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The term 'mirror sign' refers to the inability to recognize the reflection of oneself in a mirror, while the ability to recognize others' faces often remains intact. In this article, we present a case of an 85-year-old woman, with probable Lewy body dementia, who stably exhibited a delusional 'mirror sign' for a period of 9 months. Following a straightforward, ecological, non-pharmacological intervention, her 'mirror sign' delusion was no longer present. [ABSTRACT FROM AUTHOR]

Background. The limitation of clinical-epidemiological know-how and evidence regarding therapeutic efficiency in depression among the elderly and extremely elderly patients has given rise to an excessive variety of practices in clinical care of these patients in the Spanish health system. The Spanish Society of Psychogeriatrics (SEPG) has raised the question of the need to unify criteria through a structured approach based on professional consensus. Objectives. To develop an expert consensus of clinical recommendations to improve the clinical treatment of depression in elderly patients in Spain, sponsored by the Spanish Society of Psychogeriatrics (SEPG). Methods. Modified Delphi Consensus, in two rounds. The study was conducted in four phases: 1) constitution of a Scientific Committee, project promoter and responsible for bibliographic review and formulation of recommendations for discussion 2) constitution of a multicenter Panel of Experts with representatives from this specialist field 3) postal survey comprised of two rounds, with interim processing of opinions and a report for the experts and 4) discussion of results during an onsite meeting of the Scientific Committee. Results. The survey evaluation was completed by 61 experts consulted, in two rounds. In the first round, consensus was reached in 39 of the 54 questions analyzed. Following interaction by the panel, this consensus was increased to a total of 46 survey items (85% of the proposed contents). It was impossible to obtain a sufficiently unanimous consensus on the remaining 8 questions, either due to differences of opinion among the professionals or a lack of established criterion in most of the experts. Conclusions. A full list of criteria and clinical recommendations for the purpose of rationalizing the treatment of depression in elderly patients and reducing excessive variability in clinical practice is presented. The recommendations are qualified in accordance with the degree of consensus of the professionals endorsing them and can be considered valid until new scientific information becomes available that justifies their review. [ABSTRACT FROM AUTHOR]

Bupropion is a monocyclic aminoketone introduced into Spain for the treatment of depression with the ex- tended release (XL) formulation that makes it possible to administer it in a single daily dose. It is metabolized in its principal active metabolite, the hydroxybupropion (OH-BUP) by the cytochrome P450 2B6 (CYP2B6), with a mean elimination half life of about 20 h. It is a norepinephrine and dopamine reuptake inhibitor with an almost null effect on the serotonin transporter. It has low (12%-35%) but persistent occupancy of the striatal dopamine transporter. It has no clinically significant effects on the histaminergic, muscarinic, alpha-adrenergic or domaminergic receptors. Its principal interactions are related with inhibition or induction of CYP2B6, responsible for the bupropion metabolism, or inhibition of CYP2D6 by bupropion. It should be used carefully together with drugs that decrease the seizure threshold. This is contraindicated during sudden suppression of alcohol or sedatives and during treatment with monoaminooxidade inhibitors. The present paper answers frequent questions posed during the clinical use of bupropion, especially under special clinical situations or during treatment with other common drugs. These situations include, among others, combined use of anti-seizure drugs, antipsychotics in psychotic depression, corticosteroids, antidiabetics, other antidepressants such as venlafaxin, oral contraceptives, hormone replacement hormone therapy, disulfiram, alcohol or abuse drugs and varenicline. [ABSTRACT FROM AUTHOR]

Objectives. To determine and compare effectiveness, tolerability and safety of venlafaxine extended release (VXR) and other conventional antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), for the treatment of elderly patients diagnosed of depressive disorder in an out-patient psychiatry setting. Methods. Multicenter, naturalistic, randomized, open-label study performed in elderly patients with depressive disorder (according to DSM-IV). Patients were randomized to 6 months of treatment with VXR or another conventional antidepressant (CA). Effectiveness was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Scale (HAM-A). Response was considered as a ≥ 50 % decrease and remission as a < 9 score in the MADRS. Results. Sample of 120 patients older than 60 years; 68 received VXR and 52 CA (SSRI: 94.1 %). Most frequently used SSRI were citalopram (40.8 %), paroxetine (24.5 %) and sertraline (20.4 %). After 6 months of treatment, VXR achieved a higher response (75 %, VXR; 50 %, CA; p = 0.048) and remission (50 %, VXR; 28.9 %, CA; p = 0.048) and a higher decrease in the HAM-A score (-14.77, VXR; -10.84, CA). There were no significant differences in compliance rates (67.6, VXR; 71.1 %, CA) and adverse reactions (14.7 %, VXR; 13.46 %, CA) between both treatment groups. Blood pressure and heart rate remained within normal, limits in both treatment groups. Conclusions. In this study, venlafaxine extended release shows higher effectiveness than other conventional antidepressants, mainly SSRIs, in the treatment of depressive elderly patients in the out-patient psychiatry setting. [ABSTRACT FROM AUTHOR]

