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1.
Nutr Neurosci ; 22(8): 596-606, 2019 Aug.
Article in English | MEDLINE | ID: mdl-29343201

ABSTRACT

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 500 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.


Subject(s)
Affect/drug effects , Attention/drug effects , Brain Waves/drug effects , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiology , Ribes , Adult , Anthocyanins/administration & dosage , Anti-Anxiety Agents/administration & dosage , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Neuropsychological Tests , Pilot Projects , Plant Extracts/administration & dosage , Plant Extracts/isolation & purification , Polyphenols/administration & dosage , Reaction Time , Young Adult
2.
Phytomedicine ; 39: 42-48, 2018 Jan 15.
Article in English | MEDLINE | ID: mdl-29433682

ABSTRACT

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 (≤ 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.


Subject(s)
Herbal Medicine/methods , Memory/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Aged , Camphanes , Double-Blind Method , Drugs, Chinese Herbal/pharmacology , Female , Healthy Volunteers , Humans , Male , Melissa/chemistry , Middle Aged , Panax notoginseng , Pilot Projects , Plants, Medicinal/chemistry , Rosmarinus/chemistry , Salvia miltiorrhiza , Tandem Mass Spectrometry , Treatment Outcome
3.
Article in English | MEDLINE | ID: mdl-28506139

ABSTRACT

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.


Subject(s)
Aging/psychology , Depressive Disorder, Major/psychology , Discrimination, Psychological , Dysthymic Disorder/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Recognition, Psychology , Young Adult
4.
Eur J Neurol ; 22(1): 106-15, e6-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25117780

ABSTRACT

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.


Subject(s)
Attention/physiology , Cognition Disorders/blood , Seasons , Vitamin D/analogs & derivatives , Aged, 80 and over , Cognition Disorders/epidemiology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Prevalence , United Kingdom/epidemiology , Vitamin D/blood , Vitamin D Deficiency/blood
5.
J Psychopharmacol ; 24(11): 1659-69, 2010 Nov.
Article in English | MEDLINE | ID: mdl-19525335

ABSTRACT

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.


Subject(s)
Attention/drug effects , Dronabinol/analogs & derivatives , Memory, Short-Term/drug effects , Mental Recall/drug effects , Affect/drug effects , Capsaicin/administration & dosage , Cognition/drug effects , Dose-Response Relationship, Drug , Double-Blind Method , Dronabinol/adverse effects , Dronabinol/pharmacology , Humans , Male , Memory/drug effects , Pain/drug therapy , Perception/drug effects , Psychomotor Performance/drug effects , Reaction Time/drug effects , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB1/drug effects , Receptor, Cannabinoid, CB1/physiology , Receptor, Cannabinoid, CB2/agonists , Receptor, Cannabinoid, CB2/drug effects , Receptor, Cannabinoid, CB2/physiology , Sensory System Agents/administration & dosage
6.
J Psychopharmacol ; 24(10): 1465-72, 2010 Oct.
Article in English | MEDLINE | ID: mdl-19460872

ABSTRACT

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.


Subject(s)
Cognition/physiology , Deficiency Diseases/physiopathology , Movement Disorders/physiopathology , Parkinson Disease/physiopathology , Tryptophan/deficiency , Aged , Aged, 80 and over , Cross-Over Studies , Deficiency Diseases/blood , Deficiency Diseases/complications , Double-Blind Method , Female , Humans , Male , Memory, Short-Term , Middle Aged , Neuropsychological Tests , Parkinson Disease/blood , Parkinson Disease/complications , Psychomotor Performance , Reaction Time , Serotonin/physiology , Severity of Illness Index , Tryptophan/administration & dosage , Tryptophan/blood
7.
Psychopharmacology (Berl) ; 202(1-3): 79-91, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18949462

ABSTRACT

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.


Subject(s)
Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Azetidines , Cognition/drug effects , Galantamine/pharmacology , Nootropic Agents/pharmacology , Pyridines , Receptors, Nicotinic/drug effects , Aged , Alzheimer Disease/metabolism , Arousal/drug effects , Female , Fluorine Radioisotopes , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Positron-Emission Tomography , Psychomotor Performance/drug effects , Radiopharmaceuticals , Reaction Time/drug effects , Space Perception/drug effects
8.
Epilepsy Behav ; 14(3): 522-8, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19111629

ABSTRACT

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.


