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[Effectiveness of donepezil on several cognitive functions in patients with Alzheimer's disease over 12 months].

OBJECTIVES: The efficacy of donepezil for the treatment of cognitive dysfuntion in Alzheimer's disease has been demonstrated. The objective [corrected] of this study was to evaluate the effectiveness of donepezil in different neuropsychological areas of mild or moderate AD patients over a period of twelve months compared with data from untreated patients (historical control). METHODS: This was an open-label study where 100 patients received donepezil 5mg or 10 mg/day for twelve months. Because the study was uncontrolled, data were compared with historical data from 81 patients who had not received anticholinesterase inhibitors. The CAMCOG neuropsychological battery was used in both groups at baseline and at month 12. RESULTS: A hundred patients (30% male and 70% female) were enrolled in the study receiving donepezil 5 or 10 mg/day (average age: 74.3 6.1 years). The historical control group consisted of 81 people (average age 72.9 6.5 years), 29.6% of whom were men. There were no significant differences with respect to age, sex and CAMCOG score at baseline. The differences within the groups were significant in the following neuropsychological areas: recent, remote and learning memory, attention, calculation and abstract verbal thinking. Differences in expressive language and learning memory between both groups were confirmed by the multivariative analysis of baseline. CONCLUSION: The rate of cognitive deterioration observed in mild to moderate AD patients receiving open-label donepezil treatment was less than expected if this cohort had not been treated. The cognitive beneficial effects observed during one year treatment with donepezil were mainly focused on memory and verbal expression.

Acetylcholine↗

Switching memory systems during learning: changes in patterns of brain acetylcholine release in the hippocampus and striatum in rats.

This experiment measured acetylcholine (ACh) release simultaneously in the hippocampus and striatum while rats were trained in a cross maze. Consistent with past findings, rats initially showed learning on the basis of place (i.e., turning to the correct position relative to the room), but after extensive training, rats shifted to learning on the basis of response (i.e., turning to the right/left to find the food). Profiles of ACh release in the hippocampus and striatum were markedly different during training. In the hippocampus, ACh release increased by approximately 60% at the onset of training and remained at that level of release throughout training, even after the rats began to show learning on the basis of turning rather than place. In the striatum, increases in ACh release occurred later, reaching asymptotic increases of 30-40%, coincident with a transition from expressing place learning to expressing response learning. These findings suggest that the hippocampal and striatal systems both participate in learning in this task, but in a manner characterized by differential activation of the neural systems. The hippocampal system is apparently engaged first before the striatum is activated and, to the extent the hippocampus is important for place learning, promotes the use of a place solution to the maze. Later in training, although the hippocampus remains activated, the striatum is also activated in a manner that may enable the use of a response strategy to solve the maze. These findings may offer a neurobiological marker of a transition during skill learning from declarative to procedural learning.

Acetylcholine↗

[Pharmacologic correction of learning and memory disorders induced by exposure to high-frequency electromagnetic radiation].

Acute exposure of rats to microwaves (12.6 chr, 2375 MHz, power density 1 mW/cm2) induced the retrograde amnesia. It was show the role of opioidergic, benzodiazepine, GABAergic and cholinergic components in the amnesic effects of microwaves. Piracetam (100 mg/kg, i. p.) and oxiracetam (10 mg/kg, i. p.) prevented the negative effects of microwaves on memory processes.

Animals↗

Impairment of spatial learning and memory in ELKL Motif Kinase1 (EMK1/MARK2) knockout mice.

The hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer's disease (AD) and of the associated cognitive decline. EMK1 (MARK2) is a serine/threonine kinase which phosphorylates tau and MAP2. An involvement of this kinase in memory functions is not established. We used a behavioral approach to study the phenotype of EMK1-null mice (EMK1-KO) as a possible model of MAP2/tau altered phophorylation. Compared to wild type mice, EMK1-KO mice did not differ in non-cognitive aspects of behavior, such as locomotion in activity cages, or anxiety in the elevated plus maze. However, they exhibited lower performance in the first stage of acquisition of a hippocampal-dependent spatial learning, as assessed in a radial water maze, although, they acquired the task with repeated training. They were again found to be impaired on re-learning a new platform position. In addition, they exhibited poor long-term retention performance. These data underline the importance on both early memory processes and long-term retrieval, of the dynamic instability of microtubules generated by the phosphorylation of MAPs.