Introduction: The care of people with schizophrenia (PWS) is usually provided in an outpatient setting by community mental health teams. However, PWS frequently require inpatient treatment because of a wide array of clinical, personal and/or social situations. Unfortunately, to our knowledge, there are no guidelines available to help psychiatrists in the decision-making process on hospital discharge for PWS. The aim of this project was to develop an expert consensus on discharge criteria for PWS after their stay in an acute inpatient psychiatric unit., Methods: Using a modified Delphi method a group of 42 psychiatrists throughout Spain evaluated four areas of interest regarding this issue: clinical symptomatology, treatment-related factors, follow-up health care units after discharge, and physical health and monitoring., Results: After two rounds, among the 64 statements, a consensus was reached for 59 (92.2%) statements. In three (17.7%) of the 17 statements on 'clinical symptomatology' and 2 (13.3%) of the 15 statements on 'follow-up health care units after discharge', a consensus was not reached; in contrast, a consensus was reached for all statements concerning 'treatment-related factors' and those concerning 'physical health and monitoring'. The consensus results highlight the importance for discharge of the control of symptoms rather than their suppression during admission and of tolerability in the selection of anantipsychotic., Discussion: Although there is a lack of relevant data for guiding the discharge of PWS after hospitalization in an acute inpatient psychiatric unit, we expect that this consensus based on expert opinion may help clinicians to take appropriate decisions., Competing Interests: JM has received grants from and served as consultant, advisor or CME speaker for the following entities: Angelini, Exeltis, Ferrer, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Qualigen, Sanofi-Aventis, Servier, Casen Recordati and the Spanish Ministry of Science and Innovation CIBERSAM. LA-O has been member of the advisory board for Exeltis; has received speaker honoraria for medical education activities from Janssen, Lundbeck, Pfizer, Esteve, Cassen. AM has served as a speaker or received honoraria from Angelini Pharma, Otsuka, Neuraxpharm and ROVI. JM-R has received grants from and served as consultant, advisor or CME speaker for the following entities: Angelini, Exeltis, Rubió, Takeda, Janssen, Lundbeck, Pfizer, Neuraxpharm, and Casen Recordati. LG-R has been member of the advisory board member for Janssen, Angelini, Otsuka; has received speaker honoraria from Lundbeck, Janssen, Angelini, and Novartis., (Copyright © 2024 Montes, Agüera-Ortiz, Mané, Martinez-Raga and Gutiérrez-Rojas.)

Introduction: Globally, depression is the most common psychiatric disorder and is frequently associated with somatic symptom disorders, including pain as a physical symptom. There is a current need to improve the detection and management of the individuals in which depression and pain coexist. Hence, the aim of this document is to provide recommendations in the diagnosis and management of patients with major depressive disorder (MDD) who have pain as a physical symptom (PPS), in order to reduce the variability of clinical practice., Material and Methods: The methodology used is based on the internationally recognized RAND/UCLA consensus method. The scientific committee, consisted of a group of eight multidisciplinary experts, defined 12 clinically relevant questions. After the systematic review of the literature, the scientific committee assessed the evidence and developed recommendations. The panel group with 15 participants validated these recommendations using a single Delphi round. To conclude, there was a final consensus meeting held to redefine with minor modifications the final recommendations., Results: The scientific committee developed a total of 19 recommendations on the diagnosis and detection, impact of PPS in MDD, treatment of MDD with associated PPS, use of healthcare resources, additional recommendations, and care coordination of these patients. Globally, a substantial level of agreement (≥80%) was reached on all items during the Delphi round. All the 19 achieved consensus, seven of them (37%) were agreed with unanimity during the Delphi round. The recommendations with higher consensus were in relation to diagnosis, impact of PPS in MDD, treatment and use of healthcare resources., Conclusions: Currently, the evidence base for patients with MDD and PPS is still being developed and this consensus statement aims to bridge that gap by providing practical recommendations., (Published by Elsevier España S.L.U.)

Recent evidence confirms the risks of discontinuity of care when young people make a transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS), although robust data are still sparse. We aimed to identify when and how patients get lost to care during transition by tracking care pathways and identifying factors which influence dropping out of care during transition. This is a retrospective observational study of 760 patients who reached the transition age boundary within 12 months before transition time and being treated at CAMHS for at least during preceding 18 months. Data were collected at two time points: last visit to CAHMS and first visit to AHMS. Socio-demographic, clinical and service utilization variables on CAMHS treatment were collected. In the 12 months leading up to the transition boundary, 46.8% of subjects (n = 356) withdrew from CAHMS without further contact with AHMS, 9.3% withdrew from CAHMS but were referred to AHMS by other services, 29% were transferred from CAHMS to AHMS, 10% remained at CAHMS and 5% patients were transferred to alternative services. Fifty-six percent of subjects experience cessation of care before the transition age. The risk of dropout increases with shorter contact time in CAMHS, is greater in subjects without pharmacological treatment, and decreases in subjects with psychosis, bipolar disorder, eating disorders, mental retardation, and neurodevelopmental disorders. This study confirms that a large number of people drop out of care as they approach the CAMHS transition and experience discontinuity of care during this critical period., (© 2022. The Author(s).)

Widespread access to emerging information and communication technologies (ICT) allows its use for the screening of diseases in the general population. At the initiative of the Spanish Confederation of Associations of Families of People with Alzheimer's disease and other dementias (CEAFA), a website (http://www.problemasmemoria.com) has been created that provides information about Alzheimer's disease and includes questionnaires to be completed by family or friends concerned about memory problems of a relative. A cross-sectional, randomized, multicenter study was performed to evaluate feasibility, validity, and user satisfaction with an electronic method of completion vs. the current method of paper-based questionnaires for clinically dementia screening completed by the informants: the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and the Alzheimer's disease-8 screening test (AD8). A total of 111 pairs were recruited by seven memory clinics. Informants completed IQCODE and AD8 questionnaires both in their paper and electronic versions. The correlation between paper and electronic versions was significantly positive for IQCODE ( r = 0.98; p < 0.001) and AD8 ( r = 0.96; p < 0.001). The execution time did not differ significantly, and participants considered their use equally easy. This study shows that an electronic version of the IQCODE and AD8 questionnaires is suitable for its online use via the internet and achieves the same results as the traditional paper versions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Agüera-Ortiz, Martín-Carrasco, Arriola-Manchola, Martínez-Lage, Pérez-Martínez, Ojea, Soler-López and García-Ribas.)

