Neuropsychiatric symptoms and ApoE genotype in older adults without dementia: a cross-sectional study.

BACKGROUND: The ApoE genotype and neuropsychiatric symptoms (NPS) are known risk factors for cognitive decline in older adults. However, the interaction between these variables is still unclear. The aim of this study was to determine the association between the presence of the ApoE ε4 allele and the occurrence of NPS in older adults without dementia. METHODS: In this cross-sectional investigation we determined the apolipoprotein E (ApoE) genotype of 74 older adults who were either cognitively normal (20.3% / Clinician Dementia Rating Scale (CDR): 0) or had mild cognitive impairment (MCI: 79.7% / CDR: 0.5). We used a comprehensive cognitive assessment protocol, and NPS were estimated by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), Mild Behavioural Impairment-Checklist (MBI-C), Hamilton Rating Scale for Depression (HAM-D), and Apathy Inventory. RESULTS: ApoE ε4 carriers had higher MBI-C total scores than ApoE ε4 noncarriers. Correlations between NPS and ApoE genotype were observed for two NPI-C domains, although in opposite directions: the ApoE ε4 allele was associated with a 1.8 unit decrease in the estimated aberrant motor disturbance score and with a 1.3 unit increase in the estimated appetite/eating disorders score. All fitted models were significant, except for the one fitted for the domain delusions from the NPI-C. Among individuals with amnestic MCI, ε4 carriers presented higher depression score (HAM-D) than noncarriers; in turn, ε4 noncarriers exhibited higher aggression score (NPI-C) than ε4 carriers. CONCLUSIONS: Our analyses showed associations between NPS and the presence of the ApoE ε4 allele in two NPI-C domains, despite the sample size. Furthermore, compared to noncarriers, the presence of the ApoE ε4 correlated positively with appetite/eating disorders and negatively with aberrant motor disturbance domain. Examination of the amnestic MCI group displayed significant, although weak, associations. Therefore, ε4 carriers exhibited higher depression scores according to the HAM-D scale compared to ε4 noncarriers. Conversely, ε4 noncarriers had higher scores in the aggression domain of the NPI-C than ε4 carriers.

Neuropsychiatric symptoms and cerebrovascular risk in non-demented elders: cross-sectional study using the mild behavioural impairment checklist (MBI-C).

BACKGROUND: Neuropsychiatric symptoms (NPS) may represent early clinical manifestations of evolving brain diseases. Studies underpin the occurrence of NPS in the context of mild cognitive impairment (MCI) and prodromal Alzheimer's disease, where symptoms referred to as 'mild behavioural impairment' (MBI) have been shown to predict conversion to dementia and to hasten cognitive/functional decline. However, the association between NPS and cerebrovascular risk factors has been poorly investigated, despite the high prevalence of the latter among individuals with MCI. The aim of the present study was to investigate the association between MBI and cerebrovascular risk in a clinical sample of non-demented elders. METHODS: Sixty-five MCI and 15 cognitively unimpaired older adults were cross-sectionally assessed with the Mild Behavioural Impairment Checklist (MBI-C), using the cut-off score > 6.5 to define positive screening. Participants were submitted to the Hachinski Ischaemic Score (HIS) to account for cerebrovascular symptoms, vascular risk, and related comorbidities. Neuroimaging scans (magnetic resonance imaging and/or 18F-fluorodeoxyglucose-positron emission tomography) and apolipoprotein E genotype were obtained. RESULTS: Positive associations were found between total MBI-C scores and increasing number of comorbidities present (0-2 comorbidities), but not with three comorbidities. Two domains of the MBI-C-impulse dyscontrol and social inappropriateness-followed the same trend of the MBI-C total score, with higher scores with the increasing numbers of comorbidities. No significant associations were found between MBI symptoms and HIS or cerebrovascular burden in neuroimaging assessment. CONCLUSION: We found weak associations between MBI-C total score and the presence of comorbidities with cerebrovascular risk, but not with structural or functional neuroimaging abnormalities or HIS. This finding may represent that the presence of comorbidities adds limited risk to the occurrence of MBI in this sample of non-demented elders.

Recommendations for the Nonpharmacological Treatment of Apathy in Brain Disorders.

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.

