Explicit memory in Alzheimer's, Huntington's, and Parkinson's diseases.

OBJECTIVE--Comparing the pattern of spared and impaired memory functions in neurodegenerative diseases known to affect different brain structures. DESIGN--Various situations of acquisition (free encoding or controlled encoding) and retrieval (immediate and delayed free and cued recall, recognition) were used. SETTING--Referral center. PATIENTS--Fifteen for each disease (ie, senile dementia of the Alzheimer type [SDAT], Parkinson's and Huntington's), matched for education, severity of dementia, and depression. MAIN OUTCOME MEASURES--Comparison of free and controlled encoding situations, relationships between memory, executive, and linguistic functions test scores. RESULTS--In the free encoding situation: no difference among the three groups, but higher numbers of intrusions and false recognitions in SDAT. In the controlled situation: cued recall and recognition scores significantly higher in Parkinson's disease and Huntington's disease than in SDAT. Memory performances correlated with executive functions test scores in Huntington's disease and Parkinson's disease, but not in SDAT. All results significant at P < .01. CONCLUSIONS--Clear distinction between the true amnesic syndrome of SDAT, compatible with lesions of hippocampus and temporal cortex, and the inefficient planning of memory processes of Huntington's disease and Parkinson's disease, which might result from a striatofrontal dysfunction.

Are explicit memory disorders of progressive supranuclear palsy related to damage to striatofrontal circuits? Comparison with Alzheimer's, Parkinson's, and Huntington's diseases.

To test the hypothesis that memory disorders of subcortico-frontal dementia result mainly from inefficiency of retrieval processes of stored information, we compared verbal learning in 15 patients with progressive supranuclear palsy, prototypical of "subcortical dementia," in free (California Verbal Learning Test) and controlled (Grober and Buschke's Test) encoding situations, with that of 19 controls, matched for age and level of education. The progressive supranuclear palsy patients showed memory deficits characterized by impaired immediate memory span, disturbed learning and consistency of recall, and abnormal number of false alarms at recognition, which were dramatically alleviated by controlled encoding associated with cued recall, using the same semantic cues. This memory profile was markedly different from that of patients with senile dementia of the Alzheimer type (n = 15), characterized by more rapid forgetting and less improvement in the controlled situation. Instead, it was similar to the memory pattern of patients with Parkinson's (n = 15) and Huntington's (n = 15) diseases. These results show a similar profile of memory disturbance in disorders involving damage to the striatofrontal system and suggest that the cortical and hippocampal lesions of PSP patients are insufficiently severe to interfere with the specific memory profile characteristic of the disease.

The neuropsychological pattern of corticobasal degeneration: comparison with progressive supranuclear palsy and Alzheimer's disease.

The pattern of cortical and subcortical neuropathologic lesions in corticobasal degeneration (CBD) should predict a specific cognitive profile in this disease. To characterize this profile and to determine its specificity by comparison with progressive supranuclear palsy (PSP) and senile dementia of the Alzheimer's type (SDAT), we used an extensive neuropsychological battery assessing global efficiency, executive functions, various tests of encoding and retrieval, dynamic motor organization, and upper limb praxis. We compared the performance of patients with CBD (n = 15) with that of controls (n = 19) matched for age and education, and with that of patients with PSP and SDAT (15 in each group), matched for severity of dementia and depression. Patients with CBD showed: (1) a moderate global deterioration; (2) a dysexecutive syndrome similar to that of patients with PSP and more severe than in SDAT; (3) explicit learning deficits, without retention difficulties and easily compensated by using the same semantic cues at encoding and retrieval as in PSP; this was in contrast with SDAT where cued recall and recognition were also impaired; (4) disorders of dynamic motor execution (temporal organization, bimanual coordination, control, and inhibition) similar to those of patients with PSP and not in SDAT; (5) asymmetric praxis disorders (posture imitation, symbolic gesture execution, and object utilization) that were not observed in PSP or SDAT. Patients with CBD show a specific neuropsychological pattern associating a dysexecutive syndrome, likely due to degeneration of the basal ganglia and prefrontal cortex, and asymmetric praxis disorders, which might be related to premotor and parietal lobe lesions. This neuropsychological profile may help to distinguish this condition clinically from other neurodegenerative diseases.

Memory for spatial location is affected in Parkinson's disease.