Apathy is one of the most prevalent, stable and persistent neuropsychiatric symptom across the neurocognitive disorders spectrum. Recent advances in understanding of phenomenology, neurobiology and intervention trials highlight apathy as an important target for clinical intervention. We conducted a comprehensive review and critical evaluation of recent advances to determine the evidence-based suggestions for future trial designs. This review focused on 4 key areas: 1) pre-dementia states; 2) assessment; 3) mechanisms/biomarkers and 4) treatment/intervention efficacy. Considerable progress has been made in understanding apathy as a treatment target and appreciating pharmacological and non-pharmacological apathy treatment interventions. Areas requiring greater investigation include: diagnostic procedures, symptom measurement, understanding the biological mechanisms/biomarkers of apathy, and a well-formed approach to the development of treatment strategies. A better understanding of the subdomains and biological mechanisms of apathy will advance apathy as a treatment target for clinical trials., Competing Interests: Conflict of Interest MEM, LA, LA-O, DRB, HB, YG, GAM, PRP, AP, KS report no conflicts with any product mentioned or concepts discussed in this article. ZI has received consultation funding from Otsuka/Lundbeck, outside the submitted work. MC has received consultation funding from Allergan, Kyowa, Reviva, Sunovion and Otsuka. HB has received consultation funding from Nutricia Australia and Biogen. KLL has received consultation fees from BioXcel, Cerevel, Eisai, Kondor, Otsuka and Praxis, outside of the submitted work. PBR has received research funding support outside of this project from Lilly, Vaccinex, National Institute on Aging, Alzheimer’s Association, Functional Neuromodulation (FNMI), Lilly, Alzheimer’s Disease Cooperative Study (ADCS), Alzheimer’s Disease Trials Research Institute (ATRI), Alzheimer’s Clinical Trials Consortium (ACTC), Richman Family Precision Medicine Center of Excellence on Alzheimer’s Disease. PBR has received income from consulting, advisory boards, and/or DSMB from GLG, Leerink, Cerevel, Cerevance, Bioxcel, Sunovion, Acadia, Food and Drug Administration, Medalink, Novo Nordisk, Noble Insights, and Synaptogen. DLS has received research support from NIH and Eisai, has participated as a paid member of a DSMB or adjudication committee with Acadia, Avanir, Janssen, and Otsuka, and has received consulting fees from Avanir and NovoNordisk (all unrelated to apathy treatment)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Workshops using arts and board games are forms of non-pharmacological intervention widely employed in seniors with neurocognitive disorders. However, clear guidelines on how to conduct these workshops are missing. The objective of the Art and Game project (AGAP) was to draft recommendations on the structure and content of workshops for elderly people with neurocognitive disorders and healthy seniors, with a particular focus on remote/hybrid workshops, in which at least a part of the participants is connected remotely. Recommendations were gathered using a Delphi methodology. The expert panel ( N = 18) included experts in the health, art and/or board games domains. They answered questions via two rounds of web-surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with the general public ( N = 101). Both the experts and the general public suggested that organizing workshops in a hybrid format (some face-to-face sessions, some virtual session) is feasible and interesting for people with neurocognitive disorders. We reported guidelines on the overall structure of workshops, practical tips on how to organize remote workshops, and a SWOT analysis of the use of remote/hybrid workshops. The guidelines may be employed by clinicians to decide, based on their needs and constraints, what interventions and what kind of workshop format to employ, as well as by researcher to standardize procedures to assess the effectiveness of non-pharmacological treatments for people with neurocognitive disorders., Competing Interests: PF was employed by the company GENIOUS Healthcare–Mindmaze Group Co. ML and LM were employed by the company Asmodee Research Co. PM was employed by the company NEHS Digital Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Manera, Agüera-Ortiz, Askenazy, Dubois, Corveleyn, Cross, Febvre-Richards, Fabre, Fernandez, Foulon, Gros, Gueyraud, Lebourhis, Malléa, Martinez, Pancrazi, Payne, Robert, Tamagno, Thümmler and Robert.)

Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials.

Background: There is high prevalence of neuropsychiatric symptoms (NPS) among dementia patients. NPS are correlated with dementia progression, functional decline, early institutionalization, and death. There is scarce evidence on the progression of NPS in the latest stages of dementia., Objective: To describe the prevalence of NPS in mild-moderate to severe dementia and to reveal the progression of each NPS over time., Methods: We studied 317 patients (77.3% female, average age: 81.5 years) with a DSM-IV-TR diagnosis of dementia. This is a cross-sectional, and a prospective longitudinal study with 78-month follow-up. We assessed cognitive status (Mini-Mental State Examination and Severe Mini-Mental State Examination), dementia severity (Global Deterioration Scale and Clinical Dementia Rating), and psychopathological measures (Neuropsychiatric Inventory, APADEM-Nursing Home, Apathy Inventory, Cornell Scale for Depression in Dementia, and Cohen-Mansfield Agitation Inventory)., Results: Overall prevalence of NPS was 94.6%, being apathy the most prevalent (66.7%) and the one whose severity increased the most with progression of dementia. Agitation/aggression, irritability, and sleeping and eating disorders also increased over time. Delusions and depressive symptoms decreased in severity with disease progression. In severe dementia, female displayed more depressive symptoms and eating disorders, while male displayed more agitation/aggression and sleep disturbances., Conclusion: NPS in dementia follow a heterogeneous course. Apathy is the most prevalent NPS and the one that worsens most significantly over time. The course of some NPS differs between sexes. Further research is required to understand the evolution of NPS at advanced stages of dementia.

A variety of medical and social factors have contributed over the last decades to the overuse of psychotropic drugs in people with dementia. One social factor is probably the frequent failure to provide adequate person-centered care, be it in the community or in institutional settings. This unfortunate reality has been reacted upon with numerous guidelines to reduce prescriptions of the most dangerous drugs (e.g., neuroleptics). Each psychotropic drug prescription can in principle be assessed around three dimensions: (a) adequate, (b) inadequate, and (c) chemical restraint. The CH emical R estraints av O idance ME thodology (CHROME) defined chemical restraint as any prescription based on organizational convenience, rather than justified with medical diagnosis. Two validation studies revealed that one of the main medical reasons of over- and miss-prescriptions was symptom-based prescription. By switching to syndrome-based prescription, a large proportion of drugs could be de-prescribed and some re-adjusted or kept. Paucity of research and weakness of data are not conclusive about the adequacy of specific drugs for the myriad of cases presented by patients with dementia and comorbid conditions. Clinical practice, however, leads us to believe that even under optimal care conditions, psychotropics might still contribute to quality of life if based on an adequate diagnosis. This article explains the rationale that underlies a syndromic approach aimed at optimizing psychotropic treatment in people with dementia whose significant suffering derives from their thought, affective, or behavioral problems. The results of previous validation studies of this new methodology will be discussed and conclusions for future results will be drawn., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Muñiz, López-Alvarez, Agüera-Ortiz, Perea and Olazarán.)

