New anti-Alzheimer drugs from biodiversity: the role of the natural acetylcholinesterase inhibitors

Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays, drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD, and natural products have played an important alternative role in the research for new acetylcholinesterase inhibitors, as exemplified through the discovery of galantamine. This profile conducts us to give in this paper an overview relating the several classes of natural products with anti-cholinesterasic activity as potential templates to the design of new selective and powerful anti-Alzheimer drugs.

Oral health of Alzheimer's patients in Sao Jose dos Campos, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Produtos naturais como candidatos a fármacos úteis no tratamento do mal de Alzheimer

Alzheimer's disease (AD) is a progressive neurodegenerative pathology with severe economic and social impact. There is currently no cure, although cholinesterase inhibitors provide effective temporary relief of symptoms in some patients. Nowadays drug research and development are based on the cholinergic hypothesis that supports the cognition improvement by regulation of the synthesis and release of acetylcholine in the brain. There are only four commercial medicines approved for treatment of AD and natural products have played an important role in the research for new acetylcholinesterase inhibitors.

Influencia de la actividad física en la enfermedad de Alzheimer: un caso clínico

Alzheimer's dementia (AD) is a neurodegenerative disorder that causes motor and cognitive decline. The aim of this study was to analyze the influence of a specific physical activity program on the cognitive, depressive symptoms and functional capacity of patients with diagnosis of probable AD. The subject, a 79-year old woman, participated in this program for three months, with 50 min sessions three times a week. The instruments used were the Cambridge Cognitive Examination; the Geriatric Depression Scale; and the Battery of the American Alliance for Health Physical Education, Recreation and Dance. The results in relationship with the depressive symptoms and functional capacity were significantly positive. There were no changes in regards to the patient's cognitive functions. In conclusion, this physical activity program seems to be an important part of the treatment for patients with AD, as it improves the functional capacity and also stimulates cognitive tasks. © 2008 Asociación Española de Fisioterapeutas.

Apatia na doença de alzheimer: Contribuição para uma visão clínica da progressão da demência

In addition to cognitive impairment, apathy is increasingly recognized as an important neuropsychiatric syndrome in Alzheimer's disease (AD). Aims: To identify the relationship between dementia severity and apathy levels, and to discuss the association of this condition with other psychopathological manifestations in AD patients. Methods: This study involved 15 AD patients (mean age: 77 years; schooling: 4.9 years), with mild, moderate and severe dementia, living in Rio Claro S P, Brazil. Procedures included evaluation of cognitive status by the Mini-Mental State Examination, Clinical Dementia Rating, and Global Deterioration Scale. Apathy syndrome was assessed by the Apathy Evaluation Scale and Neuropsychiatric Inventory (NPI-apathy domain). Other psychopathological manifestations such as depression were also considered. Results: Patients with more severe dementia presented higher levels of apathy, reinforcing the hypothesis that apathy severity aggravates as the disease progresses. Using the Spearman coefficient correlation an association was identified between the MMSE and Apathy Evaluation Scale (r=0.63; p=0.01), and also between the MMSE and NPI-apathy domain (r=0.81; p=0.01). Associations were also found between the Global Deterioration Scale and Apathy Evaluation Scale (r=0.58; p=0.02), and between the Global Deterioration Scale and NPI-apathy domain (r=0.81; p=0.01). Conclusions: Apathy is a distinct syndrome among patients with AD and increases with global deterioration.

Oral health of the elderly with Alzheimer's disease

Objective: The objective of this study was to describe the oral health of elderly people diagnosed with Alzheimer's disease (AD). Study Design: Thirty elderly subjects with AD (mild, moderate, and severe) and 30 without AD (controls) were included in the study. Volunteer-reported oral health data were collected using the General Oral Health Assessment Index (GOHAI). Demographic and oral characteristics were assessed, including the number of natural teeth; number of decayed, missing, and filled teeth (DMTF); oral health index (OHI); removable prosthesis conditions; and oral pathologies. Results: GOHAI values were similar for both groups. Compared with the controls, the subjects with AD had a higher age, DMTF, OHI, and number of oral pathologies and a lower educational level and number of natural teeth. Conclusions: Elderly subjects with AD had poorer oral health than those without the disease. Despite the positive self-perception of their oral health, the oral health of subjects with AD tended to decline as their disease progressed. © 2012 Elsevier Inc.

