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1.
Front Aging Neurosci ; 10: 255, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30186154

RESUMO

Alzheimer's disease (AD) is the most common form of dementia, with no means of cure or prevention. The presence of abnormal disease-related proteins in the population is, in turn, much more common than the incidence of dementia. In this context, the cognitive reserve (CR) hypothesis has been proposed to explain the discontinuity between pathophysiological and clinical expression of AD, suggesting that CR mitigates the effects of pathology on clinical expression and cognition. fMRI studies of the human connectome have recently reported that AD patients present diminished functional efficiency in resting-state networks, leading to a loss in information flow and cognitive processing. No study has investigated, however, whether CR modifies the effects of the pathology in functional network efficiency in AD patients. We analyzed the relationship between CR, pathophysiology and network efficiency, and whether CR modifies the relationship between them. Fourteen mild AD, 28 amnestic mild cognitive impairment (aMCI) due to AD, and 28 controls were enrolled. We used education to measure CR, cerebrospinal fluid (CSF) biomarkers to evaluate pathophysiology, and graph metrics to measure network efficiency. We found no relationship between CR and CSF biomarkers; CR was related to higher network efficiency in all groups; and abnormal levels of CSF protein biomarkers were related to more efficient networks in the AD group. Education modified the effects of tau-related pathology in the aMCI and mild AD groups. Although higher CR might not protect individuals from developing AD pathophysiology, AD patients with higher CR are better able to cope with the effects of pathology-presenting more efficient networks despite pathology burden. The present study highlights that interventions focusing on cognitive stimulation might be useful to slow age-related cognitive decline or dementia and lengthen healthy aging.

2.
Alzheimers Dement (N Y) ; 4: 473-480, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30258976

RESUMO

Introduction: Information about how physical exercise affects patients with amnestic mild cognitive impairment (aMCI) due to Alzheimer's disease (AD) is still missing. This study evaluated the impact of multicomponent exercise training on cognition and brain structure in aMCI subjects with cerebral spinal fluid positive AD biomarkers. Methods: Forty aMCI subjects were divided in training (multicomponent exercise thrice a week for 6 months) and nontraining groups. Assessments included cardiorespiratory fitness, neurocognitive tests, and a structural magnetic resonance imaging using 3.0 T scanner. FreeSurfer software analyzed hippocampal volume and cortical thickness. Results: The training group showed increased volume in both hippocampi and better performance in episodic memory test after 6 months. In contrast, the nontraining group declined in functional activities, recognition, and cardiorespiratory fitness for the same period. Discussion: Multicomponent exercise seems to improve hippocampal volume and episodic memory, and maintains VO2max in aMCI due to AD.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30035341

RESUMO

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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-29845446

RESUMO

The clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls. The protein levels of all APP secretases were significantly higher in platelets compared to leukocytes. We found statistically a significant decrease in ADAM10 (52.5%, p < 0.0001) and PSEN1 (32%, p = 0.02) in platelets from AD patients compared to controls, but not in leukocytes. Combining all three secretases to generate receiver-operating characteristic (ROC) curves, we found a good discriminatory effect (AD vs. controls) when using platelets (the area under the curve-AUC-0.90, sensitivity 88.9%, specificity 66.7%, p = 0.003), but not in leukocytes (AUC 0.65, sensitivity 77.8%, specificity 50.0%, p = 0.2). Our findings indicate that platelets represent a better biological matrix than leukocytes to address the peripheral level of APP secretases. In addition, combining the protein level of ADAM10, BACE1, and PSEN1 in platelets, yielded a good accuracy to discriminate AD from controls.