Subject(s)
Acetamides/adverse effects , Acetamides/therapeutic use , Anticonvulsants/adverse effects , Anticonvulsants/therapeutic use , Carbamazepine/adverse effects , Carbamazepine/therapeutic use , Cognition/drug effects , Epilepsy/drug therapy , Epilepsy/psychology , Psychomotor Performance/drug effects , Acetamides/administration & dosage , Adolescent , Adult , Aged , Anticonvulsants/administration & dosage , Attention/drug effects , Carbamazepine/administration & dosage , Child , Double-Blind Method , Female , Humans , Male , Memory, Short-Term/drug effects , Middle Aged , Neuropsychological Tests , Recognition, Psychology/drug effects , Reference Values , Reproducibility of Results , Treatment Outcome , Young Adult
9.
Neurobiol Learn Mem ; 90(2): 404-12, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18620875

ABSTRACT

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.


Subject(s)
Alzheimer Disease/diagnostic imaging , Cognition Disorders/diagnostic imaging , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Neuropsychological Tests , Positron-Emission Tomography , Receptors, Nicotinic/physiology , Aged , Aged, 80 and over , Alzheimer Disease/classification , Attention/physiology , Brain/diagnostic imaging , Choice Behavior/physiology , Discrimination Learning/physiology , Female , Fluorine Radioisotopes , Humans , Inhibition, Psychological , Male , Memory, Short-Term/physiology , Middle Aged , Orientation/physiology , Problem Solving/physiology , Psychomotor Performance/physiology , Pyridines , Reaction Time/physiology , Verbal Learning/physiology
10.
Neurology ; 70(19 Pt 2): 1858-66, 2008 May 06.
Article in English | MEDLINE | ID: mdl-18458219

ABSTRACT

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.


Subject(s)
Antihypertensive Agents/administration & dosage , Benzimidazoles/administration & dosage , Cognition Disorders/drug therapy , Cognition Disorders/etiology , Hypertension/complications , Hypertension/drug therapy , Tetrazoles/administration & dosage , Aged , Aged, 80 and over , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Angiotensin II Type 1 Receptor Blockers/adverse effects , Angiotensins/metabolism , Antihypertensive Agents/adverse effects , Benzimidazoles/adverse effects , Biphenyl Compounds , Blood Pressure/drug effects , Blood Pressure/physiology , Cerebral Arteries/drug effects , Cerebral Arteries/metabolism , Cerebral Arteries/physiopathology , Cognition/drug effects , Cognition/physiology , Cognition Disorders/physiopathology , Double-Blind Method , Drug Administration Schedule , Female , Humans , Hypertension/physiopathology , Male , Neuropsychological Tests , Placebos , Tetrazoles/adverse effects , Treatment Outcome
11.
J Psychopharmacol ; 21(1): 65-70, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16533867

ABSTRACT

The present study aimed to systematically assess acute, dose-related behavioural effects of an extract of guaraná plant for the first time in humans. This double-blind, counterbalanced, placebo-controlled study (n=26) assessed the acute mood and cognitive effects throughout the day of four different doses (37.5 mg, 75 mg, 150 mg and 300 mg) of a standardised guaraná extract (PC-102). Assessment included the Cognitive Drug Research computerized test battery and Bond-Lader mood scales. Guaraná improved secondary memory performance and increased alert and content mood ratings. The two lower doses produced more positive cognitive effects than the higher doses. This research supports previous findings of cognitive improvements following 75 mg guaraná and provides the first exploration of different dose effects of guaraná in humans. The findings suggest that the effects cannot be attributed to caffeine alone.