Analysis of Variance↗

Measuring cognition in menopause research: a review of test use.

OBJECTIVE: To examine critically how various aspects of memory functions have been assessed in menopause-related research. METHOD: Twenty peer-reviewed articles on the menopause and cognitive functioning published between 1991 and 2000 were identified through a computerized Medline search. All studies utilized healthy non-demented women, and assessed specific aspects of cognitive functioning using standardized tests rather than self-reporting of perceived functioning. RESULTS: Measures used to assess attention and concentration, verbal memory, learning and verbal expression, visual memory, concept formation and reasoning have all been reviewed. Findings from studies assessing attention and concentration demonstrate inconsistent results with regard to hormone levels or menopausal status. Although five measures of verbal learning and memory have been considered, no articles published in the past decade have reported unequivocal results for any one measure. Only one study reviewed found significant differences in measures of verbal expression between hormone therapy users and non-users. In addition, no strong association between estrogen level and visual memory was identified in the studies reviewed. CONCLUSIONS: This careful analysis demonstrates that, within the studies of cognitive abilities of menopausal women reviewed in this article, a wide variety of tests have been used. However, the body of literature considered neither consistently nor conclusively demonstrates a clear effect of exogenous hormone therapy on memory. It is suggested that verbal memory, visual memory, concept formation and reasoning should be simultaneously investigated in future research, and that covariate measures of attention and concentration, verbal expression and reasoning are also included. In addition, within each specific domain, the psychometric properties of tests, the populations they were intended to assess and the specific aspects of cognitive function they were designed to address need to be more closely considered.

Cognition↗

Effects of vasopressin and analogue [d(CH2)1(5), Tyr (Me)2, Val4, delta 3Pro7)] AVP on learning and memory in rats chronically treated with ethanol.

Rats with impaired active and passive avoidance induced by chronic administration of ethanol were studied. Vasopressin (AVP) and analogue (d(CH2)1(5), Tyr (Me)2, Val4, delta 3Pro7] AVP (icv, 2 micrograms) eliminated the toxic effect of ethanol, and analogue AVP improved retrieval of passive avoidance situation in both control and postalcohol groups of rats. Chronically administered ethanol markedly depressed the ability to learn. AVP administered icv markedly delayed extinction of conditioned avoidance situation in both groups of rats, and did not influence acquisition in this test. Analogue AVP has no influence on extinction and acquisition in the control and post-alcohol groups of rats.

Animals↗

Opposite effects depending on learning and memory demands in dorsomedial prefrontal cortex lesioned rats performing an olfactory task.

In this study, the functional properties of the dorsomedial prefrontal cortex (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue olfactory discrimination task, dmPFC lesioned animals improved performance across sessions more rapidly than operated control animals. In an olfactory task using fixed interval training, animals with similar lesions were impaired. Both effects, although opposite, can be explained by a temporal processing deficit. The present results seem to indicate that the dmPFC is required for timing, classified as part of non-declarative memory. As reference memory improved in the lesioned animals, the finding is that the dmPFC supports non-declarative memory and thus interacts with declarative memory in the long-term formation of the associations between a particular stimulus (olfactory cue) and particular responses.

Animals↗

Influence of increased motor activity on learning and memory in albino rats.

The experiment has been carried out with 20 male Wistar rats with initial age 30 +/- 5 days, equally divided in two groups: controls and motor-loaded rats. The experimental animals ran five days a week on a treadmill covering 60,540 m for 133 training sessions. Afterwards using a multi-chamber semi-automated labyrinth it was found that systematic and dosed motor loading leads to significant improvement of both learning and retention. The results obtained are examined as a consequence of the biochemical and morphofunctional changes developing in the central nervous system under the effect of prolonged motor activity.

Animals↗

Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept.

Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.

Animals↗

The effects of peripheral D-amphetamine, 4-OH amphetamine, and epinephrine on maintained discharge in the locus coeruleus with reference to the modulation of learning and memory by these substances.