Background: Alzheimer's disease (AD) and other forms of dementia are among the most common causes of disability in the elderly. Dementia is often accompanied by depression, but specific diagnostic criteria and treatment approaches are still lacking. This study aimed to gather expert opinions on dementia and depressed patient management to reduce heterogeneity in everyday practice. Methods: Prospective, multicenter, 2-round Modified Delphi survey with 53 questions regarding risk factors (11), signs and symptoms (7), diagnosis (8), and treatment (27) of depression in dementia, with a particular focus on AD. The questionnaire was completed by a panel of 37 expert physicians in neurodegenerative diseases (19 neurologists, 17 psychiatrists, and 1 geriatrician). Results: Consensus was achieved in 40 (75.5%) of the items: agreement in 33 (62.3%) and disagreement in 7 (13.2%) of them. Among the most relevant findings, depression in the elderly was considered an early sign (prodromal) and/or a dementia risk factor, so routine cognitive check-ups in depressed patients should be adopted, aided by clinical scales and information from relatives. Careful interpretation of neuropsychological assessment must be carried out in patients with depression as it can undermine cognitive outcomes. As agreed, depression in early AD is characterized by somatic symptoms and can be differentiated from apathy by the presence of sadness, depressive thoughts and early-morning awakening. In later-phases, symptoms of depression would include sleep-wake cycle reversal, aggressive behavior, and agitation. Regardless of the stage of dementia, depression would accelerate its course, whereas antidepressants would have the opposite effect. Those that improve cognitive function and/or have a dual or multimodal mode of action were preferred: Duloxetine, venlafaxine/desvenlafaxine, vortioxetine, tianeptine, and mirtazapine. Although antidepressants may be less effective than in cognitively healthy patients, neither dosage nor treatment duration should differ. Anti-dementia cholinesterase inhibitors may have a synergistic effect with antidepressants. Exercise and psychological interventions should not be applied alone before any pharmacological treatment, yet they do play a part in improving depressive symptoms in demented patients. Conclusions: This study sheds light on several unresolved clinical challenges regarding depression in dementia patients. Further studies and specific recommendations for this comorbid patient population are still needed., Competing Interests: LA-O has received grants from and served as consultant, advisor, or CME speaker for Janssen-Cilag, Exeltis, Lundbeck, Pfizer, Neuraxpharm, Sanofi-Aventis, and Servier. JO has received honoraria to participate in courses, lectures, congresses, and scientific advisory boards from several pharmaceutical companies including Exeltis, Janssen, Lundbeck, Angelini, Pfizer, Otsuka, and Esteve. JL-Á has prepared a monograph on this Delphi consensus with the financial help of Exeltis Pharmaceuticals Holding, S.L. JM has received grants from and served as consultant, advisor, or CME speaker for Almirall, Angelini, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Ferrer, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Qualigen, Recordati, Sanofi-Aventis, Servier, and the Spanish Ministry of Science and Innovation (CIBERSAM). CP has received honoraria to participate in courses and lectures and has been invited to congresses and scientific advisory boards from several pharmaceutical companies including Exeltis, Janssen, Lundbeck, Angelini, Pfizer, and Casen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Agüera-Ortiz, García-Ramos, Grandas Pérez, López-Álvarez, Montes Rodríguez, Olazarán Rodríguez, Olivera Pueyo, Pelegrin Valero and Porta-Etessam.)

Major and minor forms of depression are significant contributors to Parkinson's disease morbidity and caregiver burden, affecting up to 50% of these patients. Nonetheless, symptoms of depression are still underrecognized and undertreated in this context due to scarcity of evidence and, consequently, consistent clinical guideline recommendations. Here, we carried out a prospective, multicentre, 2-round modified Delphi survey with 49 questions about the aetiopathological mechanisms of depression in Parkinson's disease (10), clinical features and connections with motor and nonmotor symptoms (10), diagnostic criteria (5), and therapeutic options (24). Items were assessed by a panel of 37 experts (neurologists, psychiatrists, and a geriatrist), and consensus was achieved in 81.6% of them. Depressive symptoms, enhanced by multiple patient circumstances, were considered Parkinson's disease risk factors but not clinical indicators of motor symptom and disease progression. These patients should be systematically screened for depression while ruling out both anhedonia and apathy symptoms as they are not necessarily linked to it. Clinical scales (mainly the Geriatric Depression Scale GDS-15) can help establishing the diagnosis of depression, the symptoms of which will require treatment regardless of severity. Efficacious and well-tolerated pharmacological options for Parkinson's comorbid depression were selective serotonin reuptake inhibitors (especially sertraline), dual-action serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine, and duloxetine), multimodal (vortioxetine, bupropion, mirtazapine, and tianeptine), and anti-Parkinsonian dopamine agonists (pramipexole, ropinirole, and rotigotine). Tricyclic antidepressants and combining type B monoamine oxidase inhibitors with serotonergic drugs have serious side effects in these patients and therefore should not be prescribed. Electroconvulsive therapy was indicated for severe and drug-refractory cases. Cognitive behavioural therapy was recommended in cases of mild depression. Results presented here are useful diagnostic and patient management guidance for other physicians and important considerations to improve future drug trial design., Competing Interests: Dr. Agüera-Ortiz has received grants from and served as consultant, advisor, or CME speaker for Janssen-Cilag, Exeltis, Lundbeck, Pfizer, Neuraxpharm, Sanofi-Aventis, and Servier. Dr. López-Álvarez has prepared a monograph on this Delphi consensus with the financial help of Exeltis Pharmaceuticals Holding S.L. Dr. Montes has received grants from and served as consultant, advisor, or CME speaker for Almirall, Angelini, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Ferrer, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Qualigen, Recordati, Sanofi-Aventis, Servier, and the Spanish Ministry of Science and Innovation (CIBERSAM). Dr. Grandas received honoraria for lecturing from Abbvie, Zambon, Exeltis, and Teva as well as research grants from Instituto de Salud Carlos III (Spanish Ministry of Health) and the European Commission (Horizon 2020)., (Copyright © 2021 Luis Agüera-Ortiz et al.)

