Italian consensus recommendations for a biomarker-based aetiological diagnosis in mild cognitive impairment patients.

BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

Recognition and management of delirium among doctors, nurses, physiotherapists, and psychologists: an Italian survey.

BACKGROUND: There are no studies that have identified the ability to recognize and manage delirium among Italian health providers caring for patients at risk. Therefore, the Italian Association of Psychogeriatrics (AIP) conducted a multicenter survey among doctors, nurses, psychologists and physiotherapists to assess their competence regarding the theme of delirium and its management in the everyday clinical practice. METHODS: The survey period was 1st June 2013 to 30th November 2013. The invitation to participate was sent via email, with publication on the AIP website. The survey included 14 questions and two case vignettes. RESULTS: A total of 648/1,500 responses were collected. Most responders were doctors (n = 322/800), followed by nurses (n = 225/500), psychologists (n = 51/100), and physiotherapists (n = 30/100). Generally, doctors and psychologists correctly defined delirium, while nurses and physiotherapists did not. The most frequently used diagnostic tools were the Confusion Assessment Method (CAM) and the Diagnostic and Statistical Manual of Mental Disorders-IV. Delirium intensity was rarely assessed. Hypoactive delirium was generally managed with non-pharmacological approaches, while hyperactive delirium with a combination of non-pharmacological and pharmacological approaches. However, possible causes of delirium were under-assessed by half of doctors and by the majority of other professionals. Nurses, psychologists and physiotherapists did not answer the case vignettes, while doctors identified the correct answer in most cases. CONCLUSIONS: This is the first Italian survey among health providers caring for patients at risk of delirium. This is also the first survey including doctors, nurses, psychologists and physiotherapists. The results emphasize the importance of training to improve knowledge of this relevant unmet medical need.

The management of hip fracture in the older population. Joint position statement by Gruppo Italiano Ortogeriatria (GIOG).

This document is a Joint Position Statement by Gruppo Italiano di OrtoGeriatria (GIOG) supported by Società Italiana di Gerontologia e Geriatria (SIGG), and Associazione Italiana Psicogeriatria (AIP) on management of hip fracture older patients. Orthogeriatric care is at present the best model of care to improve results in older patients after hip fracture. The implementation of orthogeriatric model of care, based on the collaboration between orthopaedic surgeons and geriatricians, must take into account the local availability of resources and facilities and should be integrated into the local context. At the same time the programme must be based on the best available evidences and planned following accepted quality standards that ensure the efficacy of the intervention. The position paper focused on eight quality standards for the management of hip fracture older patients in orthogeriatric model of care. The GIOG promotes the development of a clinic database with the aim of obtaining a qualitative improvement in the management of hip fracture.

Consensus and variations in opinions on delirium care: a survey of European delirium specialists.

BACKGROUND: There are still substantial uncertainties over best practice in delirium care. The European Delirium Association (EDA) conducted a survey of its members and other interested parties on various aspects of delirium care. METHODS: The invitation to participate in the online survey was distributed among the EDA membership. The survey covered assessment, treatment of hyperactive and hypoactive delirium, and organizational management. RESULTS: A total of 200 responses were collected (United Kingdom 28.6%, Netherlands 25.3%, Italy 15%, Switzerland 9.7%, Germany 7.1%, Spain 3.8%, Portugal 2.5%, Ireland 2.5%, Sweden 0.6%, Denmark 0.6%, Austria 0.6%, and others 3.2%). Most of the responders were doctors (80%), working in geriatrics (45%) or internal medicine (14%). Ninety-two per cent of the responders assessed patients for delirium daily. The most commonly used assessment tools were the Confusion Assessment Method (52%) and the Delirium Observation Screening Scale (30%). The first-line choice in the management of hyperactive delirium was a combination of non-pharmacological and pharmacological approaches (61%). Conversely, non-pharmacological management was the first-line choice in hypoactive delirium (67%). Delirium awareness (34%), knowledge (33%), and lack of education (13%) were the most commonly reported barriers to improving the detection of delirium. Interestingly, 63% of the responders referred patients after an episode of delirium to a follow-up clinic. CONCLUSIONS: This is the first systematic survey involving an international group of specialists in delirium. Several areas of lack of consensus were found. These results emphasise the importance of further research to improve care of this major unmet medical need.

Mental Health among Geriatric Healthcare Workers in Italy during the COVID-19 Pandemic: Results from a National Survey.