5.
J Alzheimers Dis ; 63(1): 93-101, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29614649

RESUMO

Telomere length (TL) is a biomarker of cell aging, and its shortening has been linked to several age-related diseases. In Alzheimer's disease (AD), telomere shortening has been associated with neuroinflammation and oxidative stress. The majority of studies on TL in AD were based on leucocyte DNA, with little information about its status in the central nervous system. In addition to other neuroprotective effects, lithium has been implicated in the maintenance of TL. The present study aims to determine the effect of chronic lithium treatment on TL in different regions of the mouse brain, using a triple-transgenic mouse model (3xTg-AD). Eighteen transgenic and 22 wild-type (Wt) male mice were treated for eight months with chow containing 1.0 g (Li1) or 2.0 g (Li2) of lithium carbonate/kg, or standard chow (Li0). DNA was extracted from parietal cortex, hippocampus and olfactory epithelium and TL was quantified by real-time PCR. Chronic lithium treatment was associated with longer telomeres in the hippocampus (Li2, p = 0.0159) and in the parietal cortex (Li1, p = 0.0375) of 3xTg-AD compared to Wt. Our findings suggest that chronic lithium treatment does affect telomere maintenance, but the magnitude and nature of this effect depend on the working concentrations of lithium and characteristics of the tissue. This effect was observed when comparing 3xTg-AD with Wt mice, suggesting that the presence of AD pathology was required for the lithium modulation of TL.

6.
Artigo em Inglês | MEDLINE | ID: mdl-27934540

RESUMO

Association between cognitive impairment and gait performance occurs in mild cognitive impairment (MCI) and Alzheimer's disease (AD), particularly under "divided attention" conditions, leading to a greater risk of falls. We studied 36 controls, 42 MCI, and 26 mild AD patients, using the Timed Up-and-Go test (TUG) under four conditions: TUG single - TUG1; TUG cognitive - TUG2; TUG manual -TUG3; TUG cognitive and manual - TUG4. Cognition was assessed using the MMSE, SKT, Exit25, and TMT (A and B). We found significant correlations between cognitive scores and TUG2 [r values (MMSE: -0.383, TMT-A: 0.430, TMT-B: 0.386, Exit25: 0.455, SKT: 0.563)] and TUG4 [(MMSE: -0.398, TMT-A: 0.384, TMT-B: 0.352,Exit25: 0.466, SKT: 0.525)] in the AD group, and between all TUG modalities and SKT in MCI and AD. Our results revealed that functional mobility impairment in cognitive dual tasks correlated to cognitive decline in AD patients and to attention and memory impairment in MCI.


Assuntos
Doença de Alzheimer , Atenção , Cognição , Disfunção Cognitiva , Marcha , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Psychiatry Neurosci ; 42(6): 366-377, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28375076

RESUMO

BACKGROUND: In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). METHODS: We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. RESULTS: Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. LIMITATIONS: The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. CONCLUSION: We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.


Assuntos
Doença de Alzheimer/fisiopatologia , Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Imagem por Ressonância Magnética , Idoso , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Disfunção Cognitiva/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Descanso
8.
J Alzheimers Dis ; 55(4): 1445-1451, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27858713

RESUMO

BACKGROUND: Abnormal amyloid-ß protein precursor (AßPP) metabolism is a key feature of Alzheimer's disease (AD). Platelets contain most of the enzymatic machinery required for AßPP processing, and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. Thus, AßPP-related molecules in platelets may be regarded as peripheral markers of AD. OBJECTIVE: We sought to determine the protein expression of the AßPP secretases (ADAM10, BACE1, and PSEN1) and AßPP ratio in platelets of patients with mild or moderate AD compared to healthy controls. We further determined whether the protein expression of these markers might be modified by chronic treatment with donepezil. METHODS: Platelet samples were obtained from patients and controls at baseline and after 3 and 6 months of continuous treatment with therapeutic doses of donepezil. The protein expression of platelet markers was determined by western blotting. RESULTS: AD patients had a significant decrease in AßPP ratio, ADAM10, and PSEN1 compared to controls at baseline, but these differences were not modified by the treatment. Nonetheless, a significant reduction in the protein expression of BACE1 was observed in patients treated with donepezil for 6 months. CONCLUSION: Our results corroborate previous findings from our group and others of decreased AßPP ratio and protein expression of ADAM10 in AD. We further show that PSEN1 is decreased in AD platelets, and that the protein expression of BACE1 is downregulated by chronic treatment with donepezil. This effect may be interpreted as evidence of disease modification.


