Neuropsychological Assessment of HIV-Infected Populations in International Settings

Resource-limited regions of the world represent the areas most affected by the global HIV epidemic. Currently, there are insufficient data on the neurocognitive effects of HIV in these areas and neuropsychological studies that have been carried out thus far are marked by inconsistent methods, test batteries, and rating systems for levels of cognitive impairment. These differences in methods, along with genetic variability of both virus and host, differences in co-infections and other co-morbidities, differences in language and culture, and infrastructural deficiencies in many international settings create challenges to the assessment of neurocognitive functioning and interpretation of neuropsychological data. Identifying neurocognitive impairment directly attributable to HIV, exploring relationships between HIV-associated neurocognitive impairment, disease variables, and everyday functioning, evaluating differences in HIV-1 subtype associated neuropathology, and determining implications for treatment remain complicated and challenging goals. Endeavors to establish a more standardized approach to neurocognitive assessments across international studies in addition to accumulating appropriate normative data that will allow more accurate rating of neuropsychological test performance will be crucial to future efforts attempting to achieve these goals.     

A MIMIC Model Approach to Research in Geriatric Neuropsychology: The Case of Vascular Dementia

The goal of the current study is to demonstrate a new methodology that can be used in neuropsychological research concerning differential diagnosis research. The multiple indicators, multiple causes (MIMIC) model is a latent variable methodology which can examine group differences on individual tests while controlling group differences in global cognitive impairment. As a demonstration, neuropsychological data from 217 dementia patients were incorporated into a MIMIC model to examine the influence of cerebrovascular disease (CVD) upon (1) dimensions of global cognitive impairment and (2) upon individual tests after controlling for global impairment. The presence of CVD in dementia (i.e., vascular dementia [VaD]) was not significantly related to dimensions of global impairment. In addition, the presence of CVD within dementia did not significantly contribute to impairment on 9 out of 10 neuropsychological tests/subscales examined after controlling global cognitive impairment. These results are discussed in the context of current vascular dementia research, and are focused primarily upon the MIMIC model methodology and suggestions for its use in future research.     

Heterogeneity of Neuropsychological Impairment in HIV Infection: Contributions from Mild Cognitive Impairment

Despite longstanding acknowledgement of the heterogeneity of HIV-associated neurocognitive disorders (HAND), existing HAND diagnostic methods classify according to the degree of impairment, without regard to the pattern of neuropsychological strengths and weaknesses. Research in mild cognitive impairment (MCI) has demonstrated that classifying individuals into subtypes by both their level and pattern of impairment, using either conventional or statistical methods, has etiologic and prognostic utility. Methods for characterizing the heterogeneity of MCI provide a framework that can be applied to other disorders and may be useful in clarifying some of the current challenges in the study of HAND. A small number of studies have applied these methods to examine the heterogeneity of neurocognitive function among individuals with HIV. Most have supported the existence of multiple subtypes of neurocognitive impairment, with some evidence for distinct clinicodemographic features of these subtypes, but a number of gaps exist. Following a review of diagnostic methods and challenges in the study of HAND, we summarize the literature regarding conventional and empirical subtypes of MCI and HAND and identify directions for future research regarding neurocognitive heterogeneity in HIV infection.     

HIV, Cognition and Women

Although the incidence of HIV in the United States is higher among men compared to women, the global proportion of women versus men who are infected has been approximately 50% since the late 1990s. Women have been under-represented in neuropsychological studies of HIV. A small number of studies have reported a significantly higher prevalence of neurocognitive impairment among HIV+ women compared to HIV− controls regardless of symptom status and with or without an AIDS diagnosis. Impairment was most evident on psychomotor tasks. The risk of neuropsychological impairment was increased among HIV+ women not on antiretroviral therapy. Age and depressive symptoms also increase neurocognitive risk. New neurocognitive studies of ovarian steroid hormones, PTSD and other psychiatric conditions are critical for addressing potential female-specific aspects of HIV-Associated Neurocognitive Disorder. Such studies will also address questions regarding involvement of the hippocampus and verbal memory, which may be of particular significance among HIV+ women.