OBJECTIVES: This study aimed to investigate the psychological impact of the COVID-19 pandemic on healthcare workers (HCWs) in geriatric settings. DESIGN: Online cross-sectional survey. SETTINGS AND PARTICIPANTS: 394 geriatric HCWs in Italy. MEASUREMENTS: The survey was developed by a multidisciplinary team and disseminated in April 2022 to the members of two geriatric scientific societies (Italian Society of Geriatrics and Gerontology and Italian Association of Psychogeriatrics). The survey examined the experiences related to the COVID-19 pandemic, as well as psychological burden and support. Work-related anxiety and distress related to the pandemic were studied using the SAVE-9 scale (Stress and Anxiety to Viral Epidemics). RESULTS: Three hundred sixty-four participants (92.4%) changed their job activity during the pandemic and about half (50.9%) failed to cope with this change, 58 (14.7%) had increased work-related anxiety, and 39 (9.9%) work-related stress levels. Three hundred forty (86.3%) participants reported acute stress reaction symptoms, including irritability, depressed mood, headache, anxiety, and insomnia, and 262 (66.5%) required psychological support, mainly from friends/relatives (57.9%) and/or colleagues (32.5%). Furthermore, 342 participants (86.8%) recognized they would benefit from informal and formal psychological support in case of future similar emergencies. CONCLUSIONS: This study highlights the high psychological burden experienced by geriatric HCWs in Italy during the COVID-19 pandemic and emphasizes the need for supportive interventions.

A prognostic model predicting recovery of walking independence of elderly patients after hip-fracture surgery. An experiment in a rehabilitation unit in Northern Italy.

UNLABELLED: A score for identifying post-hip-fracture surgery patients at various levels (high, medium, and low) of risk for unsuccessful recovery of pre-fracture walking ability was developed. Three hundred ninety-eight HF patients were enrolled in the study. The score significantly and independently predicted failure to walk independently at discharge, failure to walk independently after 12 months, and death after 12 months. The score may be useful for clinicians and healthcare administrators to target populations for rehabilitative programs. INTRODUCTION: To develop a model predicting at the time that elderly hip-fracture (HF) patients undergo rehabilitation if they will have recovered walking independence at discharge. METHODS: Data from all patients admitted to a Department of Rehabilitation in Italy between January 2001 and June 2008 after HF surgery were used. Variables concerning cognitive, clinical, functional, and social parameters were evaluated. Predominant measures were identified through correspondence analysis, and a variable score was defined. Three risk classes (minimum, moderate, and high) were identified and univariate and multivariate logistic regressions were used to assess the model's predictivity and risk classes for the various outcomes. RESULTS: Three hundred ninety-eight HF patients were enrolled. The variables selected to construct the score were age, gender, body mass index, number of drugs being taken, the Mini Mental State Examination, the Instrumental Activity of Daily Living, and the pre-fracture Barthel index. According to univariate analysis, the score was not better than the pre-fracture Barthel's index, but, according to multivariate analysis, it was an independent predictor for all the outcomes, while the pre-fracture Barthel index predicted only outcomes at discharge. In particular, the score significantly predicted failure to walk independently at discharge, failure to walk independently after 12 months, and death after 12 months. CONCLUSIONS: A method of identifying post-HF surgery patients at various levels (high-, medium-, and low-) of risk for unsuccessful recovery of pre-fracture walking ability has been designed. The method may be useful for clinicians and healthcare administrators to target populations for rehabilitative programs.

Addendum to 'Efficacy of music therapy treatment based on cycles of sessions: a randomised controlled trial' (Raglio et al., 2010).

OBJECTIVES: The aim of this paper is to provide further detail about the results of a randomised controlled study published in this journal (Raglio et al., 2010, 14, 900-904), in which we assessed the efficacy of music therapy (MT) on the behavioural disturbances in people with moderate-severe dementia. METHODS: Sixty patients were randomly assigned to the experimental (MT and standard care) and control group (standard care only). The experimental group received three cycles of 12 MT sessions each, three times a week. Each cycle of treatment was followed by one month of washout period, while the standard care activities continued over time. RESULTS: The impact of the treatment (12 MT sessions) was reliable on NPI global scores, as the interaction Time by Group was significant (F(1,49) = 4.09, p = 0.049). After the end of the treatment the NPI global scores of the experimental and control groups tended to become similar, as both groups worsened (Time effect: F(1,48) = 4.67, p = 0.014) and the difference between them disappeared (F < 1). Interaction Time by Group was not significant. CONCLUSIONS: The study confirms that active MT determines a positive response and can amplify and strengthen the efficacy of therapeutic interventions towards people with dementia.

Efficacy of music therapy treatment based on cycles of sessions: a randomised controlled trial.

