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Background: Nursing home placement (NHP) can be the final step of patients with Alzheimer's disease. Objective: We aimed to identify NHP predictors among 508 people with dementia with a 3-year follow-up. Methods: We analyzed data from the international observational RECage study, involving 508 people with especially Alzheimer's disease and comparing a cohort enrolled by five centers with a Special Care Unit for BPSD (behavioral and psychological symptoms of dementia) and another one enrolled by six centers lacking this facility. The tertiary objective of the study was to assess the possible role of the SCU-B in delaying NHP. We assessed the relationship of the baseline characteristics with NHP by means of univariate analysis followed by Cox's multivariate model. Results: Patients' mean age was 78.1 years, 54.9% were women. Diagnosis mean age was 75.4 (±8.32) years; the main diagnosis was Alzheimer's disease (296; 58.4%). During follow-up, 96 (18.9%) patients died and 153 (30.1%) were institutionalized without a statistically significant difference between the two cohorts (pâ=â0.9626). The mean NHP time was 902 (95% CI: 870-934). The multivariable analysis without death as a competing risk retained four independent predictors of NHP: age increase (hazard ratio (HR)â=â1.023, 95% CI: 1.000-1.046), patient education level increase (HRâ=â1.062, 95% CI: 1.024-1.101), Neuropsychiatric Inventory total increase (HRâ=â1.018; 95% CI: 1.011-1.026), and total Mini-Mental State Examination as a favorable factor (HRâ=â0.948, 95% CI: 0.925-0.971). Gender (females versus males: HRâ=â1.265, 95% CI: 0.899-1.781) was included in the final Cox's model for adjusting the estimates for. Conclusions: Our data partially agree with the predictors of NHP in literature including the effect of high education level. No caregivers' factors were statistically significant. Clinical trial registration: NCT03507504.
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Enfermedad de Alzheimer , Anciano , Femenino , Humanos , Masculino , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/epidemiología , Cuidadores/psicología , Pueblo Europeo , Casas de Salud , Modelos de Riesgos Proporcionales , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) bring complexity in the clinical management of people with dementia; therefore, it is important to evaluate different models of care, such as Special Care Units (SCU-B).â¥Objective:To evaluate the SCU-B effectiveness toward alleviating BPSD and improving the quality of life (QoL) of patients and their caregivers.â¥Methods:ReCAGE was a multicenter, controlled, longitudinal study where 508 patients with BPSD were enrolled in two cohorts: 262 patients from centers endowed with a SCU-B, and 246 from centers without SCU-B. Statistical analyses included factorial ANCOVA for comparison among centers. The primary endpoint was effectiveness of the SCU-B, measured through the Neuropsychiatric Inventory (NPI) changes. Secondary endpoints were change in QoL of patients and caregivers, and the tertiary endpoint was time to nursing home admission.â¥Results:The NPI scores decreased in both arms, with a statistically significant difference from baseline to 36 months (pâ<â0.0001) in both cohorts. Over time, NPI decreased more steeply during the first year in the SCU-B arm, but in the following two years the slope was clearly in favor of the control arm. This different pattern of the two cohorts reached statistical significance at the interaction "cohort by time" (pâ<â0.0001). Conflicting results were found regarding the outcomes of quality of life, while there were no differences in time to institutionalization in both cohorts.â¥Conclusion:The RECage study did not confirm the long-term superiority of the pathway comprising a SCU-B. A post-hoc analysis revealed data supporting their acute effectiveness during behavioral crises.