Assuntos
Doença de Alzheimer/sangue , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Plaquetas/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Regulação para Baixo/efeitos dos fármacos , Indanos/farmacologia , Piperidinas/farmacologia , Proteína ADAM10/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Ácido Aspártico Endopeptidases/genética , Plaquetas/metabolismo , Inibidores da Colinesterase/uso terapêutico , Donepezila , Feminino , Humanos , Indanos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Piperidinas/uso terapêutico , Presenilina-1/metabolismo , Fatores de Tempo
9.
Neuropsychiatr Dis Treat ; 12: 2105-14, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27601905

RESUMO

Despite the lower prevalence of severe mood disorders in the elderly as compared to younger adults, late-life depression and bipolar disorder (BD) are more strongly associated with negative outcomes related to the presence of medical comorbidities, cognitive deficits, and increased suicide risk and overall mortality. The mechanisms that contribute to these associations are probably multifactorial, involving pathological factors related directly and indirectly to the disease itself, ranging from biological to psychosocial factors. Most of the accumulated knowledge on the nature of these associations derives from naturalistic and observational studies, and controlled data are still scarce. Nonetheless, there has clearly been a recent growth of the scientific interest on late-life BD and geriatric depression. In the present study, we review the most relevant studies on prevalence, clinical presentation, and cognitive/functional impact of mood disorders in elderly. Several clinical-epidemiological studies were dedicated to the study of the prevalence of mood disorders in old age in distinct settings; however, fewer studies investigated the underlying neurobiological findings and treatment specificities in late-life depression and BD. In the present study, we further discuss the implications of these findings on the management of mood disorders in older adults.

10.
Arq Neuropsiquiatr ; 74(7): 549-54, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27487375

RESUMO

Mild impairment in activities of daily living (ADL) can occur in Mild Cognitive Impairment (MCI), but the nature and extent of these difficulties need to be further explored. The Canadian occupational performance measure (COPM) is one of the few individualized scales designed to identify self-perceived difficulties in ADL. The present study investigated impairments in ADL using the COPM in elderly with MCI. A total of 58 MCI patients were submitted to the COPM for studies of its validity and reliability. The COPM proved a valid and consistent instrument for evaluating ADL in elderly MCI patients. A total of 74.6% of the MCI patients reported difficulties in ADL. Of these problems, 41.2% involved self-care, 31.4% productivity and 27.4% leisure. This data further corroborates recent reports of possible functional impairment in complex ADL in MCI.


Assuntos
Atividades Cotidianas/psicologia , Disfunção Cognitiva/fisiopatologia , Avaliação da Deficiência , Idoso , Brasil , Feminino , Humanos , Atividades de Lazer/psicologia , Masculino , Terapia Ocupacional/métodos , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Reprodutibilidade dos Testes , Autorrelato , Estatísticas não Paramétricas , Análise e Desempenho de Tarefas
11.
Arq. neuropsiquiatr ; 74(7): 549-554, tab
Artigo em Inglês | LILACS-Express | ID: lil-787365

RESUMO

ABSTRACT Mild impairment in activities of daily living (ADL) can occur in Mild Cognitive Impairment (MCI), but the nature and extent of these difficulties need to be further explored. The Canadian occupational performance measure (COPM) is one of the few individualized scales designed to identify self-perceived difficulties in ADL. The present study investigated impairments in ADL using the COPM in elderly with MCI. A total of 58 MCI patients were submitted to the COPM for studies of its validity and reliability. The COPM proved a valid and consistent instrument for evaluating ADL in elderly MCI patients. A total of 74.6% of the MCI patients reported difficulties in ADL. Of these problems, 41.2% involved self-care, 31.4% productivity and 27.4% leisure. This data further corroborates recent reports of possible functional impairment in complex ADL in MCI.


