point of presentation people are screened for cognitive functions. Socio-demographic characteristics along with lifestyles and dietary habits, medical history, drugs, functional status, and anthropometric measurements are also recorded. Individuals suspected to have cognitive impairment at the screening phase undergo a clinical evaluation including a neurological examination and a Magnetic Resonance Imaging (MRI) scanning (both structural and functional). Stool and blood samples for the gut microbiota analysis and for the evaluation of putative biological markers are also collected. For each subject with a confirmed diagnosis of Mild Cognitive Impairment (MCI), two cognitively intact controls of the same sex and age are visited. We intend to enrol at least 683 individuals for the screening phase and 240 persons for the clinical assessment. DISCUSSION: The NutBrain is an innovative study that incorporates modern and advanced technologies (i.e. microbiome and neuroimaging) into traditional epidemiologic design. The study represents a unique opportunity to address key questions about the role of modifiable risk factors on cognitive impairment, with a particular focus on dietary habits and their association with gut microbiota and markers of the brain-aging process. These findings will help to encourage and plan lifestyle interventions, for both prevention and treatment, aiming at promoting healthy cognitive ageing. TRIAL REGISTRATION: Trial registration number NCT04461951 , date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov ).

Specific nutrient patterns are associated with higher structural brain integrity in dementia-free older adults.

Optimal nutrition may play a beneficial role in maintaining a healthy brain. However, the relationship between nutrient intake and brain integrity is largely unknown. We investigated the association of specific nutrient dietary patterns with structural characteristics of the brain. Within the population-based Swedish National study on Aging and Care-Kungsholmen (SNAC-K), a cross-sectional study of 417 dementia-free participants aged ≥60 years who underwent structural magnetic resonance imaging (MRI) scans during 2001-2003, was carried-out. Data on dietary intake were collected using a food frequency questionnaire, from which intake of 21 nutrients was estimated. By principal component analysis, five nutrient patterns were extracted: (1) NP1 was characterized by fiber, vitamin C, E, ß-carotene, and folate [Fiber&Antioxidants], (2) NP2 by eicosapentaenoic (EPA, 20:5 ω-3) and docosahexaenoic (DHA, 22:6 ω-3) polyunsaturated fatty acids (PUFAs), proteins, cholesterol, vitamin B3, B12, and D [long chain (LC) ω-3PUFAs&Proteins], (3) NP3 by α-linoleic (18:2 ω-6) and α-linolenic (18:3 ω-3) PUFAs, monounsaturated fatty acids (MUFAs), and vitamin E [MUFAs&ω-3,6PUFAs], (4) NP4 by saturated fatty acids (SFAs), trans fats, MUFAs, and cholesterol [SFAs&Trans fats], (5) NP5 by B-vitamins, retinol, and proteins [B-Vitamins&Retinol]. Nutrient patterns scores were tertiled with the lowest tertile as reference, and were related to total brain volume (TBV) and white matter hyperintensities volume (WMHV) using linear regression models adjusting for potential confounders. In the multi-adjusted model, compared to the lowest intake for each pattern, the highest intake of NP1 (ß = 11.11, P = 0.009), NP2 (ß = 7.47, P = 0.052), and NP3 (ß = 10.54, P = 0.005) was associated with larger TBV whereas NP5 was related to smaller TBV (ß = -12.82, P = 0.001). The highest intake of NP1 was associated with lower WMHV (ß = -0.32, P = 0.049), whereas NP4 was associated with greater WMHV (ß = 0.31, P = 0.036). In sum, our results suggest that the identified brain-health specific nutrient combinations characterized by higher intake of fruit, vegetables, legumes, olive and seed oils, fish, lean red meat, poultry and low in milk and dairy products, cream, butter, processed meat and offal, were strongly associated with greater brain integrity among older adults.

Adherence to recommendations and clinical outcomes of patients hospitalized for stroke: the role of the admission ward-a real-life investigation from Italy.

