Paulo Renato Canineu

A controlled clinical trial on the effects of motor intervention on balance and cognition in institutionalized elderly patients with dementia

Purpose: To analyse the effects of two interventions on the cognition and balance of institutionalized elderly people with mixed dementia. Methods: Fifty-four participants were allocated into three groups. Group 1 was assisted by an interdisciplinary programme comprising physiotherapy, occupational therapy and physical education. A physiotherapist alone carried out the intervention in group 2. Group 3 was considered as control. Assessors were blinded to guarantee the absence of bias. Cognitive functions were analysed with the Mini-Mental State Examination and the Brief Cognitive Screening Battery. Balance was assessed with the Berg Balance Scale and the Timed Get-Up-and-Go Test. Multiple analysis of variance (MANOVA) was used to test possible main effects of the interventions. Results: The results showed benefits on the balance of subjects in both groups 1 (F=3.9, P<0.05) and 2 (F=3.1, P<0.05), compared with group 3. MANOVA did not indicate benefits on the cognitive functions between groups 1 and 3 (F=1.1, P>0.05) and groups 2 and 3 (F=1.6, P>0.05). However, univariate analysis indicated some benefits of the interdisciplinary intervention on two specific domains measured by the Brief Cognitive Screening Battery (F=26.5, P<0.05; F=4.4, P<0.05). Conclusion: Six months of multidisciplinary or physiotherapeutic intervention were able to improve a persons balance. Although global cognition did not improve through treatment, when the intervention was carried out on a multidisciplinary basis we observed an attenuation in the decline of global cognition on two specific cognitive domains. Exercises applied in different contexts may have positive outcomes for people with dementia.

Neurobiological Correlates of Apathy in Alzheimer's Disease and Mild Cognitive Impairment: A Critical Review

BACKGROUND In Alzheimers disease (AD) and mild cognitive impairment (MCI), apathy was associated with faster clinical deterioration. Studies involving neurobiological correlates such as neuroimaging and biomarkers have presented distinct results. OBJECTIVE This work aimed to analyze neurobiological correlates of apathy in AD and MCI based on evidence from the literature involving brain neuroimaging and classical AD biomarkers. METHODS This review comprised studies published from 1996 to June 2013 from the Pubmed database. The studies were divided into Part I (neuroimaging) and Part II (chemical biomarkers). The analysis included the identification of brain regions involved and assessments of apathy and cognition. We found 68 publications: 33 fulfilled the inclusion criteria; 35 were case reports or were not clear about the measurements of apathy and were excluded. From the 33 eligible studies, 26 were classified into part I, and 7 studies were included in part II. We created specific criteria to appropriately classify the quality level of each publication. RESULTS Prefrontal regions and the anterior cingulate were the leading brain areas associated with apathy in AD and MCI. Other regions, including cortical and subcortical structures, have also been implicated in this syndrome. CONCLUSIONS Abnormalities in frontal regions (associated with impairments in planning and decision making) and anterior cingulate (related to emotional blunting and loss of motivation) were the crucial structures associated with apathy in AD and MCI.

Neuropsychiatric symptoms in the prodromal stages of dementia

Purpose of review To critically discuss the neuropsychiatric symptoms in the prodromal stages of dementia in order to improve the early clinical diagnosis of cognitive and functional deterioration. Recent findings Current criteria for cognitive syndrome, including Alzheimers disease, comprise the neuropsychiatric symptoms in addition to cognitive and functional decline. Although there is growing evidence that neuropsychiatric symptoms may precede the prodromal stages of dementia, these manifestations have received less attention than traditional clinical hallmarks such as cognitive and functional deterioration. Depression, anxiety, apathy, irritability, agitation, sleep disorders, among other symptoms, have been hypothesized to represent a prodromal stage of dementia or, at least, they increase the risk for conversion from minor neurocognitive disorder to major neurocognitive disorder. Longitudinal investigations have provided increased evidence of progression to dementia in individuals with minor neurocognitive disorder when neuropsychiatric symptoms also were present. Summary Although neuropsychiatric symptoms are strongly associated with a higher risk of cognitive and functional deterioration, frequently the clinician does not acknowledge these conditions as increasing the risk of dementia. When the clinician accurately diagnoses neuropsychiatric symptoms in the prodromal stage of dementia, he could early establish appropriate treatment and, may be, delay the beginning of clinical and functional deterioration.

Anti-dementia medications: current prescriptions in clinical practice and new agents in progress

Almost three decades after the publication of the first clinical studies with tacrine, the pharmacological treatment of Alzheimer’s disease (AD) remains a challenge. Randomized clinical trials have yielded evidence of significant – although modest and transient – benefit from cholinergic replacement therapy for people diagnosed with AD, and disease modification with antidementia compounds is still an urgent, unmet need. The natural history of AD is very long, and its pharmacological treatment must acknowledge different needs according to the stage of the disease process. Cognitive and functional deterioration evolves gradually since the onset of clinical symptoms, which may be preceded by several years or perhaps decades of silent, presymptomatic neurodegeneration. Therefore, the pharmacological treatment of AD must ideally comprise both a symptomatic effect to preserve or improve cognition and a disease-modifying effect to tackle the progression of the pathological process. Primary prevention is the ultimate goal, should these strategies be delivered to patients with preclinical AD. In this article, we briefly address the pharmaceutical compounds that are currently used for the symptomatic treatment of AD and discuss the ongoing strategies designed to modify its natural course.