Are the striato-frontal neuronal circuits implicated in learning of item-specific spatial coordinates? To answer this question, we compared the performance of 20 patients with Parkinson's disease to that of 14 controls matched for age, global cognitive efficiency and mood, on a visuo-spatial learning task with little involvement of motor and constructive functions, allowing control of encoding and comparison of free recall, cued recall and recognition. Compared to controls, patients showed a severe memory impairment for visuo-spatial location of pictures, contrasting with relative preservation of verbal memory, and mild difficulties in perceptive visuo-spatial and executive functions. These results implicate striato-frontal neuronal circuits in memory for spatial location.

Is impaired memory for spatial location in Parkinson's disease domain specific or dependent on 'strategic' processes?

Spatial memory has been found to be impaired in Parkinson's disease (PD). To determine the nature of the deficit, we compared the performance of'standard' levodopa-treated patients with PD to that of matched control subjects in different situations: (i) spatial versus verbal conditional associative learning; (ii) 'global' versus 'local' contextual encoding; (iii) pattern span and related supraspan learning. The relationship between dopaminergic depletion, which characterizes the disease, and the impaired memory processes was investigated by comparing the performance of 'de novo' not yet treated PD patients to that of matched control subjects. Both groups of PD patients were impaired in all situations requiring strategic processes, shared a decreased pattern span and had a normal visuospatial learning once the pattern span was taken into account. All these results suggest that the memory deficit for spatial location observed in PD results mainly from a disturbance of strategic processes and from decreased attentional resources, which may be due, at least in part, to the dopaminergic depletion and related striatofrontal dysfunction.

Memory for spatial location in 'de novo' parkinsonian patients.

A deficit in memory for spatial location was recently reported in typical non-demented parkinsonian patients ('standard'). Is this deficit related to dopamine depletion? Such an association would reinforce the suggestion that striato-frontal neuronal circuits are implicated in memory for item-specific spatial coordinates. To answer this question, we compared the performance of 10 recently diagnosed and not yet treated parkinsonian patients ('de novo'), in which the neurobiochemical deficit is considered to involve mainly the nigrostriatal dopaminergic system, to that of 14 controls matched for age, global cognitive efficiency and mood, on a visuospatial learning test. The task required little motor or constructive functions and was designed to allow control of encoding and comparison of free recall, cued recall and recognition. Compared to controls, 'de novo' patients displayed a lower performance in memory for visuospatial location of pictures, contrasting with relative preservation of verbal memory, perceptive visuospatial and executive functions. These results confirm the sensitivity of visuospatial memory even at an early stage of Parkinson's disease and suggest the implication of the nigrostriatal dopaminergic system, and associated striato-frontal neuronal circuits, in executive processes needed for spatial location learning.

The influence of semantic and perceptual encoding on recognition memory in Alzheimer's disease.

Previous results from a population of patients with Alzheimer's disease (Dalla Barba and Goldblum, 1996) demonstrated that the ability of patients to make a semantic association between two items was significantly and positively correlated to their performance on a yes/no recognition task for the same items and that patients who were impaired on the semantic task did significantly worse on the recognition task than patients who were unimpaired on the semantic task. These findings gave support to a hierarchical model of organization of human memory in which episodic memory depends on the integrity of semantic memory. The present study further investigates the relationship between semantic memory deficits and episodic recognition memory in 15 patients with Alzheimer's disease and 15 controls, as a function of their semantic and perceptual encoding abilities and of their cognitive impairment in other domains. The results confirmed the previous findings and showed that, although patients heavily relied on perceptual analysis, this type of encoding did not enhance their recognition memory. Correlations analyses showed that some patients who were not impaired in the semantic association, but with particularly low scores on a verbal fluency task presented with a pattern, in recognition memory tasks, that suggests a possible early involvement of frontal lobes in this subgroup of patients.

Is the HM story only a "remote memory"? Some facts about hippocampus and memory in humans.