We undertook a randomised controlled trial to assess whether a music therapy (MT) scheme of administration, including three working cycles of one month spaced out by one month of no treatment, is effective to reduce behavioural disturbances in severely demented patients. Sixty persons with severe dementia (30 in the experimental and 30 in the control group) were enrolled. Baseline multidimensional assessment included demographics, Mini Mental State Examination (MMSE), Barthel Index and Neuropsychiatry Inventory (NPI) for all patients. All the patients of the experimental and control groups received standard care (educational and entertainment activities). In addition, the experimental group received three cycles of 12 active MT sessions each, three times a week. Each 30-min session included a group of three patients. Every cycle of treatment was followed by one month of wash-out. At the end of this study, MT treatment resulted to be more effective than standard care to reduce behavioural disorders. We observed a significant reduction over time in the NPI global scores in both groups (F(7,357) = 9.06, p < 0.001) and a significant difference between groups (F(1,51) = 4.84, p < 0.05) due to a higher reduction of behavioural disturbances in the experimental group at the end of the treatment (Cohen's d = 0.63). The analysis of single NPI items shows that delusions, agitation and apathy significantly improved in the experimental, but not in the control group. This study suggests the effectiveness of MT approach with working cycles in reducing behavioural disorders of severely demented patients.

Clinical Presentation of COVID19 in Dementia Patients.

OBJECTIVE: No studies analyzing the role of dementia as a risk factor for mortality in patients affected by COVID-19. We assessed the prevalence, clinical presentation and outcomes of dementia among subjects hospitalized for COVID19 infection. DESIGN: Retrospective study. SETTING: COVID wards in Acute Hospital in Brescia province, Northern Italy. PARTICIPANTS: We used data from 627 subjects admitted to Acute Medical wards with COVID 19 pneumonia. MEASUREMENTS: Clinical records of each patients admitted to the hospital with a diagnosis of COVID19 infection were retrospectively analyzed. Diagnosis of dementia, modalities of onset of the COVID-19 infection, symptoms of presentation at the hospital and outcomes were recorded. RESULTS: Dementia was diagnosed in 82 patients (13.1%). The mortality rate was 62.2% (51/82) among patients affected by dementia compared to 26.2% (143/545) in subjects without dementia (p<0.001, Chi-Squared test). In a logistic regression model age, and the diagnosis of dementia resulted independently associated with a higher mortality, and patients diagnosed with dementia presented an OR of 1.84 (95% CI: 1.09-3.13, p<0.05). Among patients diagnosed with dementia the most frequent symptoms of onset were delirium, especially in the hypoactive form, and worsening of the functional status. CONCLUSION: The diagnosis of dementia, especially in the most advanced stages, represents an important risk factor for mortality in COVID-19 patients. The clinical presentation of COVID-19 in subjects with dementia is atypical, reducing early recognition of symptoms and hospitalization.

Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from the corpus striatum.

Nigral basal adenylate cyclase and dopamine-sensitive adenylate cyclase, glutamate decarboxylase, choline acetyltransferase, and tyrosine hydroxylase activities were measured in rats with hemitransections at various levels or with electrolytic lesions of the medial forebrain bundle or the crus cerebri. The loss of nigral dopamine-sensitive adenylate cyclase activity after the various brain lesions was correlated with loss of nigral glutamic acid decarboxylase but not that of tyrosine hydroxylase; nigral choline acetyltransferase was unaffected in all cases. The data indicate that the nigral dopamine-sensitive adenylate cylase activity may be localized on neurons afferent to the nigra, probably originating from the globus pallidus and possibly from the tail of the caudate. The results suggest that dopamine, released from nigral dendrites, may influence dopaminergic activity indirectly by modulating impulses transmitted to the nigrostriatal neurons through the crus cerebri.

Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients.

BACKGROUND: Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium internationally are hindering cross-talk and collaborative research. In the English literature, synonyms of delirium such as the Intensive Care Unit syndrome, acute brain dysfunction, acute brain failure, psychosis, confusion, and encephalopathy are widely used. This often leads to scientific "confusion" regarding published data and methodology within studies, which is further exacerbated by organizational, cultural and language barriers. OBJECTIVE: We undertook this multinational effort to identify conflicts in terminology and phenomenology of delirium to facilitate communication across medical disciplines and languages. METHODS: The evaluation of the terminology used for acute brain dysfunction was determined conducting communications with 24 authors from academic communities throughout countries/regions that speak the 13 variants of the Romanic languages included into this manuscript. RESULTS: In the 13 languages utilizing Romanic characters, included in this report, we identified the following terms used to define major types of acute brain dysfunction: coma, delirium, delirio, delirium tremens, délire, confusion mentale, delir, delier, Durchgangs-Syndrom, acute verwardheid, intensiv-psykose, IVA-psykos, IVA-syndrom, akutt konfusion/forvirring. Interestingly two terms are very consistent: 100 % of the selected languages use the term coma or koma to describe patients unresponsive to verbal and/or physical stimuli, and 100% use delirium tremens to define delirium due to alcohol withdrawal. Conversely, only 54% use the term delirium to indicate the disorder as defined by the DSM-IV as an acute change in mental status, inattention, disorganized thinking and altered level of consciousness. CONCLUSIONS: Attempts towards standardization in terminology, or at least awareness of differences across languages and specialties, will help cross-talk among clinicians and researchers.

