RESUMO
Although inflammation has been associated with cognitive impairment in dementia, less is known about its role in the cognition of middle to older aged healthy people. This study utilised baseline data from the Australian Research Council Longevity Intervention (ARCLI) trial to investigate the relationship between markers of systemic inflammation (TNF-α, IL-6, IL-1ß, INF-γ, IL-2, IL-4, IL-10 and hsCRP) and cognitive function in 286 healthy volunteers aged 60-75â¯years. We assessed cognitive functioning across domains including attention, speed of memory, working memory and episodic memory using the Cognitive Drug Research test battery. Only IFN-γâ¯was related to cognitive function, being associated with greater odds of having low continuity of attention (log2 IFN-γ OR, 1.46; 95 % CI, 1.18-1.85). The relationship between episodic memory, speed of memory and inflammation varied with BMI. In high BMI participants, increased inflammation was associated with worse cognitive function, while this association was reversed in those with low BMI. Outside of the influence of IFN-γ on attention, low-grade systemic inflammation was not robustly associated with cognitive function in this sample of middle to older aged healthy people. Further research is required to understand the role of BMI in the intersection of inflammation and cognitive function.
Assuntos
Atenção/fisiologia , Cognição/fisiologia , Inflamação/metabolismo , Interferon gama/metabolismo , Memória Episódica , Memória de Curto Prazo/fisiologia , Idoso , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
There is a growing body of evidence from randomized controlled trials which indicates that consumption of berries has a positive effect upon the cognitive function of healthy adults. It has been recommended that studies combining cognitive and physiological measures be undertaken in order to strengthen the evidence base for the putative effects of flavonoid consumption on cognitive outcomes. This pilot study utilized a randomized, double-blind and placebo controlled crossover design to assess the influence of the acute administration of anthocyanin-rich blackcurrant juice, standardized at 500â mg of polyphenols, on mood and attention. Additionally, this trial used electroencephalography (EEG) to assess if any changes in cognitive performance are associated with changes in localized prefrontal cortex neuronal activity in nine healthy young adults. Outcomes from the pilot EEG data highlight an anxiolytic effect of the consumption of a single serve blackcurrant juice, as indexed by a suppression of α spectral power, and an increase in the slow wave δ and θ spectral powers. There was also an indication of greater alertness and lower fatigue, as indexed by an increase in ß power and suppression of α spectral power. Outcomes from the CogTrack™ system indicated a small acute increase in reaction times during the digit vigilance task.
Assuntos
Afeto/efeitos dos fármacos , Atenção/efeitos dos fármacos , Ondas Encefálicas/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Ribes , Adulto , Antocianinas/administração & dosagem , Ansiolíticos/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Projetos Piloto , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Polifenóis/administração & dosagem , Tempo de Reação , Adulto JovemRESUMO
OBJECTIVE: To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function. METHODS: Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤â¯62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). RESULTS: Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p < 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed. CONCLUSION: This pilot study indicates that an oral preparation of SRM at the selected dose and for the period of administration is more effective than a placebo in supported verbal episodic memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment.
Assuntos
Medicina Herbária/métodos , Memória/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Idoso , Canfanos , Método Duplo-Cego , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Melissa/química , Pessoa de Meia-Idade , Panax notoginseng , Projetos Piloto , Plantas Medicinais/química , Rosmarinus/química , Salvia miltiorrhiza , Espectrometria de Massas em Tandem , Resultado do TratamentoRESUMO
OBJECTIVE: Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. METHOD: Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. RESULTS: Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. CONCLUSION: Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan.