Neuropsychological impairment in Parkinson's disease without dementia

Cognitive dysfunction in Parkinson's Disease (PD) has been consistently reported, but little is known about cognitive impairment in PD patients without dementia, and its association with clinical characteristics, neuropsychiatric disturbance and functional activities. Therefore, we evaluated 52 non-demented PD patients, 22 of them with mild cognitive impairment (PD-MCI) who were matched with 52 healthy controls. Our results confirm the existence of dysfunction in information processing speed, executive function, verbal memory and visuo-perceptual processing in PD. On the other hand, PD-MCI was associated with advanced age at the onset of PD, more neuropsychiatric symptoms, caregiver stress and functional problems. The study supports the hypothesis that specific neuropsychological impairments may act as modulators of functional impairment in PD, for instance slowness of information processing.     

Apathy is associated with lower mental and physical quality of life in persons infected with HIV

HIV infection is associated with lower health-related quality of life (HRQoL), which is influenced by immunovirological factors, negative affect, neurocognitive impairment, and functional dependence. Although apathy is a common neuropsychiatric sequela of HIV infection, emerging findings regarding its unique role in lower HRQoL have been mixed. The present study was guided by Wilson and Cleary's (1995), model in examining the association between apathy and physical and mental HRQoL in 80 HIV+ individuals who completed a neuromedical examination, neuropsychological assessment, structured psychiatric interview, and a series of questionnaires including the SF-36. Apathy was measured using a composite of the apathy subscale of the Frontal Systems Behavioral Scale and the vigor-activation subscale of the Profile of Mood States. Independent of major depressive disorder, neurocognitive impairment, functional status, and current CD4 count, apathy was strongly associated with HRQoL. Specifically, apathy and CD4 count were significant predictors of physical HRQoL, whereas apathy and depression were the only predictors of mental HRQoL. All told, these findings suggest that apathy plays a unique role in HRQoL and support the importance of assessing and managing apathy in an effort to maximize health outcomes among individuals with HIV disease.     

Slowly progressive pure dysgraphia with late apraxia of speech: a further variant of the focal cerebral degeneration

We report a longitudinal neuropsychological investigation of a patient with slowly progressive pure dysgraphia. Cognitive analysis of writing errors suggested a selective impairment of the graphemic buffer. After about seven years, the patient developed an apraxia of speech. No other linguistic or generalized cognitive impairment occurred subsequently, so that, twelve years after the beginning of the disease, the patient showed complete independence in daily life and still remained professionally active. Functional neuroimaging revealed hypoperfusion confined to left fronto-temporal lobe. This well-recognizable syndrome does not fit any of the cases described previously in the literature. This report therefore, adds another variant to heterogeneous clinical spectrum of focal neurodegenerative disorders, further suggesting the opportunity of their distinction from pathological processes leading to dementia.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Cognitive Neurorehabilitation of HIV-associated Neurocognitive Disorders: A Qualitative Review and Call to Action

Despite significant advances in the virologic management of HIV infection over the last two decades, effective treatments for HIV-associated neurocognitive disorders (HAND) remain elusive. While pharmacological interventions have yielded some success in improving neurocognitive outcomes in HIV, there is a dearth of rigorous studies examining the efficacy of cognitive rehabilitation for remediating HIV-associated neurocognitive impairment. This qualitative review summarizes and critiques the emerging literature on cognitive and behavioral treatments for HAND, which provides many reasons for optimism, but also has major limitations that underscore the scope of the work that lies ahead. Considering the notable real-world consequences of HAND, the development, validation, and clinical deployment of cognitive neurorehabilitation interventions tailored to the needs of persons living with HIV infection is a priority for clinical neuroAIDS investigators. In describing potential future directions for this endeavor, particular attention was paid to the application of cognitive neuropsychological principles in developing theory-driven approaches to managing HAND, improving everyday functioning, and enhancing HIV health outcomes.     