Noninvasive brain stimulation for behavioural and psychological symptoms of dementia: A systematic review and meta-analysis.

BACKGROUND: Pharmacological and conventional nonpharmacological treatments for behavioural and psychological symptoms of dementia (BPSD) have only modest efficacy. Furthermore, pharmacotherapy carries the risk of important side effects. Noninvasive brain stimulation (repetitive transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS)) are valuable and safe for cognitive function in Alzheimer disease (AD). However, there have been few studies, and there is no consensus, regarding the use of these techniques to treat BPSD. METHODS: We performed a systematic review of the literature and meta-analysis of studies reporting the effect of rTMS or tDCS on BPSD. RESULTS: Seven articles were included: five randomized, controlled clinical trials and two open-label clinical trials. Five studies investigated the effects of rTMS and two the effects of tDCS. Both studies using tDCS reported no evidence of efficacy on BPSD, while two of the three RCTs using rTMS found statistically significant benefits. In an exploratory meta-analysis with four of the RCT studies, we did not find evidence of efficacy of noninvasive brain stimulation techniques, with an overall effect of -0.02 (95% CI = -0.90, 0.94; I2  = 85%). However, when we used only the data from the studies that applied rTMS, we found a positive effect on BPSD, with an overall effect of -0.58 (95% CI = -1.02, -0.14; I2  = 0%). With regards to the adverse effects reported, these were mild and not clinically relevant. CONCLUSIONS: Our results establish a tendency for efficacy of rTMS protocols on BPSD, while corroborating their safety and tolerability, suggesting the need for further research.

A survey on the prevalence of apathy in elderly people referred to specialized memory centers.

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.

An intervention to reduce neuropsychiatric symptoms and caregiver burden in dementia: Preliminary results from a randomized trial of the tailored activity program-outpatient version.

OBJECTIVE: To evaluate the efficacy of the tailored activity program-outpatient version (TAP-O) and to reduce neuropsychiatric symptoms (NPS) in patients with dementia and caregiver burden compared with a control group (psychoeducation intervention). METHODS: Twenty-one persons with dementia and their caregivers were recruited and randomized. The intervention group received TAP-O, designed for outpatients with dementia and their caregivers. TAP-O consisted of eight sessions in which an occupational therapist assessed the patient's abilities and interests; prescribed tailored activities; and educated caregivers about dementia, NPS, and how to implement meaningful activities in the daily routine. The control group received eight sessions of a psychoeducation intervention about dementia and NPS. RESULTS: Compared with controls, patients receiving TAP-O had a significant decrease in hallucination (P = 0.04), agitation (P = 0.03), anxiety (P = 0.02), aggression (P = 0.01), sleep disorder (P = 0.02), aberrant motor behavior (P = 0.02), and in caregiver burden (P = 0.003). CONCLUSIONS: Findings suggest that TAP-O may be an effective nonpharmacological strategy to reduce NPS of outpatients with dementia and to minimize caregiver burden.

Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder.

OBJECTIVES: Cognitive decline is part of the long-term outcome for many individuals with bipolar disorder (BD). The ε4 allele (APOE*4) of apolipoprotein E (APOE) is a well-established risk factor for dementia in Alzheimer's disease (AD). However, its contribution to the risk of cognitive deterioration in BD has not yet been determined. Our aim was to analyze the APOE genotype association with cognitive status in a sample of older adults with BD and compare this to the association in individuals with AD, individuals with mild cognitive impairment (MCI), and healthy controls. METHODS: Participants (n = 475) were allocated to four groups: individuals with BD (n = 77), those with AD (n = 211), those with MCI (n = 43), and healthy controls (n = 144) according to clinical and neuropsychological assessment. APOE was genotyped by real-time polymerase chain reaction. Tukey's honest significant difference test and Pearson's chi-squared test were used to compare diagnostic groups. RESULTS: Subjects with BD were similar to controls with respect to the distribution of the APOE genotype (p = 0.636) and allele frequencies (p = 0.481). Significant differences were found when comparing the AD group to the BD group or to controls (APOE genotype: p < 0.0002; allele frequencies: p < 0.001). APOE*4 was significantly increased in the AD group when compared to the BD group (p = 0.031) and controls (p < 0.0001). The cognitively impaired BD subgroup (Mini-Mental State Examination below the cutoff score and/or neuropsychological assessment compatible with MCI) had a statistically significant higher frequency of APOE*2 compared to the AD group (p = 0.003). CONCLUSIONS: APOE*4 is not associated with the diagnosis of BD and does not impact the occurrence of dementia in BD. Given the distinct clinical and biological features of cognitive impairment in BD, we hypothesized that dementia in BD is unrelated to AD pathological mechanisms.