OBJECTIVE: To determine whether out-of-hospital healthcare and adverse outcomes are better in stroke patients admitted to a neurology ward compared with those admitted to general wards. METHODS: Beneficiaries of the National Health Service from the Italian Lombardy Region who were discharged alive after hospital admission during the year 2009 for ischemic stroke (9776 patients) or intracerebral or subarachnoid hemorrhage (1102 patients) entered into the cohort and were followed until 2012. Exposure of interest was the ward type where inpatients were admitted (neuro vs. general wards). Outcomes were out-of-hospital healthcare (i.e., drug prescriptions, diagnostic procedures, and laboratory clinical evaluations) and adverse clinical outcomes (i.e., all-cause death and hospital readmission). Exposure-outcome associations were investigated. High-dimensional propensity score methodology was used for taking into account confounders. Mediation analysis was used to verify whether the association between ward type and clinical outcomes is mediated by out-of-hospital adherence to healthcare. RESULTS: Better adherence to out-of-hospital healthcare received from patients discharged from neuro, rather than general, wards was observed being the proportions of adherent patients 42.4% and 39.5%, respectively. Compared with general wards, discharge from neuro was associated with reduced 3-year emergency admissions (from 50.1 to 47.5% among ischemic stroke patients) and reduced 3-year mortality (from 37.5 to 27.0% among hemorrhagic stroke patients). From 10 to 15% of outcome risk, reductions were mediated by better adherence to out-of-hospital healthcare. CONCLUSIONS: For patients with acute ischemic and hemorrhagic stroke, admission to neuro vs. general wards is associated with better out-of-hospital healthcare and long-term adverse outcomes.

The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015".

BACKROUND: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium. AIM: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients. METHODS: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age > 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment). RESULTS: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia. DISCUSSION: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents. CONCLUSION: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence.

A Point Prevalence Study of Delirium in Italian Nursing Homes.

BACKGROUND: Delirium is a common geriatric syndrome. Few studies have been conducted in nursing home (NH) residents. The aim of this project was to perform a point prevalence study of delirium in Italian NHs. METHODS: Data collected in 71 NHs are presented. Inclusion criteria were age ≥65 years and native Italian speaker. Exclusion criteria were coma, aphasia, and end-of-life status. Sociodemographic and medical data were recorded. Delirium was assessed using the Assessment Test for Delirium and Cognitive Impairment (4-AT). Patients with a 4-AT score ≥4 were considered to have delirium. Motor subtype was evaluated using the Delirium Motor Subtype Scale (DMSS). RESULTS: A total of 1,454 patients were evaluated (mean age 84.4 ± 7.4 years, 70.2% female), of whom 535 (36.8%) had delirium. In multivariate logistic regression analysis, variables significantly associated with delirium were education (OR 0.94, 95% CI 0.91-0.97), dementia (OR 3.12, 95% CI 2.38-4.09), functional dependence (OR 6.13, 95% CI 3.08-12.19 for ADL score 0; OR 1.99, 95% CI 1.03-3.84 for ADL score 1-5), malnutrition (OR 4.87, 95% CI 2.68-8.84), antipsychotics (OR 2.40, 95% CI 1.81-3.18), and physical restraints (OR 2.48, 95% CI 1.71-3.59). CONCLUSION: Delirium is common in older NH residents. Simple assessment tools might facilitate its recognition in this vulnerable population.

Different Exposures to Risk Factors Do Not Explain the Inverse Relationship of Occurrence Between Cancer and Neurodegenerative Diseases: An Italian Nested Case-control Study.

