Inferior Parietal Perfusion, Lateralization, and Neuropsychological Dysfunction in Alzheimer's Disease

The severity of inferior parietal perfusion deficits in Alzheimer's disease (AD) is strongly associated with global intellectual decline. The relationship to specific losses of neuropsychological functioning, however, is less clear, as is the relative importance of the side (left vs. right) of hemispheric deficit. In this study, 53 patients with probable AD and 35 elderly controls received both a resting¹³³Xe rCBF measurement and neuropsychological examination. AD patients demonstrated the expected bilateral deficits in inferior parietal perfusion, as well as impairment on measures of mental status, intelligence, verbal and visual memory, attention, language, and construction abilities. The severity of this bilateral parietal deficit, in turn, was associated with virtually all of these AD-related neuropsychological impairments, most strongly with declining Performance IQ. Left-sided deficits correlated better with overall declines in IQ, as well as with declining attention and language fluency. Right-sided deficits, on the other hand, correlated best with declines in mental status and—paradoxically—verbal memory and contributed independently to declines in Full Scale and Performance IQ. In terms of the number and strength of their association to neuropsychological measures, left-sided deficits appear much more predictive of cognitive decline in AD. Right-sided deficits, however, may be most important for predicting aspects of performance skill that are only indirectly assessed in standard paper-and-pencil format. Overall, it appears that both sides make significant, but independent contributions to general functional decline in AD, but that left-sided deficits are more closely associated with cognitive decline as measured by most standard neuropsychological measures.     

Validation of distinct amnesic and executive type memory deficit in a psychiatric sample based on retrieval performance

Studies of localized brain dysfunctions have revealed connections between patterns of cognitive dysfunction and specific profiles of memory impairment. The amnesic type of memory impairment is defined by deficits in both free recall and recognition memory, whereas the dysexecutive memory impairment is characterized by retrieval deficits, i.e. a disproportional impairment in free recall relative to recognition memory. The present study tests whether classifications of psychiatric patients into recall impaired only (= RO group) and Recall and Recognition impaired (= RR group) correspond to the executive type and amnesic type of memory impairment. The alternative hypothesis is that the two groups merely differ in degree of neuropsychological and psychiatric disturbance. Forty-four subjects impaired on California Verbal Learning Test (CVLT) were selected from a larger database of 103 impaired and non-impaired subjects with schizophrenia or recurrent major depression. Subjects were classified into RO and RR groups and compared on measures of memory strategy (recency effect and interference on CVLT), overall neuropsychological function (Stroop Test and WAIS-R similarity) and psychiatric symptom load (positive and negative symptoms). Repeated measures ANOVA showed no effects of group, i.e. the RR group did not perform consistently below the RO group with regard to memory strategy, neuropsychological function or psychiatric symptom load. Two out of three analyses showed group x test interaction, supporting the dissociation of distinct executive and amnesic profiles among psychiatric patients. The RO group was more susceptible to interference but had better recency score than the RR group. The RO had higher negative symptoms while the RR group had higher positive symptoms.     

Central executive system impairment in traumatic brain injury

The aim of the present study was to identify cognitive functions affected by traumatic brain injury (TBI) and to verify the mechanism underlying cognitive impairment. More precisely, cognitive deficits following TBI can be considered as a consequence of (a) a speed processing deficit, that is a general slowing of perceptual, motor and cognitive subroutines; (b) an impairment of the Central Executive System of working memory (CES).Thirty-seven patients were submitted to a neuropsychological battery, aimed to evaluate different cognitive functions.Results showed severe deficits in speed processing, divided attention,working memory, executive functions and long term memory.Regression analyses, performed to test the two hypotheses, showed that the working memory deficit hypothesis is able to explain divided attention, executive functions and long term memory deficits more than speed processing hypothesis.     

Reduced short-term memory capacity in Alzheimer's disease: The role of phonological,lexical, and semantic processing

Individuals with Alzheimer's disease (AD) are often reported to have reduced verbal short-term memory capacity, typically attributed to their attention/executive deficits. However, these individuals also tend to show progressive impairment of semantic, lexical, and phonological processing which may underlie their low short-term memory capacity. The goals of this study were to assess the contribution of each level of representation (phonological, lexical, and semantic) to immediate serial recall performance in 18 individuals with AD, and to examine how these linguistic effects on short-term memory were modulated by their reduced capacity to manipulate information in short-term memory associated with executive dysfunction. Results showed that individuals with AD had difficulty recalling items that relied on phonological representations, which led to increased lexicality effects relative to the control group. This finding suggests that patients have a greater reliance on lexical/semantic information than controls, possibly to make up for deficits in retention and processing of phonological material. This lexical/semantic effect was not found to be significantly correlated with patients’ capacity to manipulate verbal material in short-term memory, indicating that language processing and executive deficits may independently contribute to reducing verbal short-term memory capacity in AD.     

