Sara Ercolani

Validation of the Five‐Item Geriatric Depression Scale in Elderly Subjects in Three Different Settings

OBJECTIVES: To test the effectiveness of a five‐item version of the Geriatric Depression Scale (GDS) for the screening of depression in community‐dwelling older subjects, hospitalized older patients, and nursing home residents.

Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment.

Alzheimers disease (AD) is the most common type of dementia in the elderly. Products of oxidative and nitrosative stress (OS and NS, respectively) accumulate with aging, which is the main risk factor for AD. This provides the basis for the involvement of OS and NS in AD pathogenesis. OS and NS occur in biological systems due to the dysregulation of the redox balance, caused by a deficiency of antioxidants and/or the overproduction of free radicals. Free radical attack against lipids, proteins, sugars and nucleic acids leads to the formation of bioproducts whose detection in fluids and tissues represents the currently available method for assessing oxidative/nitrosative damage. Post-mortem and in-vivo studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment (MCI). In addition to their individual role, biomarkers for OS and NS in AD are associated with altered bioenergetics and amyloid-beta (Abeta) metabolism. In this review we discuss the main results obtained in the field of biomarkers of oxidative/nitrosative stress in AD and MCI in humans, in addition to their potential role as a tool for diagnosis, prognosis and treatment efficacy in AD.

A Systematic Review of Neuropsychiatric Symptoms in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is a clinical concept proposed as an intermediate state between normal aging and dementia. This condition has multiple heterogeneous sources, including clinical presentation, etiology, and prognosis. Recently, the prevalence and associated features of neuropsychiatric symptoms (NPS) in MCI have been described. We systematically searched the PubMed database (last accessed on August 31, 2008) for articles on NPS in MCI. Included articles used strict selection criteria, and outcome variables were extracted in duplicate; of the 27 articles included, 14 (52%) used prospective cohorts. The global prevalence of NPS in MCI ranged from 35% to 85%. The most common behavioral symptoms were depression, anxiety, and irritability. Hospital-based samples reported a higher global prevalence of NPS than population-based studies; this discrepancy probably reflected differences in demographics, study setting, MCI diagnostic criteria, and behavioral instruments used. Prospective studies showed that NPS, particularly depression, may represent risk factors for MCI or predictors for the conversion of MCI to Alzheimers disease (AD). NPS are very prevalent in subjects with MCI, displaying a similar pattern of symptoms compared to dementia and AD. Large cohort studies using standardized MCI criteria and behavioral instruments are required to evaluate the prognostic role of NPS in MCI.

An ontology-based personalization of health-care knowledge to support clinical decisions for chronically ill patients

Chronically ill patients are complex health care cases that require the coordinated interaction of multiple professionals. A correct intervention of these sort of patients entails the accurate analysis of the conditions of each concrete patient and the adaptation of evidence-based standard intervention plans to these conditions. There are some other clinical circumstances such as wrong diagnoses, unobserved comorbidities, missing information, unobserved related diseases or prevention, whose detection depends on the capacities of deduction of the professionals involved. In this paper, we introduce an ontology for the care of chronically ill patients and implement two personalization processes and a decision support tool. The first personalization process adapts the contents of the ontology to the particularities observed in the health-care record of a given concrete patient, automatically providing a personalized ontology containing only the clinical information that is relevant for health-care professionals to manage that patient. The second personalization process uses the personalized ontology of a patient to automatically transform intervention plans describing health-care general treatments into individual intervention plans. For comorbid patients, this process concludes with the semi-automatic integration of several individual plans into a single personalized plan. Finally, the ontology is also used as the knowledge base of a decision support tool that helps health-care professionals to detect anomalous circumstances such as wrong diagnoses, unobserved comorbidities, missing information, unobserved related diseases, or preventive actions. Seven health-care centers participating in the K4CARE project, together with the group SAGESA and the Local Health System in the town of Pollenza have served as the validation platform for these two processes and tool. Health-care professionals participating in the evaluation agree about the average quality 84% (5.9/7.0) and utility 90% (6.3/7.0) of the tools and also about the correct reasoning of the decision support tool, according to clinical standards.

Cognitive impairment is the major risk factor for development of geriatric syndromes during hospitalization: results from the GIFA study.

Objective: To detect the main factors associated with the occurrence of specific geriatric syndromes (namely pressure sores, fecal incontinence, urinary incontinence and falls) in elderly patients during hospitalization. Design: Observational prospective study. Setting: Eighty-one community and university hospitals throughout Italy. Participants: 13,729 patients aged 65 years and more, consecutively admitted to medical or geriatric acute wards during 20 months in the period between 1991 and 1998. Measurements: Occurrence of pressure sores, fecal incontinence, urinary incontinence and falls during the stay in hospital. Results: Pressure sores were already present in 3% of hospitalized subjects, fecal incontinence in 7.3%, while urinary incontinence, evaluated on a subgroup of total population (4,268 subjects), had a prevalence of 22.3%. During hospitalization (mean stay of 15 days), 74 subjects developed new pressure sores, 55 became fecal and 35 urinary incontinent, and 279 subjects had at least one episode of fall. In multivariate analyses, cognitive impairment, advanced age (85+ years), length of stay (more than 3 weeks) and severe disability were the main independent predictors of development of the four geriatric syndromes, with cognitive impairment as the most significant risk factor for all the four outcomes (OR 4.9, 95% CI 2.4–9.9 for pressure sores; OR 6.3, 95% CI 3.0–13.0 for fecal incontinence; OR 5.3, 95% CI 2.3–12.0 for urinary incontinence; OR 1.6, 95% CI 1.2–2.3 for falls). Conclusion: Very old people have a significant increased risk of several geriatric syndromes during the stay in hospital, particularly if it is long and they are cognitively impaired. A standardized comprehensive geriatric evaluation at admission could be helpful in detecting all subjects at risk and preventing the development of hospital-acquired geriatric syndromes.