A brief (one-hour) quantitative neuropsychological assessment with three performance-based tests: strong concordance with proficiency scores for a more extensive test battery

Raw scores for each of several dozens of traditional and more recently developed neuropsychological tests were correlated with an impairment index composed of all of these scores from the records of 162 patients who had been assessed following impacts of substantial mechanical energies. A score of either less than 20 correct binaural responses for a dichotic word listening task, more than 99 sec. for Trails B, and more than 3.8 min. to complete the Tactual Performance Test with both hands correctly classified 85% of patients whose z scores were less than -1.0 (below average) or -1.0 or above (average) for a composite neurocognitive index. The results suggest that these three tests, administrable within about one hour, may be employed as a more objective criterion rather than "clinical impressions" for discerning if patients require more extensive neuropsychological testing.     

What Do We Know About Neuropsychological Aspects Of Schizophrenia?

Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems.     

Feasibility of telecognitive assessment in dementia

Videoconferencing (VC) technology has been used successfully to provide psychiatric services to patients in rural and otherwise underserved settings. VC-based diagnostic interviewing has shown good agreement with conventional face-to-face diagnosis of dementia in several investigations, but extension of this technology to neurocognitive assessment has received little attention. To this end, the authors administered a brief battery of common neuropsychological tests via VC technology (telecognitive) and traditional face-to-face methods to 14 older persons with mild cognitive impairment (MCI) and 19 persons with mild to moderate Alzheimer's disease (AD). Highly similar test scores were obtained when participants were tested in-person or via VC. Telecognitive assessment appears to be a valid means to conduct neuropsychological evaluation of older adults with cognitive impairment. Furthermore, continued development of VC technology has implications for expanding neuropsychological assessment options in under-served populations.     

Neurocognitive outcomes in pediatric HIV

Cognitive impairment has long been associated with the natural history of HIV among vertically infected children. In children, HIV may have a direct or indirect impact on the developing brain, may lead to global or highly specific consequences, and may be responsible for minor cognitive consequences or, conversely, long-term and severe disability. This differential impact is related to multiple factors that influence the individual expression of the virus in any given child. This review provides an overview of the relevant literature on neurocognitive outcomes for infants, children, and youth vertically infected with HIV, with attention to those factors impacting neurocognitive outcome within a developmental framework. Research findings in both the era preceding and following the introduction of combined therapies are reviewed, since many of the issues identified prior to state-of-the-art treatment currently available in the United States and other developed countries still apply in much of the developing world. Intervention issues and directions for future research are also discussed.     

The effects of motor neurone disease on language: further evidence

It might sound surprising that Motor Neurone Disease (MND), regarded still by many as the very example of a neurodegenerative disease affecting selectively the motor system and sparing the sensory functions as well as cognition, can have a significant influence on language. In this article we hope to demonstrate that language dysfunction is not only a pronounced and well documented symptom in some MND patients but also that the study of language in MND can address interesting theoretical questions about the representation of language and conceptual knowledge in the brain. After a brief introduction delineating clinical and pathological features of the disease we discuss the evidence available in the literature for language dysfunction in MND. We then present linguistic data from our own study of seven patients with MND/dementia/aphasia syndrome focusing on the dissociation between noun and verb processing. To illustrate the clinical, neuropsychological and linguistic aspects of MND we describe in more detail the patient E.N., a pathologically confirmed case of MND/dementia. Finally, we attempt to characterise the nature of the linguistic impairment in MND in the light of current debates about the mechanisms underlying noun/verb dissociation.     

Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A comparison with early and advanced Parkinson's disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.     

