Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: assessment of attentional and mnemonic function using CANTAB

Sahakian, Barbara J.; Owen, Adrian M.; Morant, Nicola; Eagger, Sarah; Boddington, Stephen; Crayton, Lissa; Crockford, Helena A.; Crooks, Maureen; Hill, Katherine E.; Levy, Raymond

doi:10.1007/bf02244644

Cited by 219 publications

(124 citation statements)

References 38 publications

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“…First, the effect sizes for each comparison were very small indicating that, even if group differences were statistically significant, they were not clinically significant and therefore not meaningful. Second, we have also found the same test battery to be sensitive to the effects of petrol abuse , psychiatric illness (Purcell et al, 1998;Pantelis et al, 1997;Cairney et al, 2001) and very early neurodegenerative disease (Currie et al, 1992(Currie et al, , 1993Collie et al, 2001) and many other studies have shown that both licit and illicit drugs alter performance on the saccadic (Tedeschi et al, 1983a, b;Hotson et al, 1986) and the cognitive function tests (Sahakian et al, 1993;Elliot et al, 1997;Robbins et al, 1997) used here. Third, we are confident that individuals in this study were heavy kava users.…”

Section: Discussionmentioning

confidence: 43%

Saccade and Cognitive Function in Chronic Kava Users

Cairney

Clough

Maruff

et al. 2003

Neuropsychopharmacol

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Kava is an extract from the Piper methysticum Forst. f. plant that has been consumed in the Pacific islands for millennia and more recently, among indigenous populations, in northern Australia and throughout the Western world as an herbal medicine. Through alterations on neuronal excitation, kava induces muscle relaxation, anasthesia, and has anxiolytic properties. There have been several isolated reports of psychotic syndromes, severe choreoathetosis and possible seizures following kava use. However, there is no conclusive evidence that kava interferes with normal cognitive processes. We tested a group of current, ex, and nonkava users among an indigenous population in northern Australia, using saccade and cognitive tests that have proven cross-cultural validity and are sensitive to subtle disruptions of the brain arising from substance abuse or neuropsychiatric illness. Despite collecting data from among the heaviest reported kava drinkers in the world, we found no impairment in cognitive or saccade function in individuals who were currently heavy kava users (and had been for up to 18 years), nor was there any impairment in individuals who had been heavy kava users in the past but had abstained for longer than 6 months. Current and ex-kava users showed a higher rate of kava dermopathy, lower body mass index, lowered blood lymphocytes and, in addition, current kava users showed elevated liver enzymes. While there has recently been increasing concern about potentially fatal liver damage attributed to kava use, we have found no evidence of brain dysfunction in heavy and long-term kava users.

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Section: Discussionmentioning

confidence: 43%

Saccade and Cognitive Function in Chronic Kava Users

Cairney

Clough

Maruff

et al. 2003

Neuropsychopharmacol

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“…Recently, a 4-choice human analog of the 5-CSRTT has been introduced (Voon et al, 2014), which compared with previous CANTAB version (Sahakian et al, 1993) was specifically designed to measure premature responses. This task has shown parallel effects for human substance abusers to those of high impulsive rats that compulsively selfadminister cocaine (Belin et al, 2008).…”

Section: Introductionmentioning

confidence: 44%

Serotonin Depletion Induces ‘Waiting Impulsivity’ on the Human Four-Choice Serial Reaction Time Task: Cross-Species Translational Significance

Worbe

Savulich

Voon

et al. 2014

Neuropsychopharmacol

111

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Convergent results from animal and human studies suggest that reducing serotonin neurotransmission promotes impulsive behavior. Here, serotonin depletion was induced by the dietary tryptophan depletion procedure (TD) in healthy volunteers to examine the role of serotonin in impulsive action and impulsive choice. We used a novel translational analog of a rodent 5-choice serial reaction time task (5-CSRTT)-the human 4-CSRTT-and a reward delay-discounting questionnaire to measure effects on these different forms of 'waiting impulsivity'. There was no effect of TD on impulsive choice as indexed by the reward delay-discounting questionnaire. However, TD significantly increased 4-CSRTT premature responses (or impulsive action), which is remarkably similar to the previous findings of effect of serotonin depletion on rodent 5-CSRTT performance. Moreover, the increased premature responding in TD correlated significantly with individual differences on the motor impulsivity subscale of the Barratt Impulsivity Scale. TD also improved the accuracy of performance and speeded responding, possibly indicating enhanced attention and reward processing. The results suggest: (i) the 4-CSRTT will be a valuable addition to the tests already available to measure impulsivity in humans in a direct translational analog of a test extensively used in rodents; (ii) TD in humans produces a qualitatively similar profile of effects to those in rodents (ie, enhancing premature responding), hence supporting the conclusion that TD in humans exerts at least some of its effects on central serotonin; and (iii) this manipulation of serotonin produces dissociable effects on different measures of impulsivity, suggesting considerable specificity in its modulatory role.

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“…Finally, treatment of AD patients with the anticholinesterase drug, tetrahydroaminoacridine (THA), improves attention and attenuates the clinical severity of dementia, but has no effect on episodic or declarative memory functions, which depend on the function of the medial temporal lobe memory systems (Sahakian et al 1993;Riekkinen et al 1998). Furthermore, THA failed to attenuate the central executive dysfunction, as it had no effect on working memory or fluency performance in AD patients (Alhainen et al 1991b;Sahakian et al 1993).…”

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confidence: 43%