In this review, we argue that a number of current data support the notion that the hippocampal formations play an important role in episodic memory in humans. We will focus on data gathered from three topics within this field: (1) the neuropsychological study of memory in degenerative diseases, which provides striking dissociations of processes, as a function of the location of cerebral lesions and of their functional consequences; (2) the description of patients' memory difficulties after unilateral medial temporal lobectomy. Given the visuo-verbal dissociation, we may anticipate that the study of the effects of such lesions may help in the understanding of the role of the hippocampus in memory, in terms of: (i) the stage of memory processing where the hippocampus is really involved (encoding, consolidation and/or retrieval); (ii) the specificity of the impairments as a function of the nature (verbal vs. visuo-spatial) of the to-be-remembered material; (3) recent evidence from imaging studies: (i) the morphological approach, which provides interesting information with the study of correlations between the volumes of diverse cerebral regions-particularly the volume of the hippocampus-and episodic memory performance and other cognitive measures; (ii) metabolic studies, using PET scan, which were first designed for correlational analyses between performance in episodic memory tasks and glucose utilization at rest in diverse regions of interest, such as the hippocampal formations; (iii) activation studies with PET and functional MRI, which are actually more straightforward, since they allow correlations between the metabolism in regions of interest and performance on line (e.g. during encoding or retrieval of information). In our view, inasmuch as such different approaches-degenerative diseases, lesions or imagery-provide convergent information, they give renewed weight to the notion according to which the hippocampal formations are critically concerned in episodic memory processes.

Reticular stimulation facilitates retrieval of a 'forgotten' maze habit.

Rats tested 25 days after training in a complex maze showed significant forgetting. Stimulation of the mesencephalic reticular formation immediately prior to retention testing facilitated performance in that stimulated rats made fewer errors (but did not run faster) than non-stimulated controls. Rats exposed to a contextual cue as a reminder before testing ran faster and made fewer errors than controls. Results are discussed in terms of forgetting being due to retrieval failure, and the reticular stimulation facilitating retrieval of information concerning the spatial configuration of the maze.

Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease.

PURPOSE: To evaluate the accuracy of hippocampal and amygdala volume measurements in diagnosing patients in the early stages of Alzheimer disease. METHODS: Measurements of the hippocampal formation, amygdala, amygdalohippocampal complex (the two measurements summed), caudate nucleus, and ventricles, normalized for total intracranial volume, were obtained on coronal sections (1.5 T, 400/13 [repetition time/echo time], 5 mm) of 13 patients in the mild (minimental status > or = 21) and five patients in the moderate stages of Alzheimer disease (10 < minimental status < 21), and eight age-matched control subjects. RESULTS: For patients with a minimental status score of 21 or greater, atrophy was significant for the amygdala and hippocampal formation (-36% and -25% for amygdala/total intracranial volume and hippocampal formation/total intracranial volume, respectively), but not for the caudate nucleus. No significant ventricular enlargement was found. For patients with a minimental status score less than 21, atrophy was more severe in all structures studied (amygdala/total intracranial volume, -40%; hippocampal formation/total intracranial volume, -45%; caudate nucleus/total intracranial volume, -21%), and ventricles were enlarged (63%). No overlap was found between Alzheimer disease and control values for the amygdalohippocampal volume, even in the mild stages of the disease. In Alzheimer disease patients, hippocampal formation volumes correlated with the minimental status. CONCLUSION: Hippocampal and amygdala atrophy is marked and significant in the mild stages of Alzheimer disease. Volumetric measurements of the amygdala and the amygdalohippocampal complex appear more accurate than those of the hippocampal formation alone in distinguishing patients with Alzheimer disease.

Cross-form priming in normal aging and in mild dementia of the Alzheimer type.

Twenty patients at early stages of Alzheimer's disease (AD), 20 elderly control subjects and 20 young subjects completed a cross-form priming task, followed by a free recall task. Results show that patients with mild AD display priming effects, and that these priming effects are strictly comparable to those obtained by elderly and young control subjects. Moreover, while the patients' performances are normal in the implicit part of the task, they are massively impaired in the explicit free recall task. These results don't support the hypothesis of a dissociation of performances between identification tasks and generation tasks in Alzheimer's disease, and show that conceptual priming can be observed at early stages of the disease, despite semantic memory impairments.

Priming for new associations in normal aging and in mild dementia of the Alzheimer type.

Recent data suggest that patients with Alzheimer's disease (AD) are able to show perceptual priming and, to some extent, conceptual priming for material which has preexisting representations in memory, and that normal elderly subjects are able to automatically activate pre-existing representations in both perceptual and conceptual priming tasks. An important question concerns the capacity of showing priming for materials without pre-existing representations in memory in normal and pathological aging. In order to address this issue, 20 patients with mild AD, 20 elderly controls and 20 young controls subjects were assessed with a paradigm of priming for new verbal associations. Neither the patients nor the normal elderly subjects demonstrated priming effects for new associations, while young subjects showed significant priming effects. These results suggest that the absence of priming for new verbal associations is attributable more to an effect of aging than to a specific effect of Alzheimer's disease.

Explicit memory, procedural learning and lexical priming in Alzheimer's disease.