Assuntos
Cognição/fisiologia , Disfunção Cognitiva/etiologia , Demência/etiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Transtorno Depressivo/psicologia , Escolaridade , Exercício Físico/psicologia , Feminino , Humanos , Hipertensão/complicações , Estilo de Vida , Masculino , Memória Episódica , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Análise Multivariada , Resolução de Problemas/fisiologia , Fatores de Risco , Comportamento Sedentário , Fumar/efeitos adversos , Comportamento SocialRESUMO
Aging and depression have been found to be associated with poorer performance in mnemonic discrimination. In the current study, a two-response format mnemonic similarity test, Cognitive Drug Research MST, was used to compare these effects. Seventy-six participants were tested; with 52 participants in the young group, aged 18-35 years, and 24 participants in the elderly group, aged 55 years or older. Twenty-two young participants and 10 elderly participants met DSM-IV criteria for MDD or dysthymia. Age-related deficits were found for lure identification and speed of response. Differences in speed of responses to lure images were found for younger depressed participants, and depressive symptom severity was found to be negatively associated with lure identification accuracy in the elderly. These findings may be viewed as putative behavioral correlates of decreased pattern separation ability, which may be indicative of altered hippocampal neurogenesis in aging and depression.
Assuntos
Envelhecimento/psicologia , Transtorno Depressivo Maior/psicologia , Discriminação Psicológica , Transtorno Distímico/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Psicológico , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, ß = 0.023, P = 0.01; highest, ß = 0.021, P = 0.02), Digit Vigilance Task (lowest, ß = 0.009, P = 0.05; highest, ß = 0.01, P = 0.02) and Power of Attention (lowest, ß = 0.017, P = 0.02; highest, ß = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, ß = 0.021, P = 0.02; highest, ß = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.
Assuntos
Atenção/fisiologia , Transtornos Cognitivos/sangue , Estações do Ano , Vitamina D/análogos & derivados , Idoso de 80 Anos ou mais , Transtornos Cognitivos/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Prevalência , Reino Unido/epidemiologia , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
OBJECTIVE: To preliminarily assess the safety and efficacy of transdermal nicotine therapy on cognitive performance and clinical status in subjects with mild cognitive impairment (MCI). METHODS: Nonsmoking subjects with amnestic MCI were randomized to transdermal nicotine (15 mg per day or placebo) for 6 months. Primary outcome variables were attentional improvement assessed with Connors Continuous Performance Test (CPT), clinical improvement as measured by clinical global impression, and safety measures. Secondary measures included computerized cognitive testing and patient and observer ratings. RESULTS: Of 74 subjects enrolled, 39 were randomized to nicotine and 35 to placebo. 67 subjects completed (34 nicotine, 33 placebo). The primary cognitive outcome measure (CPT) showed a significant nicotine-induced improvement. There was no statistically significant effect on clinician-rated global improvement. The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment. Safety and tolerability for transdermal nicotine were excellent. CONCLUSION: This study demonstrated that transdermal nicotine can be safely administered to nonsmoking subjects with MCI over 6 months with improvement in primary and secondary cognitive measures of attention, memory, and mental processing, but not in ratings of clinician-rated global impression. We conclude that this initial study provides evidence for nicotine-induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that 6 months of transdermal nicotine (15 mg/day) improves cognitive test performance, but not clinical global impression of change, in nonsmoking subjects with amnestic MCI.
Assuntos
Disfunção Cognitiva/tratamento farmacológico , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Atenção/efeitos dos fármacos , Atenção/fisiologia , Peso Corporal/efeitos dos fármacos , Disfunção Cognitiva/psicologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Rememoração Mental/efeitos dos fármacos , Testes Neuropsicológicos , Projetos Piloto , Escalas de Graduação Psiquiátrica , Tempo de Reação/efeitos dos fármacos , Sinais Vitais/efeitos dos fármacosRESUMO
In a randomized, double-blind placebo controlled trial, 63 middle-aged volunteers aged between 40 and 65 years were administered a daily chocolate drink containing 250 mg or 500 mg cocoa flavanols versus a low cocoa flavanol (placebo) drink over a 30-day period. Participants were tested at baseline as well as at the end of the treatment period on a test of Spatial Working Memory. Steady State Probe Topography (SST) was used to assess neurocognitive changes associated with cocoa flavanol supplementation during the completion of the Spatial Working Memory task. SST is an electrophysiological technique which utilizes a 13 Hz diffuse visual flicker in order to generate a steady state visually evoked potential (SSVEP). Changes in the amplitude and phase of the SSVEP response after 30 days were compared between treatment groups. Behavioral measures of accuracy and reaction time were not found to be significantly different between treatment groups, while average SSVEP amplitude and phase differences at a number of posterior parietal and centro-frontal sites were found to be significantly different between groups during memory encoding, the working memory hold period and retrieval. In the absence of significant behavioral effects, these differences in brain activation can be interpreted as evidence of increased neural efficiency in spatial working memory function associated with chronic cocoa flavanol consumption.