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Demencia , Humanos , Anciano , Demencia/psicología , Calidad de Vida , Estudios Longitudinales , Estudios Prospectivos , Cuidadores/psicologíaRESUMEN
BACKGROUND: One of the most widely used instruments for assessing agitation in dementia patients is the Cohen-Mansfield Agitation Inventory (CMAI), nevertheless no global score has been proposed. The aim of this study is: (a) to conduct a confirmatory (CFA) and exploratory factor analysis (EFA) of CMAI on people with dementia and Psychological and Behavioral Symptoms (BPSD), and (b) to propose an alternative structure, based on clinical criteria including all CMAI items. METHODS: Confirmatory and exploratory factor analyses were carried out on the CMAI 29 items administered at baseline to 505 patients with dementia (PwD) and BPSD enrolled in the international observational RECage study. RESULTS: The three-factor structure has not been confirmed by the CFA, whilst the EFA was carried out respectively on 25 items disregarding 4 items with a prevalence ≤5% and then on 20 items disregarding 9 items with a prevalence ≤10%. The four-factor structure explaining 56% of the variance comprised Physically Aggressive behavior, Verbally Aggressive behavior, Physically non-aggressive behavior, and Physically and verbally aggressive behavior. CONCLUSIONS: A new grouping of all items according to a clinical criterion is proposed, allowing for a more sensible evaluation of the symptoms leading to better differentiation.
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OBJECTIVE: Behavioral and psychological symptoms of dementia (BPSD) profiles vary depending on etiology in patients with mild-to-moderate BPSD. It is not known if similar differences exist in patients with severe BPSD. METHODS: We analyzed data collected at baseline in 398 patients with severe BPSD (NPI ≥ 32) and defined diagnosis of dementia (Alzheimer's disease [AD] 297; frontotemporal dementia [FTD] 39; Lewy body disease/Parkinsonian dementia [LBD/PD] 31; and vascular dementia [VD] 31) included in the European multicenter cohort RECAGE. RESULTS: Mean total NPI was 52.11 (18.55). LBD/PD patients demonstrated more hallucinations, more anxiety and more delusions than patients with other dementia. FTD patients had less delusions and more disinhibition than patients with other neurodegenerative disorders. These profiles overlapped partially with those reported in the literature in patients with less severe symptoms. CONCLUSION: Patients with severe BPSD display different and specific profiles of neuropsychiatric symptoms depending on dementia etiology.
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Enfermedad de Alzheimer , Demencia Vascular , Demencia Frontotemporal , Enfermedad por Cuerpos de Lewy , Humanos , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/diagnóstico , Escalas de Valoración Psiquiátrica , Enfermedad de Alzheimer/psicología , Enfermedad por Cuerpos de Lewy/psicología , Demencia Vascular/complicacionesRESUMEN
BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are quite challenging problems during the dementia course. Special Care Units for people with dementia (PwD) and BPSD (SCU-B) are residential medical structures, where BPSD patients are temporarily admitted, in case of unmanageable behavioral disturbances at home. OBJECTIVE: RECage (REspectful Caring for AGitated Elderly) aspires to assess the short and long-term effectiveness of SCU-Bs toward alleviating BPSD and improving the quality of life (QoL) of PwD and their caregivers. METHODS: RECage is a three-year, prospective study enrolling 500 PwD. Particularly, 250 community-dwelling PwDs presenting with severe BPSD will be recruited by five clinical centers across Europe, endowed with a SCU-B, for a short period of time; a second similar group of 250 PwD will be followed by six other no-SCU-B centers solely via outpatient visits. RECage's endpoints include short and long-term SCU-B clinical efficacy, QoL of patients and caregivers, cost-effectiveness of the SCU-B, psychotropic drug consumption, caregivers' attitude toward dementia, and time to nursing home placement. RESULTS: PwD admitted in SCU-Bs are expected to have diminished rates of BPSD and better QoL and their caregivers are also expected to have better QoL and improved attitude towards dementia, compared to those followed in no-SCU-Bs. Also, the cost of care and the psychotropic drug consumption are expected to be lower. Finally, PwD followed in no-SCU-Bs are expected to have earlier admission to nursing homes. CONCLUSION: The cohort study results will refine the SCU-B model, issuing recommendations for implementation of SCU-Bs in the countries where they are scarce or non-existent.