Several studies reported that cancer is less frequent in persons with Alzheimer's and Parkinson's Diseases (AD/PD) and vice-versa. We evaluated whether a different distribution of known nongenetic risk factors for cancer and AD/PD, might explain their inverse relationship of occurrence. We nested 2 case-control studies in a subsample of a large cohort of 1,000,000 resident in Lombardy Region in Italy (n=1515), followed-up for cancer and AD/PD occurrence since 1991 until 2012. Conditional logistic regression was performed to determine the odds ratios (OR) and 95% confidence intervals (CI) of AD/PD in subjects with and without cancer and the risk of cancer in those with and without AD/PD. A total of 54 incident cases of AD/PD and 347 cancer cases were matched with 216 and 667 controls, respectively. After controlling for low education, obesity, history of hypertension, diabetes, dyslipidemia, physical activity, smoking habit, alcohol consumption, and dietary habit, cancer was found inversely associated with the risk of AD/PD (OR, 0.66; 95% CI, 0.32-1.38), and the risk of cancer in AD/PD was similarly reduced (OR, 0.42; 95% CI, 0.20-0.91). Different exposures to nongenetic risk factors of both diseases do not explain their competitive relationship of occurrence.

Clinical Features Associated with Delirium Motor Subtypes in Older Inpatients: Results of a Multicenter Study.

OBJECTIVE: To date motor subtypes of delirium have been evaluated in single-center studies with a limited examination of the relationship between predisposing factors and motor profile of delirium. We sought to report the prevalence and clinical profile of subtypes of delirium in a multicenter study. METHODS: This is a point prevalence study nested in the "Delirium Day 2015", which included 108 acute and 12 rehabilitation wards in Italy. Delirium was detected using the 4-AT and motor subtypes were measured with the Delirium Motor Subtype Scale (DMSS). A multinomial logistic regression was used to determine the factors associated with delirium subtypes. RESULTS: Of 429 patients with delirium, the DMSS was completed in 275 (64%), classifying 21.5% of the patients with hyperactive delirium, 38.5% with hypoactive, 27.3% with mixed and 12.7% with the non-motor subtype. The 4-AT score was higher in the hyperactive subtype, similar in the hypoactive, mixed subtypes, while it was lowest in the non-motor subtype. Dementia was associated with all three delirium motor subtypes (hyperactive, OR 3.3, 95% CI: 1.2-8.7; hypoactive, OR 2.8, 95% CI: 1.2-6.5; mixed OR 2.6, 95% CI: 1.1-6.2). Atypical antipsychotics were associated with hypoactive delirium (OR 0.23, 95% CI: 0.1-0.7), while intravenous lines were associated with mixed delirium (OR 2.9, 95% CI: 1.2-6.9). CONCLUSIONS: The study shows that hypoactive delirium is the most common subtype among hospitalized older patients. Specific clinical features were associated with different delirium subtypes. The use of standardized instruments can help to characterize the phenomenology of different motor subtypes of delirium.

EMpowerment of PArents in THe Intensive Care Questionnaire: Translation and Validation in Italian PICUs.

OBJECTIVES: To translate and validate the EMpowerment of PArents in THe Intensive Care questionnaire to measure parent satisfaction and experiences in Italian PICUs. DESIGN: Prospective, multicenter study. SETTING: Four medical/surgical Italian PICUs in three tertiary hospitals. PATIENTS: Families of children, 0-16 years old, admitted to the PICUs were invited to participate. Inclusion criteria were PICU length of stay greater than 24 hours and good comprehension of Italian language by parents/guardians. Exclusion criteria were readmission within 6 months and parents of a child who died in the PICU. INTERVENTIONS: Distribution, at PICU discharge, of the EMpowerment of PArents in THe Intensive Care questionnaire with 65 items divided into five domains and a six-point rating scale: 1 " certainly no" to 6 "certainly yes." MEASUREMENTS AND MAIN RESULTS: Back and forward translations of the EMpowerment of PArents in THe Intensive Care questionnaire between Dutch (original version) and Italian languages were deployed. Cultural adaptation of the instrument was confirmed by a consultation with a representative parent group (n = 10). Totally, 150 of 190 parents (79%) participated in the study. On item level, 12 statements scored a mean below 5.0. The Cronbach's α, measured for internal consistency, on domain level was between 0.67 and 0.96. Congruent validity was measured by correlating the five domains with four gold standard satisfaction measures and showed adequate correlations (rs, 0.41-0.71; p < 0.05). No significant differences occurred in the nondifferential validity testing between three children's characteristics and the domains; excepting parents with a child for a surgical and planned admission were more satisfied on information and organization issues. CONCLUSIONS: The Italian version of the EMpowerment of PArents in THe Intensive Care questionnaire has satisfactory reliability and validity estimates and seems to be appropriate for Italian PICU setting. It is an important instrument providing benchmark data to be used in the process of quality improvement toward the development of a family-centered care philosophy within Italian PICUs.