Subject(s)
Affect/drug effects , Caffeine/pharmacology , Cognition/drug effects , Psychotropic Drugs/pharmacology , Theobromine/pharmacology , Theophylline/pharmacology , Administration, Oral , Adult , Attention/drug effects , Caffeine/administration & dosage , Capsules , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Memory/drug effects , Psychotropic Drugs/administration & dosage , Reference Values , Theobromine/administration & dosage , Theophylline/administration & dosage
12.
Neurology ; 65(10): 1654-6, 2005 Nov 22.
Article in English | MEDLINE | ID: mdl-16301500

ABSTRACT

In a 24-week, randomized, double-blind, placebo-controlled, multicenter study of rivastigmine, 487 patients with dementia associated with Parkinson disease underwent assessment of attention on the Cognitive Drug Research computerized cognitive assessment system before dosing and 16 and 24 weeks later. Significant benefits of rivastigmine over placebo were seen on all aspects of attention assessed: sustained attention, focused attention, consistence of responding, and central processing speed.


Subject(s)
Attention/drug effects , Dementia/drug therapy , Dementia/etiology , Neuroprotective Agents/administration & dosage , Parkinson Disease/complications , Phenylcarbamates/administration & dosage , Aged , Aged, 80 and over , Attention/physiology , Cognition/drug effects , Cognition/physiology , Cognition Disorders/drug therapy , Cognition Disorders/etiology , Cognition Disorders/psychology , Corpus Striatum/drug effects , Corpus Striatum/physiopathology , Dementia/psychology , Dose-Response Relationship, Drug , Double-Blind Method , Female , Frontal Lobe/drug effects , Frontal Lobe/physiopathology , Humans , Male , Middle Aged , Neural Pathways/drug effects , Neural Pathways/physiopathology , Neuropsychological Tests , Placebos , Reaction Time/drug effects , Reaction Time/physiology , Rivastigmine , Treatment Outcome
13.
Physiol Behav ; 83(5): 699-709, 2005 Jan 17.
Article in English | MEDLINE | ID: mdl-15639154

ABSTRACT

Members of the Sage family, such as Salvia officinalis and Salvia lavandulaefolia, have a long history of use as memory-enhancing agents coupled with cholinergic properties that may potentially be relevant to the amelioration of the cognitive deficits associated with Alzheimer's disease. The current study utilised a placebo-controlled, double-blind, balanced, crossover design in order to comprehensively assess any mood and cognition modulation by S. lavandulaefolia. Twenty-four participants received single doses of placebo, 25 microl and 50 microl of a standardised essential oil of S. lavandulaefolia in an order dictated by a Latin square. Doses were separated by a 7-day washout period. Cognitive performance was assessed prior to the day's treatment and at 1, 2.5, 4 and 6 h thereafter using the Cognitive Drug Research (CDR) computerised test battery. Subjective mood ratings were measured using Bond-Lader visual analogue scales. The primary outcome measures were scores on the five cognitive factors that can be derived by factor analysis of the task outcomes from the CDR battery. The results showed that administration of S. lavandulaefolia resulted in a consistent improvement for both the 25- and 50-microl dose on the 'Speed of Memory' factor. There was also an improvement on the 'Secondary Memory' factor for the 25-microl dose. Mood was consistently enhanced, with increases in self-rated 'alertness', 'calmness' and 'contentedness' following the 50-microl dose and elevated 'calmness' following 25 microl. These results represent further evidence that Salvia is capable of acute modulation of mood and cognition in healthy young adults. The data also suggest that previous reports of memory enhancement by Salvia may be due to more efficient retrieval of target material.


Subject(s)
Affect/drug effects , Cognition/drug effects , Oils, Volatile/pharmacology , Salvia/chemistry , Adolescent , Adult , Attention/drug effects , Dose-Response Relationship, Drug , Humans , Male , Memory, Short-Term , Mental Recall/drug effects , Neuropsychological Tests , Psychomotor Performance , Reading , Time Factors , Visual Perception/drug effects
14.
Neurology ; 63(11): 2091-6, 2004 Dec 14.
Article in English | MEDLINE | ID: mdl-15596755

