Françoise Lekeu

Gait analysis in elderly adult patients with mild cognitive impairment and patients with mild Alzheimer’s disease: simple versus dual task: a preliminary report

Background/Aims:  The aim of this study was to assess gait characteristics during simple and dual task in patients with mild cognitive impairment (MCI) and compare them with those of healthy elderly subjects and mild Alzheimer’s disease (AD) patients.

Brain correlates of performance in a free/cued recall task with semantic encoding in Alzheimer disease.

The goal of this study was to explore in patients with Alzheimers disease (AD) the brain correlates of free and cued recall performance using an adaptation of the procedure developed by Grober and Buschke (1987). This procedure, which ensures semantic processing and coordinates encoding and retrieval, has been shown to be very sensitive to an early diagnosis of AD. Statistical parametric mapping (SPM 99) was used to establish clinicometabolic correlations between performance at free and cued verbal recall and resting brain metabolism in 31 patients with AD. Results showed that patients score on free recall correlated with metabolic activity in right frontal regions (BA 10 and BA 45), suggesting that performance reflected a strategic retrieval attempt. Poor retrieval performance was tentatively attributed to a loss of functional correlation between frontal and medial temporal regions in patients with AD compared with elderly controls. Performance on cued recall was correlated to residual metabolic activity in bilateral parahippocampal regions (BA 36), suggesting that performance reflected retrieval of semantic associations, without recollection in AD. In conclusion, this study demonstrates that the diagnostic sensitivity for Alzheimers disease of the cued recall performance in the Grober and Buschke procedure (1987) depends on the activity of parahippocampal regions, one of the earliest targets of the disease. Moreover, the results suggest that the poor performance of patients with AD during free and cued recall is related to a decreased connectivity between parahippocampal regions and frontal areas.

Deep dysphasia: Further evidence on the relationship between phonological short-term memory and language processing impairments

We report a cognitive investigation of a case of deep dysphasia appearing in the context of primary progressive aphasia. Over a period of 5 years, patient CO presented progressive difficulties in word finding and in oral comprehension, while nonverbal cognitive functions remained preserved. As in other deep dysphasic patients, COs repetition performance showed marked imageability and lexicality effects, and semantic paraphasias. The same effects were observed in writing-to-dictation. Regularisation errors occurred in word reading. COs short-term memory span was less than two words. A cognitive analysis of language processing revealed difficulties in phoneme identification and rhyme judgement, in detecting grammatical class for orally presented words, and in oral and written naming. The interpretation of COs deep dysphasic symptoms within interactive models of language processing confirmed the importance of a phonological short-term storage impairment as an explanatory factor of deep dysphasia.

Apathy and Executive Dysfunction in Alzheimer Disease

Apathy, defined as a reduction in voluntary goal-directed behaviors, is one of the most common behavioral symptoms encountered in Alzheimer disease (AD). However, the processes underlying the different components of apathy are still unclear. The aim of this study was to explore a particularly important aspect of executive function in daily life: multitasking [assessed with the Modified Six Elements Task (MSET)], and its relationship with apathy in AD. Sixty-seven participants (37 AD patients matched with 30 control participants) were screened using the MSET. Simultaneously, a close relative of each patient was given the Apathy Inventory, which assesses 3 distinct dimensions of apathy (lack of initiative, lack of interest, and emotional blunting). AD patients presented significantly more multitasking deficits than control participants. In addition, regression analyses revealed that the number of rule breaks on the MSET (inability to perform several tasks in a predefined time observing a number of rules) was the best predictor of apathy, and especially of lack of initiative. These results suggest that the relation between lack of initiative and multitasking has a specific character and that mechanisms underlying multitasking constitute a key component of goal-directed behaviors.

The California Verbal Learning Test and other standard clinical neuropsychological tests to predict conversion from mild memory impairment to dementia.

This study describes the neuropsychological assessment of 34 patients with questionable Alzheimers disease (QAD) followed up for 3 years. Several measures were selected from the California Verbal Learning Test (CVLT) and compared to other cognitive tasks to assess the best neuropsychological indices for (a) detecting early memory impairment in QAD and (b) predicting conversion to AD. Concerning detection, the results indicated that a recall measure depending on semantic categorization (short-delay cued recall) signaled a memory deficit in stable QAD patients, suggesting that episodic and semantic memory problems are involved in the early cognitive impairments of stable QAD patients. However, the conversion to AD was best predicted by the initial performance at the recency index (score reflecting high reliance on working memory), corroborating the idea that AD patients (even at the questionable stage) essentially rely on preserved phonological loop functioning in memory tasks. Finally, an additional impairment in visuospatial memory (Reys figure) provided a good discriminant value to distinguish converters from stable QAD patients, showing that various cognitive disabilities deteriorate in AD.

Effects of Alzheimer's disease on the recognition of novel versus familiar words: neuropsychological and clinico-metabolic data.