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Adaptación Psicológica , Cuidadores/psicología , Demencia/psicología , Vida Independiente/psicología , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Demencia/terapia , Europa (Continente) , Femenino , Humanos , Masculino , Estudios Prospectivos , Psicotrópicos/uso terapéutico , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
The treatment of Alzheimer's disease (AD) in the field of non-pharmacological interventions is a challenging issue, given the limited benefits of the available drugs. Cognitive training (CT) represents a commonly recommended strategy in AD. Recently, repetitive transcranial magnetic stimulation (rTMS) has gained increasing attention as a promising therapeutic tool for the treatment of AD, given its ability of enhancing neuroplasticity. In the present randomized, double-blind, sham-controlled study, we aimed at investigating the add-on effect of a high frequency rTMS protocol applied over the left dorsolateral prefrontal cortex (DLPFC) combined with a face-name associative memory CT in the continuum of AD pathology. Fifty patients from a very early to a moderate phase of dementia were randomly assigned to one of two groups: CT plus real rTMS or CT plus placebo rTMS. The results showed that the improvement in the trained associative memory induced with rTMS was superior to that obtained with CT alone. Interestingly, the extent of the additional improvement was affected by disease severity and levels of education, with less impaired and more educated patients showing a greater benefit. When testing for generalization to non-trained cognitive functions, results indicated that patients in CT-real group showed also a greater improvement in visuospatial reasoning than those in the CT-sham group. Interestingly, this improvement persisted over 12 weeks after treatment beginning. The present study provides important hints on the promising therapeutic use of rTMS in AD.
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Enfermedad de Alzheimer/psicología , Enfermedad de Alzheimer/terapia , Terapia Cognitivo-Conductual/métodos , Disfunción Cognitiva/psicología , Disfunción Cognitiva/terapia , Estimulación Magnética Transcraneal/métodos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico , Cognición/fisiología , Disfunción Cognitiva/diagnóstico , Terapia Combinada/métodos , Método Doble Ciego , Femenino , Humanos , Masculino , Memoria/fisiología , Persona de Mediana Edad , Corteza Prefrontal/fisiología , Resultado del TratamientoRESUMEN
BACKGROUND: Early onset dementias (EOD) are rare neurodegenerative dementias that present before 65 years. Genetic factors have a substantially higher pathogenetic contribution in EOD patients than in late onset dementia. OBJECTIVE: To identify known and/or novel rare variants in major candidate genes associated to EOD by high-throughput sequencing. Common-risk variants of apolipoprotein E (APOE) and prion protein (PRNP) genes were also assessed. METHODS: We studied 22 EOD patients recruited in Memory Clinics, in the context of studies investigating genetic forms of dementia. Two methodological approaches were applied for the target-Next Generation Sequencing (NGS) analysis of these patients. In addition, we performed progranulin plasma dosage, C9Orf72 hexanucleotide repeat expansion analysis, and APOE genotyping. RESULTS: We detected three rare known pathogenic mutations in the GRN and PSEN2 genes and eleven unknown-impact mutations in the GRN, VCP, MAPT, FUS, TREM2, and NOTCH3 genes. Six patients were carriers of only common risk variants (APOE and PRNP), and one did not show any risk mutation/variant. Overall, 69% (nâ=â9) of our early onset Alzheimer's disease (EAOD) patients, compared with 34% (nâ=â13) of sporadic late onset Alzheimer's disease (LOAD) patients and 27% (nâ=â73) of non-affected controls (ADNI, whole genome data), were carriers of at least two rare/common risk variants in the analyzed candidate genes panel, excluding the full penetrant mutations. CONCLUSION: This study suggests that EOD patients without full penetrant mutations are characterized by higher probability to carry polygenic risk alleles that patients with LOAD forms. This finding is in line with recently reported evidence, thus suggesting that the genetic risk factors identified in LOAD might modulate the risk also in EOAD.