Apatia, funções cognitivas e funcionalidade motora em idosos com doença de Alzheimer

The aims of this study were to characterize the presence of apathy in patients with AD, determine the relationship between apathy, motor function and cognitive function, and to verify differences among patients stratified by level of apathy in relation to cognitive and motor abilities. Methods: A cross-sectional study was conducted of 37 patients with AD. The following tests were used: MoCA, the Frontal Assessment Battery, Verbal Fluency, Clock Drawing Test, Andreotti & Okuma Battery Tests, Sit and Reach, Resistance of Upper Limbs - AAHPERD Battery Test, Sit and Lift Chair and the Apathy domain of the Neuropsychiatric Inventory. After verifying the normality of the data distribution, comparisons were made using Student's t-test and the U Mann Whitney test; relationships were also assessed using Pearson's and Spearman's correlation coefficients. All analyses were considered to be statistically significant at a p-value of 0.05. Results: 46% of participants in this study showed mild symptoms of apathy. Significant and weak associations were found (p=0.04) between apathy and the attention domain on the MoCA and between apathy and the Walk Test. Analysis of differences in cognitive and motor functions according to participants' level of apathy revealed no significant differences for any of the variables. Conclusion: Apathy was reflected in attention and the Walk Test, suggesting these variables may be related to cognitive and functional decline in AD patients.

Efeitos do treinamento com pesos nas funções cognitivas de idosos com doença de Alzheimer

Deterioration in cognitive functions is characteristic in Alzheimer's disease (AD) and may be associated with decline in daily living activities with consequent reduced quality of life. Objective: To analyze weight training effects on cognitive functions in elderly with AD. Subjects: 34 elderly with AD were allocated into two groups: Training Group (TG) and Social Gathering Group (SGG). Methods: Global cognitive status was determined using the Mini-Mental State Exam. Specific cognitive functions were measured using the Brief Cognitive Battery, Clock Drawing Test and Verbal Fluency Test. The protocols were performed three times a week, one hour per session. The weight training protocol consisted of three sets of 20 repetitions, with two minutes of rest between sets and exercises. The activities proposed for the SGG were not systematized and aimed at promoting social interaction among patients. The statistical analyses were performed with the U Mann Whitney and Wilcoxon tests for group comparisons. All analyses were considered statistically significant at a p-value of 0.05. Results: There were no significant differences associated to the effects of the practice of weight training on cognition in AD patients. Conclusion: In this study, no improvement in cognitive functions was evident in elderly with AD who followed a low intensity resistance exercise protocol. Thus, future studies could evaluate the effect of more intense exercise programs.

Adaptive walking in alzheimer's disease

The aim of this study is to analyze dual-task effects on free and adaptive gait in Alzheimer's disease (AD) patients. Nineteen elders with AD participated in the study. A veteran neuropsychiatrist established the degree of AD in the sample. To determine dual-task effects on free and adaptive gait, patients performed five trials for each experimental condition: free and adaptive gait with and without a dual-task (regressive countdown). Spatial and temporal parameters were collected through an optoelectronic tridimensional system. The central stride was analyzed in free gait, and the steps immediately before (approaching phase) and during the obstacle crossing were analyzed in adaptive gait. Results indicated that AD patients walked more slowly during adaptive gait and free gait, using conservative strategies when confronted either with an obstacle or a secondary task. Furthermore, patients sought for stability to perform the tasks, particularly for adaptive gait with dual task, who used anticipatory and online adjustments to perform the task. Therefore, the increase of task complexity enhances cognitive load and risk of falls for AD patients. © 2012 Diego Orcioli-Silva et al.