Cognitive impairment in late-life bipolar disorder is not associated with Alzheimer's disease pathological signature in the cerebrospinal fluid.

OBJECTIVES: Cognitive impairment is a common feature of late-life bipolar disorder (BD). Yet, there is limited information on the biological mechanisms associated with this process. It is uncertain whether cognitively impaired patients with BD may present the Alzheimer's disease (AD) bio-signature in the cerebrospinal fluid (CSF), defined as a combination of low concentrations of the amyloid-beta peptide (Aß1-42 ) and high concentrations of total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau). In this study, we sought to determine whether cognitive impairment in elderly patients with BD is associated with the AD CSF bio-signature. METHODS: Seventy-two participants were enrolled in the study. The test group comprised older adults with BD and mild cognitive impairment (BD-MCI; n = 16) and the comparison groups comprised patients with dementia due to AD (n = 17), patients with amnestic MCI (aMCI; n = 14), and cognitively healthy older adults (control group; n = 25). CSF samples were obtained by lumbar puncture and concentrations of Aß1-42 , T-tau and P-tau were determined. RESULTS: CSF concentrations of all biomarkers were significantly different in the AD group compared to all other groups, but did not differentiate BD-MCI subjects from aMCI subjects and controls. BD-MCI patients had a non-significant reduction in CSF Aß1-42 compared to controls, but this was still higher than in the AD group. Concentrations of T-tau and P-tau in BD-MCI patients were similar to those in controls, and significantly lower than those in AD. CONCLUSIONS: Cognitively impaired patients with BD do not display the so-called AD bio-signature in the CSF. We therefore hypothesize that cognitive deterioration in BD is not associated with the classical pathophysiological mechanisms observed in AD, i.e., amyloid deposition and hyperphosphorylation of microtubule-associated tau protein.

Association of neuropsychiatric syndromes with global clinical deterioration in Alzheimer's disease patients.

BACKGROUND: Data on the relationship between behavioral disturbances in Alzheimer's disease (AD) and global clinical deterioration is still controversial. The purpose of this study was to explore potential correlations of neuropsychiatric syndromes with global clinical deterioration in patients with AD, with particular consideration on severity levels of dementia. METHODS: AD patients (n = 156) aged 76.7 years from Brazilian clinical centers were assessed to diagnose the five neuropsychiatric syndromes measured by the Neuropsychiatric Inventory-Clinician rating scale (NPI-C): psychosis, agitation, affective, apathy, and sleep. These syndromes were then analyzed for their correlation with the Global Deterioration Scale (GDS). To analyze the association of neuropsychiatric syndromes with the GDS, considering the total sample and patients grouped by dementia severity levels, we applied the coefficient of multiple correlation (Ryy), adjusted multiple linear regression, and the coefficient of determination (R2yx). We tested the significance of correlation coefficients using the Student t-test for simple correlations (a single independent variable) and analysis of variance (ANOVA) for multiple correlations. ANOVA was also used to compare means of demographic and some clinical variables at different levels of dementia. RESULTS: For the total sample, apathy and agitation syndromes were most strongly correlated (0.74; 0.72, respectively) with clinical deterioration according to the GDS, followed by psychosis (0.59), affective (0.45), and sleep syndromes (0.34). Agitation significantly correlated with mild and moderate dementia (CDR 1: 0.45; and CDR 2: 0.69, respectively). At CDR 2, agitation and affective syndromes were most strongly correlated (0.69; 0.59, respectively) with clinical deterioration while at CDR 3, the apathy syndrome was most strongly correlated with clinical deterioration (0.52). CONCLUSIONS: Agitation, apathy, and affective disorders were the syndromes most strongly correlated with global deterioration in AD patients, becoming more evident at severe stages of dementia.