Neuropsychiatric symptoms in amnestic and nonamnestic mild cognitive impairment.

BACKGROUND: The information regarding neuropsychiatric symptoms in the subtypes of mild cognitive impairment (MCI) is inadequate. OBJECTIVE: To describe the behavioral neuropsychiatric symptoms of MCI in two subgroups of MCI patients with different neuropsychological characteristics. METHODS: MCI patients are classified as amnestic (aMCI) if they have a prominent memory impairment, either alone or with other cognitive impairments (multiple domains with amnesia), or nonamnestic (naMCI) if a single nonmemory domain is impaired alone or in combination with other nonmemory deficits (multiple domains without amnesia). The Neuropsychiatric Inventory (NPI) was administrated to detect behavioral and psychological disturbances observed by the caregiver. RESULTS: 120 subjects were analyzed: 94 were classified as aMCI and 26 as naMCI. Subjects with aMCI were more compromised than those with naMCI on global cognitive functions. About 85% of MCI patients had some neuropsychiatric symptoms evaluated with the NPI and the most prevalent symptom was depression, followed by anxiety. A significantly higher prevalence of hallucinations and sleep disorders has been observed in the naMCI group in comparison with the aMCI group. CONCLUSION: Neuropsychiatric symptoms occur in the majority of persons with MCI and may be the earliest manifestation of different diseases, each one associated with different clinical profiles at the stage of MCI.

Effectiveness of a cognitive rehabilitation program in mild dementia (MD) and mild cognitive impairment (MCI): a case control study.

Data support the evidence that neuropsychological rehabilitation is effective in Alzheimer disease (AD), to strengthen the pharmacological treatment to delay the progression of dementia. At moment, a few studies have examined the efficacy of non-pharmacological treatment in MCI. This is a controlled study that assesses the effectiveness of neuropsychological rehabilitation on cognitive and behavioral symptoms and functional status in a group of community-dwelling subjects with MCI and MD. Our results demonstrate that a systematic rehabilitation, that provides a computerized cognitive program training, produces an improvement in cognitive and affective status of patients with MCI and MD, while a rehabilitation program not providing a punctual stimulation of cognitive functions, does not have significant effects.

The Italian version of the pain assessment in advanced dementia (PAINAD) scale.

Pain is an unpleasant sensory and emotional experience. It's recognized to be modified by individual memory, expectation, and emotion. The most accurate evidence of pain and its intensity is based on patient's description and self-report. One of the main problems in assessing pain in dementia concerns with the impairment of communication and memory. Unfortunately, the most used tools to evaluate pain have been developed for normal aging people, requiring verbal and cognitive skills. Therefore, proper instruments are urged to be developed, tested, and validated to assess pain in a cognitively impaired population. The purpose of this study was to assess the validity of the PAINAD in the Italian version as a reliable tool for measuring pain in demented people.

Altered vessel signalling molecules in subjects with Downs syndrome.

Downs syndrome (DS) is the most frequent human chromosomal abnormality and is associated with mental retardation. Some evidence indicates that certain inflammatory molecules may be increased in DS. Proinflammatory and vasoactive molecules in the blood of non demented subjects with DS were measured in the present investigation. Plasma levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1) and C reactive protein (CRP) were measured in child (2-14 years), adult (20-50 yrs) and elderly (> 60 yrs) DS subjects. Increased plasma levels of IL-6 and MCP-1 were present in DS. Plasma levels of VEGF were increased only in DS adults. Positive linear correlation between IL-6 and MCP-1 levels was present. However, no subclinical inflammation was apparent in DS, since neopterin and CRP levels were within the normal range. An altered regulation of these molecules might interfere with some processes involved in cognitive performances of DS subjects.

Clinical characteristics and risk factors of delirium in demented and not demented elderly medical inpatients.