Awareness of memory task impairment versus everyday memory difficulties in dementia

The study investigated different types of awareness of memory dysfunction in dementia, specifically judgements concerning memory task performance or appraisal of everyday memory functioning and also exploring the neuropsychological correlates of such awareness. This was investigated in 76 people with dementia, comprising 46 patients with Alzheimer's disease (AD) and 30 patients with vascular dementia (VaD). The Memory Awareness Rating Scale (Clare et al., 2002, Neuropsychol Rehabil, 12, 341–362) was used, which includes an Objective‐Judgement Discrepancy (OJD) technique involving comparison of subjective evaluation of performance on specific memory tasks with actual performance, and a Subjective Rating Discrepancy (SRD) technique, which compares self versus informant judgement of everyday memory function. The AD and VaD groups showed lower awareness than a normal control group for both types of measures, the AD group showing less awareness than the VaD group on the OJD measure. Regression analyses supported associations for both groups between memory impairment and the OJD measure and between naming impairment and the SRD measure. The findings are discussed in terms of neurocognitive theories accounting for loss of awareness in dementia.     

Reduced short-term memory capacity in Alzheimer's disease: the role of phonological, lexical, and semantic processing

Individuals with Alzheimer's disease (AD) are often reported to have reduced verbal short-term memory capacity, typically attributed to their attention/executive deficits. However, these individuals also tend to show progressive impairment of semantic, lexical, and phonological processing which may underlie their low short-term memory capacity. The goals of this study were to assess the contribution of each level of representation (phonological, lexical, and semantic) to immediate serial recall performance in 18 individuals with AD, and to examine how these linguistic effects on short-term memory were modulated by their reduced capacity to manipulate information in short-term memory associated with executive dysfunction. Results showed that individuals with AD had difficulty recalling items that relied on phonological representations, which led to increased lexicality effects relative to the control group. This finding suggests that patients have a greater reliance on lexical/semantic information than controls, possibly to make up for deficits in retention and processing of phonological material. This lexical/semantic effect was not found to be significantly correlated with patients' capacity to manipulate verbal material in short-term memory, indicating that language processing and executive deficits may independently contribute to reducing verbal short-term memory capacity in AD.     

Episodic memory effects of gamma frequency precuneus transcranial magnetic stimulation in Alzheimer's disease: A randomized multiple baseline study

Episodic memory decline is the prominent neuropsychological feature of typical Alzheimer's Disease (AD), for which current treatments have a limited clinical response. Recently, gamma entrainment therapy has been used as a non-invasive treatment in AD, providing evidence that it may have the potential to alleviate brain pathology and improve cognitive function in AD patients. At the same time, the precuneus (PC) has been recognized as a key area involved in AD related memory deficits and as a key node of the Default Mode Network. This study aimed to investigate the effectiveness of a 40 Hz Transcranial Magnetic Stimulation (TMS) intervention, delivered bilaterally to the precuneus for 10 days, in improving the patients' episodic memory performance. Secondary outcome variables investigated included general cognitive function, semantic and spatial memory, as well as attention and executive function. A concurrent multiple baseline design across five cases was employed. Four patients completed the study. Visual analysis combined with effect size indices were used to evaluate changes across phases. An increase in the average level of immediate recalled words was observed in three out of four patients. Effect size indices indicated significant improvement of attention skills in two patients. No treatment effect was observed for semantic and visual memory, or for executive function. An immediate treatment effect was observed in all patients' general cognitive function as assessed with the Alzheimer's Disease Assessment Scale (mean reduction of 5 points), which was maintained and improved further three months post-treatment. The neuropsychological evaluations indicated improved performance three months post-treatment in immediate and delayed recall, attention, phonological verbal fluency, anxiety, and neuropsychiatric symptoms. This study provides preliminary evidence for the efficacy of a novel non-pharmacological treatment using gamma-band TMS in addressing cognitive dysfunction in AD.     