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Demencia/genética , Secuenciación de Nucleótidos de Alto Rendimiento/tendencias , Edad de Inicio , Anciano , Alelos , Apolipoproteínas E/genética , Proteína C9orf72/genética , Femenino , Estudios de Asociación Genética , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Presenilina-2/genética , Proteínas Priónicas/genética , Estudios Retrospectivos , Medición de RiesgoRESUMEN
IMPORTANCE: Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. OBJECTIVE: To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. DESIGN, SETTING, AND PARTICIPANTS: The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. RESULTS: Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P < .001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P < .001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P < .001; effect size Cohen d = 1.04) and decreased by 29.9% in amyloid-negative (P < .001; d = -1.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P < .001). CONCLUSIONS AND RELEVANCE: Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed.
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Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/metabolismo , Compuestos de Anilina , Disfunción Cognitiva/diagnóstico , Glicoles de Etileno , Tomografía de Emisión de Positrones/normas , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Femenino , Humanos , Masculino , Tomografía de Emisión de Positrones/métodos , Valor Predictivo de las PruebasRESUMEN
The new concept of palliative care supports the idea of palliation as an early approach to patients affected by disabling and life-limiting disease which focuses on the patient's quality of life along the entire course of disease. This model moves beyond the traditional concept of palliation as an approach restricted to the final stage of disease and widens the fields of intervention. There is a growing awareness of the importance of palliative care not only in oncological diseases but also in many other branches of medicine, and it appears particularly evident in the approach to many of the most frequent neurological diseases that are chronic, incurable and autonomy-impairing illnesses. The definition and implementation of palliative goals and procedures in neurology must take into account the specific features of these conditions in terms of the complexity and variability of symptoms, clinical course, disability and prognosis. The realization of an effective palliative approach to neurological diseases requires specific skills and expertise to adapt the concept of palliation to the peculiarities of these diseases; this approach should be realized through the cooperation of different services and the action of a multidisciplinary team in which the neurologist should play a central role to identify and face the patient's needs. In this view, it is paramount for the neurologist to be trained in these issues to promote the integration of palliative care in the care of neurological patients.
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Cuidadores , Enfermedades del Sistema Nervioso/psicología , Enfermedades del Sistema Nervioso/terapia , Cuidados Paliativos/métodos , HumanosRESUMEN
In 2011, the so-called Dubois criteria introduced the use of biomarkers in research (in particular, brain amyloid positron emission tomography imaging and the cerebrospinal fluid levels of tau/fosfo-tau and beta-amyloid 1-42) for the early or preclinical diagnosis of Alzheimer's disease. Even so, we are looking at an increased use of these markers in clinical practice. In the 1960s, Alzheimer's disease was considered a rare form of presenile dementia, but gradually it has been recognized as the prevalent form of old-age dementia. As a consequence, what was once regarded as an inevitable outcome of old age is now recognized as a true disease. Several factors contributed to this paradigm shift, in particular a longer lifespan, new techniques of in vivo study of the central nervous system, and the pressure exerted by the pharmaceutical industry and patient groups. The current lack of disease-modifying therapies and the high incidence of mild cognitive impairment, which is a risk factor for dementia, raise a series of clinical ethical problems ranging from how diagnosis is communicated to how resources are used. This article offers a conceptual scheme through which these issues can be addressed.
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Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/líquido cefalorraquídeo , Proteínas de la Membrana/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Enfermedad de Alzheimer/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Investigación Biomédica/ética , Diagnóstico Diferencial , Progresión de la Enfermedad , Diagnóstico Precoz , Humanos , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
New knowledge from scientific research on vegetative state (VS) and its consequences in clinical practice are reviewed. The ambiguity of the concept of consciousness and the difficult issue of its moral significance are then examined. The Authors stress the need for longitudinal prognostic studies, the promotion of an expert widespread use of standardized behavioural scales, and recommend that the ethical debate about VS rely upon the widest consensus of the scientific community.