"Delirium Day": a nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool.

BACKGROUND: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. METHODS: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. RESULTS: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. CONCLUSIONS: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys.

Exposure to vehicular traffic is associated to a higher risk of hospitalization for bronchiolitis during the first year of life.

BACKGROUND: The most common cause of hospitalization for children younger than age one is bronchiolitis. Several prenatal and environmental risk factors may affect the incidence of hospitalization for bronchiolitis. The aim of this study was to investigate the relation between exposure to vehicular traffic and the incidence of hospitalization for bronchiolitis in children during their first year of life in Italy. METHODS: A multicenter prospective birth cohort study, where equal numbers of newborns of 33-34, 35-37 and ≥38 wGA were recruited at birth (1814 children) in 30 Italian neonatology units. Two interviewer-administered questionnaires were used to collect data. The first interview was carried out at the end of the Italian epidemic season. The second interview was carried out when the child was one year old. Data on possible prenatal, perinatal, and postnatal/environmental risk factors and on vehicular traffic density in the zone of residence were collected. On each interview, parents were also asked about any hospitalizations of the child. The outcome measure was the hospitalization for bronchiolitis (International Health Service ICD-9 code 466). RESULTS: Univariate analysis demonstrated that exposure to air pollution due to vehicular traffic, was significantly associated with an increased risk of hospitalization for bronchiolitis. The adjusted risk from logistic regression model confirmed that children exposed to air pollution due to vehicular traffic were at increased risk of hospitalization for bronchiolitis. CONCLUSIONS: Exposure to air pollution due to vehicular traffic may increase the risk of hospitalization for bronchiolitis in the first year of life.

Prenatal tobacco smoke exposure increases hospitalizations for bronchiolitis in infants.

BACKGROUND: Tobacco smoke exposure (TSE) is a worldwide health problem and it is considered a risk factor for pregnant women's and children's health, particularly for respiratory morbidity during the first year of life. Few significant birth cohort studies on the effect of prenatal TSE via passive and active maternal smoking on the development of severe bronchiolitis in early childhood have been carried out worldwide. METHODS: From November 2009 to December 2012, newborns born at ≥ 33 weeks of gestational age (wGA) were recruited in a longitudinal multi-center cohort study in Italy to investigate the effects of prenatal and postnatal TSE, among other risk factors, on bronchiolitis hospitalization and/or death during the first year of life. RESULTS: Two thousand two hundred ten newborns enrolled at birth were followed-up during their first year of life. Of these, 120 (5.4%) were hospitalized for bronchiolitis. No enrolled infants died during the study period. Prenatal passive TSE and maternal active smoking of more than 15 cigarettes/daily are associated to a significant increase of the risk of offspring children hospitalization for bronchiolitis, with an adjHR of 3.5 (CI 1.5-8.1) and of 1.7 (CI 1.1-2.6) respectively. CONCLUSIONS: These results confirm the detrimental effects of passive TSE and active heavy smoke during pregnancy for infants' respiratory health, since the exposure significantly increases the risk of hospitalization for bronchiolitis in the first year of life.

Mediterranean diet and other lifestyle factors in relation to 20-year all-cause mortality: a cohort study in an Italian population.

