The profile of executive functioning in amnestic mild cognitive impairment: disproportionate deficits in inhibitory control.

Amnestic mild cognitive impairment (aMCI) represents a group of individuals who are highly likely to develop Alzheimer's disease (AD). Although aMCI is typically conceptualized as involving predominantly deficits in episodic memory, recent studies have demonstrated that deficits in executive functioning may also be present, and thorough categorization of cognitive functioning in MCI may improve early diagnosis and treatment of AD. We first provide an extensive review of neuropsychology studies that examined executive functioning in MCI. We then present data on executive functioning across multiple sub-domains (divided attention, working memory, inhibitory control, verbal fluency, and planning) in 40 aMCI patients (single or multiple domain) and 32 normal elderly controls (NECs). MCI patients performed significantly worse than NECs in all 5 sub-domains, and there was impairment (>1.0 SD below the mean of NECs) in all sub-domains. Impairment on each test was frequent, with 100% of MCI patients exhibiting a deficit in at least one sub-domain of executive functioning. Inhibitory control was the most frequently and severely impaired. These results indicate that executive dysfunction in multiple sub-domains is common in aMCI and highlights the importance of a comprehensive neuropsychological evaluation for fully characterizing the nature and extent of cognitive deficits in MCI.

Characterizing the memory changes in persons with mild cognitive impairment.

Persons with mild cognitive impairment (MCI) do not meet criteria for Alzheimer's disease (AD) but are at high risk for developing the disease. Presence of a memory deficit is a key component in the characterization of MCI. This chapter presents empirical studies that attempt to describe and understand the nature of the memory deficit in MCI with a focus on episodic memory and working memory. Cross-sectional studies report prominent deficits of episodic memory characterized by impaired encoding of the contextual information that makes up complex events. This results in reduced free and cued recall, impaired recognition, and impaired associative learning. Although semantic encoding is found to be impaired in conditions that rely on explicit and intentional retrieval, preserved semantic processing is found with automatic conditions of testing. Studies indicate the presence of a partial deficit of working memory with the ability to divide attention being most severely impaired. However, there appears to be heterogeneity as to the extent of the working memory impairment. The presence of vascular anomalies on MRI, as well as being in a more advanced stage in the continuum from MCI to AD, are associated with more severe and more pervasive working memory deficits. Finally, longitudinal studies indicate that the combination of episodic and working memory deficits represents a strong predictor of progression from MCI to AD.

Pharmacotherapy of aphasia: myth or reality?

Pharmacotherapy of aphasia had been discussed for the last twenty years with first bromocriptine and amphetamine and then serotoninergic, GABAergic and cholinergic agents. Here, we reviewed the MEDLINE available reports of drug therapy for aphasia. So far, proofs of efficiency were found indubitable for none of the studied molecules. However, some of them showed limited efficiency (piracetam and amphetamine). Moreover, drug therapies for aphasia were less efficient alone than when they were associated with speech therapy.

ERP measures of auditory word repetition and translation priming in bilinguals.

Motivated by the demonstration of similarly localized adaptation of the hemodynamic response in a first (L1) and second (L2) language, this study examined event-related brain potentials (ERPs) to spoken words in L1 and L2 in 15 English-French bilinguals. We examined whether the temporal pattern of N400 adaptation due to within-language repetitions (i.e., repetition priming) was similar in L1 and L2 and whether the release from adaptation elicited by a within-language word change was similar. Furthermore, using word changes across language, we examined the phonological mismatch negativity (PMN) and N400 components to determine the kind of information activated during translation priming. In contrast to within-language repetition, we expected between-language repetition (i.e., translations) to be characterized by conceptual rather than lexical/phonological word form priming. Overall, the pattern of adaptation and release from adaptation was similar in L1 and L2, with evidence of delayed semantic analysis in L2 in the form of a later N400 effect. A change in language (L1 to L2) elicited a similar pattern of PMN and N400 activity compared to a within-language change in meaning in L1, suggesting that neither word form nor conceptual information was available on-line for the forward translation. In contrast, the presence of strong PMN but minimal N400 effects for L2-to-L1 translations suggests that conceptual but not phonological information is available on-line for backwards translation. L2 proficiency influenced the extent to which conceptual representations were activated by translations. These data are discussed in light of current models of bilingual word processing and suggest modality differences in the pattern of activation of lexical and conceptual information.

The impact of attentional training on event-related potentials in older adults.