Variability in Obstacle Clearance May (Not) Indicate Cognitive Disorders in Alzheimer Disease.

The aim of this study was to investigate obstacle clearance and its variability in individuals with Alzheimer dementia (AD) as well as healthy elderly individuals while they approached and crossed an obstacle in their path. Fifteen people with AD and 15 age-matched/sex-matched healthy individuals (control group) participated in this study. Clinical assessment of both groups was performed by a neuropsychiatrist. Spatial-temporal parameters of 5 trials of unobstructed walking and 5 trials of obstacle crossing during walking (approach and crossing phases) were measured using a 3-dimensional optoelectronic system. The results indicated that individuals with AD showed higher variability in the approach phase for stride length and the horizontal distance from their trailing limb foot to the obstacle. However, their gait variability in the crossing phase was similar to the control group. In addition, the individuals with AD were found to walk slowly and with a short stride length in both conditions. In conclusion, individuals with AD had increased gait variability while approaching an obstacle during walking, indicating a deficit in planning to avoid obstacles that could be related to cognitive disorders. However, gait variability during the crossing phase may not be indicative of cognitive disorders in AD.

Caregiver report versus clinician impression: disagreements in rating neuropsychiatric symptoms in Alzheimer's disease patients.

BACKGROUND: The measurement of neuropsychiatric symptoms (NPS) in dementia is often based on caregiver report. Challenges associated with providing care may bias the caregiver's recognition and reporting of symptoms. Given potential problems associated with caregiver report, clinicians may improve measurement by drawing from a wider array of available data and by applying clinical judgment. OBJECTIVE: The objective of this study is to evaluate potential disagreements between caregiver report and clinician impression when rating psychopathological manifestations from the same patient with dementia. METHODS: Three hundred twelve participants (156 patients with Alzheimer's disease [AD] and 156 caregivers) were studied using the Neuropsychiatric Inventory-Clinician Rating Scale. We considered disagreement to be present when caregiver ratings were significantly higher or lower (p < 0.05) than NPS ratings by clinicians of the same patient. To evaluate whether disagreements were related to dementia severity, we repeated comparisons across levels defined by the clinical dementia rating. RESULTS: The most common disagreements involved ratings of agitation, depression, anxiety, apathy, irritability, and aberrant motor behavior especially in patients with mild dementia. There were fewer discrepancies in moderate or severe dementia. The most consistent disagreements involved global ratings of depression where caregiver scores ranged from +22.5 higher to -4.5 lower than clinician rating. CONCLUSIONS: Caregivers may have incomplete perception of patient NPS mainly in mild dementia. NPS ratings might be confounded by cultural beliefs, sometimes leading caregiver to interpret symptoms as part of "normal" aging.

Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network.

Neuropsychiatric syndromes are highly prevalent in Alzheimer's disease (AD), but their neurobiology is not completely understood. New methods in functional magnetic resonance imaging, such as intrinsic functional connectivity or "resting-state" analysis, may help to clarify this issue. Using such approaches, alterations in the default-mode and salience networks (SNs) have been described in Alzheimer's, although their relationship with specific symptoms remains unclear. We therefore carried out resting-state functional connectivity analysis with 20 patients with mild to moderate AD, and correlated their scores on neuropsychiatric inventory syndromes (apathy, hyperactivity, affective syndrome, and psychosis) with maps of connectivity in the default mode network and SN. In addition, we compared network connectivity in these patients with that in 17 healthy elderly control subjects. All analyses were controlled for gray matter density and other potential confounds. Alzheimer's patients showed increased functional connectivity within the SN compared with controls (right anterior cingulate cortex and left medial frontal gyrus), along with reduced functional connectivity in the default-mode network (bilateral precuneus). A correlation between increased connectivity in anterior cingulate cortex and right insula areas of the SN and hyperactivity syndrome (agitation, irritability, aberrant motor behavior, euphoria, and disinhibition) was found. These findings demonstrate an association between specific network changes in AD and particular neuropsychiatric symptom types. This underlines the potential clinical significance of resting state alterations in future diagnosis and therapy.

Validation of the Brazilian version of the apathy inventory.