RESUMO A presença de dificuldades leves no desempenho de atividades da vida diária (AVD) pode estar presente no comprometimento cognitivo leve (CCL), mas sua natureza e extensão devem ser melhor exploradas. A medida canadense de desempenho ocupacional (COPM) é uma das poucas escalas individualizadas de autorrelato destinadas a identificar dificuldades no desempenho de AVDs. Este estudo investigou as dificuldades em AVDs através da COPM em idosos com CCL. 58 idosos com CCL foram submetidos à validação da COPM. A COPM se mostrou um instrumento válido e consistente para avaliar desempenho de AVDs em idosos com CCL. 74,6% dos idosos relatou alguma dificuldade no desempenho de AVDs, sendo 41,2% em auto-cuidado, 31,4% na produtividade e de 27,4% no lazer. Estes dados acrescentam evidências à recente literatura em que afirma que há comprometimento nas AVDs em CCL.

12.
Bipolar Disord ; 18(1): 71-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26877211

RESUMO

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.


Assuntos
Doença de Alzheimer/genética , Apolipoproteína E4/genética , Transtorno Bipolar/genética , Transtornos Cognitivos/genética , Disfunção Cognitiva/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Apolipoproteínas E/genética , Transtorno Bipolar/complicações , Transtornos Cognitivos/complicações , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Testes Neuropsicológicos , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco
13.
Int Psychogeriatr ; 28(5): 779-86, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26673910

RESUMO

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.


Assuntos
Doença de Alzheimer/psicologia , Apatia , Agitação Psicomotora/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Modelos Lineares , Masculino , Testes Neuropsicológicos , Inventário de Personalidade , Escalas de Graduação Psiquiátrica
14.
Rev. psiquiatr. clín. (São Paulo) ; 42(6): 153-156, Nov.-Dec. 2015. tab
Artigo em Inglês | LILACS-Express | ID: lil-767838

RESUMO

Abstract Background Non-pharmalogical interventions represent an important complement to standard pharmalogical treatment in dementia. Objective This study aims to evaluate the effects of a multidisciplinary rehabilitation program on cognitive ability, quality of life and depression symptoms in patients with Alzheimer’s disease (AD) and cognitive impairment without dementia (CIND). Methods Ninety-seven older adults were recruited to the present study. Of these, 70 patients had mild AD and were allocated into experimental (n = 54) or control (n = 16) groups. Two additional active comparison groups were constituted with patients with moderate AD (n = 13) or with CIND (n = 14) who also received the intervention. The multidisciplinary rehabilitation program lasted for 12 weeks and was composed by sessions of memory training, recreational activities, verbal expression and writing, physical therapy and physical training, delivered in two weekly 6-hour sessions. Results As compared to controls, mild AD patients who received the intervention had improvements in cognition (p = 0.021) and quality of life (p = 0.003), along with a reduction in depressive symptoms (p < 0.001). As compared to baseline, CIND patients displayed at the end of the intervention improvements in cognition (p = 0.005) and depressive symptoms (p = 0.011). No such benefits were found among patients with moderate AD.Discussion: This multidisciplinary rehabilitation program was beneficial for patients with mild AD and CIND. However, patients with moderate dementia did not benefit from the intervention.

15.
Rev. psiquiatr. clín. (São Paulo) ; 42(6): 157-160, Nov.-Dec. 2015. tab
Artigo em Inglês | LILACS-Express | ID: lil-767840