Different aspects of memory functions were studied in two groups of patients with Alzheimer's disease (AD) and in normal elderly controls. The tests included: explicit memory tests with free and cued recall, and recognition measures; learning of a motor skill; learning of a perceptual skill with verbal material; a priming task with the word stem completion paradigm. The data confirmed that, besides severe impairment for all measures of explicit memory, AD patients were able to learn and retain normally a motor skill in the rotor pursuit task, even across a long retention interval. Moreover, sparing of procedural learning was not restricted to motor tasks, since patients learned normally a mirror-reading task, demonstrating (a) rapid acquisition of the procedure, and (b) acquisition of item-specific information for repeated words. This last effect is accounted for in terms of repetition priming effects rather than of explicit memory strategies, since patients had also normal repetition effect in the word stem completion paradigm.

Specificity of memory deficits after right or left temporal lobectomy.

An impairment of verbal memory has consistently been associated with resection of the left dominant temporal lobe, whereas non-verbal memory deficits have been less reliably observed following resection of the right temporal lobe. Such a dissociation may be due to material-specific differences of processing between verbal and non-verbal information. Alternatively, the influence of the left and right limbic structures may vary according to the stage of memory processing. The aim of the study was to test these hypotheses by comparing verbal and spatial learning in patients with left or right temporal lobe resection for intractable epilepsy, using verbal and visuospatial memory tasks with the same design: control of encoding, multiple trial learning, free and cued recall, short and long delays. The results showed: (1) a similar pattern of learning and recall in the two groups; (2) a higher performance in spatial learning for patients with left temporal lobe resection and in verbal learning for patients with right temporal lobe resection; (3) material-specific effects characterized by a higher sensitivity to cues in the verbal domain and a better retention of information during delays in the spatial domain. These results suggest parallel processing of the two temporal lobes at the various memory stages, rather than an interaction between memory stage and side of the lesion similar to that already proposed for the frontal lobes. They also confirm a double dissociation between verbal/spatial information processing and side of temporal lobe resection.

Selective facilitative effect of post-trial reticular stimulation in discriminative learning in the rat.

Ninety-eight Sprague-Dawley rats, implanted with electrodes in the mesencephalic tegmentum (reticular activating system, RAS) served as subjects in two experiments. In the first experiment (n = 42) we investigated the effects of a RAS stimulation (5 µ A, 300 Hz, 90 sec in duration) on the acquisition of a positively reinforced light-dark discrimination in a T-maze. In the second experiment (n = 56) the reinforcement and the treatment were dissociated by comparing the effects of the RAS stimulation administered after correct or incorrect choices, during the same discrimination task. In the two experiments, despite large differences in learning conditions, the results show a considerable learning facilitation by administering the RAS stimulation immediately after each trial. This facilitation does not seem to be due to an interaction between reinforcement and stimulation, since the results of experiment 2 show the maximum facilitation in animals stimulated after each (non-reinforced) error, compared to subjects stimulated after each (reinforced) correct choice. These results are discussed both in terms of consolidation processes and in terms of comparison of the cue values of S(+) and S(-) in a discriminative learning situation.

[Procedural learning and Parkinson disease: implication of striato-frontal loops]. / Apprentissage procédural et maladie de Parkinson: implication des boucles striato-frontales.

OBJECTIVE: To investigate procedural learning in non demented patients with idiopathic Parkinson's disease (PD). BACKGROUND: Experimental evidence implicate the basal ganglia in procedural learning. Selective impairment has more recently been described in patients with frontal lesions. METHODS: The performance of 20 demented patients and 15 matched normal controls was studied in the serial reaction time task (SRTT). Performance on procedural task was further compared with that of 9 normal controls and with patients' performance on tests assessing explicit memory, executive functions and global efficiency. RESULTS: The group of patients with PD showed impaired procedural learning. The difference of response time between the repeated and the non-repeated blocks was smaller in PD when compared to controls. Subsequent analyses separated PD patients into two subgroups according to their performance on SRTT, measured by the rebound effect. PD patients whose learning was normal differed from PD patients whose learning was impaired on performance in tests sensitive to frontal lobe dysfunction. CONCLUSION: These results confirm the implication of the striatum in procedural learning and suggest that performance on cognitive procedural learning depends on the striato-frontal circuits.

[Cognitive functions and the basal ganglia: the model of Parkinson disease]. / Fonctions cognitives et noyaux gris centraux: le modèle de la maladie de Parkinson.