ABSTRACT

OBJECTIVE: To quantify visual discrimination, space-motion, and object-form perception in patients with Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD). METHODS: The authors used a cross-sectional study to compare three demented groups matched for overall dementia severity (PDD: n = 24; DLB: n = 20; AD: n = 23) and two age-, sex-, and education-matched control groups (PD: n = 24, normal controls [NC]: n = 25). RESULTS: Visual perception was globally more impaired in PDD than in nondemented controls (NC, PD), but was not different from DLB. Compared to AD, PDD patients tended to perform worse in all perceptual scores. Visual perception of patients with PDD/DLB and visual hallucinations was significantly worse than in patients without hallucinations. CONCLUSIONS: Parkinson disease dementia (PDD) is associated with profound visuoperceptual impairments similar to dementia with Lewy bodies (DLB) but different from Alzheimer disease. These findings are consistent with previous neuroimaging studies reporting hypoactivity in cortical areas involved in visual processing in PDD and DLB.


Subject(s)
Lewy Body Disease/complications , Parkinson Disease/complications , Perceptual Disorders/etiology , Visual Perception , Activities of Daily Living , Aged , Aged, 80 and over , Cognition , Cohort Studies , Discrimination, Psychological , Extrapyramidal Tracts/physiopathology , Female , Form Perception , Hallucinations/etiology , Humans , Lewy Body Disease/psychology , Male , Motion Perception , Parkinson Disease/psychology , Psychomotor Performance , Reflex, Abnormal , Severity of Illness Index , Space Perception , Vision Tests
15.
Pharmacol Biochem Behav ; 79(3): 401-11, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15582012

ABSTRACT

Extracts from the plant guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. To date, little research in humans has examined the potential psychoactive effects of these extracts. Extracts of Panax ginseng, which are often sold in combination with guarana, contain similar potentially active components, and have been shown to modulate cognitive performance. In this double-blind, counterbalanced, placebo-controlled study, the cognitive and mood effects of separate single doses of: 75 mg of a dried ethanolic extract of guarana (approx 12% caffeine), 200 mg of Panax ginseng (G115), and their combination (75 mg/200 mg), were assessed in 28 healthy young (18-24) participants. On each day of the study (separated by a 7-day washout), cognitive performance and subjective mood were assessed pre-dose and at 1, 2.5, 4 and 6 h post-dose using the Cognitive Drug Research computerised assessment battery, Serial subtraction tasks and Bond-Lader mood scales. In comparison to placebo, all three treatments resulted in improved task performance throughout the day. In the case of guarana, improvements were seen across 'attention' tasks (but with some evidence of reduced accuracy), and on a sentence verification task. While also increasing the speed of attention task performance, both ginseng and the ginseng/guarana combination also enhanced the speed of memory task performance, with little evidence of modulated accuracy. Guarana and the combination, and to a lesser extent ginseng, also led to significant improvements in serial subtraction task performance. These results provide the first demonstration in humans of the psychoactive effects of guarana, and confirmation of the psychoactive properties of ginseng. Given the low caffeine content (9 mg) of this dose of guarana extract, the effects are unlikely to be attributable to its caffeine content.


Subject(s)
Cognition/drug effects , Panax , Paullinia , Psychomotor Performance/drug effects , Adult , Cognition/physiology , Double-Blind Method , Drug Combinations , Drug Interactions/physiology , Female , Humans , Male , Plant Extracts/administration & dosage , Psychomotor Performance/physiology
16.
Pharmacol Biochem Behav ; 75(3): 669-74, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12895685

ABSTRACT

Sage (Salvia) has a longstanding reputation in British herbal encyclopaedias as an agent that enhances memory, although there is little evidence regarding the efficacy of sage from systematized trials. Based on known pharmacokinetic and binding properties, it was hypothesised that acute administration of sage would enhance memory in young adult volunteers. Two experiments utilised a placebo-controlled, double-blind, balanced, crossover methodology. In Trial 1, 20 participants received 50, 100 and 150 microl of a standardised essential oil extract of Salvia lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 microl of a standardised essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a 7-day washout period with treatment order determined by Latin squares. Assessment was undertaken using the Cognitive Drug Research computerised test battery prior to treatment and 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults.