This study explored recognition memory performance for novel versus familiar words in Alzheimers disease (AD) patients and normal controls (NCs), using an adaptation of E. Tulving and N. Krolls (1995) procedure. Results showed that both groups exhibited more hits and more false alarms for familiar than for novel words. The groups did not differ in the recognition of familiar words, reflecting preserved familiarity processes in AD. However, AD patients made more false alarms than NCs in the recognition of novel words, reflecting impairment of recollection processes in AD. A positron emission tomography analysis of clinico-metabolic correlations in AD patients showed a correlation between recognition of novel words and right hippocampal activity, whereas recognition of familiar words was more related to metabolic activity in the left posterior orbitofrontal cortex.

Exploring the effect of action familiarity on SPTs recall performance in Alzheimer's disease

This study examined the performance of normal controls (NC) and Alzheimer’s disease (AD) patients on free recall, semantic cued recall and object cued recall of both subject-performed tasks (SPTs) and verbal descriptions of actions, by controlling familiarity of actions associated to objects. The results showed that both groups performed better after SPT encoding than after verbal encoding, in all three types of recall. In addition, this SPT advantage was greater for AD patients than for NC in the object cued recall test, emphasizing AD patients’ sensibility to the congruence of cues between encoding and retrieval conditions. Following verbal encoding, NC showed a better recall for less familiar actions than for highly familiar actions, whereas AD patients exhibited the opposite pattern. These results reflect that AD patients did not benefit from a distinctiveness effect at encoding for improving subsequent retrieval of verbal information, probably due to a reduced level of elaboration during encoding. However, there was no effect of action familiarity on recall performance by both groups following SPT encoding. These results suggest that memory for verbal actions and SPTs is governed by different principles. In addition, they demonstrate the robustness of the SPT effect in AD patients, who were able to improve memory performance in the SPT condition not only with highly familiar actions but also with less familiar actions.

Verbal learning in Alzheimer's disease and mild cognitive impairment: fine-grained acquisition and short-delay consolidation performance and neural correlates

The aim of this study was to examine correlations between acquisition and short-delay consolidation and brain metabolism at rest measured by fluorodeoxyglucose positron emission tomography (FDG-PET) in 44 Alzheimers disease (AD) patients, 16 patients with mild cognitive impairment (MCI) who progressed to dementia (MCI-AD), 15 MCI patients who remained stable (MCI-S, 4-8 years of follow-up), and 20 healthy older participants. Acquisition and short-delay consolidation were calculated respectively as mean gained (MG) and lost (ML) access to items of the California Verbal Learning Task. MG performance suggests that acquisition is impaired in AD patients even at predementia stage (MCI-AD). ML performance suggests that short-delay consolidation is deficient only in confirmed AD patients. Variations in acquisition performance in control participants are related to metabolic activity in the anterior parietal cortex, an area supporting task-positive attentional processes. In contrast, the acquisition deficit is related to decreased activity in the lateral temporal cortex, an area supporting semantic processes, in patients at an early stage of AD and is related to metabolic activity in the hippocampus, an area supporting associative processes, in confirmed AD patients.

Metabolic correlates of clinical heterogeneity in questionable Alzheimer’s disease

Thirty-four subjects with questionable Alzheimers disease (QAD) were included in a 3-year prospective study and underwent neuropsychological testing and measurement of brain metabolism using FDG-PET at entry. Seventeen patients (50%) did not convert to AD during the follow-up period. Compared to elderly controls of similar age, the cerebral activity of non-converters was reduced in the dorsolateral prefrontal cortex. Moreover, the variability of metabolism in the posterior cingulate cortex was related to their visuospatial memory performance, while disparity in parietal activity was related to their verbal memory performance. These results demonstrate the cerebral metabolic heterogeneity of patients with QAD. Initial functional images of converters showed that activity was already impaired in the posterior cingulate, lateral temporal cortex, anterior cingulate and orbitofrontal cortex. This metabolic pattern is consistent with a pre-dementia stage of AD, and highlights the fact that significant frontal metabolic involvement may be associated with impaired activity in posterior associative cortices in very early AD.

Apathy in aging: Are lack of interest and lack of initiative dissociable?

Apathy is common in aging and generally defined on the basis of three dimensions: lack of initiative, lack of interest and emotional blunting. Curiously, no study until now has examined the associations and dissociations between these dimensions in elderly people (with or without dementia). These questions were addressed in two studies. In the first study, we explored the distribution of scores and the relationships between the three dimensions of apathy in 56 patients with dementia, focusing mainly on lack of initiative and lack of interest. Apathy was hetero-evaluated with the Apathy Inventory (AI), a scale widely used to assess the apathy dimensions in aging. In the second study, given the AIs limitations, we investigated in more detail the relationship between lack of initiative and interest in 115 elderly people using a new questionnaire specifically designed to assess these two dimensions. Results showed that lack of initiative was closely related to lack of interest (Study 1). Although we used a more specific questionnaire, these facets of apathy did not constitute two separable dimensions, but reflected a common main factor of apathy in aging (Study 2). Thus, the distinction between lack of initiative and lack of interest seems questionable. Only a multifactorial approach that includes the various psychological factors involved in apathy would enable one to gain a better understanding of the different manifestations of apathy and to highlight possible dissociations between them.