Assuntos
Bebidas , Cacau , Potenciais Evocados Visuais/efeitos dos fármacos , Flavonoides/farmacologia , Memória de Curto Prazo/efeitos dos fármacos , Nootrópicos/farmacologia , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Potenciais Evocados Visuais/fisiologia , Feminino , Flavonoides/administração & dosagem , Flavonóis/farmacologia , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Nootrópicos/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologiaRESUMO
OBJECTIVES: Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) has become a standard clinical trials outcome for cognition, but has been recognized as deficient in areas including coverage of cognitive domains, sensitivity and standardization. Computerized test batteries may address some of these issues. The cognitive drug research computerized assessment (CDR) system is validated in Alzheimer's disease (AD). This study was designed to further evaluate validity in relation to ADAS-Cog, mini mental state examination (MMSE) and cerebrospinal fluid (CSF) biomarkers and psychometric properties, in a population of Alzheimer's patients on stable anticholinesterase treatment. MATERIALS AND METHODS: Patients completed cognition assessments, CSF and blood sampling at baseline and 6 months later. Data for 65 patients were evaluated. RESULTS: The CDR system demonstrated good psychometric properties in this population. Measures of psychomotor speed showed possible sensitivity to decline over 6 months. CONCLUSIONS: There are a number of methodological problems with current cognition assessment methodology for clinical trials. Computerized measures and in particular millisecond reaction time measures, may address many of these issues.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Inibidores da Colinesterase/uso terapêutico , Cognição , Testes Neuropsicológicos , Atenção , Feminino , Humanos , Masculino , Memória , Psicometria , Desempenho Psicomotor , Reprodutibilidade dos TestesRESUMO
Interactions between the 5-HT system and the dopaminergic system and cholinergic system may be important in determining cognitive function and motor function in Parkinson's disease (PD). Previous studies have shown effects of reducing serotonin function, by acute tryptophan depletion (ATD), on neuropsychological function. In particular, an adverse effect on verbal memory has been demonstrated. This study compared with the effects of ATD on cognitive and motor function in PD and healthy control subjects. The effects of ATD were investigated in a double-blind, placebo-controlled, counterbalanced, cross-over, randomised design in 20 patients with PD and 35 healthy controls matched for age, gender and premorbid IQ. There was a differential group effect of ATD on global cognitive function whereby the mean score on the modified mini mental state examination during ATD was lower than placebo in PD but higher in controls. There was a similar pattern of effects on verbal recognition. In a visual recognition task, ATD improved performance in the PD but not in the control group. In terms of psychomotor speed, there was also a group-specific effect with reduced latency of response during ATD in the PD group but increased latency in the control group. ATD has subtle neuropsychological effects, which differ significantly between PD and healthy control subjects. This suggests that the dopaminergic and cholinergic deficit of PD significantly modulates the effects of serotonin depletion, resulting in positive effects in some domains. Further investigation on the effects of specific serotonin antagonists may be merited in PD.