Introduction: Present knowledge about depression in the elderly is still scarce and often controversial, despite its high frequency and impact. This article reports the results and most relevant conclusions of a Delphi-based consensus on geriatric depression promoted by the Spanish Psychogeriatric Association., Methods: A 78-item questionnaire was developed by 7 highly specialized geriatric psychiatrists and was evaluated using the Modified Delphi technique in two rounds answered by 35 psychiatrists with an extensive expertise in geriatric depression. The topics and number of questions (in brackets) covered were: concepts, clinical aspects, and risk factors (12); screening and diagnosis (7); psychotic depression (17); depression and dementia (5); antidepressant drug treatment (18); non-pharmacological biological treatments (5); psychotherapeutic treatments (4); comorbidity and preventive aspects (6); professional training needed (4). In addition, the expert panel's opinion on the antidepressants of choice in 21 common comorbid conditions and on different strategies to approach treatment-resistant cases in terms of both efficacy and safety was assessed., Results: After the two rounds of the Delphi process, consensus was reached for 59 (75.6%) of the 78 items. Detailed recommendations are included in the text. Considering pharmacological treatments, agomelatine was the most widely mentioned drug to be recommended in terms of safety in comorbid conditions. Desvenlafaxine, sertraline, and vortioxetine, were the most frequently recommended antidepressants in comorbid conditions in general. Combining parameters of efficacy and safety, experts recommended the following steps to address cases of treatment resistance: 1. Escalation to the maximum tolerated dose; 2. Change of antidepressant; 3. Combination with another antidepressant; 4. Potentiation with an antipsychotic or with lamotrigine; 5. Potentiation with lithium; 6. Potentiation with dopamine agonists or methylphenidate., Discussion and Conclusions: Consensus was reached for a high number of items as well as for the management of depression in the context of comorbid conditions and in resistant cases. In the current absence of sufficient evidence-based information, our results can be used to inform medical doctors about clinical recommendations that might reduce uncertainty in the diagnosis and treatment of elderly patients with depressive disorders., (Copyright © 2020 Agüera-Ortiz, Claver-Martín, Franco-Fernández, López-Álvarez, Martín-Carrasco, Ramos-García and Sánchez-Pérez.)

Apathy is a common neuropsychiatric syndrome observed across many neurocognitive and psychiatric disorders. Although there are currently no definitive standard therapies for the treatment of apathy, nonpharmacological treatment (NPT) is often considered to be at the forefront of clinical management. However, guidelines on how to select, prescribe, and administer NPT in clinical practice are lacking. Furthermore, although new Information and Communication Technologies (ICT) are beginning to be employed in NPT, their role is still unclear. The objective of the present work is to provide recommendations for the use of NPT for apathy, and to discuss the role of ICT in this domain, based on opinions gathered from experts in the field. The expert panel included 20 researchers and healthcare professionals working on brain disorders and apathy. Following a standard Delphi methodology, experts answered questions via several rounds of web-surveys, and then discussed the results in a plenary meeting. The experts suggested that NPT are useful to consider as therapy for people presenting with different neurocognitive and psychiatric diseases at all stages, with evidence of apathy across domains. The presence of a therapist and/or a caregiver is important in delivering NPT effectively, but parts of the treatment may be performed by the patient alone. NPT can be delivered both in clinical settings and at home. However, while remote treatment delivery may be cost and time-effective, it should be considered with caution, and tailored based on the patient's cognitive and physical profile and living conditions., (Copyright © 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Describe and validate the CHROME (CHemical Restraints avOidance MEthodology) criteria., Design: Observational prospective longitudinal study., Setting: Single nursing home in Las Palmas de Gran Canaria, Spain., Participants: 288 residents; mean age: 81.6 (SD 10.6). 77.4% had dementia., Intervention: Multicomponent training and consultancy program to eliminate physical and chemical restraints and promote overall quality care. Clinicians were trained in stringent diagnostic criteria of neuropsychiatric syndromes and adequate psychotropic prescription., Measurements: Psychotropic prescription (primary study target), neuropsychiatric syndromes, physical restraints, falls, and emergency room visits were semi-annually collected from December 2015 to December 2017. Results are presented for all residents and for those who had dementia and participated in the five study waves (completer analysis, n=107)., Results: For the study completers, atypical neuroleptic prescription dropped from 42.7% to 18.7%, long half-life benzodiazepines dropped from 25.2% to 6.5%, and hypnotic medications from 47.7% to 12.1% (p<0.0005). Any kind of fall evolved from 67.3 to 32.7 (number of falls by 100 residents per year). Physicians' diagnostic confidence increased, while the frequency of diagnoses of neuropsychiatric syndromes decreased (p<0.0005)., Conclusions: Implementing the CHROME criteria reduced the prescription of the most dangerous medications in institutionalized people with dementia. Two independent audits found no physical or chemical restraint and confirmed prescription quality of psychotropic drugs. Adequate diagnosis and independent audits appear to be the keys to help and motivate professionals to optimize and reduce the use of psychotropic medication. The CHROME criteria unify, in a single compendium, neuropsychiatric diagnostic criteria, prescription guidelines, independent audit methodology, and minimum legal standards. These criteria can be easily adapted to other countries.