The aim of the present analysis was to evaluate the association of the Mediterranean diet (MeDi), smoking habits and physical activity with all-cause mortality in an Italian population during a 20-year follow-up study. A total of 1693 subjects aged 40-74 who enrolled in the study in 1991-5 were asked about dietary and other lifestyle information at baseline. Adherence to the MeDi was evaluated by the Mediterranean dietary score (MedDietScore). A healthy lifestyle score was computed by assigning 1 point each for a medium or high adherence to the MedDietScore, non-smoking and physical activity. Cox models were used to assess the associations between lifestyle factors and healthy lifestyle scores and all-cause mortality, adjusting for potential confounders. The final sample included 974 subjects with complete data and without chronic disease at baseline. During a median of 17·4 years of follow-up, 193 people died. Subjects with high adherence to the MedDietScore (hazard ratio (HR) 0·62, 95 % CI 0·43, 0·89)), non-smokers (HR 0·71, 95 % CI 0·51, 0·98) and physically active subjects (HR 0·55, 95 % CI 0·36, 0·82) were at low risk of death. Each point increase in the MedDietScore was associated with a significant 5 % reduction of death risk. Subjects with 1, 2 or 3 healthy lifestyle behaviours had a significantly 39, 56, and 73 % reduced risk of death, respectively. A high adherence to MeDi, non-smoking and physical activity were strongly associated with a reduced risk of all-cause mortality in healthy subjects after long-term follow-up. This reduction was even stronger when the healthy lifestyle behaviours were combined.

Position paper of the Italian Society for the study of Dementias (SINDEM) on the proposal of a new lexicon on Alzheimer disease.

A panel of Italian neurologists of the Italian Society for the study of Dementias (SINDEM) discussed the recently proposed new lexicon for Alzheimer disease (AD) and the related diagnostic criteria for the different phases of the disease (Preclinical AD, prodromal AD and Alzheimer's dementia) (Dubois et al. in Lancet Neurol 6:734-746, 2007; in Lancet Neurol 9:1118-1127, 2010). The aim of this discussion was to reach a consensus, among the Italian neurologists involved in the study and care of persons with dementia, in particular in reference to the potential use of the proposed diagnostic criteria in clinical practice. After having critically revised the scientific evidence related to the new lexicon and to the new proposed diagnostic criteria, the panel concluded that the proposed new diagnostic criteria and the new proposed lexicon for AD are conceptually attractive. However, the evidence about the instrumental and laboratory markers for the diagnosis of the preclinical and asymptomatic states of the disease are, until to now, insufficient to support the routine clinical use of these investigations.

Association between prescription of conventional or atypical antipsychotic drugs and mortality in older persons with Alzheimer's disease.

BACKGROUND/AIMS: To evaluate whether dementia patients prescribed antipsychotic drugs have a higher mortality compared to unexposed patients, and to investigate whether there are differences in mortality associated with exposure to conventional versus atypical antipsychotic drugs. METHODS: Retrospective population cohort study with information gathered from the Italian Health Information System. All 4,369 residents of Milan (Italy) aged 60 years or older who were newly prescribed an antidementia drug (donepezil, rivastigmine or galantamine) from January 2002 to June 2008 were included. All new users of antipsychotic drugs in this cohort were categorized according to conventional (n = 156) or atypical (n = 806) drug exposure. The mortality risks of users of conventional or atypical antipsychotics compared to nonusers were evaluated with survival analysis, considering exposure to antipsychotic drugs as a time-dependent variable. RESULTS: Mortality was increased two- and fivefold in users of atypical and conventional antipsychotics, respectively, with respect to nonusers. CONCLUSIONS: Dementia patients prescribed antipsychotic drugs had a higher risk of death. This risk was highest for those prescribed conventional antipsychotics. At least part of the excess mortality may be due to the underlying neuropsychiatric symptoms that prompted the use of antipsychotics rather than a direct medication effect.

Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

OBJECTIVES: Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. DESIGN: Cross-sectional, multicenter, clinical study. PARTICIPANTS: A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. MEASUREMENTS: All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. RESULTS: Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N = 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N = 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. CONCLUSIONS: The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.