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Parkinson's disease is accompanied by cognitive disorders which may affect procedural memory. Procedural memory uses a specific knowledge resource that expresses itself through pre-established acting procedures. The aim of this study was to better define the characteristics of procedural memory, first of all, by trying to determine the level of involvement of that memory in the acquisition process (during learning and/or during procedure maintenance), then by specifying the effect of the type of resource involved (verbal or motor). To achieve this, we compared the mnestic performances of 20 recent-onset parkinsonian patients with those of 20 healthy controls, using two memory tasks with a fixed rule (poetry, visuomotor tracking). Result analysis revealed that parkinsonian patients had more difficulty than controls in learning the two rules, regardless of the material involved. Their deficiencies were often associated with an impairment of executive functions, and the procedural memory problems described in parkinsonian patients are linked to the involvement of these resources in the various tasks.

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Performances of 12 patients with Alzheimer's disease (AD), 15 healthy elderly subjects and 20 young healthy volunteers were compared on two episodic memory tests. The first, a learning test of semantically related words, enabled an assessment of the effect of semantic relationships on word learning by controlling the encoding and retrieval processes. The second, a dual coding test, is about the assessment of automatic processes operating during drawings encoding. The results obtained demonstrated quantitative and qualitative differences between the population. Manifestations of episodic memory deficit in AD patients were shown not only by lower performance scores than in elderly controls, but also by the lack of any effect of semantic cues and the production of a large number of extra-list intrusions. Automatic processes underlying dual coding appear to be spared in AD, although more time is needed to process information than in young or elderly subjects. These findings confirm former data and emphasize the preservation of certain memory processes (dual coding) in AD which could be used in future therapeutic approaches.

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1. Findings in cognitive psychology and neuropsychology have led to consider the existence of several mnestic systems. This study focuses on a now clearly established distinction between the procedural and the declarative memories. 2. The aim of the present study was to try and determine which of the two acquisition steps (learning and automation) is affected by Parkinsonians' mnestic difficulties, and to verify if these difficulties are linked to the skill content (declarative or motor). 3. To answer these questions, 20 Parkinsonians under treatment underwent specific tests: the maze test and the arithmetic alphabet test. 4. Results show that, by comparison with 20 matched healthy individuals, the deficiencies observed in Parkinson's disease affect both the declarative and the motor skills. In addition, Parkinsonians suffer difficulties in both acquisition steps: learning and automation. 5. These results could account for the cognitive and motor disturbances observed in Parkinson's disease; these abnormalities should be among the pharmacological targets in future.

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Assessment of memory performance is now well established. However, the normal form of assessment does not evaluate memory problems encountered during daily activities, a situation relevant to the evaluation of drug effects on memory components. The present study examines the ecological validity of psychometric tests. 49 individuals, from 20 to 89 years old without any identified pathology were included in the study, with the aim of establishing correlations between an autoquestionnaire of memory, a standard memory battery (SM9) and a daily memory video test (DMV). No correlation was found between self-estimation and objective tests or DMV. A strong correlation (r = 0.81) was found between SM9 and DMV. Imaged information and verbal coding appear to be essential parameters of objective tests. These results confirm the ecological validity of the objective psychometric tests and in particular of SM9.

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Thirty five subjects (age: 45-69 years) with subjective memory loss, without any other neuropsychiatric or somatic disease, were recruited in a phase II study. This double blind randomized versus placebo controlled study compared the effects of minaprine (200 mg/d) with placebo, in two parallel groups, during 2 months, on memory, attention and vigilance. Three psychometric tests were the main criteria of assessment: a standardized battery of memory tests (SM 5), the dual-coding test, the analysis of choice reaction times (CRT) and the critical flicker fusion point (CFF). A positive effect of minaprine was detected on words delayed recall (p = 0.028) and immediate recognition of words (p = 0.049). The global clinical tests (CGI, MacNair scale) were not statistically modified. Tolerability of minaprine and placebo were comparable. A positive pharmacodynamic activity on mnemonic performance is thus demonstrated in favour of minaprine (200 mg/d) in this specific population characterized by a memory complaint. These results would lead to a phase III study in which the main criteria would be global scales in order to confirm the clinical reliability of the present results.

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A detailed analysis of the mnestic deficits associated with Parkinson's disease (PD) contributes to explaining the cognitive disorders and their well documented consequences. This study was designed to show that, in PD declarative as well as procedural memory is severely impaired. Three tests designed to explore this aspect of mnestic functioning were proposed to a group of 16 parkinsonian patients whose motoricity was controlled: inverted reading, braille reading, sound form association. The results obtained, compared with those of young and aged controls, show that PD is associated with marked deficits in both declarative and procedural memory. Declarative memory impairment was similar to that observed in the control population (healthy elderly subjects, age-matched with the PD patients) but more marked in PD subjects. The procedural memory deficit was linked with age and pathology. Procedural memory involves a variety of processing modules dedicated to the type of information (visual, auditive, tactile codes). The deficits observed were more like a loss of automatism than procedural impairment stricto sensu ('knowing how'). It would be worth pursuing research by studying akinesia and motor disorders from the angle of automatic memory impairment.