Subject(s)
Memory/drug effects , Nootropic Agents/pharmacology , Oils, Volatile/pharmacology , Salvia , Acetylcholinesterase/metabolism , Adolescent , Adult , Animals , Cattle , Double-Blind Method , Female , Humans , Male , Memory/physiology
17.
Neuropsychopharmacology ; 28(10): 1871-81, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12888775

ABSTRACT

Melissa officinalis (Lemon balm) is a herbal medicine that has traditionally been attributed with memory-enhancing properties, but which is currently more widely used as a mild sedative and sleep aid. In a previous study it was demonstrated that a commercial Melissa extract led to dose-specific increases in calmness, and dose-dependent decrements in timed memory task performance. However, the extract utilized in that study did not exhibit in vitro cholinergic receptor-binding properties. The current study involved an initial screening of samples of M. officinalis for human acetylcholinesterase inhibition and cholinergic receptor-binding properties. The cognitive and mood effects of single doses of the most cholinergically active dried leaf were then assessed in a randomized, placebo-controlled, double-blind, balanced crossover study. Following the in vitro analysis, 20 healthy, young participants received single doses of 600, 1000, and 1600 mg of encapsulated dried leaf, or a matching placebo, at 7-day intervals. Cognitive performance and mood were assessed predose and at 1, 3, and 6 h postdose using the Cognitive Drug Research computerized assessment battery and Bond-Lader visual analog scales, respectively. In vitro analysis of the chosen extract established IC(50) concentrations of 0.18 and 3.47 mg ml(-1), respectively, for the displacement of [(3)H]-(N)-nicotine and [(3)H]-(N)-scopolamine from nicotinic and muscarinic receptors in the human cerebral cortex tissue. However, no cholinesterase inhibitory properties were detected. The most notable cognitive and mood effects were improved memory performance and increased 'calmness' at all postdose time points for the highest (1600 mg) dose. However, while the profile of results was overwhelmingly favorable for the highest dose, decrements in the speed of timed memory task performance and on a rapid visual information-processing task increased with decreasing dose. These results suggest that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer's disease. The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation.


Subject(s)
Affect/drug effects , Central Nervous System/drug effects , Cognition/drug effects , Melissa/chemistry , Receptors, Cholinergic/metabolism , Adolescent , Adult , Analysis of Variance , Attention/drug effects , Central Nervous System/metabolism , Dose-Response Relationship, Drug , Electronic Data Processing , Female , Humans , In Vitro Techniques , Inhibitory Concentration 50 , Male , Memory/drug effects , Neuropsychological Tests , Nicotine/pharmacokinetics , Plant Extracts/classification , Plant Extracts/pharmacology , Protein Binding , Psychomotor Performance/drug effects , Reaction Time/drug effects , Scopolamine/pharmacokinetics , Time Factors
18.
Anaesthesia ; 57(9): 868-76, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12190751

ABSTRACT

Flumazenil is traditionally administered intravenously to reverse the adverse effects of over sedation with benzodiazepines. The aim of this study was to test postoperative cognitive and psychomotor recovery from midazolam conscious sedation, following reversal with orally administered flumazenil. It was hypothesised that when administered by the oral route, flumazenil may enhance recovery over a prolonged period, thus increasing safety. Eighteen patients requiring intravenous midazolam sedation for dental treatment completed a randomised, double-blind, crossover trial. Following treatment the patients' sedation was reversed using either flumazenil or saline (as placebo), administered orally, on alternate appointments. Assessment of mood and cognitive function were undertaken using ClinPhone.cdr(R), a highly sensitive and specific computerised battery of cognitive tests administered by telephone prior to sedation and every hour for seven hours post reversal. Results indicate that within 20 min of administration, oral flumazenil is capable of partially reversing some cognitive and psychomotor impairments but the attentional and stimulus discrimination effects of midazolam sedation still remain.