The Impact of Neuropsychological Deficits on Functional Stroke Outcomes

This review examines the available literature on neuropsychological outcomes of stroke and the literature on the ability of specific areas of neuropsychological deficit to predict functional stroke outcome. The literature reviewed indicates that post-stroke deficits in executive function, memory, language, and speed of processing are common, with those identified as having progressive ‘post-stroke dementia’ presenting with a similar, though more impaired profile, with increased impairments particularly noted in the area of memory. It is clear that some aspects of neuropsychological functioning (e.g., presence of neglect, aphasia, anosognosia; and verbal memory and attention deficits) show promise as a means of predicting post-stroke functional outcomes. Examining the available literature, it becomes evident that there is a need for long-term, large scale (i.e., population based) follow-up studies, evaluating likely long-term neuropsychological outcomes of stroke and their prognostic utility.     

A critical appraisal of the role of neuropsychological deficits in preschool ADHD

The present study aimed at improving our understanding of the role of neuropsychological deficits in preschool Attention Deficit Hyperactivity Disorder (ADHD). The study included 52 children in the ADHD group and 72 controls (age 4–6 years). Both laboratory measures and teacher reports of executive deficits (i.e., working memory, inhibition, and shifting), delay-related behaviors (i.e., the preference for minimizing delay), and emotional functions (i.e., emotion recognition and regulation) were included. Variable-oriented analyses were complemented with person-oriented analyses (i.e., identifying the proportion of patients considered impaired). Results showed that the ADHD group differed from controls with regard to all measures of executive functioning and most measures of delay-related behaviors, but few differences were found for emotional functioning. A substantial subgroup (23%) of children with ADHD did not have a neuropsychological deficit in any domain. There were subgroups with executive or delay-related deficits only, but no pure emotional subgroup. The overlap between different neuropsychological deficits was much larger when teacher reports were used as opposed to laboratory measures. Regarding functional impairments, large mean differences were found between the ADHD group and controls. However, neuropsychological deficits were not able to explain individual variations in daily life functioning among children with ADHD. In conclusion, the present study identified some important methodological and theoretical issues regarding the role of neuropsychological functioning in preschool ADHD.     

A model‐based approach to limb apraxia in Alzheimer's disease

Limb apraxia is a neurological deficit characterized by an inability to pantomime and/or imitate gestures, which can result from neurodegenerative disorders such as Alzheimer's disease (AD). The major goal of the study was to describe comprehensively the apraxia deficits observed in AD patients and to relate those deficits to general cognitive status, measures of daily activity, and other neuropsychological measures. Limb apraxia was assessed on a variety of conceptual and gesture production tasks in 30 AD patients. As a group, AD patients were impaired across gesture production tasks: of note was the greater impairment in imitation, as opposed to pantomime, which was especially pronounced when patients were imitating with a delay. Imitation performance was best predicted by measures of visuospatial processing, while imitation with delay was best predicted by measures of working memory. In addition, pantomime in response to pictures of tools was less accurate than Pantomime to Verbal Command and holding the tool during performance did not decrease the participants' impairment, while introducing a verbal cue during imitation increased the severity of deficits. Furthermore, investigation into patterns of deficits clearly demonstrated that the nature of limb apraxia deficits observed in AD can be quite heterogeneous and that dissociations between the conceptual and the production system exist. Finally, we also report on significant correlations between general cognitive status and limb apraxia.     

Neuropsychological function and memory suppression in conversion disorder

Conversion disorder (CD) is a condition where neurological symptoms, such as weakness or sensory disturbance, are unexplained by neurological disease and are presumed to be of psychological origin. Contemporary theories of the disorder generally propose dysfunctional frontal control of the motor or sensory systems. Classical (Freudian) psychodynamic theory holds that the memory of stressful life events is repressed. Little is known about the frontal (executive) function of these patients, or indeed their general neuropsychological profile, and psychodynamic theories have been largely untested. This study aimed to investigate neuropsychological functioning in patients with CD, focusing on executive and memory function. A directed forgetting task (DFT) using words with variable emotional valence was also used to investigate memory suppression. 21 patients and 36 healthy controls completed a battery of neuropsychological tests and patients had deficits in executive function and auditory‐verbal (but not autobiographical) memory. The executive deficits were largely driven by differences in IQ, anxiety and mood between the groups. A subgroup of 11 patients and 28 controls completed the DFT and whilst patients recalled fewer words overall than controls, there were no significant effects of directed forgetting or valence. This study provides some limited support for deficits in executive, and to a lesser degree, memory function in patients with CD, but did not find evidence of altered memory suppression to support the psychodynamic theory of repression.     

Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease

Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out‐patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.     