Assuntos
Cognição/fisiologia , Deficiências Nutricionais/fisiopatologia , Transtornos dos Movimentos/fisiopatologia , Doença de Parkinson/fisiopatologia , Triptofano/deficiência , Idoso , Idoso de 80 Anos ou mais , Estudos Cross-Over , Deficiências Nutricionais/sangue , Deficiências Nutricionais/complicações , Método Duplo-Cego , Feminino , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/sangue , Doença de Parkinson/complicações , Desempenho Psicomotor , Tempo de Reação , Serotonina/fisiologia , Índice de Gravidade de Doença , Triptofano/administração & dosagem , Triptofano/sangueRESUMO
This was a double-blind, randomised, placebo-controlled, crossover study of the acute cognitive and subjective effects of nabilone 1-3 mg in healthy male volunteers. The Cognitive Drug Research computerised system (CDR system) was used to assess changes in attention, working and episodic memory. In addition, a number of self-ratings were conducted including those of mood, alertness and perceived drug effects. Impairments to attention, working and episodic memory and self-ratings of alertness were evident. Volunteers also experienced a number of subjective drug effects. These data demonstrate that acute doses of nabilone in the range 1-3 mg produce clear cognitive and subjective effects in healthy volunteers, and therefore they may be used as reference data in the future study of peripherally acting cannabinoids believed to be free from such effects.
Assuntos
Atenção/efeitos dos fármacos , Dronabinol/análogos & derivados , Memória de Curto Prazo/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Afeto/efeitos dos fármacos , Capsaicina/administração & dosagem , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Dronabinol/efeitos adversos , Dronabinol/farmacologia , Humanos , Masculino , Memória/efeitos dos fármacos , Dor/tratamento farmacológico , Percepção/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/efeitos dos fármacos , Receptor CB1 de Canabinoide/fisiologia , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/efeitos dos fármacos , Receptor CB2 de Canabinoide/fisiologia , Fármacos do Sistema Sensorial/administração & dosagemRESUMO
INTRODUCTION: The nicotinic acetylcholine receptor (nAChR) system plays a regulatory role in a number of cognitive processes. Cholinesterase inhibitors (i.e., galantamine) that potentiate cholinergic neurotransmission improve cognitive function in Alzheimer's disease (AD); however, the relationship between these effects and associated changes in nAChRs are yet to be established in vivo. MATERIALS AND METHODS: 2-[18F]Fluoro-A-85380 (2-FA) binds to nAChRs and with positron emission tomography (PET) imaging provides a composite measure of receptor density and ligand affinity. This study aimed to: (1) quantify nAChRs in vivo in 15 drug-naïve patients with mild AD before and after chronic treatment with galantamine, using 2-FA and PET, and (2) examine the relationship between treatment-induced changes in nAChRs and improvements in cognitive function. Participants were nonsmokers and underwent extensive cognitive testing and a PET scan after injection of approximately 200 MBq of 2-FA on two occasions (before and after 12 weeks, galantamine treatment). A 3-day washout period preceded the second scan. Brain regional 2-FA binding was assessed through a simplified estimation of distribution volume (DV(S)). RESULTS: Performance on global measures of cognition significantly improved following galantamine treatment (p < 0.05). This improvement extended to specific cognitive measures of language and verbal learning. No significant differences in nAChR DV(S) before and after galantamine treatment were found. The treatment-induced improvement in cognition was not correlated with regional or global nAChR DV(S), suggesting that changes in nAChRs may not be responsible for the improvements in cognition following galantamine in patients with mild AD.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia , Azetidinas , Cognição/efeitos dos fármacos , Galantamina/farmacologia , Nootrópicos/farmacologia , Piridinas , Receptores Nicotínicos/efeitos dos fármacos , Idoso , Doença de Alzheimer/metabolismo , Nível de Alerta/efeitos dos fármacos , Feminino , Radioisótopos de Flúor , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Desempenho Psicomotor/efeitos dos fármacos , Compostos Radiofarmacêuticos , Tempo de Reação/efeitos dos fármacos , Percepção Espacial/efeitos dos fármacosRESUMO
BACKGROUND: Cognitive deficits, in particular deficits of attention and executive function, may affect postural sway and balance in Parkinson's disease (PD). Our objective was to determine whether measures of attention were associated with falls in a large cohort of subjects with PD studied prospectively. METHODS: Patients meeting UK PD Society Brain Bank Criteria were included. Assessment included UPDRS III and the Cognitive Drug Research computerised assessment battery (CDR) from which Power of Attention, Continuity of Attention, cognitive reaction time and reaction time variability were derived. Falls were assessed prospectively using monthly fall diaries returned over a year following baseline assessment. RESULTS: One hundred and sixty four subjects completed fall diary datasets. One hundred and three (63%) fell one or more times during the 12 month period. Regression analysis revealed an association of fall frequency with poorer Power of Attention and increased reaction time variability, which was retained after correcting for UPDRS scores. CONCLUSIONS: Reduced power of attention and increased reaction time variability are associated with increased fall frequency in PD. This has implications for the identification of those most at risk of falling, and for the management and prevention of falls in this patient group.