Background: Comprehensive clinicopathological studies of neuropsychiatric symptoms (NPS) in dementia are lacking., Objective: To describe the pathological correlations of NPS in a sample of institutionalized people with dementia., Methods: We studied 59 people who were consecutively admitted to a nursing home and donated their brain. Correlations between pathological variables and NPS upon admission (n = 59) and at one-year follow-up assessment (n = 46) were explored and confirmed using bivariate and multivariate statistical methods., Results: Mean (SD) age at admission was 83.2 (6.4) years and mean (SD) age at demise was 85.4 (6.6); 73% of the subjects were female and 98% presented advanced dementia. The most frequent etiological diagnosis was Alzheimer's disease (AD; 74.6% clinical diagnosis, 67.8% pathological diagnosis). The pathological diagnosis of AD was associated with aggression (β est 0.31), depression (β est 0.31), anxiety (β est 0.38), and irritability (β est 0.28). Tau stage correlated with aggressive symptoms (β est 0.32) and anxiety (βest 0.33). Coexistence of AD and Lewy body pathology was associated with depression (β est 0.32), while argyrophilic grains were associated with eating symptoms (β est 0.29). Predictive models were achieved for apathy, including cognitive performance, basal ganglia ischemic lesions, and sex as predictors (R2 0.38) and for sleep disorders, including pathological diagnosis of AD and age at demise (R2 0.18) (all p-values <0.05, unadjusted)., Conclusion: AD was the main pathological substrate of NPS in our sample of very elderly people with advanced dementia. However, correlations were mild, supporting a model of focal/asymmetric rather than diffuse brain damage, along with relevance of environmental and other personal factors, in the genesis of those symptoms.

Background: Psychotic symptoms are common in Alzheimer's disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice., Objective: To establish research criteria for the diagnosis of psychosis in AD., Methods: The International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria., Results: Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers., Conclusion: We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.

Drugs with anticholinergic action are widely prescribed in the elderly population due to their potential clinical benefits. However, these benefits are limited by adverse effects which may be serious in particular circumstances. This review presents different aspects of the use of anticholinergics in old age with a focus in psychogeriatric patients. We critically review published data on benefits and disadvantages of anticholinergics, which are often controversial. Prevalence, pathophysiology and measurement methods of the anticholinergic action of drugs are discussed. We also present the most important drawbacks resulting from its use, including effects on cognition in healthy and cognitively impaired people, in aged schizophrenia patients, emergence of delirium and psychiatric symptoms, influence in functionality, hospitalization, institutionalization and mortality, and the potential benefits and limitations of their discontinuation. Finally, we suggest practical recommendations for the safe use of anticholinergics in clinical conditions affecting elderly patients, such as dementia, schizophrenia and acute hallucinatory episodes, depression, anxiety, Parkinson's disease, cardiovascular conditions and urinary incontinence., (Copyright © 2019 López-Álvarez, Sevilla-Llewellyn-Jones and Agüera-Ortiz.)

Background: Apathy is a pervasive neuropsychiatric syndrome in people with neurocognitive and psychiatric disorders. The diagnostic criteria for apathy (DCA) have been revised in 2018., Objectives: Employing the 2018 DCA, in the present study, we investigated in groups of elderly subjects suffering from different neuropsychiatric disorders (a) the apathy prevalence; (b) the most commonly affected apathy dimensions (behavior/cognition, emotion, and social interaction); (c) the sensitivity and specificity of those dimensions for apathy diagnosis; and (d) the concurrent validity of 2018 DCA compared with the 2009 DCA., Methods: This multicenter survey included 166 subjects. Each center checked the presence of apathy in subjects belonging to the following DSM-5 diagnoses: mild neurocognitive disorders (mild NCDs); major NCDs; affective disorders (Aff D); and subjective cognitive decline (SCD)., Results: The frequency of apathy varied significantly based on the diagnostic groups (0% of subjects with apathy in the SCD group; 25% in the mild NCD group; 77% in the major NCD group; and 57% in the Aff. D group). All subjects with apathy fulfilled the criteria for the behavior/cognition dimension, 73.1% fulfilled the criteria for the emotion dimension, and 97.4% fulfilled the criteria for the social interaction dimension. Behavior/cognition showed the highest sensitivity, the copresence of emotion and social interaction the highest specificity. The concordance between the 2009 and the 2018 DCA indicated an almost perfect agreement., Conclusions: These results are consistent with previous reports and confirm that the social interaction dimension added to the 2018 DCA is present in most of subjects with apathy referred to specialized memory centers., (© 2019 John Wiley & Sons, Ltd.)

Background: Apathy is a very common behavioural and psychological symptom across brain disorders. In the last decade, there have been considerable advances in research on apathy and motivation. It is thus important to revise the apathy diagnostic criteria published in 2009. The main objectives were to: a) revise the definition of apathy; b) update the list of apathy dimensions; c) operationalise the diagnostic criteria; and d) suggest appropriate assessment tools including new technologies., Methods: The expert panel (N = 23) included researchers and health care professionals working on brain disorders and apathy, a representative of a regulatory body, and a representative of the pharmaceutical industry. The revised diagnostic criteria for apathy were developed in a two-step process. First, following the standard Delphi methodology, the experts were asked to answer questions via web-survey in two rounds. Second, all the collected information was discussed on the occasion of the 26th European Congress of Psychiatry held in Nice (France)., Results: Apathy was defined as a quantitative reduction of goal-directed activity in comparison to the patient's previous level of functioning (criterion A). Symptoms must persist for at least four weeks, and affect at least two of the three apathy dimensions (behaviour/cognition; emotion; social interaction; criterion B). Apathy should cause identifiable functional impairments (criterion C), and should not be fully explained by other factors, such as effects of a substance or major changes in the patient's environment (Criterion D)., Conclusions: The new diagnostic criteria for apathy provide a clinical and scientific framework to increase the validity of apathy as a clinical construct. This should also help to pave the path for apathy in brain disorders to be an interventional target., (Copyright © 2018 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: We conducted a longitudinal study to explore the clinical and pathological correlates of cerebral microbleeds (CMBs) in institutionalized patients with dementia., Methods: Clinical and magnetic resonance imaging (MRI) data were extracted from 182 nursing home patients (mean age [standard deviation]: 81.3 [6.9], 78.0% female, and 83.4% moderate to severe dementia), which were divided according to the CMBs number and location. One-year follow-up data were obtained from 153 patients, and postmortem pathological diagnosis was available in 40 patients., Results: Cerebral microbleeds were observed in 42.9% of patients and were associated with MRI ischemic lesions ( P < .0005). In the adjusted analysis, lobar CMB predicted worsening of parkinsonism (standardized β: 0.43) and gait (standardized β: 0.24). A pathological diagnosis of Alzheimer's disease was less frequent in the brains of patients with lobar and deep CMB (33.3% vs 85.3%; P < .05)., Conclusion: Cerebral microbleeds were linked to cerebrovascular disease and predicted motor deterioration in institutionalized people with advanced dementia.

