Anne-Marie Ergis

Motor and cognitive improvements in patients with Huntington's disease after neural transplantation.

BACKGROUND Huntingtons disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntingtons disease. METHODS After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity. FINDINGS The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntingtons disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two. INTERPRETATION Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntingtons disease.

Qualitative analysis of verbal fluency in depression

The aim of this study was to analyze qualitative aspects of verbal fluency in depression. Phonemic and semantic output was scored for word clustering and switching between clusters in depressed patients and normal control subjects. Depressed patients (n=25) and normal control subjects (n=19) were administered both phonemic and semantic fluency tasks. All patients were also evaluated with executive card sorting tests. Patients with depression produced fewer words on the semantic fluency task than controls and showed normal performance on the phonemic fluency tasks. The deficit on semantic fluency of depressed patients was related to a reduced number of switches with normal cluster sizes. The number of switches in depression was associated with a reduced ability to shift mental set on card sorting tests, suggesting that verbal fluency impairment reflects general executive problems in depression.

Retest effects and cognitive decline in longitudinal follow-up of patients with early HD

Objective: To assess the natural progression of cognitive impairment in Huntington’s disease (HD) and to reveal factors that may mask this progression. Background: Although numerous cross-sectional studies reported cognitive deterioration at different stages of the disease, progressive cognitive deterioration has been, up to now, difficult to demonstrate in neuropsychological longitudinal studies. Methods: The authors assessed 22 patients in early stages of HD at yearly intervals for 2 to 4 years (average, 31.2 ± 10 months), using a comprehensive neuropsychological battery based on the Core Assessment Program for Intracerebral Transplantation in Huntington’s Disease (CAPIT-HD). Results: The authors observed a significant decline in different cognitive functions over time: these involved primarily attention and executive functions but also involved language comprehension, and visuospatial immediate memory. Episodic memory impairment that was already present at the time of enrollment did not show significant decline. The authors found a significant retest effect at the second assessment in many tasks. Conclusion: Many attention and executive tasks adequately assess the progression of the disease at an early stage. For other functions, the overlapping of retest effects and disease progression may confuse the results. High interindividual and intraindividual variability seem to be hallmarks of the disease.

Problem-solving abilities in unipolar depressed patients: comparison of performance on the modified version of the Wisconsin and the California sorting tests

Problem solving relies on such abilities as decision-making, planning, initiation and hypothesis testing. Although problem-solving deficits have been consistently reported in depression, the specific nature of these deficits is not fully elucidated. In order to assess and isolate cognitive processes underlying problem-solving impairments in depression, depressed patients and normal controls were evaluated with the modified version of the Wisconsin Card Sorting Test (WCST) and the California Card Sorting Test (CCST). The California Card Sorting Test, unlike the modified WCST, provides several different measures of concept generation, concept identification and concept execution. Compared with controls, depressed patients did not show any deficits on all the measures of the modified WCST. In contrast, depressed patients evidenced mild impairment on the CCST with a specific deficit on concept generation but no major problems in concept identification and concept execution. The deficit in concept generation may be rooted in multiple factors such as hypothesis-testing deficits, a loss of cognitive flexibility and a conservative style of response. Since a positive relation between problem-solving deficits and the mean duration of the depressive episode was observed, problem-solving abilities might be predictive of poorer outcome in patients with unipolar affective disorders.

Episodic memory and organizational strategy in free recall in unipolar depression: The role of cognitive support and executive functions

Executive functioning and memory impairment have been demonstrated in adults with depression. Executive functions and memory are related, mainly when the memory tasks require controlled processes (attentional resource demanding processes)—that is, when a low cognitive support (external aid) is provided. A cross-sectional study was carried out on 45 participants: 21 with depression, and 24 healthy controls matched for age, verbal ability, education level, and anxiety score. Cognitive support was manipulated by providing a categorized word list at encoding, presented either clustered (high cognitive support) or randomized (low cognitive support) to both depressed and healthy adults. The number of words recalled was calculated, and an index of clustering was computed to assess organizational strategies. Participants were also administered cognitive tests (executive functions, cognitive speed, and categorical fluency) to explore the mediators of organizational strategies. Depressed participants had greater difficulty recalling and organizing the words, but the differences between the two groups were reduced for both measures when high cognitive support was provided at encoding. Healthy adults performed better on all cognitive tests. Statistical analyses revealed that in the depressed group, executive functions were the only variable associated with clustering and only when low cognitive support was provided. These findings support the view that the decrement in executive function due to depression may lead to impairment in organization when this mnemonic strategy has to be self-initiated.