BACKGROUND: Apathy is a frequent neuropsychiatric condition in neurodegenerative disorders, depression, and often in mild cognitive impairment. The Apathy Inventory (AI) is a reliable instrument for improving the accuracy of the apathy diagnosis. The aim was to establish the validity of the Apathy Inventory for the Brazilian community. METHODS: We established the concurrent validity, internal consistency, inter-rater reliability, and the sensitivity and specificity of AI for the Brazilian community in a cohort of 175 individuals with Alzheimer's disease, Parkinson's disease, depression, mild cognitive impairment, and healthy controls. The three dimensions of the AI (emotional blunting, lack of initiative, and lack of interest) were compared with the Apathy domain of the Neuropsychiatric Inventory-Clinician rating scale (NPI-C) in an independent scheme. RESULTS: The analyses demonstrated high correlation coefficients in AI's individual dimensions and in AI-total score (F = 0.965). Concerning the NPI-C/Apathy domain, intra-class correlation coefficients were also high (F = 0.977). Concurrent validity was high according to both raters on AI dimensions × NPI-C/Apathy domain and regarding total score (rater 1: rho = 0.956 vs. rater 2: rho = 0.970). The internal consistency of the AI was also high concerning the AI's individual dimensions and total score (rater 1: 0.945 vs. rater 2: 0.958). CONCLUSION: We observed high internal consistency, high concurrent validity, and inter-rater reliability of the Apathy Inventory. In addition, we found that its sensitivity and specificity were high. We suggest that the Brazilian version of the Apathy Inventory would be an appropriate instrument to identify the apathy syndrome in Brazilian patients.

The Brazilian version of the Neuropsychiatric Inventory-Clinician rating scale (NPI-C): reliability and validity in dementia.

BACKGROUND: Patients with dementia may be unable to describe their symptoms, and caregivers frequently suffer emotional burden that can interfere with judgment of the patient's behavior. The Neuropsychiatric Inventory-Clinician rating scale (NPI-C) was therefore developed as a comprehensive and versatile instrument to assess and accurately measure neuropsychiatric symptoms (NPS) in dementia, thereby using information from caregiver and patient interviews, and any other relevant available data. The present study is a follow-up to the original, cross-national NPI-C validation, evaluating the reliability and concurrent validity of the NPI-C in quantifying psychopathological symptoms in dementia in a large Brazilian cohort. METHODS: Two blinded raters evaluated 312 participants (156 patient-knowledgeable informant dyads) using the NPI-C for a total of 624 observations in five Brazilian centers. Inter-rater reliability was determined through intraclass correlation coefficients for the NPI-C domains and the traditional NPI. Convergent validity included correlations of specific domains of the NPI-C with the Brief Psychiatric Rating Scale (BPRS), the Cohen-Mansfield Agitation Index (CMAI), the Cornell Scale for Depression in Dementia (CSDD), and the Apathy Inventory (AI). RESULTS: Inter-rater reliability was strong for all NPI-C domains. There were high correlations between NPI-C/delusions and BPRS, NPI-C/apathy-indifference with the AI, NPI-C/depression-dysphoria with the CSDD, NPI-C/agitation with the CMAI, and NPI-C/aggression with the CMAI. There was moderate correlation between the NPI-C/aberrant vocalizations and CMAI and the NPI-C/hallucinations with the BPRS. CONCLUSION: The NPI-C is a comprehensive tool that provides accurate measurement of NPS in dementia with high concurrent validity and inter-rater reliability in the Brazilian setting. In addition to universal assessment, the NPI-C can be completed by individual domains.

New treatment strategies for Alzheimer's disease: is there a hope?

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, and corresponds to the most common cause of dementia worldwide. Although not fully understood, the pathophysiology of AD is largely represented by the neurotoxic events triggered by the beta-amyloid cascade and by cytoskeletal abnormalities subsequent to the hyperphosphorylation of microtubule-associated Tau protein in neurons. These processes lead respectively to the formation of neuritic plaques and neurofibrillary tangles, which are the pathological hallmarks of the disease. Clinical benefits of the available pharmacological treatment for AD with antidementia drugs (namely cholinesterase inhibitors and memantine) are unquestionable, although limited to a temporary, symptomatic support to cognitive and related functions. Over the past decade, substantial funding and research have been dedicated to the search and development of new pharmaceutical compounds with disease-modifying properties. The rationale of such approach is that by tackling key pathological processes in AD it may be possible to attenuate or even change its natural history. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and Tau pathology in AD, focusing on pharmaceutical compounds undergoing phase 2 and phase 3 randomized controlled trials.