Background: Progression of dementia is often associated with the emergence of neuropsychiatric symptoms (NPS), though there is recent evidence that NPS may occur in prodromal dementia (PrD) and impact clinical course. Mood and anxiety symptoms are the NPS that tend to occur most frequently in PrD and thus have been most extensively studied. Comparatively, there has been little focus on psychotic symptoms in PrD., Methods: The authors review the existing literature on psychosis in PrD, including the functional psychosis of early and late onset, with a focus on epidemiology, phenomenology, and clinical course and treatment considerations., Results: Patients with psychotic disorders at baseline such as schizophrenia may be more at risk for developing dementia over time, although this is not completely clear. Psychotic symptoms are likely more common in PrD than previously understood based on factor analysis studies, although they are much more common in established dementia. Variability in findings may reflect the heterogeneous nature of PrD studies to date and the lack of inclusion of patients with late onset psychosis in most clinical studies. The presence of psychosis in patients with PrD may be associated with a worse prognosis in terms of mortality and conversion to dementia., Conclusions: Research to date suggests that psychosis in PrD may be more common than previously thought and impact clinical course negatively. Future studies incorporating patients with late onset psychotic disorders, and focusing on the impact of early recognition and treatment, are required to more fully understand the role of psychosis in PrD.

Background: Country-specific data on resource use and costs associated with Alzheimer's disease (AD) help inform governments about the increasing need for medical and financial support as the disease increases in prevalence., Methods: GERAS II, a prospective observational study, assessed resource use, costs, and health-related quality of life (HRQoL) among patients with AD and their caregivers in Spain. Community-dwelling patients aged ≥55 years with probable AD, and their primary caregivers, were recruited by study investigators during routine clinical practice and assessed as having mild, moderate, or moderately severe/severe (MS/S) AD dementia based on patient Mini-Mental State Examination scores. Costs of AD were calculated by applying costs to resource-use data obtained in caregiver interviews using the Resource Utilization in Dementia instrument. Total societal costs included patients' health and social care costs and caregiver informal care costs. Baseline results are presented., Results: Total mean monthly societal costs/patient (2013 values) were €1514 for mild (n = 116), €2082 for moderate (n = 118), and €2818 for MS/S AD dementia (n = 146) (p value <0.001 between groups). Caregiver informal care costs comprised most of the total societal costs and differed significantly between groups (€1050, €1239, €1580, respectively; p value = 0.013), whereas patient healthcare costs did not. Across AD dementia severity groups, patient HRQoL (measured by proxy) decreased significantly (p value <0.001), caregiver subjective burden significantly increased (p value <0.001) and caregiver HRQoL was similar., Conclusions: Societal costs associated with AD in Spain were largely attributable to caregiver informal care costs and increased with increasing AD dementia severity.

Objective: Apathy is one of the most frequent symptoms of dementia, whose underlying neurobiology is not well understood. The objective was to analyze the correlations of apathy and its dimensions with gray and white matter damage in the brain of patients with advanced Alzheimer's disease (AD)., Methods: The setting of the study was at the Alzheimer Center Reina Sofía Foundation Research Unit. Participants include 37 nursing home patients with moderate to severe AD, 78.4% were women, and mean Standard Deviation (SD) age is 82.7 (5.8). Several measurements were taken: severe mini-mental state examination and Global Deterioration Scale for cognitive and functional status, Neuropsychiatric Inventory for behavioral problems, and Apathy In Dementia-Nursing Home Version Scale for apathy, including total score and subscores of emotional blunting, deficit of thinking, and cognitive inertia. 3T magnetic resonance imaging measures (voxel-based morphometry, fluid-attenuated inversion recovery, and diffusion tensor imaging) were also conducted., Results: Moderate levels of apathy (mean Apathy In Dementia-Nursing Home Version Scale: 31.1 ± 18.5) were found. Bilateral damage to the corpus callosum and internal capsule was associated with apathy severity (cluster size 2435, p < 0.0005, family-wise error [FWE]-corrected). A smaller and more anteriorly located region of the right internal capsule and corpus callosum was associated with higher emotional blunting (cluster size 334, p < 0.0005, FWE-corrected). Ischemic damage in the right periventricular frontal region was associated with higher deficit of thinking (cluster size 3805, p < 0.005, FWE-corrected)., Conclusions: Brain damage related to apathy may have different features in the advanced stages of AD and differs between the three apathy dimensions. Besides atrophy, brain connectivity and vascular lesions are relevant in the study of apathy, especially in the more severe stages of dementia. Further magnetic resonance imaging studies should include multimodal techniques. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Neuropsychiatric symptoms (NPS) are frequent in dementia. These symptoms are also present in patients with mild cognitive impairment (MCI) and can even constitute the first manifestations of a neurodegenerative process, preceding the development of cognitive symptoms. The presence of NPS is associated with higher rates of conversion to dementia in healthy persons and patients with MCI. Recognizing the importance of NPS, the Alzheimer Association created a working group that has designed the ISTAART criteria for mild behavioral impairment (MBI), including the following areas of assessment: motivation, affect, impulse control, social appropriateness and thoughts/perception. The ISTAART criteria allow identification of NPS to prospectively assess the risk of a person developing dementia. The Mild Behavioral Impairment-Checklist (MBI-C) has subsequently been developed, which allows the MBI construct to be specifically assessed by quantifying the distinct symptoms, thus enhancing the clinical utility of this construct in clinical practice and research., (Copyright © 2017 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities., Methods: The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs., Results: Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches., Discussion: Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention., (Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background: Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer's Research and Treatment - Alzheimer's Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described., Objective: To develop an instrument based on ISTAART-AA MBI criteria., Methods: Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults., Results: We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician., Conclusion: The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes.