Neuropsychological Characteristics of Dementia with Lewy Bodies and Parkinson’s Disease with Dementia: Differentiation, Early Detection, and Implications for “Mild Cognitive Impairment” and Biomarkers

Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are neurodegenerative conditions sharing a disorder of α-synuclein metabolism. Temporal differences in the emergence of symptoms and clinical features warrant the continued clinical distinction between DLB and PDD. While DLB and PDD groups’ neuropsychological profiles often differ from those in Alzheimer’s disease (AD), the diagnostic sensitivity, specificity, and predictive values of these profiles remain largely unknown. PDD and DLB neuropsychological profiles share sufficient similarity to resist accurate and reliable differentiation. Although heterogeneous cognitive changes (predominantly in memory and executive function) may manifest earlier and more frequently than previously appreciated in Parkinson’s disease (PD), and executive deficits may be harbingers of dementia, the enthusiasm to uncritically extend the concept of mild cognitive impairment (MCI) to PD should be tempered. Instead, future research might strive to identify the precise neuropsychological characteristics of the prodromal stages of PD, PDD, and DLB which, in conjunction with other potential biomarkers, facilitate early and accurate diagnosis, and the definition of neuroprotective, neurorestorative, and symptomatic treatment endpoints.     

Neuropsychological Differences Between Frontotemporal Dementia and Alzheimer's Disease: A Review

This paper surveys the similarities and differences between frontotemporal dementia (FTD) and Alzheimer's disease (AD). The review covers findings primarily from neuropsychological studies on memory, language, attention/executive function, and visuospatial abilities. However, neuropsychiatric and neuroimaging data are also briefly discussed. Distinguishing features of both FTD and AD are described in order to present a comprehensive clinical picture of these dementing diseases, which is essential for the process of differential diagnosis. The cause of specific cognitive deficits is also considered. Our comprehensive review of the empirical literature reveals that AD is characterized by early memory loss and visuospatial problems, while among the main features of FTD are behavioral abnormalities and executive dysfunctions.     

Anosognosia for Memory Impairment in Addiction: Insights from Neuroimaging and Neuropsychological Assessment of Metamemory

In addiction, notably Alcohol Use Disorder (AUD), patients often have a tendency to fail to acknowledge the reality of the disease and to minimize the physical, psychological, and social difficulties attendant to chronic alcohol consumption. This lack of awareness can reduce the chances of initiating and maintaining sobriety. Presented here is a model focusing on compromised awareness in individuals with AUD of mild to moderate cognitive deficits, in particular, for episodic memory impairment—the ability to learn new information, such as recent personal experiences. Early in abstinence, alcoholics can be unaware of their memory deficits and overestimate their mnemonic capacities, which can be investigated with metamemory paradigms. Relevant neuropsychological and neuroimaging results considered suggest that the alcoholics’ impairment of awareness of their attenuated memory function can be a clinical manifestation explained mechanistically by neurobiological factors, including compromise of brain systems that result in a mild form of mnemonic anosognosia. Specifically, unawareness of memory impairment in AUD may result from a lack of personal knowledge updating attributable to damage in brain regions or connections supporting conscious recollection in episodic memory. Likely candidates are posterior parietal and medial frontal regions known to be integral part of the Default Mode Network (DMN) and the insula leading to an impaired switching mechanism between the DMN and the Central-Executive Control (i.e., Lateral Prefronto-Parietal) Network. The cognitive concepts and neural substrates noted for addictive disorders may also be relevant for problems in self-identification of functional impairment resulting from injury following war-related blast, sport-related concussion, and insidiously occurring dementia.     

Which Executive Functioning Deficits Are Associated With AD/HD,ODD/CD and Comorbid AD/HD+ODD/CD?

This study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3)~whether a combination of AD/HD and ODD/CD is associated with EF deficits (and the possibility that there is no association between EF deficits and AD/HD or ODD/CD in isolation). Subjects were 99~children ages 6–12 years. Three putative domains of EF were investigated using well-validated tests: verbal fluency, working memory, and planning. Independent of ODD/CD, AD/HD was associated with deficits in planning and working memory, but not in verbal fluency. Only teacher rated AD/HD, but not parent rated AD/HD, significantly contributed to the prediction of EF task performance. No EF deficits were associated with ODD/CD. The presence of comorbid AD/HD accounts for the EF deficits in children with comorbid AD/HD+ODD/CD. These results suggest that EF deficits are unique to AD/HD and support the model proposed by R. A. Barkley (1997).     