Multimodal exercise intervention improves frontal cognitive functions and gait in Alzheimer's disease: A controlled trial

Aim: The objective of the present study was to investigate the effect of a multimodal exercise intervention on frontal cognitive functions and kinematic gait parameters in patients with Alzheimer's disease. Methods: A sample of elderly patients with Alzheimer's disease (n=27) were assigned to a training group (n=14; aged 78.0±7.3years) and a control group (n=13; aged 77.1±7.4years). Multimodal exercise intervention includes motor activities and cognitive tasks simultaneously. The participants attended a 1-h session three times a week for 16weeks, and the control participants maintained their regular daily activities during the same period. The frontal cognitive functions were evaluated using the Frontal Assessment Battery, the Clock Drawing Test and the Symbol Search Subtest. The kinematic parameters of gait-cadence, stride length and stride speed were analyzed under two conditions: (i) free gait (single task); and (ii) gait with frontal cognitive task (walking and counting down from 20 - dual task). Results and discussion: The patients in the intervention group significantly increased the scores in frontal cognitive variables, Frontal Assessment Battery (P<0.001) and Symbol Search Subtest (P<0.001) after the 16-week period. The control group decreased the scores in the Clock Drawing Test (P=0.001) and increased the number of counting errors during the dual task (P=0.008) after the same period. Conclusion: The multimodal exercise intervention improved the frontal cognitive functions in patients with Alzheimer's disease. © 2012 Japan Geriatrics Society.

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. © 2013 Wiley Periodicals, Inc.

Effects of resistance training on the performance of activities of daily living in patients with Alzheimer's disease

Aim: The objective of this study was to investigate the effects of resistance training in activities of daily living performance in Alzheimer's disease (AD) patients. Methods: An exploratory and longitudinal study, lasting for 16weeks, with the participation of 34 patients divided equally in: the training group (TG), who participated in a resistance training protocol (three sets of 20 repetitions in five exercises); and the social gathering group (SGG), who participated in a social interaction protocol (i.e. group dynamics, writing and reading activities). Results: We observed significant differences between the groups in moving around the house, climbing stairs, standing up from the floor and putting on socks tests. Conclusion: This study showed that resistance training improves agility, lower limb strength, balance and flexibility in AD patients, while SGG protocol is important to improve the agility. © 2012 Japan Geriatrics Society.

White matter abnormalities associated with Alzheimer's disease and mild cognitive impairment: A critical review of MRI studies

In this article, the authors aim to present a critical review of recent MRI studies addressing white matter (WM) abnormalities in Alzheimer's disease (AD) and mild cognitive impairment (MCI), by searching PubMed and reviewing MRI studies evaluating subjects with AD or MCI using WM volumetric methods, diffusion tensor imaging and assessment of WM hyperintensities. Studies have found that, compared with healthy controls, AD and MCI samples display WM volumetric reductions and diffusion tensor imaging findings suggestive of reduced WM integrity. These changes affect complex networks relevant to episodic memory and other cognitive processes, including fiber connections that directly link medial temporal structures and the corpus callosum. Abnormalities in cortico-cortical and cortico-subcortical WM interconnections are associated with an increased risk of progression from MCI to dementia. It can be concluded that WM abnormalities are detectable in early stages of AD and MCI. Degeneration of WM networks causes disconnection among neural cells and the degree of such changes is related to cognitive decline. © 2013 2013 Expert Reviews Ltd.

Effect of a multimodal exercise program on sleep disturbances and instrumental activities of daily living performance on Parkinson's and Alzheimer's disease patients

Aim: To assess the contribution of a multimodal exercise program on the sleep disturbances (SD) and on the performance of instrumental activities daily living (IADL) in patients with clinical diagnosis of Alzheimer's disease (AD) and Parkinson's disease patients (PD). Methods: A total of 42 consecutive patients (23 training group, 19 control group) with PD and 35 demented patients with AD (19 trained group, 16 control group) were recruited. Participants in both training groups carried out three 1-h sessions per week of a multimodal exercise program for 6 months. The Pfeffer Questionnaire for Instrumental Activities and the Mini-Sleep Questionnaire were used to assess the effects of the program on IADL and SD respectively. Results: Two-way ancova showed interactions in IADL and SD. Significant improvements were observed for these variables in both intervention groups, and maintenance or worsening was observed in control groups. The analysis of effect size showed these improvements. Conclusion: The present study results show that a mild to moderate intensity of multimodal physical exercises carried out on a regular basis over 6 months can contribute to reducing IADL deficits and attenuating SD. © 2013 Japan Geriatrics Society.