Background: Goals of treating major depressive disorder (MDD) include achieving remission and avoiding relapse. It is possible that patients may have a broader view of remission than what is captured via clinician-rated scales. This patient perspective may, in turn, have an impact on treatment outcomes., Methods: The association between a broader conceptualization of remission, based on the Remission from Depression Questionnaire (RDQ) score at baseline, and being in symptomatic remission after 6 months was evaluated in subjects (N = 613) with MDD in symptomatic remission at baseline (17-item Hamilton Rating Scale for Depression [HAMD-17] ≤7). Specific aspects of depression were assessed from physician and patient perspectives as secondary endpoints. A backwards selection strategy was used to statistically model remission status and determine association of factors with potential to influence remission., Results: At month 6, after adjustment for baseline HAMD-17 score, there was no association between baseline RDQ score and symptomatic remission status (HAMD-17), relapse, composite remission status, healthcare resource utilization, or quality of life. There was no association between functional impairment scores at baseline (Sheehan Disability Scale and Social and Occupational Functioning Assessment Scale) and symptomatic remission status (HAMD-17) at month 6., Conclusions: This study indicates that RDQ-constructs are independent from symptomatic remission. Symptom severity at study entry appeared to be the only significant predictor of eventual relapse during the 6-month follow-up period. However, our results also suggest that the current definition of remission that is based on symptom reduction should be further elaborated and that alternative or additional definitions should be considered in determining remission.

Neuropsychiatric symptoms (NPS) are common in dementia and in predementia syndromes such as mild cognitive impairment (MCI). NPS in MCI confer a greater risk for conversion to dementia in comparison to MCI patients without NPS. NPS in older adults with normal cognition also confers a greater risk of cognitive decline in comparison to older adults without NPS. Mild behavioral impairment (MBI) has been proposed as a diagnostic construct aimed to identify patients with an increased risk of developing dementia, but who may or may not have cognitive symptoms. We propose criteria that include MCI in the MBI framework, in contrast to prior definitions of MBI. Although MBI and MCI can co-occur, we suggest that they are different and that both portend a higher risk of dementia. These MBI criteria extend the previous literature in this area and will serve as a template for validation of the MBI construct from epidemiologic, neurobiological, treatment, and prevention perspectives., (Copyright © 2016 The Alzheimer's Association. All rights reserved.)

Introduction: Alzheimer's disease (AD) is a major threat for the well-being of an increasingly aged world population. The physiopathological mechanisms of late-onset AD are multiple, possibly heterogeneous, and not well understood. Different combinations of variables from several domains (i.e., clinical, neuropsychological, structural, and biochemical markers) may predict dementia conversion, according to distinct physiopathological pathways, in different groups of subjects., Methods: We launched the Vallecas Project (VP), a cohort study of non-demented people aged 70-85, to characterize the social, clinical, neuropsychological, structural, and biochemical underpinnings of AD inception. Given the exploratory nature of the VP, multidimensional and machine learning techniques will be applied, in addition to the traditional multivariate statistical methods., Results: A total of 1169 subjects were recruited between October 2011 and December 2013. Mean age was 74.4 years (SD 3.9), 63.5% of the subjects were women, and 17.9% of the subjects were carriers of at least one ε4 allele of the apolipoprotein E gene. Cognitive diagnoses at inclusion were as follows: normal cognition 93.0% and mild cognitive impairment (MCI) 7.0% (3.1% amnestic MCI, 0.1% non-amnestic MCI, 3.8% mixed MCI). Blood samples were obtained and stored for future determinations in 99.9% of the subjects and 3T magnetic resonance imaging study was conducted in 89.9% of the volunteers. The cohort is being followed up annually for 4 years after the baseline., Conclusion: We have established a valuable homogeneous single-center cohort which, by identifying groups of variables associated with high risk of MCI or dementia conversion, should help to clarify the early physiopathological mechanisms of AD and should provide avenues for prompt diagnosis and AD prevention.

Aims: Pilot studies applying a humanoid robot (NAO), a pet robot (PARO) and a real animal (DOG) in therapy sessions of patients with dementia in a nursing home and a day care center., Methods: In the nursing home, patients were assigned by living units, based on dementia severity, to one of the three parallel therapeutic arms to compare: CONTROL, PARO and NAO (Phase 1) and CONTROL, PARO, and DOG (Phase 2). In the day care center, all patients received therapy with NAO (Phase 1) and PARO (Phase 2). Therapy sessions were held 2 days per week during 3 months. Evaluation, at baseline and follow-up, was carried out by blind raters using: the Global Deterioration Scale (GDS), the Severe Mini Mental State Examination (sMMSE), the Mini Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), the Apathy Scale for Institutionalized Patients with Dementia Nursing Home version (APADEM-NH), the Apathy Inventory (AI) and the Quality of Life Scale (QUALID). Statistical analysis included descriptive statistics and non-parametric tests performed by a blinded investigator., Results: In the nursing home, 101 patients (Phase 1) and 110 patients (Phase 2) were included. There were no significant differences at baseline. The relevant changes at follow-up were: (Phase 1) patients in the robot groups showed an improvement in apathy; patients in NAO group showed a decline in cognition as measured by the MMSE scores, but not the sMMSE; the robot groups showed no significant changes between them; (Phase 2) QUALID scores increased in the PARO group. In the day care center, 20 patients (Phase 1) and 17 patients (Phase 2) were included. The main findings were: (Phase 1) improvement in the NPI irritability and the NPI total score; (Phase 2) no differences were observed at follow-up.