Subject(s)
Antidotes/pharmacology , Cognition/drug effects , Flumazenil/pharmacology , Hypnotics and Sedatives/antagonists & inhibitors , Midazolam/antagonists & inhibitors , Psychomotor Performance/drug effects , Administration, Oral , Adult , Affect/drug effects , Anesthesia Recovery Period , Attention/drug effects , Conscious Sedation/methods , Cross-Over Studies , Dental Anxiety/prevention & control , Double-Blind Method , Humans , Memory, Short-Term/drug effects , Middle Aged , Postoperative Care/methods , Psychometrics , Reaction Time/drug effects
19.
Pharmacol Biochem Behav ; 72(4): 953-64, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12062586

ABSTRACT

Melissa officinalis (lemon balm) is a traditional herbal medicine, which enjoys contemporary usage as a mild sedative, spasmolytic and antibacterial agent. It has been suggested, in light of in vitro cholinergic binding properties, that Melissa extracts may effectively ameliorate the cognitive deficits associated with Alzheimer's disease. To date, no study has investigated the effects on cognition and mood of administration of Melissa to healthy humans. The present randomised, placebo-controlled, double-blind, balanced-crossover study investigated the acute effects on cognition and mood of a standardised extract of M. officinalis. Twenty healthy, young participants received single doses of 300, 600 and 900 mg of M. officinalis (Pharmaton) or a matching placebo at 7-day intervals. Cognitive performance was assessed using the Cognitive Drug Research (CDR) computerised test battery and two serial subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. In vitro IC(50) concentrations for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue were also calculated. Results, utilising the cognitive factors previously derived from the CDR battery, included a sustained improvement in Accuracy of Attention following 600 mg of Melissa and time- and dose-specific reductions in both Secondary Memory and Working Memory factors. Self-rated "calmness," as assessed by Bond-Lader mood scales, was elevated at the earliest time points by the lowest dose, whilst "alertness" was significantly reduced at all time points following the highest dose. Both nicotinic and muscarinic binding were found to be low in comparison to the levels found in previous studies.


Subject(s)
Affect/drug effects , Cognition/drug effects , Melissa/chemistry , Adult , Arousal/drug effects , Attention/drug effects , Dose-Response Relationship, Drug , Humans , Memory/drug effects , Memory, Short-Term/drug effects , Plant Extracts/pharmacology , Psychomotor Performance/drug effects , Reaction Time/drug effects , Reading , Receptors, Muscarinic/drug effects , Receptors, Nicotinic/drug effects
20.
Physiol Behav ; 75(5): 739-51, 2002 Apr 15.
Article in English | MEDLINE | ID: mdl-12020739

ABSTRACT

It has previously been demonstrated in separate studies that single doses of Ginkgo biloba, Panax ginseng, and a combination of the two extracts can improve different aspects of cognitive performance in healthy young volunteers. The present study directly compared the effects of single doses of G. biloba, ginseng, and a product combining the two on aspects of mood and cognitive performance in the same cohort of healthy, young adult volunteers. The study followed a randomised placebo-controlled, double-blind, balanced, cross-over design. Twenty participants received 360 mg of ginkgo, 400 mg of ginseng, 960 mg of a product combining the two extracts, and a matching placebo. Treatment order was dictated by random allocation to a Latin square, with a 7-day wash-out period between treatments. Cognitive testing comprised completion of the Cognitive Drug Research (CDR) computerised assessment battery and two serial subtraction mental arithmetic tasks. Mood was assessed with Bond-Lader visual analogue scales. Following a baseline cognitive assessment, further test sessions took place 1, 2.5, 4, and 6 h after the day's treatment was taken. The results largely supported previous findings. All three treatments were associated with improved secondary memory performance on the CDR battery, with the ginseng condition evincing some improvement in the speed of performing memory tasks and in the accuracy of attentional tasks. Following ginkgo and the ginkgo/ginseng combination performance of both the Serial Threes and Serial Sevens, subtraction tasks was also improved at the later testing sessions. No modulation of the speed of performing attention tasks was evident. Improvements in self-rated mood was also found following ginkgo and to a lesser extent the combination product.


Subject(s)
Affect/drug effects , Cognition/drug effects , Ginkgo biloba , Panax , Plant Extracts/pharmacology , Adolescent , Adult , Affect/physiology , Analysis of Variance , Attention/drug effects , Attention/physiology , Cognition/physiology , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Memory/drug effects , Memory/physiology , Reaction Time/drug effects , Reaction Time/physiology , Time Factors
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