Convergent and divergent oscillatory aberrations during visuospatial processing in HIV-related cognitive impairment and Alzheimer's disease.

Adults with HIV frequently develop a form of mild cognitive impairment known as HIV-associated neurocognitive disorder (HAND), but presumably cognitive decline in older persons with HIV could also be attributable to Alzheimer's disease (AD). However, distinguishing these two conditions in individual patients is exceedingly difficult, as the distinct neural and neuropsychological features are poorly understood and most studies to date have only investigated HAND or AD spectrum (ADS) disorders in isolation. The current study examined the neural dynamics underlying visuospatial processing using magnetoencephalography (MEG) in 31 biomarker-confirmed patients on the ADS, 26 older participants who met criteria for HAND, and 31 older cognitively normal controls. MEG data were examined in the time-frequency domain, and a data-driven approach was utilized to identify the neural dynamics underlying visuospatial processing. Both clinical groups (ADS/HAND) were significantly less accurate than controls on the task and exhibited stronger prefrontal theta oscillations compared to controls. Regarding disease-specific alterations, those with HAND exhibited stronger alpha oscillations than those on the ADS in frontoparietal and temporal cortices. These results indicate both common and unique neurophysiological alterations among those with ADS disorders and HAND in regions serving visuospatial processing and suggest the underlying neuropathological features are at least partially distinct.

Spatially resolved neural slowing predicts impairment and amyloid burden in Alzheimer's disease.

An extensive electrophysiological literature has proposed a pathological 'slowing' of neuronal activity in patients on the Alzheimer's disease spectrum. Supported by numerous studies reporting increases in low-frequency and decreases in high-frequency neural oscillations, this pattern has been suggested as a stable biomarker with potential clinical utility. However, no spatially resolved metric of such slowing exists, stymieing efforts to understand its relation to proteinopathy and clinical outcomes. Further, the assumption that this slowing is occurring in spatially overlapping populations of neurons has not been empirically validated. In the current study, we collected cross-sectional resting state measures of neuronal activity using magnetoencephalography from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal biomarker-negative older adults. From these data, we compute and validate a new metric of spatially resolved oscillatory deviations from healthy ageing for each patient on the Alzheimer's disease spectrum. Using this Pathological Oscillatory Slowing Index, we show that patients on the Alzheimer's disease spectrum exhibit robust neuronal slowing across a network of temporal, parietal, cerebellar and prefrontal cortices. This slowing effect is shown to be directly relevant to clinical outcomes, as oscillatory slowing in temporal and parietal cortices significantly predicted both general (i.e. Montreal Cognitive Assessment scores) and domain-specific (i.e. attention, language and processing speed) cognitive function. Further, regional amyloid-ß accumulation, as measured by quantitative 18F florbetapir PET, robustly predicted the magnitude of this pathological neural slowing effect, and the strength of this relationship between amyloid-ß burden and neural slowing also predicted attentional impairments across patients. These findings provide empirical support for a spatially overlapping effect of oscillatory neural slowing in biomarker-confirmed patients on the Alzheimer's disease spectrum, and link this effect to both regional proteinopathy and cognitive outcomes in a spatially resolved manner. The Pathological Oscillatory Slowing Index also represents a novel metric that is of potentially high utility across a number of clinical neuroimaging applications, as oscillatory slowing has also been extensively documented in other patient populations, most notably Parkinson's disease, with divergent spectral and spatial features.

Screening for cognitive impairment in older adults with hematological malignancies using the Montreal Cognitive Assessment and neuropsychological testing.