Pantomimes are special gestures which rely on working memory

The case of a patient is reported who presented consistently with overt deficits in producing pantomimes in the absence of any other deficits in producing meaningful gestures. This pattern of spared and impaired abilities is difficult to reconcile with the current layout of cognitive models for praxis. This patient also showed clear impairment in a dual-task paradigm, a test taxing the co-ordination aspect of working memory, though performed normally in a series of other neuropsychological measures assessing language, visuo-spatial functions, reasoning function, and executive function. A specific working memory impairment associated with a deficit of pantomiming in the absence of any other disorders in the production of meaningful gestures suggested a way to modify the model to account for the data. Pantomimes are a particular category of gestures, meaningful, yet novel. We posit that by their very nature they call for the intervention of a mechanism to integrate and synthesise perceptual inputs together with information made available from the action semantics (knowledge about objects and functions) and the output lexicon (stored procedural programmes). This processing stage conceived as a temporary workspace where gesture information is actively manipulated, would generate new motor programmes to carry out pantomimes. The model of gesture production is refined to include this workspace.     

Neuropsychological profile in patients with schizotypal personality disorder or schizophrenia

Neuropsychological impairments have been consistently reported in patients with schizophrenia. As little is known whether subjects with schizotypal personality disorder exhibit neurocognitive dysfunction similar to that in schizophrenia, we assessed the neuropsychological profile of 15 subjects with schizotypal personality disorder and compared it with that for 15 patients with schizophrenia and for 15 psychiatrically normal volunteers. All participants were administered a standard neuropsychological battery assessing language ability, spatial ability, visuomotor function, verbal memory, visual memory, auditory attention, visual attention, and executive function. Performance on most of the cognitive domains was impaired in patients with schizotypal personality disorder but less than patients with schizophrenia. Specifically, impairment in verbal memory and visuomotor ability in patients with schizotypal personality disorder and patients with schizophrenia were comparable, while patients with schizophrenia performed worse on the test of executive function than did patients with schizotypal personality disorder. As a whole, cognitive deficits in patients with schizotypal personality disorder were qualitatively similar to, but quantitatively milder than, those for patients with schizophrenia. The results suggest that cognitive abilities related to frontotemporal lobe function are disturbed across these schizophrenia-spectrum disorders.     

Neuropsychological subgroups of adolescents with conduct disorder

Närhi, V., Lehto‐Salo, P., Ahonen, T. & Marttunen, M. (2010). Neuropsychological subgroups of adolescents with conduct disorder. Scandinavian Journal of Psychology, 51, 278–284. In group‐level studies adolescents with conduct disorder (CD) have been found to have deficiencies in verbal and executive functions. Teichner and Golden (2000) addressed the neuropsychological heterogeneity of CD, and hypothesized the existence of six neuropsychologically different subgroups. We used that theoretical basis to identify subgroups among 77 adolescents with CD and 48 controls. Among subjects with CD we identified subjects with no, diffuse, verbal and executive function deficits, but none with specific memory or visuo‐spatial deficits. In total, neuropsychological deficits altogether were more common among subjects with CD relative to controls, as were specific verbal deficits. Subgroups did not differ in gender distribution, comorbidity of psychiatric disorders, type or severity of CD, or number of psychosocial risk factors. Among subjects with CD, learning disabilities were common. CD is neuropsychologically a heterogeneous disorder, and neuropsychological deficits should be taken into account in assessing and planning interventions for adolescents with CD.     

Can cognitive and behavioural disorders differentiate frontal variant-frontotemporal dementia from Alzheimer's disease at early stages?

Frontal variant-Frontotemporal dementia (fvFTD) and Alzheimer's disease (AD) patients matched for severity of dementia at the Clinical Dementia Rating (CDR) received neuropsychological testing in order to explore if the dysexecutive disorder might characterise fvFTD at early stage, when AD is dominated by the episodic memory defect. We also determined if the behavioural syndrome was more severe in fvFTD than AD, and if specific patterns of behavioural symptoms could differentiate the two types of dementia, using the Neuropsychiatry Inventory (NPI). AD patients performed worse than fvFTD not only in memory but also in executive tasks. Apathy and eating disorders proved to be more severe or frequent in fvFTD even if the two groups did not differ in the total NPI score. CDR score significantly correlated with the NPI score in fvFTD and with the MMSE in AD. Our data confirm that the memory disorders may differentiate the two types of dementia; however, the dysexecutive syndrome is as severe, and even more severe in AD. The severity of the behavioural syndrome is comparable in the two groups but the nature of the behavioural disorders may vary to some extent. We conclude that AD dementia at early stage is a behavioural-cognitive syndrome, while in fvFTD the behavioural disorders appear when the cognitive deficit is still relatively mild.