Assuntos
Acidentes por Quedas , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Doença de Parkinson/complicações , Idoso , Antiparkinsonianos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Doença de Parkinson/tratamento farmacológico , Valor Preditivo dos Testes , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologiaRESUMO
An international trial comparing remacemide hydrochloride with carbamazepine was undertaken in individuals with newly diagnosed epilepsy using a novel double-blind, parallel-group, double triangular sequential design. Patients with two or more partial or generalized tonic-clonic seizures in the previous year were randomized to remacemide or carbamazepine and titrated to a target dose of 600 mg/day. Subsequent dosage adjustments were allowed while maintaining the blind. Repeated assessments of neuropsychological function and mood were carried out using computerized and conventional measures. The trial was completed 20 months after initiation, following the second interim analysis. Efficacy as measured by seizure recurrence showed remacemide to be inferior to carbamazepine. Baseline cognitive and neuropsychological measures showed impairment across the whole patient population. Cognitive/neuropsychological performance at 8, 24, and 48 weeks was compared with that at baseline. Significant deterioration was seen on measures of information processing speed and attention after treatment with carbamazepine. The study data provide evidence for the utility and sensitivity of a number of cognitive assessments, which may be employed in future trials of antiepileptic drugs.
Assuntos
Acetamidas/efeitos adversos , Acetamidas/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Cognição/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Epilepsia/psicologia , Desempenho Psicomotor/efeitos dos fármacos , Acetamidas/administração & dosagem , Adolescente , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Atenção/efeitos dos fármacos , Carbamazepina/administração & dosagem , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Reconhecimento Psicológico/efeitos dos fármacos , Valores de Referência , Reprodutibilidade dos Testes , Resultado do Tratamento , Adulto JovemRESUMO
The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.
Assuntos
Antioxidantes/farmacologia , Cognição/efeitos dos fármacos , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Seguimentos , Hormônio do Crescimento Humano/efeitos dos fármacos , Hormônio do Crescimento Humano/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Análise por Pareamento , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Extratos VegetaisRESUMO
Neuronal nicotinic acetylcholine receptors (nAChRs) are critical for higher order cognitive processes. Post-mortem studies suggest reductions in nAChRs (particularly the alpha(4)beta(2) subtype) with ageing and in Alzheimer's disease (AD). This study aimed to; (1) quantify nAChR distribution in vivo with 2-[18F]fluoro-A-85380 (2-FA) in 15 early AD patients compared to 14 age-matched, healthy controls (HC) and (2) correlate nAChR distribution with cognitive performance in both groups. All participants were non-smokers and underwent cognitive testing along with a dynamic PET scan after injection of 200 MBq of 2-FA. Brain regional 2-FA binding was assessed through a simplified estimation of Distribution Volume (DV(S)). The AD group differed significantly from HC on all cognitive measures employed, with impairments on measures of attention, working memory, language, executive function, visuospatial ability, verbal learning and verbal memory (p<.05). Contrary to post-mortem data this study found no evidence of in vivo nAChR loss in early AD despite significant cognitive impairment. Furthermore, no correlation between nAChR and cognitive performance was found for either group. The findings of the current study suggest preservation of nAChRs early in AD supporting previous studies. It is possible that while the clinical 2-FA PET method described here may be insensitive in detecting changes in early AD, such changes may be detected in more advanced stages of the illness.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Receptores Nicotínicos/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/classificação , Atenção/fisiologia , Encéfalo/diagnóstico por imagem , Comportamento de Escolha/fisiologia , Aprendizagem por Discriminação/fisiologia , Feminino , Radioisótopos de Flúor , Humanos , Inibição Psicológica , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Orientação/fisiologia , Resolução de Problemas/fisiologia , Desempenho Psicomotor/fisiologia , Piridinas , Tempo de Reação/fisiologia , Aprendizagem Verbal/fisiologiaRESUMO