Cognitive changes have long been observed in patients with degenerative diseases or focal lesions that involve primarily subcortical structures. Generally speaking, the deficits that have been reported in these diseases are similar and include: slowing of central processing; defective use of memory stores; impaired behavioural regulation in sorting tasks; disorders of plaining in tower-related tasks; and impaired manipulation of internal representation of visuo-spatial stimuli. Given the modulatory role of the basal ganglia and related structures, these disorders might result from more fundamental deficits concerning the allocation of attentional resources, the temporal organization of behaviour, the maintenance of representations in working memory or the self-elaboration of internal strategy, all of which resemble dysfunctions of processes that are commonly considered to be controlled by the frontal lobes. This suggests a functional continuity between the basal ganglia and association areas of the prefrontal cortex. The recent description in primates of parallel, segregated loops that interconnect well-defined subregions of the basal ganglia to discrete areas of the prefrontal cortex via the thalamus may give some support to this hypothesis.

[Dementia and memory: morphologic imagery with MRI]. / Démences et mémoires: imagerie morphologique par IRM.

Modern imaging techniques, and notably magnetic resonance imaging (MRI) enable an increasingly precise exploration of primary degenerative dementias. The main contribution of imaging is to demonstrate lesion localizations which confirm the degenerative nature of the observed disorders, contributing to an understanding of the correlation between clinical signs and causal lesions. The development of techniques quantifying cerebral volume which can be applied to an analysis of small structures such as the hippocampus coupled with a better understanding of primary degenerative dementias allow more specific study of the atrophy than could be obtained with a global assessment of ventricular dilatation. More recently, the development of MRI methods studying brain perfusion open the way for noninvasive exploration of perfusion anomalies in these patients.

[Deficits in memory retrieval: an argument in favor of frontal subcortical dysfunction in depression]. / Les troubles de la récupération mnésique: un argument en faveur d'un dysfonctionnement des structures sous-cortico-frontales dans la dépression.

UNLABELLED: While numerous studies have objective quantitative and qualitative deficits of memory in depressed patients, the mechanisms of these impairments are not well established. The study reported here was designed to assess encoding and retrieval processes in depression and to define the specific nature of memory failure associated with this disorder. METHODS: Ten inpatients with major depression responding to DSM III-R criteria and ten normal controls were included in this study. All subjects were assessed with a neuropsychological battery including: a) subtests of Weschsler memory scale (digit span, logical memory); b) verbal fluency (letter); c) two tasks assessing executive functions (cognitive estimate, Nelson's test); d) two explicit tasks of verbal learning (California Verbal Learning Test and Grober & Buschke's procedure) which measure memory performance in various conditions of encoding (incidental vs controlled) and of recollection (free recall, cued recall and recognition). Severity of depression was assessed with the MADRS and the Retardation Rating Scale for Depression. RESULTS: Although there was no difference between patients and controls on digit span and logical memory tasks, depressed patients exhibited a deficit in verbal learning with CVLT and Grober & Buschke's procedure. On California Verbal Learning Test, depressive subjects performed poorly in free recall and demonstrated poor consistency. Patients show free recall improvement across trials 1 or 5 and this learning effect didn't differ from controls. Score of patients and controls on cued recall and recognition were at the same level. Grober & Buschke's procedure confirmed these results. Despite a control of encoding processes during the initial presentation of the words, free recall measure revealed significant difference between groups. Like controls, patients recalled almost all items when semantic cues was provided and their recognition results showed a ceiling effect. Consistency indexes of free recall and cued recall differed significantly between groups. Verbal fluency and frontal tasks didn't allow to distinguish the depressive patients from controls. DISCUSSION: Depressive subjects exhibited a deficit in free recall and poor consistency while cued recall and recognition were normal. Patient's results in free recall are characterized by difficulties in planning and in maintaining retrieval strategies. These findings suggest that memory failure in depression could reflect an impairment in retrieval processes depending on executive functions controlled by the subcortical structures.

["Boxer's dementia" without motor signs]. / "Démence pugilistique" sans signes moteurs.

BACKGROUND: The neurological complications related to boxing include dementia. Boxer's dementia is generally associated with severe motor impairment. CASE REPORT: A former professional boxer presented dementia with no motor signs. The diagnostic discussion was based on clinical observations, and neuropsychological and supplementary explorations, and eliminated all other etiological hypotheses. DISCUSSION: This case draws attention to the possibility of cognitive disorders without motor impairment in the neurological complications of boxing.