Discrepancies between standardized measures of cognitive level and Halstead-Reitan impairment indices as inferences of brain damage following head injuries

z scores for measures of intelligence, memory, educational achievement, and neuropsychological impairment were obtained for 193 patients who had sustained impacts of mechanical energy to their skulls. Two sets of normative data, adjusted for age and sex and not adjusted for these variables, were employed to compute indices of neurocognitive proficiency (the inverse of impairment). 80% or 76 of the 96 patients whose Halstead-Reitan Indices were greater than 0.4 displayed scores for neurocognitive proficiency that were two or more standard deviations below the averages of their scores for intelligence, memory, and educational achievement. None of the patents whose Impairment Indices were 0.4 or less displayed this discrepancy. There were no statistically significant differences between these two groups of patients with respect to the presence of unconsciousness following the injury or the duration of posttraumatic memory disruptions. The results indicate that quantitative scores for neuropsychological impairments are still the most accurate criteria to discern brain dysfunction within the mild to moderate range.     

The Brief Cognitive Impairment Scale (BCIS): preliminary investigation of a severe-stage dementia test emphasizing cognitive processing and interpersonal tolerance

We describe the development and validation of The Brief Cognitive Impairment Scale (BCIS), a cognitive screening instrument designed for persons with severe-stage dementia. Psychometric analyses were performed on neuropsychological data from long-term care residents (N = 247) who completed a brief battery of tests, including the BCIS. A principle component analysis yielded three factors that provide insight into how persons with severe dementia cognitively process information and may tolerate specific aspects of social stimulation, such as during personal care. A BCIS cut score can be used to identify severe dementia with a sensitivity of .82, a specificity of .84, and an area under the curve of .89. It may be used by clinicians or caregivers when advanced dementia is suspected, as an alternative to measures with suspected floor effects, when residents cannot tolerate more demanding assessment tools, and as part of non-pharmacologic treatment plans for behavior disturbances associated with dementia.     

Modeling the Ecological Validity of Neurocognitive Assessment in Adults with Acquired Brain Injury

Neuropsychologists are increasingly asked to make judgments regarding treatment options and rehabilitation strategies in addition to evaluating the degree and scope of neuropsychological impairment following acquired brain injuries. The capacity to make informed clinical decisions relies upon research investigating the relationships between neuropsychological and psychosocial status (i.e., ecological validity). Unfortunately, much of this research employs exploratory analyses, an approach that can lead to theoretical ambiguity and ad-hoc interpretations. The current availability and accessibility of analytical tools, like structural equation modeling (SEM), however, permits the testing of specific hypotheses regarding ecological validity and promotes a-priori theory development. In the current study, a theory-driven model of the ecological validity of a neurocognitive assessment was tested against data obtained from individuals with acquired brain injury using SEM. The results provide confirmatory evidence for the ecological validity of neurocognitive constructs and empirical support for a theory-driven analytical approach to ecological validity research.     

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.     

Neurocognitive Manifestations of Human Immunodeficiency Virus

Is human immunodeficiency virus still a terminal condition? Recent advances in treatment have significantly reduced both mortality and morbidity associated with HIV, but these treatments have not been successful in eradicating the virus itself. As such, HIV has evolved into a chronic condition that is complicated by neurocognitive factors. Cognitive difficulties associated with HIV are characterized by a subcortical pattern with primary deficits in information processing speed and psychomotor speed. These deficits interfere with the ability of patients to complete important instrumental activities of daily living even in the absence of dementia. Treatment of HIV improves neurocognitive functioning, but the regimens are complex and patient adherence is critical. Cognitive factors can negatively impact treatment adherence, which in turn results in poorer immunological, cognitive, and psychiatric outcome. This cycle emphasizes the important interrelationships between symptom expression and treatment outcome in patients with HIV. The nature of these relationships will change with further developments in treatment regimens such as once-daily dosing. Less complex treatment approaches should improve health outcome as well as provide additional opportunities to further understand the impact of HIV on brain function.