Safety limits of antidepressant use plus combinations: focus on cardiovascular function

BACKGROUND Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. OBJECTIVES To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities. METHOD Studies were included in the review according to the following criteria: a) clinical trials (placebo-controlled or not) or case reports; b) short- or long-term interventions with antidepressants; c) prescription of newer generation antidepressants as first-line treatment; d) samples of adult or adult-old patients. From a total of 301 articles addressing the association between antidepressants and cardiovascular adverse events as primary or secondary outcomes, we selected 30 controlled clinical trials and 10 case reports. RESULTS In most clinical studies, the effects of antidepressants on cardiac function are usually computed as secondary outcome variables, however with limited information. Conversely, case reports tend to present more comprehensive sets of clinical and laboratorial parameters, but the generalization of such data is limited by the small number of observations. The occurrence of QTc prolongation (with increased risk of torsade de pointes) has been reported. Aging, higher dosages of antidepressants, drug interaction, and pre-existing cardiovascular comorbidities were found as risk factors for the aforementioned cardiovascular and ECG abnormalities. CONCLUSION Prescribing antidepressants requires caution given their potential impact on cardiac function, and the clinician should carefully monitor cardiovascular and ECG parameters particularly in cases with underlying heart disease.

ARE CEREBROSPINAL FLUID BIOMARKERS A USEFUL TOOL TO DISCRIMINATE PATIENTS WITH MILD COGNITIVE IMPAIRMENT FROM HEALTHY INDIVIDUALS WITH NO COGNITIVE DETERIORATION

tial correlations between intrinsic connectivity network and cognitive domains adjusted for age gender and education are depicted. All correlations are significant (P<0.05) except for the VIS correlation to recognition memory(). D1⁄4 significant (P<0.05) higher z-score than other networks in the same group with lower z-scores. Cyan: SMN, Somatomotor Network; Purple: VIS, Visual network; Dark blue: LIN, Limbic Network; Pink: VAN, Ventral Attention; Green: DAN, Dorsal Attention; Yellow: FPN, Frontoparietal Network; Red: DMN, Default Mode Network; TMT B: Trail Making Test B; TMT B min A: Trail Making test A subtracted from TMT B. Figure 1. Greymatter atrophy within intrinsic connectivity networks. Mean and standard deviations of z-scores of grey matter atrophy are depicted within the different intrinsic connectivity networks for each AD stage. All z-scores are significant (* p<0.05) except for those in the amyloid-positive control group (CN+). D1⁄4 significant (p<0.05) higher z-score than all other networks in the same group with lower z-scores. CN-, amyloid-negative cognitively normal control group; CN+, amyloid-positive cognitively normal control group; EMCI+, group of amyloid-positive subjects with early mild cognitive impairment; LMCI+, group of amyloid-positive subjects with late mild cognitive impairment; AD+, group of amyloid-positive subjects diagnosed with Alzheimer’s disease dementia. Cyan: SMN, Somatomotor Network; Purple: VIS, Visual network; Dark blue: LIN, Limbic Network; Pink: VAN, Ventral Attention; Green: DAN, Dorsal Attention; Yellow: FPN, Frontoparietal Network; Red: DMN, Default Mode Network. Poster Presentations: Tue P1056

DEPRESSION AND CEREBROSPINAL FLUID BIOMARKERS OF ALZHEIMER’S PATHOLOGY IN MILD COGNITIVE IMPAIRMENT

distribution. Seventeen participants exhibited anterior dominant pattern (SVCI_A group), while 28 participants showed posterior dominant pattern (SVCI_P group). Results: The SVCI_A group showed higher frontal/global standardizes uptake value ratio (SUVR) 1.05 6 0.04 versus 0.98 6 0.04, p<0.001) while the SVCI_P group greater occipital/global (0.94 6 0.05 versus 1.05 6 0.08, p<0.001) SUVR ratio. The SVCI_A group was more likely to have APOE4 than the SVCI_P group. (70.6% versus 32.1%, p1⁄40.012) There were no significant differences of any cognitive domains between two groups. The frequencies of strictly lobar MBs or CSS tended to be higher in SVCI_P group than SVCI_A group, although there were also no statistical significances (strictly lobar CMBs: 17.9% versus 0.0%, p1⁄40.281; CSS: 14.3% versus 5.9%, p1⁄40.135). The SVCI_P group was more likely to have CAA patients (25.0% versus 5.9%, p1⁄40.132) Conclusions:Our findings suggested that SVCI with Ab (+) might be classified into anterior predominant amyloid and posterior predominant amyloid groups, which may reflect their underlying pathomechanisms.

IS THE CAMBRIDGE COGNITIVE TEST (CAMCOG) A USEFUL TOOL TO PREDICT THE PATHOLOGICAL STATUS OF CEREBROSPINAL FLUID IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT (MCI)

(typing) a text based upon presented images. A randomised set of 50 validated images was created for this purpose; the images belonging to two categories: living & non-living. Firstly, the participants (n1⁄440 healthy elderly) performed a typing task, which provided information about the typing speed of each individual. Secondly, two narrative writing tasks were carried out, one simple and one complex. The data were collected with the keystroke logging program Inputlog, which logs and time stamps keystroke activity to reconstruct and describe text production processes. The data were analysed using a selection of writing process and product variables, such as general writing process measures, detailed pause analysis, linguistic analysis and text length. The intrapersonal interkey transition times from the typing task were taken into account as a covariate. Results:The texts from the narrative tasks were significantly longer compared to previous studies, providing sufficient text and process data for analyses. The healthy elderly did take significantly more time to produce the complex than the simple text. Nevertheless, the number of words per minute remained comparable between simple and complex. The pauses within and before words varied, even when taking personal typing abilities (obtained by the typing task) into account. Conclusions:Neuropsychological language test can be used to characterise cognitive decline upon aging. Previous studies have already revealed that there are difference between DAT patients and cognitive healthy elderly on a number of key variables. Since the healthy elderly had no difficulty producing a text of significant length, the narrative writing tasks can be used for process analyses to compare cognitive decline in healthy aging and Alzheimer’s disease.