Tocopherols and tocotrienols plasma levels are associated with cognitive impairment

Vitamin E includes 8 natural compounds (4 tocopherols, 4 tocotrienols) with potential neuroprotective activity. α-Tocopherol has mainly been investigated in relation to cognitive impairment. We examined the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimers disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people. Compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD.

Cognitive Performance in Elderly Patients Undergoing Carotid Endarterectomy or Carotid Artery Stenting: A Twelve-Month Follow-Up Study

Background: It is still a matter of debate if and to what extent carotid endarterectomy (CEA) and carotid artery stenting (CAS) impair cognitive functioning in the elderly. Methods: We conducted a nonrandomized clinical trial on subjects with asymptomatic carotid artery stenosis comparing CEA (n = 28; 24 males and 4 females; 72.6 ± 5.8 years old) with CAS (n = 29; 17 males and 12 females; 75.1 ± 5.7 years old). Cognition, mood and functional status were evaluated by a broad spectrum of tests performed on the day prior to carotid reopening as well as 3 and 12 months after. Results: No significant differences in scores on cognitive tests including the Babcock story recall test and Rey’s auditory verbal learning test (memory), category naming test (verbal fluency), trail-making test parts A and B (attention and executive function) and controlled oral word association test (executive functioning) were observed 3 and 12 months after carotid reopening independent of the technique used. Only scores on the copy drawing test (visuospatial and constructional abilities) slightly but significantly (p < 0.05) worsened in the CAS group 12 months after the intervention. No significant differences between the CEA and CAS groups were detected regarding mood and functional status after 3 and 12 months. Conclusions: CEA and CAS seem to be safe procedures in elderly patients in terms of cognitive, mood and functional status in the short and long term. CAS might be preferred for the shorter hospital stay, but further studies with a larger number of old and oldest old subjects with a longer follow-up are needed to better understand the cost-effectiveness of both treatments.

Vascular risk factors in mild cognitive impairment subtypes. Findings from the ReGAl project.

Background and Aim: To investigate the role of vascular risk factors in different subtypes of mild cognitive impairment (MCI) in a multicentric, clinic-based, cross-sectional study. Methods: Two-hundred and seven subjects with MCI were included in the study: 33 with single non-memory MCI (snmMCI), 42 with multiple-domain amnestic MCI (mdMCI-a) and 132 with amnestic MCI (aMCI). Several clinical vascular risk factors and magnetic resonance imaging (MRI) brain lesions were evaluated. Results: snmMCI showed a higher frequency of ischaemic heart disease and of transient ischaemic attack (TIA)/stroke, a higher Hachinski ischaemic score and a higher frequency of white-matter lesions on MRI compared to aMCI. Subjects with mdMCI-a showed clinical characteristics similar to aMCI, except for a higher frequency of a history of TIA/stroke. Conclusion: Our findings suggest that snmMCI may be considered a vascular cognitive disorder.

Interaction of CTSD and A2M polymorphisms in the risk for Alzheimer's disease

The proteins cathepsin D, encoded by CTSD gene, and alpha2-macroglobulin, encoded by A2M gene, are involved in the biochemical pathway leading to deposition of beta-amyloid. In these proteins two amino acid polymorphisms (CTSD-Ala/Val C-->T and A2M-Ile/Val A-->G) have been associated with an increased risk for Alzheimers disease (AD), but conflicting results have been reported. We studied the association and the mutual interactions of the CTSD-C/T and A2M-A/G polymorphisms with sporadic AD in 100 patients with late-onset AD and 136 healthy elderly subjects as controls. The CTSD-T allele and the CTSD-C/T genotype are significantly more frequent in AD than in controls. The odds ratio (OR) for CTSD-T subjects is 1.93 [95% confidence interval (CI)=1.01-3.72], and 2.07 (95% CI=1.01-4.21) after adjustment for age, sex and APOE epsilon4+ status, while no significant association was found for the A2M-A/G polymorphism. The coexistence of the CTSD-T with the A2M-G allele synergistically increased the OR for AD to 2.69 (95% CI=1.13-6.34) [2.82 (95% CI=1.12-7.17) after adjustment], and to 3.29 (95% CI=1.33-8.16) if estimated for the allelic combination. Our data suggest that the CTSD-T allele of the CTSD-C/T polymorphism is associated with an increased relative risk for late-onset AD and, more interestingly, the combination of CTSD-T with the A2M-G allele seems to increase this risk.

Validation Study of the Italian Addenbrooke's Cognitive Examination Revised in a Young-Old and Old-Old Population

Aims: The main aims of the study were the translation and the subsequent validation in Italian of the Addenbrooke’s Cognitive Examination Revised (ACE-R), and the evaluation of its usefulness in discriminating cognitively normal subjects from patients with mild dementia in an elderly population. Methods: The ACE-R was translated and adapted into Italian. The Italian ACE-R was administered to a group of 179 elderly subjects (72 cognitively healthy and 107 subjects with mild dementia, mean age 75.4 ± 6.4 years). The group was stratified into two subsamples according to age, i.e. a young-old (<75 years) and an old-old (≧75 years) group, in order to evaluate the sensitivity and specificity of the test in detecting dementia in different age strata of elderly subjects. Results: The reliability of the Italian ACE-R was extremely good (α-coefficient = 0.85). Two different cutoffs were identified for young-old (cutoff 79; sensitivity 90% and specificity 80%) and old-old subjects (cutoff 60; sensitivity 82% and specificity 100%). Conclusions: The Italian ACE-R is a valid screening tool to detect dementia, especially in the old-old population, which represents not only the fastest growing age group but also the group at the highest risk of dementia in Western countries.