BACKGROUND: Hypertension is associated with impaired cognitive function but the effect of antihypertensive treatment on cognitive function is unclear. METHODS: We investigated the effect of treatment of hypertension on cognition with the angiotensin-receptor-blocker, candesartan, in a placebo-controlled, double-blind, randomized controlled trial at one center participating in the Study on Cognition and Prognosis in the Elderly. A total of 257 older adults with hypertension (mean age 76 years, blood pressure 165 +/- 8/88 +/- 7 mm Hg) were recruited from general practice and treated with 8-16 mg candesartan or placebo once daily, for a mean follow-up period of 44 months. Additional antihypertensive therapy was permitted in both groups to achieve treatment targets. Cognitive function was measured using the Cognitive Drug Research computerized assessment battery, trail-making tests, and verbal fluency. Data from annual assessments were used to calculate individual coefficients of decline by regressing composite test scores over time for five cognitive domains. RESULTS: The blood pressure difference between groups at study close was 8/3 mm Hg. The candesartan group showed less decline in attention (0.004 vs -0.036, p = 0.04) and episodic memory (0.14 vs -0.22, p = 0.04) compared to placebo, a similar trend for speed of cognition (-2.3 vs -17.4, p = 0.15), but no differences in working memory (0.0014 vs 0.0010, p = 0.90) or executive function (-0.0031 vs -0.0023, p = 0.95). Effect sizes were in the small-to-moderate range. CONCLUSIONS: The potential for blood pressure-lowering with angiotensin-receptor-blockers to reduce the rate of decline of specific areas of cognitive function in older patients with hypertension warrants further investigation to determine clinical efficacy.
Assuntos
Anti-Hipertensivos/administração & dosagem , Benzimidazóis/administração & dosagem , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Tetrazóis/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Angiotensinas/metabolismo , Anti-Hipertensivos/efeitos adversos , Benzimidazóis/efeitos adversos , Compostos de Bifenilo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Artérias Cerebrais/efeitos dos fármacos , Artérias Cerebrais/metabolismo , Artérias Cerebrais/fisiopatologia , Cognição/efeitos dos fármacos , Cognição/fisiologia , Transtornos Cognitivos/fisiopatologia , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Testes Neuropsicológicos , Placebos , Tetrazóis/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Atypical antipsychotics may be beneficial in treating the core psychopathology of anorexia nervosa (AN). METHODS: An 8 week open-label study of quetiapine was conducted in eight severely ill DSM-IV AN patients consecutively admitted to a specialist eating disorders unit. Participants were assessed by EDE-12, MADRS, YBOCS, SAPS-delusions and CDR neuropsychological battery at baseline, 4 weeks and 8 weeks, and by weekly body mass index (BMI), CGI and extrapyramidal scores. Quetiapine doses ranged from 50 mg to 800 mg per day, according to efficacy and tolerability. RESULTS: Seven participants completed 4 weeks and five participants completed 8 weeks. All participants had clinically significant levels of specific eating disorders psychopathology, and mild to moderately severe depressive symptomatology. Apart from initial mild sedation, no subjects experienced any significant adverse events. Over 4 weeks there was no significant difference in BMI, but a significant difference in the EDE-12 restraint score. There were significant differences on BMI and EDE-12 restraint subscale scores over 8 weeks. CONCLUSIONS: A double-blind placebo controlled study is required to further evaluate the therapeutic utility of quetiapine in severely ill AN patients beyond multidisciplinary specialist intervention.