OBJECTIVES: The primary objective of the current study is to describe the prevalence and profile of cognitive domains affected in older adults with hematological malignancies evaluated for hematopoietic cell transplantation (HCT) using the Montreal Cognitive Assessment (MoCA) and neuropsychological tests. The secondary objective is to determine if a specific MoCA cut-off score would correlate with the identification of cognitive impairment detected by neuropsychological tests. This would facilitate interpretation of cognitive screening and referral of patients who would likely need further neuropsychological testing. MATERIALS AND METHODS: Fifty-one patients 60 years and older who were evaluated for HCT were assessed using a battery of standardized neuropsychological tests and MoCA. We analyzed Receiver Operating Characteristics (ROC) comparing MoCA scores and four different neuropsychological test criteria for cognitive impairment. RESULTS: The prevalence of cognitive impairment detected by neuropsychological tests was 53 to 70.6% using the criteria for patients with cancer by the International Cancer Cognition Task Force (ICCTF). The following cognitive domains were most affected: language, learning and memory, visuospatial skills, and executive function. MoCA is an appropriate screening test for cognitive impairment. Using the ICCTF criteria, 86 to 100% of patients are correctly classified as having significant cognitive impairment on neuropsychological tests using a cut-off score of 20 or less. CONCLUSION: There is a high prevalence of cognitive impairment identified by neuropsychological tests in older patients with hematological malignancies evaluated for HCT. Identification of an appropriate MoCA cut-off score in this population is important to identify patients who would benefit from further assessment.

CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson's disease.

Animal models and clinical studies have linked the innate and adaptive immune system to the pathology of Parkinson's disease (PD). Despite such progress, the specific immune responses that influence disease progression have eluded investigators. Herein, we assessed relationships between T cell phenotype and function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort and a validation cohort, totaling 113 PD patients and 96 age- and environment-matched caregivers were examined by flow cytometric analysis and T cell proliferation assays. Increased effector/memory T cells (Tem), defined as CD45RO+ and FAS+ CD4+ T cells and decreased CD31+ and α4ß7+ CD4+ T cells were associated with progressive Unified Parkinson's Disease Rating Scale III scores. However, no associations were seen between immune biomarkers and increased age or disease duration. Impaired abilities of regulatory T cells (Treg) from PD patients to suppress effector T cell function was observed. These data support the concept that chronic immune stimulation, notably Tem activation and Treg dysfunction is linked to PD pathobiology and disease severity, but not disease duration. The association of T cell phenotypes with motor symptoms provides fresh avenues for novel biomarkers and therapeutic designs.

The influence of caregiver mastery on depressive symptoms.

PURPOSE: The purpose of this study was to explore how the relationship between care recipients' problem behaviors and caregivers' depressive symptoms varies as a function of caregiver mastery, controlling for the effects of caregiver age, gender, and relationship to the care recipient in caregivers of people with primary malignant brain tumor (PMBT). DESIGN: A cross-sectional design was used to gather data via telephone interviews from 95 caregivers of people with primary malignant brain tumor, recruited from 2003 to 2004 from a brain tumor treatment center, two national support groups, and a statewide cancer registry. METHODS: Measures for the study included the Neuropsychiatric Inventory-Questionnaire, Caregiver Mastery, and the Center for Epidemiologic Studies-Depression. A stepwise regression procedure was used to evaluate potential moderating and mediating relationships. FINDINGS: Data did not indicate that caregiver mastery was a moderating variable. The analysis showed caregiver mastery as a partial mediator, with both a direct effect of care recipients' problem behaviors on caregivers' depressive symptoms and an indirect effect through caregiver mastery. Concerning the indirect effect, care recipients' problem behaviors were related to lower levels of caregiver mastery, which in turn were related to more depressive symptoms in caregivers. CONCLUSIONS: Findings showed a link between care recipients' problem behaviors and caregivers' depressive symptoms, a relationship that has not been well established in oncology. This association indicates one mechanism through which problem behaviors in the care recipient might lead to caregiver depressive symptoms.

Predictors of distress in caregivers of persons with a primary malignant brain tumor.

The purpose of this cross-sectional, descriptive study was to identify predictors of distress for family caregivers of persons with a primary malignant brain tumor (PMBT). The effect of the care recipient's functional, cognitive, and neuropsychiatric status on caregiver burden and depressive symptoms was examined through telephone interviews with 95 caregivers. Care recipients' neuropsychiatric status consistently affected caregivers' depressive symptoms and burden, and assisting with activities of daily living affected burden related to caregivers' schedules and health. The care recipient's cognitive status and need for assistance with instrumental activities of daily living did not affect any outcome variable. Results may help identify caregivers at risk for negative outcomes, and suggest interventions to improve caregivers' emotional health.