Recollection training and transfer effects in Alzheimer’s disease: Effectiveness of the repetition-lag procedure

OBJECTIVE This study was designed to extend the use of a memory training technique, known as the repetition-lag procedure, to Alzheimer patients. The specificity of this procedure is to target the process of recollection for improvement. METHOD A group of 12 patients were trained individually for 6h. The training procedure consisted of a series of yes/no recognition tasks in which some words were repeated throughout the test list across gradually increasing delays. Their performance was evaluated on pre-and-post tests and compared with a recognition practice group and a no contact control group. RESULTS Initially, recollection training patients only performed accurately when the delay between repetitions consisted of one intervening word, but by the end of training their performance increased up to four-word intervals. Interestingly, these benefits generalized to other measures of memory, such as working memory, visual memory and source recognition. CONCLUSIONS Effectiveness of the repetition-lag procedure in Alzheimers disease is discussed.

Les troubles précoces de la mémoire épisodique dans la maladie d’Alzheimer

Resume Les patients atteints de maladie d’Alzheimer (MA) presentent de maniere tres precoce des troubles de memoire episodique. Ces deficits de performances refletent des troubles specifiques a une ou plusieurs des etapes de l’encodage, du stockage et/ou de la recuperation, mais egalement la creation de faux souvenirs, comme la production d’intrusions et les fausses reconnaissances. Le premier objectif de cet article est de presenter les principaux travaux qui ont permis de mieux comprendre la nature des troubles de memoire episodique dans cette pathologie, ainsi que les travaux plus recents qui se sont interesses aux faux souvenirs. Dans la deuxieme partie de cet article, nous proposons une revue de la litterature des troubles de memoire prospective, memoire des intentions, qui permet de se rappeler d’actions a realiser dans le futur. En effet, cette memoire, bien qu’encore peu exploree, est egalement atteinte de maniere massive des les premiers stades de la MA, car elle requiert le fonctionnement d’autres capacites cognitives qui sont perturbees tres tot. L’evaluation des performances en memoire prospective pourrait donc contribuer au diagnostic precoce de la maladie d’Alzheimer.

Intermittent theta burst stimulation over left BA10 enhances virtual reality-based prospective memory in healthy aged subjects

Prospective memory (PM) refers to a complex cognitive ability that underpins the delayed execution of previously formulated intentions. PM performance declines early in normal aging and this process is accentuated in Alzheimers disease. The left frontopolar cortex (BA10) has been consistently assigned a major role in PM functioning, but whether it can be noninvasively modulated to enhance PM performance in aged people has not been addressed so far. Here, we investigated the effects of modulating left BA10 by means of theta burst stimulation (TBS), using either excitatory (intermittent TBS), inhibitory (continuous TBS) or control (vertex) TBS in healthy aged subjects. The behavioral effects were assessed using a reliable and ecological virtual reality PM task that included both event- and time-based retrievals. As compared with vertex stimulation, event-based PM performance significantly improved after excitatory stimulation, whereas inhibitory stimulation had no significant effect. Additionally, and across the different types of stimulation, performance for congruent links between the event-based PM cue and the action to be performed was significantly better as compared with incongruent links. In conclusion, intermittent TBS might provide a relevant interventional strategy to counteract the decline of cognitive functions and memory abilities in normal aging.

Evaluation des capacités de mémoire épisodique de sujets âgés illettrés

Assessing cognitive functions in illiterate people is a difficult task because most of the neuropsychological tests exploring episodic memory have been validated in formally educated people, are based on verbal material and, therefore, require a good knowledge of language. Two episodic memory tests (TNI93 and TMA93) designed to be used for cognitive impairment screening in illiterate people have been designed, then validated in a multicultural low-educated population. Four hundred and thirty seven subjects aged 60 and over, living in the Seine-Saint-Denis district, received a medical check up offered by the National Health Service and their episodic memory performance was examined with these screening tests. The performance obtained on these tests depends both on age and educational level, as expected. Normative data for screening purpose in population with low education and/or not fluent with the language of the examiner are presented.

Effects of the dopamine agonist piribedil on prefrontal temporal cortical network function in normal aging as assessed by verbal fluency.

Normal aging has been associated with impaired performance in verbal fluency suggesting a prefrontal temporal cortical network (PFTCN) deficiency. In this study, we investigated the effects of a 2-month treatment period with a dopaminergic agonist (DA) on PFTCN function. Forty healthy, elderly volunteers were assessed on semantic and phonemic verbal fluency after two months of a placebo or a DA treatment (i.e. piribedil 50 mg/day) in a double-blind crossover design. Protocols were scored considering clustering, (i.e. production of words within semantic or phonemic categories, depending on the integrity of temporal lobe), and switching (i.e. the ability to shift between clusters, depending on frontal lobe functioning). Results revealed no significant main effect of the DA treatment on either verbal fluency variables but showed a significant interaction with working memory capacities, with high-capacity span subjects improving phonemic switching on DA whereas low-capacity span subjects performed more poorly on the drug than off. These data are consistent with the literature and confirm the crucial link between working memory capacities and dopamine agonist effects. The present study also provides evidence that pharmacological remediation of age-related cognitive decline has to be taken into consideration.