Assuntos
Anorexia Nervosa/tratamento farmacológico , Antipsicóticos/uso terapêutico , Dibenzotiazepinas/uso terapêutico , Adulto , Anorexia Nervosa/psicologia , Antipsicóticos/efeitos adversos , Nível de Alerta/efeitos dos fármacos , Índice de Massa Corporal , Delusões/psicologia , Depressão/psicologia , Dibenzotiazepinas/efeitos adversos , Discinesia Induzida por Medicamentos/epidemiologia , Humanos , Masculino , Testes Neuropsicológicos , Comportamento Obsessivo/psicologia , Escalas de Graduação Psiquiátrica , Fumarato de Quetiapina , Tempo de Reação/efeitos dos fármacos , Aumento de PesoRESUMO
OBJECTIVES: The aim of this study was to get insight into the central effects of TC-1734 (renamed AZD3480), a selective agonist at the neuronal nicotinic receptor of the alpha4beta2 subtype. MATERIALS AND METHODS: Electroencephalography (EEG) techniques and computerized cognitive tests were performed in young, healthy male volunteers during two double-blind and placebo-controlled studies: a rising single dose crossover study (from 2 to 320 mg) and a rising repeated dose study with a parallel group design (50, 100, and 200 mg). RESULTS: In contrast to acute administration, administration of AZD3480 over 10 days produced statistically significant enhancement of several cognitive measures (attention and episodic memory) compared to placebo. Regarding EEG data, AZD3480 showed acceleration of the alpha centroid and of the alpha peak in the single-dose study. This EEG profile of the acceleration type was confirmed in the repeated dose study on both day 1 and day 10, with the greatest effect observed with the highest dose. The EEG pattern shown for AZD3480 was consistent with that previously described with other drugs known to improve attention and vigilance (including nicotine). In addition, subjects dosed with AZD3480 showed a statistically significant increase in mismatch negativity (MMN) amplitude at 50 and 200 mg while reducing MMN latency (200 mg only), suggesting an improvement of pre-attentional mechanisms. CONCLUSION: These early data in healthy subjects provide encouragement to consider development of AZD3480 as a novel agent for the treatment of cognitive decline in the elderly, including age-associated memory impairment and/or dementia of the Alzheimer's type.
Assuntos
Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Nootrópicos/farmacologia , Piridinas/farmacologia , Receptores Nicotínicos/efeitos dos fármacos , Administração Oral , Adulto , Ritmo alfa/efeitos dos fármacos , Atenção/efeitos dos fármacos , Encéfalo/metabolismo , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Humanos , Masculino , Memória/efeitos dos fármacos , Agonistas Nicotínicos/administração & dosagem , Nootrópicos/administração & dosagem , Piridinas/administração & dosagem , Receptores Nicotínicos/metabolismo , Valores de Referência , Fatores de TempoRESUMO
OBJECTIVE: Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were otherwise well controlled with nasal continuous positive airway pressure (nCPAP). We assessed the ability of armodafinil to improve wakefulness and cognition and reduce fatigue in this population. METHODS: In this 12-week, randomized, double-blind study, patients (n=259) received armodafinil (150 mg) or placebo once daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI-C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. RESULTS: At final visit, mean (SD) MWT sleep latency increased from baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs. 53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil significantly improved episodic secondary memory (P=0.0102) and patient-estimated wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo. Armodafinil did not adversely affect nCPAP use. The most common adverse event associated with armodafinil was headache. Sleep macroarchitecture was not altered by armodafinil. CONCLUSION: Adjunct treatment with armodafinil significantly improved alertness, overall clinical condition, and long-term memory. Armodafinil also reduced fatigue and the impact of sleepiness on daily activities in patients with OSA/HS who have residual excessive sleepiness notwithstanding regular use of nCPAP. Armodafinil was well tolerated.