Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study.

BACKGROUND: Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory, as measured by verbal recall. METHODS: Eighty patients aged at least 6 years but less than 21 years with low-grade glioma were treated with RT to 54 Gy on a phase II protocol. Patients underwent age-appropriate cognitive testing at baseline, 6 months posttreatment, yearly through 5 years posttreatment, year 7 or 8, and year 10 posttreatment. Random coefficient models were used to estimate the longitudinal trends in cognitive assessment scores. RESULTS: Median neurocognitive follow-up was 9.8 years. There was a significant decline in short-delay recall (slope = -0.01 standard deviation [SD]/year, P < 0.001), total recall (slope = -0.09 SD/y, P = 0.005), and long-delay recall (slope = -0.01 SD/y, P = 0.002). On multivariate regression, after accounting for hydrocephalus, decline in short-delay recall was associated with the volume of right (slope = -0.001 SD/y, P = 0.019) or left hippocampus (slope = -0.001 SD/y, P = 0.025) receiving 40 Gy (V40 Gy). On univariate regression, decline in total recall was only associated with right hippocampal dosimetry (V40 Gy slope = -0.002, P = 0.025). In children <12 years, on univariate regression, decline in long-delay recall was only associated with right (V40 Gy slope = -0.002, P = 0.013) and left (V40 Gy slope = -0.002, P = 0.014) hippocampal dosimetry. CONCLUSION: In this 10-year longitudinal study, greater hippocampal dose was associated with a greater decline in delayed recall. Such findings might be informative for radiation therapy planning, warranting prospective evaluation.

Visual associations cued recall A Paradigm for Measuring Episodic Memory Decline in Alzheimer's Disease.

Repeated measurements of episodic memory are needed for monitoring amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). Most episodic memory tests may pose a challenge to patients, even when they are in the milder stages of the disease. This cross-sectional study compared floor effects of the Visual Association Test (VAT) and the Rey Auditory Verbal Learning Test (RAVLT) in healthy elderly controls and in patients with aMCI or AD (N = 125). A hierarchical multiple regression analysis was used to examine whether linear or quadratic trends best fitted the data of cognitive test performance across global cognitive impairment. Results showed that VAT total scores decreased linearly across the range of global cognitive impairment, whereas RAVLT total scores showed a quadratic trend, with total scores levelling off for 90% of aMCI patients and 94% of AD patients. We conclude that the VAT shows few if any floor effects in patients with aMCI and mild AD and is therefore a potentially promising cognitive test for monitoring episodic memory impairment.

Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans.

This is the first controlled study demonstrating the beneficial effects of transcranial laser stimulation on cognitive and emotional functions in humans. Photobiomodulation with red to near-infrared light is a novel intervention shown to regulate neuronal function in cell cultures, animal models, and clinical conditions. Light that intersects with the absorption spectrum of cytochrome oxidase was applied to the forehead of healthy volunteers using the laser diode CG-5000, which maximizes tissue penetration and has been used in humans for other indications. We tested whether low-level laser stimulation produces beneficial effects on frontal cortex measures of attention, memory and mood. Reaction time in a sustained-attention psychomotor vigilance task (PVT) was significantly improved in the treated (n=20) vs. placebo control (n=20) groups, especially in high novelty-seeking subjects. Performance in a delayed match-to-sample (DMS) memory task showed also a significant improvement in treated vs. control groups as measured by memory retrieval latency and number of correct trials. The Positive and Negative Affect Schedule (PANAS-X), which tracks self-reported positive and negative affective (emotional) states over time, was administered immediately before treatment and 2 weeks after treatment. The PANAS showed that while participants generally reported more positive affective states than negative, overall affect improved significantly in the treated group due to more sustained positive emotional states as compared to the placebo control group. These data imply that transcranial laser stimulation could be used as a non-invasive and efficacious approach to increase brain functions such as those related to cognitive and emotional dimensions. Transcranial infrared laser stimulation has also been proven to be safe and successful at improving neurological outcome in humans in controlled clinical trials of stroke. This innovative approach could lead to the development of non-invasive, performance-enhancing interventions in healthy humans and in those in need of neuropsychological rehabilitation.

Principal component analysis of the P600 waveform: RF and gender effects.

The aim of the present study was to examine the patterns of activation of the P600 waveform of the event-related potentials (ERP), applying principal component analysis (PCA) and repeated measures ANOVA, and whether these patterns are RF and gender dependent. The ERPs of thirty-nine healthy subjects (20 male and 19 female) were recorded during an auditory memory task in the presence and absence of RF, similar to that emitted by mobile phones. Both PCA and ANOVA produced congruent results, showing that activation of the P600 component occurs early and more intensely in the region of the posterior electrodes and in a less intense manner in the central electrodes. Conversely, the activation at the anterior electrodes arises later with a considerably reduced intensity. In the absence of RF female subjects exhibited significantly lower amplitudes at anterior electrodes and earlier latencies at central electrodes than male subjects. These differences disappear in the presence of RF. Consequently, the P600 component follows distinct patterns of activation in the anterior, central and posterior brain areas and gender differences are observed simultaneously at several electrodes within these areas. Finally, the gender-related functional architecture with regard the P600 component appears to be RF sensitive. In conclusion, the application of the PCA procedure provides an adequate model of the spatially distributed event-related dynamics that correspond to the P600 waveform.

Learning, retrieval, and recognition are compromised in aMCI and mild AD: are distinct episodic memory processes mediated by the same anatomical structures?

Performance of different episodic memory processes in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) and their anatomical correlates are not completely understood. We evaluated the performance of 48 subjects (17 with aMCI, 15 with mild AD, and 16 controls) on the Rey Auditory Verbal Learning Test (RAVLT). A brain MRI voxel-based morphometry (VBM) analysis was run with the aim of evaluating the correlations between RAVLT and gray matter density. All memory processes were compromised in aMCI and mild AD. Also, the same cerebral structures were involved in all RAVLT stages. Learning and delayed recall were more related to the medial prefrontal cortex and hippocampi, whereas recognition was more related to the thalamic nuclei and caudate nucleus, particularly in the left side. Our findings suggest that these structures may act as a complex functional system and are involved in the acquisition of new information.