Electroconvulsive therapy for treating patients with agitation and related behavioral disorders due to dementia: a systematic review.

Behavioral disturbances are clinically relevant in patients with dementia, and pharmacological regimens to mitigate these symptoms have provided limited results. Proven to be effective in several psychiatric conditions, electroconvulsive therapy is a potentially beneficial strategy for treating severe agitation due to dementia. Objective: This review aimed to examine the publications on the efficacy, safety and tolerability of electroconvulsive therapy in treating patients with agitation due to dementia. Methods: We performed a systematic analysis on the electroconvulsive therapy to treat patients with dementia and coexisting severe agitation. Articles were classified according to the level of evidence based on methodological design. Patients received an acute course of electroconvulsive therapy, often followed by maintenance intervention. Results: We selected 19 studies (156 patients; 64.1% women; 51-98 years old), which met the inclusion criteria: one case-control study by chart analysis (level of evidence 2); one open-label study (level of evidence 3); three historical/retrospective chart analyses (level of evidence 4); and 14 case series/reports (level of evidence 5). No randomized, sham-controlled clinical trials (level of evidence 1) were identified, which represents the main methodological weakness. Some patients had postictal delirium, cardiovascular decompensation and cognitive changes, lasting for a short time. Conclusions: Overall, patients achieved significant improvement in agitation. However, the main finding of the present review was the absence of methodological design based on randomized and sham-controlled clinical trials. Despite methodological limitations and side effects requiring attention, electroconvulsive therapy was considered a safe and effective treatment of patients with severe agitation and related behavioral disorders due to dementia.

Distúrbios comportamentais são clinicamente relevantes em pacientes com demência, e regimes farmacológicos para mitigar esses sintomas têm proporcionado resultados limitados. Comprovadamente eficaz em diversas condições psiquiátricas, a eletroconvulsoterapia é uma estratégia potencialmente benéfica para o tratamento de pacientes com agitação grave na demência. Objetivos: Esta revisão examina as publicações sobre eficácia, segurança e tolerabilidade da eletroconvulsoterapia no tratamento de pacientes com agitação na demência. Métodos: Realizamos uma análise sistemática da eletroconvulsoterapia no tratamento de pacientes com demência e agitação grave. Os artigos foram classificados quanto ao nível de evidência com base no delineamento metodológico. Os pacientes receberam um curso agudo de eletroconvulsoterapia, frequentemente seguido de manutenção. Resultados: Foram selecionados 19 estudos (156 pacientes; 64,1% mulheres; 51­98 anos): um estudo caso-controle desenvolvido com base na análise de prontuários (nível de evidência 2); um estudo aberto (nível de evidência 3); três estudos de análise retrospectiva de prontuários (nível de evidência 4); e 14 séries/relatos de casos (nível de evidência 5). Não foram identificados ensaios clínicos randomizados e controlados com placebo (nível de evidência 1), fator que representa a principal fragilidade metodológica. No entanto, o principal achado da presente revisão consistiu na ausência de desenho metodológico baseado em ensaios clínicos randomizados e controlados com placebo. Em geral, os efeitos colaterais foram transitórios e bem tolerados. Alguns pacientes apresentaram delirium pós-ictal, descompensação cardiovascular e alterações cognitivas por períodos breves. Conclusões: No geral, os pacientes obtiveram melhora significativa na agitação. No entanto, o principal achado da presente revisão foi a ausência de delineamento metodológico baseado em ensaios clínicos randomizados e controlados com placebo. Apesar das limitações metodológicas e dos efeitos adversos, a eletroconvulsoterapia foi considerada um tratamento seguro e eficaz em pacientes com agitação grave e com outros distúrbios comportamentais clinicamente relevantes na demência.

Functional dependence and caregiver burden in Alzheimer's disease: a controlled trial on the benefits of motor intervention.