RESUMO

Abstract Background Family members providing continuous care to demented patients suffer from severe burden that impairs quality of life and often evolves to depression. Objective This study aims to evaluate the effect of psychodynamic group psychotherapy (PGT) compared to body awareness therapy (BAT) on caregiver burden, depressive symptoms, and quality of life among family caregivers to Alzheimer disease (AD) patients. Methods Thirty-seven healthy family caregivers were randomly allocated to receive PGT (n = 20) or BAT (n = 17). Interventions were administered in the format of 14 weekly group sessions. Outcome measures were: modification of scores on Zarit Burden Scale, Beck Depression Inventory and WHO-QoL Scale. Results Participants in the PGT group displayed significant reduction on burden (p = 0.01) and depression scores (p = 0.005), and improved quality of life (p = 0.002), whereas those in the BAT group showed improvements in burden of care (p = 0.001) and quality of life (p = 0.01), but not on depressive symptoms (p = 0.13). Discussion Psychodynamic psychotherapy was associated with amelioration of depressive symptoms, but overall benefits on burden of care and quality of life were similar irrespective of the type of intervention, i.e., psychologically-oriented or not. We hypothesize that these interventions can be complementary to improve depression and burden of care among family caregivers of AD patients.

16.
Molecules ; 20(11): 19878-85, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26556322

RESUMO

BACKGROUND: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. OBJECTIVE: To investigate the effect of lithium on cytosolic phospholipase A2 (PLA2) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer's disease (AD). METHODS: Primary cultures of cortical and hippocampal neurons were treated for 7 days with different concentrations of lithium chloride (0.02 mM, 0.2 mM and 2 mM). A radio-enzymatic assay was used to determine the total activity of PLA2 and two PLA2 subtypes: cytosolic calcium-dependent (cPLA2); and calcium-independent (iPLA2). RESULTS: cPLA2 activity increased by 82% (0.02 mM; p = 0.05) and 26% (0.2 mM; p = 0.04) in cortical neurons and by 61% (0.2 mM; p = 0.03) and 57% (2 mM; p = 0.04) in hippocampal neurons. iPLA2 activity was increased by 7% (0.2 mM; p = 0.04) and 13% (2 mM; p = 0.05) in cortical neurons and by 141% (0.02 mM; p = 0.0198) in hippocampal neurons. CONCLUSION: long-term lithium treatment increases membrane phospholipid metabolism in neurons through the activation of total, c- and iPLA2. This effect is more prominent at sub-therapeutic concentrations of lithium, and the activation of distinct cytosolic PLA2 subtypes is tissue specific, i.e., iPLA2 in hippocampal neurons, and cPLA2 in cortical neurons. Because PLA2 activities are reported to be reduced in Alzheimer's disease (AD) and bipolar disorder (BD), the present findings provide a possible mechanism by which long-term lithium treatment may be useful in the prevention of the disease.


Assuntos
Lítio/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosfolipases A2/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Feminino , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Gravidez , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Ratos
17.
Neuromolecular Med ; 17(3): 326-32, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26138246

RESUMO

There is little information on the dynamics of BDNF in the CSF in the continuum between healthy aging, MCI and AD. We included 128 older adults (77 with amnestic MCI, 26 with AD and 25 healthy controls). CSF BDNF level was measured by ELISA assay, and AD biomarkers (Aß42, T-Tau and P-Tau181) were measured using a Luminex xMAP assay. CSF BDNF levels were significantly reduced in AD subjects compared to MCI and healthy controls (p = 0.009). Logistic regression models showed that lower CSF BDNF levels (p = 0.008), lower CSF Aß42 (p = 0.005) and lower MMSE scores (p = 0.007) are significantly associated with progression from MCI to AD. The present study adds strong evidence of the involvement of BDNF in the pathophysiology of neurodegenerative changes in AD. Interventions aiming to restore central neurotrophic support may represent future therapeutic targets to prevent or delay the progression from MCI to AD.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Fator Neurotrófico Derivado do Encéfalo/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteínas E/genética , Biomarcadores , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Disfunção Cognitiva/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas tau/líquido cefalorraquidiano
18.
Behav Neurol ; 2015: 287843, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26160997