OBJECTIVES: to evaluate the differences in clinical characteristics and risk factors of delirium in elderly medical inpatients according to the presence or not of dementia. DESIGN: cross-sectional, observational study. SETTING: acute medical care unit (ACU) of a general hospital. PARTICIPANTS: 330 patients aged 65 and older consecutively admitted on a 24-week period. MEASUREMENTS: Functional status, cognitive abilities, severity of acute illness (Acute Physiology, Age and Chronic Health Evaluation (APACHE II) score), Confusion Assessment Method (CAM), Delirium Rating Scale (DRS) and One Day Fluctuation Scale (ODFS). RESULTS: patients with delirium represent 19.1% of the sample, 41.0% of which had also dementia. Hyperactive form of delirium was 41.0%; hypoactive 11.0% and mixed 48.0%. In non demented patients, the delirious patients showed higher APACHE II score, more severe functional decline, poorer cognitive status respect to not delirious. In demented patients no differences were found in APACHE II score and cognitive status among delirious and not delirious subjects. In this group, functional decline (p = .012), acute infection (p = .007), psychotropic drugs use (p = .028) and severe hypoalbuminemia (p = .036) represented risk factors for the onset of delirium. Demented patients had higher perceptual disturbances (p = .040) and less severe delusions (p = .001), while total DRS score do not differs in the two groups. According to ODFS, delirium episode was more fluctuating in patients with dementia. CONCLUSION: clinical characteristics and risk factors of delirium are different in demented and not demented elderly inpatients. Patients with dementia are vulnerable to delirium at lower levels of medical acuity than non-demented patients.

Characterization of the gamma-aminobutyric acid receptor system in human brain gliomas.

The properties of [3H]-gamma-aminobutyric acid [( 3H]GABA) binding were studied in biopsied specimens from normal human brain and from 18 cases of human brain gliomas, made up of 6 astrocytomas, 6 glioblastomas, 3 oligodendrogliomas, and 3 medulloblastomas. In fresh membranes obtained from normal gray and white matter one population of Na+-dependent GABA receptors was observed, while in the frozen Triton X-100-treated membranes two distinct populations of Na+-independent binding sites were detected. Specific GABA binding sites in brain gliomas were shown only in frozen Triton X-100-treated membranes. As in normal tissue, these receptors are Na+-independent and bind [3H]GABA with two distinct affinity components. The biochemical profiles of [3H]GABA binding to membranes obtained from different tumors of glial origin are quite similar and cannot be related to the degree of malignancy of the neoplasia.

Multiple forms of protein kinase from normal human brain and glioblastoma.

The biochemical characteristics of the protein kinase (PK; adenosine triphosphate-protein phosphotransferase, EC 2.7.1.37) isozymes in subcellular preparations from normal human brain cortex and glioblastoma were investigated after chromatography on diethylaminoethyl cellulose, and the following results have been obtained. Two major isozyme forms, eluted by 50 and 200 mM phosphate buffer, are present in both cytosol and membrane-derived preparations from cerebral cortex. Furthermore, these isozyme forms have properties similar to those referred to as type I and type II cyclic adenosine 3':5'-monophosphate-dependent PK. In these chromatographic isozymes, cyclic adenosine 3';5'-monophosphate is more active in stimulating the basal PK enzyme than is cyclic guanosine 3':5'-monophosphate. In glioblastoma, the PK activity from cytosol and particulate preparations is resolved by diethylaminoethyl cellulose in four peaks. In cytosol, the major portion of the enzyme is eluted with a 300 mM buffer (about 50% of the total basal PK activity) and is cyclic nucleotide dependent. On the contrary, in glioblastoma particulate, the PK enzyme is mainly eluted at 50 and 100 mM buffer; neither of these isozymes is cyclic nucleotide dependent. As for cytosol, only the particulate isozyme eluted at 300 mM buffer is strongly activated by cyclic nucleotides. Finally, in both glioblastoma subcellular preparations, only a type II cyclic adenosine 3':5'-monophosphate-dependent PK is present.

Dopamine-sensitive adenylyl cyclase in human caudate nucleus. A study in control subjects and schizophrenic patients.

Striatal adenylyl cyclase activity from autopsied human brain is selectively stimulated by low concentrations of dopamine. Under the experimental conditions used, norepinephrine was about three times less potent than dopamine. Histamine and serotonin were ineffective. The stimulation by dopamine was competitively inhibited by haloperidol. There was no difference between the basal adenylyl cyclase activity or its level after dopamine stimulation between nine control subjects without a psychiatric history and seven patients with chronic schizophrenia.