D-Amphetamine, 4-OH amphetamine, and epinephrine have been shown in many behavioral studies to facilitate memory when given post-training. The effect of these drugs on the maintained discharge of cells in the locus coeruleus (LC) was investigated using a route of administration (intraperitoneal) and a log-dose range of these drugs comparable to those used in the behavioral experiments. D-Amphetamine profoundly suppressed maintained discharge: an inhibitory effect was observed at every dose (0.1, 1.0, 10.0 mg/kg). In contrast, only the highest dose of 4-OH amphetamine (8.2 mg/kg) inhibited activity in the LC, and this effect was a modest one. Unlike the amphetamines, epinephrine (500 micrograms/kg) elevated maintained discharge. These results are discussed in the context of the hypothesized involvement of the LC in the enhancement of memory by these drugs.

Amphetamines↗

NBQX does not affect learning and memory tasks in mice: a comparison with D-CPPene and ifenprodil.

The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX) did not impair working memory measured as alternation behavior in the Y-maze in mice. No depressant effect on alternation was detected even when NBQX impaired locomotion measured as the total number of arm entries. Similar profile of action in the Y-shaped maze was observed after administration of an anti-ischemic drug ifenprodil. In contrast, the N-methyl-D-aspartate (NMDA) antagonist (D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylate (D-CPPene) impaired spontaneous alternation. In the step-through passive avoidance task, mice were trained to avoid dark compartment entry. NBQX and ifenprodil did not impair learning in this task when administered before or immediately after training. In contrast, D-CPPene disturbed acquisition when administered before but not immediately after training or before retention test. These observations suggest that AMPA receptors are not critically involved in the formation of spatial working memory and acquisition (storage) in the passive avoidance, and have no effect on recall (retrieval) from long-term memory.

Animals↗

Effects of T-82, a novel acetylcholinesterase inhibitor, on impaired learning and memory in passive avoidance task in rats.

Effects of 2-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dihydro-9-methoxy-1H-pyrrolo[3,4-b]quinolin-1-one hemifumarate (T-82), a new quinoline derivative, on drug- and basal forebrain lesion-induced amnesia models were examined in rats. Scopolamine (0.5 mg/kg, i.p.) and cycloheximide (1.5 mg/kg, s.c.) shortened the step-through latency in the passive avoidance task. T-82 significantly ameliorated amnesia induced by scopolamine or cycloheximide at the dose of 0.03, 0.1 and 0.3 mg/kg, p.o., and 0.3 and 1.0 mg/kg, p.o., respectively. Basal forebrain lesions with ibotenic acid shortened the step-through latency in passive avoidance task. An acute (0.1 and 0.3 mg/kg, p.o.) or subacute (0.03-0.3 mg/kg, p.o., for 7 days) treatment of T-82 significantly reversed the shortened latency. These results suggest that T-82 may ameliorate the impairment of memory induced by acetylcholinergic dysfunction.

Amnesia↗

NDRAM: nonlinear dynamic recurrent associative memory for learning bipolar and nonbipolar correlated patterns.

This paper presents a new unsupervised attractor neural network, which, contrary to optimal linear associative memory models, is able to develop nonbipolar attractors as well as bipolar attractors. Moreover, the model is able to develop less spurious attractors and has a better recall performance under random noise than any other Hopfield type neural network. Those performances are obtained by a simple Hebbian/anti-Hebbian online learning rule that directly incorporates feedback from a specific nonlinear transmission rule. Several computer simulations show the model's distinguishing properties.

Algorithms↗

Gender differences in learning and memory after pediatric traumatic brain injury.

Thirty boys and 30 girls who sustained a traumatic brain injury (TBI) were evaluated within 1 year post injury with the California Verbal Learning Test-children's Version (CVLT-C; D. C. Delis, J. H. Kramer, E. Kaplan, & B. A. Ober, 1994). Boys had statistically significantly lower performance on the CVLT-C than girls in the absence of statistically significant group differences on various demographic and neurological variables. Although the effect size for this difference was modest (eta2 = .09), gender accounted for a statistically significant amount of the variance (5%) in CVLT-C scores in addition to effects of injury severity and age. It is concluded that male gender is associated with an increased risk for retrieval deficits after pediatric TBI, possibly because of reduced speed or efficiency of information processing.

Brain↗