BACKGROUND: Cognitive decline has a negative impact on functional activities in Alzheimer's disease. Investigating the effects of motor intervention with the intent to reduce the decline in functionality is an expected target for patients and caregivers. The aim of this study was to verify if a 6-month motor intervention programme promoted functionality in Alzheimer's patients and attenuated caregivers' burden. METHODS: The sample comprised 32 community patients with Alzheimer's disease and their 32 respective caregivers. Patients were divided into two groups: 16 participated in the motor intervention programme and 16 controls. Subjects performed 60 minutes of exercises, three times per week during the 6-month period, to improve flexibility, strength, agility and balance. Caregivers followed the procedures with their patients during this period. Functionality was evaluated by the Berg Functional Balance Scale and the Functional Independence Measure. Caregivers completed the Neuropsychiatric Inventory Caregiver Distress Scale and the Zarit Carer Burden Scale. Two-way ANOVA was used to verify the interaction between time (pre- and post-intervention) and the motor intervention program. RESULTS: While patients in the motor programme preserved their functionality, as assessed by the Functional Independence Measure, the controls suffered a relative decline (motor intervention group: from 109.6 to 108.4 vs controls: from 99.5 to 71.6; P= 0.01). Patients from motor intervention also had better scores than the controls on functional balance assessed by Berg scale (F: 22.2; P= 0.001). As assessed by the Neuropsychiatric Inventory and Zarit scale, burden was reduced among caregivers whose patients participated in the motor intervention programme compared with caregivers whose patients did not participate in this programme (Neuropsychiatric Inventory, caregiver's part: F: 9.37; P= 0.01; Zarit: F: 11.28; P= 0.01). CONCLUSION: Patients from the motor intervention group showed reduced functional decline compared to the controls, and there was an associated decrease in caregivers' burden.

Decision tree-based classification as a support to diagnosis in the Alzheimer's disease continuum using cerebrospinal fluid biomarkers: insights from automated analysis.

OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers add accuracy to the diagnostic workup of cognitive impairment by illustrating Alzheimer's disease (AD) pathology. However, there are no universally accepted cutoff values for the interpretation of AD biomarkers. The aim of this study is to determine the viability of a decision-tree method to analyse CSF biomarkers of AD as a support for clinical diagnosis. METHODS: A decision-tree method (automated classification analysis) was applied to concentrations of AD biomarkers in CSF as a support for clinical diagnosis in older adults with or without cognitive impairment in a Brazilian cohort. In brief, 272 older adults (68 with AD, 122 with mild cognitive impairment [MCI], and 82 healthy controls) were assessed for CSF concentrations of Aß1-42, total-tau, and phosphorylated-tau using multiplexed Luminex assays; biomarker values were used to generate decision-tree algorithms (classification and regression tree) in the R statistical software environment. RESULTS: The best decision tree model had an accuracy of 74.65% to differentiate the three groups. Cluster analysis supported the combination of CSF biomarkers to differentiate AD and MCI vs. controls, suggesting the best cutoff values for each clinical condition. CONCLUSION: Automated analyses of AD biomarkers provide valuable information to support the clinical diagnosis of MCI and AD in research settings.

Treatment of dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

There is currently no cure for neurodegenerative or vascular dementias, but some pharmacological and non-pharmacological interventions may contribute to alleviate symptoms, slow disease progression and improve quality of life. Current treatment approaches are based on etiology, symptom profile and stage of dementia. This manuscript presents recommendations on pharmacological and non-pharmacological treatments of dementia due to Alzheimer's disease, vascular cognitive impairment, frontotemporal dementia, Parkinson's disease dementia, and dementia with Lewy bodies.

Atualmente não há tratamento curativo para as demências neurodegenerativas ou para a demência vascular, mas algumas intervenções farmacológicas e não farmacológicas podem contribuir para aliviar os sintomas, retardar a progressão da doença e melhorar a qualidade de vida. As abordagens terapêuticas atuais são baseadas na etiologia, no perfil dos sintomas e no estágio da demência. Neste artigo apresentamos recomendações sobre os tratamentos farmacológicos e não farmacológicos da demência devida à doença de Alzheimer, comprometimento cognitivo vascular, demência frontotemporal, demência da doença de Parkinson e demência com corpos de Lewy.