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One of the aims of cognitive psychology is to breakdown complex tasks into their most basic components. The components of explicit (declarative) and implicit (procedural) memory were thus analyzed in undemented, non-depressed Parkinsonian patients under anti-Parkinsonian treatment, and compared with young and elderly healthy subjects. Three series of experiments were conducted in 61 patients in total. Statistically significant results revealed an impairment of explicit memory (verbal recall of words and drawings) with preserved recall of faces, in Parkinsonians. Implicit memory was also deficient, only in association tests (sound-form; arithmetical alphabet) and maze tests. Braille reading tests and Toronto tower tests did not discriminate between Parkinsonians and elderly subjects. Lastly, analyzing learning and automation revealed a dysfunctioning in Parkinsonian patients. All these data indicate a dysregulation of the cortical-sub-cortical systems, not essentially pre-frontal, and not necessarily dopaminergic. Cognitively, it appears that procedural and implicit memories should be dissociated conceptually.

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The effect of zopiclone (7.5 mg) on attention, vigilance and memory components was evaluated during a nocturnal period in comparison to a placebo, to zolpidem (10 mg) and to flunitrazepam (1 mg) in a double blind, randomized study, after administration of a single dose in 16 young healthy volunteers. It appears that there is a clear effect on attention and vigilance; this effect is apparent during the kinetic phase of the absorption of the medication. The effect on memory is transient and is absent four hours after the ingestion of the drug. The objective results are not strictly consistent with the chronology of the subjective parameters (Leeds scale - Visual Analogue Scale). The three hypnotics under comparison do not fundamentally differ except in their kinetic/pharmacodynamic effect relationship. One important fact, taking the parameters as a whole, is that there is no objective "residual" effect.

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The subjects of this double-blind study were 18 elderly men and women (mean age, 69.3 years) with slight age-related memory impairment. In a crossover-study design, each subject received placebo or an extract of Ginkgo biloba (EGb 761) (320 mg or 600 mg) 1 hour before performing a dual-coding test that measures the speed of information processing; the test consists of several coding series of drawings and words presented at decreasing times of 1920, 960, 480, 240, and 120 ms. The dual-coding phenomenon (a break point between coding verbal material and images) was demonstrated in all the tests. After placebo, the break point was observed at 960 ms and dual coding beginning at 1920 ms. After each dose of the ginkgo extract, the break point (at 480 ms) and dual coding (at 960 ms) were significantly shifted toward a shorter presentation time, indicating an improvement in the speed of information processing.

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In this study, the various components of the memory process were analysed in 25 non-demented parkinsonian patients (PP). A battery of tests was used to explore words, drawings and semantic organization of items. Results were compared with young (n = 22) and elderly (n = 11) healthy controls. Scores were correlated with the characteristics of Parkinson disease. Recall of words and drawings was significantly disturbed in PP. In contrast, the recognition of drawings and faces was not impaired. A high degree of interindividual difference in performance was observed; it was strictly correlated with age but not with the features of parkinsonism. A specific pattern of memory impairment can be described in parkinsonism, which would suggest and support the theory that different pathogenic mechanisms are involved in ageing and in parkinsonian patients.

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The respective effects of three antidepressant drugs (moclobemide, 450 mg/j; viloxazine, 300 mg/j; maprotiline, 150 mg/j) on vigilance, attention, and memory were compared. Young depressed outpatients (n = 46) entered a double-blind, randomized, monocentre clinical trial lasting for 6 weeks. Drug actions were assessed through the regular determination of critical flicker fusion point (CFF), reaction times (SRT), and a battery to measure memory components. None of the three drugs caused deterioration in cognitive functions. On the other hand, moclobemide improved both vigilance and attention (CFF, SRT) and some crucial components of memory (general memory scores, delayed word recall, recognition of familiar faces). This effect was rapid, stable, and superior to those of viloxazine and maprotiline. It may be explained by moclobemide's selective and reversible inhibition of monoamine oxidase A, as well as by the lack of any anticholinergic action.

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Knowledge on the diverse processes involved in memory has been gained from multiple approaches, all necessary for the development of molecules aimed at enhancing memory. However, the neurobiological aspects of apprenticeship and memory remain to be fully elucidated. Long-term storage of information in the nervous system is under the control of glycoprotein synthesis. The chemistry of storage has been extensively studied in mollusks because of their simple neuroarchitecture. In mammals, the phenomenon of hippocampic long-term potentialization (HLTP), to a large extent linked to modification of glutamatergic transmissions, has been demonstrated. Stimulation of N-methyl-DL-aspartase (NMDA) receptors induces an influx of calcium, which is needed for HLTP maintenance, as are the activation of protein kinase C (PKC) and the synthesis of new proteins, for example calmodulin. At the molecular level, a cascade of biochemical events leads to modifications of neuronal connections, thus constituting the basis of memory. Memory-improving substances can be classified according to their theoretical mechanism of action: molecular pharmacology (agents inducing phenomena that mimic HLTP), neurotransmission (molecules acting on the cholinergic, noradrenergic, serotoninergic, GABAergic or dopaminergic systems), pathophysiology (substances antagonizing or correcting anomalies responsible for the memory deficiency, i.e., the cognitive enhancers). The development of memory-enhancing drugs has encountered many obstacles, notably the difficulty in evaluating the effectiveness of a medication in improving memory. It is imperative that guidelines be established for the clinical and experimental development of such substances as well as the standardization of tests in animals and man.

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Rather than reviewing once again the published literature on drugs which are capable of modifying the memory process, the authors stress the methodological difficulties which impede the development of such products. At the moment, substances which act on neurotransmission systems, and in particular cholinergic and gabaergic agents, seem to be good candidates. The choice of the molecule to be studied in man depends on the neurochemical physiopathology of the memory disorder which one seeks to correct. For this reason, one tries to select an animal model of memory which is closest to the clinical situation pertaining to man on which the tested molecule might act favorably.

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