Attentional control declines in older adults and is paralleled by changes in event-related brain potentials (ERPs). The N200 is associated with attentional control, thus training-related improvements in attentional control should be paralleled by enhancements to the N200. Older participants were randomly assigned to 1 of 3 groups, which focused on training different levels of attentional control: (1) single-task training (single), where participants trained on 2 tasks in isolation; (2) fixed divided attention training (fixed), where participants trained on 2 tasks simultaneously; and (3) variable divided attention training (variable), where participants trained on 2 tasks simultaneously but were instructed to alternatively prioritize each of the 2 tasks. After training, the amplitude of the N200 wave increased in dual-task conditions for the variable group, and this enhancement was correlated with improved dual-task performance. Participants in the variable group also had the greatest improvement in the ability to modulate their allocation of attention in accordance with task instructions to the less salient and less complex of the 2 tasks. Training older adults to modulate their division of attention between tasks improves neural functions associated with attentional control of the trained tasks.

Identifying training modalities to improve multitasking in older adults.

Studies that have measured the effects of attentional training have relied on a range of training formats, which may vary in their efficacy. In particular, it is unclear whether programs that practice dual-tasking are more effective in improving divided attention than programs focusing on flexible allocation priority training. The aims of this study were as follows: (1) to compare the efficacy of different types of attentional training formats and (2) to assess transfer to distal measures. Forty-two healthy older adults were randomly assigned to one of three training groups. In the SINGLE training condition, participants practiced a visual detection and an alphanumeric equation task in isolation. In the FIXED training condition, participants practiced both tasks simultaneously with equal attention allocated to each. In the VARIABLE training condition, participants varied the attentional priority allocated to each task. After training, all participants improved their performance on the alphanumeric equation task when performed individually, including those in the SINGLE training condition. Participants in the FIXED training condition improved their divided attention, but only the participants in the VARIABLE training condition showed a greater capacity to vary their attentional priorities according to the instructions. Regarding transfer, all groups improved their performance on the 2-back condition, but only the VARIABLE and FIXED conditions resulted in better performance on the 1-back condition. Overall, the study supports the notion that attentional control capacities in older adults are plastic and can be improved with appropriate training and that the type of training determines its impact on divided attention.

The pattern and loci of training-induced brain changes in healthy older adults are predicted by the nature of the intervention.

There is enormous interest in designing training methods for reducing cognitive decline in healthy older adults. Because it is impaired with aging, multitasking has often been targeted and has been shown to be malleable with appropriate training. Investigating the effects of cognitive training on functional brain activation might provide critical indication regarding the mechanisms that underlie those positive effects, as well as provide models for selecting appropriate training methods. The few studies that have looked at brain correlates of cognitive training indicate a variable pattern and location of brain changes--a result that might relate to differences in training formats. The goal of this study was to measure the neural substrates as a function of whether divided attentional training programs induced the use of alternative processes or whether it relied on repeated practice. Forty-eight older adults were randomly allocated to one of three training programs. In the single repeated training, participants practiced an alphanumeric equation and a visual detection task, each under focused attention. In the divided fixed training, participants practiced combining verification and detection by divided attention, with equal attention allocated to both tasks. In the divided variable training, participants completed the task by divided attention, but were taught to vary the attentional priority allocated to each task. Brain activation was measured with fMRI pre- and post-training while completing each task individually and the two tasks combined. The three training programs resulted in markedly different brain changes. Practice on individual tasks in the single repeated training resulted in reduced brain activation whereas divided variable training resulted in a larger recruitment of the right superior and middle frontal gyrus, a region that has been involved in multitasking. The type of training is a critical factor in determining the pattern of brain activation.

Executive functions in frontotemporal dementia and Lewy body dementia.

Diagnosis of different types of dementia is often based on clinical symptomatology rather than underlying pathology; therefore, accurate diagnosis depends on a thorough description of cognitive functioning in different dementias. Furthermore, direct comparison of cognitive functions between different types of dementia is necessary for differential diagnosis. Executive dysfunction is common in several types of dementia, including frontotemporal dementia (FTD) and Lewy body dementia (LBD); however, FTD and LBD patients have never been directly compared on measures of executive functioning. The authors compared the performance of 17 FTD and 15 LBD patients on 6 measures of executive functioning in terms of statistical group differences, mean severity of clinical impairment in comparison to normal controls, and frequency of impairment. Results indicated a remarkably similar pattern of performance across all areas examined in terms of mean performance, as well as degree and frequency of impairment. Only the Stroop test produced results that could potentially differentiate the patient groups. These findings suggest that both FTD and LBD should be considered disorders involving executive dysfunction.