RESUMO

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique with potential to improve memory. Mild cognitive impairment (MCI), which still lacks a specific therapy, is a clinical syndrome associated with increased risk of dementia. This study aims to assess the effects of high-frequency repetitive TMS (HF rTMS) on everyday memory of the elderly with MCI. We conducted a double-blinded randomized sham-controlled trial using rTMS over the left dorsolateral prefrontal cortex (DLPFC). Thirty-four elderly outpatients meeting Petersen's MCI criteria were randomly assigned to receive 10 sessions of either active TMS or sham, 10 Hz rTMS at 110% of motor threshold, 2,000 pulses per session. Neuropsychological assessment at baseline, after the last session (10th) and at one-month follow-up, was applied. ANOVA on the primary efficacy measure, the Rivermead Behavioural Memory Test, revealed a significant group-by-time interaction (p = 0.05), favoring the active group. The improvement was kept after one month. Other neuropsychological tests were heterogeneous. rTMS at 10 Hz enhanced everyday memory in elderly with MCI after 10 sessions. These findings suggest that rTMS might be effective as a therapy for MCI and probably a tool to delay deterioration.


Assuntos
Disfunção Cognitiva/terapia , Memória/fisiologia , Córtex Motor/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento
19.
Rev. psiquiatr. clín. (São Paulo) ; 42(3): 69-73, May-Jun/2015. ilus, tab, graf
Artigo em Inglês | LILACS | ID: lil-797117

RESUMO

There is evidence from animal and in vitro models of the protective effects of caffeine in Alzheimer’s disease. The suggested mechanisms through which caffeine may protect neurons against Alzheimer’s disease pathology include the facilitation of beta-amyloid clearance, upregulation of cholinergic transmission, and increased neuronal plasticity and survival. Epidemiological studies support that Alzheimer’s disease patients consume smaller amounts of coffee beverages throughout their lives as compared to age-matched cognitively healthy individuals. Objective: The aim of the present study was to determine whether the negative association between Alzheimer’s disease and coffee consumption may be influenced by a common genetic predisposition, given the fact that the pattern of coffee consumption is determined by both environmental and genetic factors. Method: We conducted an in silico search addressing the association between genetic polymorphisms related to coffee consumption and the diagnosis of Alzheimer’s disease. We further investigated the interactions between genes located in regions bearing these polymorphisms. Results: Our analysis revealed no evidence for a genetic association (nor interaction between related proteins) involving coffee consumption and Alzheimer’s disease. Discussion: The negative association between Alzheimer’s disease and coffee consumption suggested by epidemiological studies is most likely due to environmental factors that are not necessarily regulated by genetic background...


Assuntos
Humanos , Feminino , Doença de Alzheimer , Cafeína/genética , Polimorfismo Genético , Alelos
20.
Rev. psiquiatr. clín. (São Paulo) ; 42(3): 69-73, May-Jun/2015. tab, graf
Artigo em Inglês | LILACS-Express | ID: lil-752374

RESUMO

Background There is evidence from animal and in vitro models of the protective effects of caffeine in Alzheimer’s disease. The suggested mechanisms through which caffeine may protect neurons against Alzheimer’s disease pathology include the facilitation of beta-amyloid clearance, upregulation of cholinergic transmission, and increased neuronal plasticity and survival. Epidemiological studies support that Alzheimer’s disease patients consume smaller amounts of coffee beverages throughout their lives as compared to age-matched cognitively healthy individuals. Objective The aim of the present study was to determine whether the negative association between Alzheimer’s disease and coffee consumption may be influenced by a common genetic predisposition, given the fact that the pattern of coffee consumption is determined by both environmental and genetic factors. Method We conducted an in silico search addressing the association between genetic polymorphisms related to coffee consumption and the diagnosis of Alzheimer’s disease. We further investigated the interactions between genes located in regions bearing these polymorphisms. Results Our analysis revealed no evidence for a genetic association (nor interaction between related proteins) involving coffee consumption and Alzheimer’s disease. Discussion The negative association between Alzheimer’s disease and coffee consumption suggested by epidemiological studies is most likely due to environmental factors that are not necessarily regulated by genetic background. .

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