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Estado de Conciencia/ética , Análisis Ético , Estado Vegetativo Persistente/diagnóstico , Estado de Conciencia/fisiología , Humanos , Estudios Longitudinales , Principios Morales , Estado Vegetativo Persistente/fisiopatologíaRESUMEN
Voting by persons with dementia raises questions about their decision-making capacity. Methods specifically addressing voting capacity of demented people have been proposed in the US, but never tested elsewhere. We translated and adapted the US Competence Assessment Tool for Voting (CAT-V) to the Italian context, using it before 2006 elections for Prime Minister. Consisting of a brief questionnaire, this tool evaluates the following decision-making abilities: understanding nature and effect of voting, expressing a choice, and reasoning about voting choices. Subjects' performance was examined in relation to dementia severity. Of 38 subjects with Alzheimer's disease (AD) enrolled in the study, only three scored the maximum on all CAT-V items. MMSE and CAT-V scores correlated only moderately (r = 0.59; P < 0.0001) with one another, reflecting the variability of subjects' performance at any disease stage. Most participants (90%), although performing poorly on understanding and reasoning items, scored the maximum on the choice measure. Our results imply that voting capacity in AD is only roughly predicted by MMSE scores and may more accurately be measured by a structured questionnaire, such as the CAT-V. Among the decision-making abilities evaluated by the CAT-V, expressing a choice was by far the least affected by the dementing process.
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The concept of brain death (BD) has been widely accepted by medical and lay communities in the Western world and is the basis of policies of organ retrieval for transplantation from brain-dead donors. Nevertheless, concerns still exist over various aspects of the clinical condition it refers to. They include the utilitarian origin of the concept, the substantial international variation in BD definitions and criteria, the equivalence between BD and the donor's biological death, the practice of retrieving organs from donors who are not brain-dead (as in non-heart-beating organ donor protocols), the proposal to abandon the dead donor rule and attempts to overcome these problems by adapting rules and definitions. Suggesting that BD, as it was originally proposed by the Harvard Committee, is more a moral than a scientific concept, we argue that current criteria do not empirically justify the definition of BD; yet they consistently identify a clinical condition in which organ retrieval can be morally and socially justified. We propose to revert to the old term of "irreversible coma" or, better yet, of "irreversible apnoeic coma", thus abandoning the presumption of diagnosing the death of all intracranial neurons and/or the patient's biological death. On the other hand, we think that a (re)definition of the vital status of donors identified on neurological criteria can only occur through a prior (re)definition of death, a task which is not only medical but societal.
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Muerte Encefálica/diagnóstico , Diagnóstico Diferencial , Humanos , Donantes de TejidosRESUMEN
OBJECTIVE: To identify correlations between clinical and neuroimaging features in sporadic chorea and to explicate the evolution of choreas of differing aetiologies. METHODS: We analysed the clinical and neuroimaging data of 51 consecutive cases (17 males, 34 females; age 16-95 years) of sporadic chorea admitted to the neurology departments of two general hospitals from January 1994 to December 1999, and two neurological institutes from January 1997. Six months later the patients were reassessed clinically and those still with chorea (20 cases) were asked to undergo the genetic tests for Huntington's disease and dentatorubropallidoluysian atrophy. RESULTS: There were 9 cases of focal dyskinesias, 18 of hemichorea, and 24 of generalised chorea; onset was acute in 17, subacute in 27, and insidious in seven. Analysis permitted classification as follows: vascular-related (21 cases); vasculitis (1 case); hypoxia (2 cases); drug-induced (7 cases); AIDS-related (5 cases), borreliosis (1 case); Sydenham's chorea (1 case); hyperglycaemia (2 cases); hyponatraemia (2 cases); Huntington's disease (HD) (5 cases) and acanthocytosis (1 case). In 3 patients neither etiological factors nor neuroradiological alterations were found. CONCLUSIONS: Although a convincing concordance between choreic signs and neuroradiological findings was possible in 4 patients only, it was possible to assign an aetiology in most cases with vascular related causes the most frequent and metabolic factors often participating. Huntington's disease is not unusual as a cause of sporadic choreas. HIV infection is an emerging cause of chorea and AIDS-related disease should be considered in young patients presenting without a family history of movement disorders. We emphasize the importance of follow-up to identify persistent chorea for which genetic testing is mandatory.