Alterations in Memory and Impact on Academic Outcomes in Children Following Allogeneic Hematopoietic Cell Transplantation.

The prevalence of late effects following allogeneic hematopoietic cell transplantation (HCT), a curative treatment for pediatric leukemia, is high: 79% of HCT recipients experience chronic medical conditions. The few extant studies of cognitive late effects have focused on intelligence and are equivocal about HCT neurotoxicity. In an archival study of 30 children (mean transplant age = 6 years), we characterize neuropsychological predictors of academic outcomes. Mean intellectual and academic abilities were average, but evidenced extreme variability, particularly on measures of attention and memory: ∼25% of the sample exhibited borderline performance or lower. Medical predictors of outcome revealed paradoxically better memory associated with more severe acute graft-versus-host disease (GVHD) and associated with steroid treatment. Processing speed and memory accounted for 69% and 61% of variance in mathematics and reading outcomes, respectively. Thus, our findings revealed neurocognitive areas of vulnerability in processing speed and memory following HCT that contribute to subsequent academic difficulties.

Treatment effects of Fast ForWord demonstrated by magnetoencephalography (MEG) in a child with developmental dyslexia.

Treatment effects of Fast ForWord, hypothesized to ameliorate temporal processing deficits, were demonstrated by magnetoencephalography in a child with dyslexia using four paradigms: Word/Non-word Reading (NW), Grapheme-to-Phoneme Matching (GP), Verbal, and Spatial Working Memory (VWM, SWM). Shifts in brain activation from right inferior frontal and temporal to left frontal, bilateral supramarginal, and transverse temporal regions occurred during GP. During NW, shifts progressed from (1) right or bilateral anterior and superior to (2) left, inferior frontal, to (3) left, superior posterior temporoparietal, to (4) left, inferior, posterior temporooccipital regions. Reading and written language improvements were noted in passage comprehension and spelling.

Long-term estrogen replacement is associated with improved nonverbal memory and attentional measures in postmenopausal women.

OBJECTIVE: To determine the cognitive domains improved or preserved by long-term hormone replacement therapy (HRT). DESIGN: A comprehensive neuropsychological test battery was administered to healthy postmenopausal women who had been treated or not treated with long-term HRT without interruption since menopause. SETTING: Women were recruited by advertisement from a university town and surrounding areas. PATIENT(S): Women 60 years or older were studied who were treated (n = 16) or not treated (n = 13) with HRT. INTERVENTION(S): Neuropsychological testing included tests of memory, verbal fluency, executive functions, attention and concentration, and psychomotor function. Tests of intellectual function, depressive symptoms, and emotional functioning assessed general functions and comparability of the groups. MAIN OUTCOME MEASURE(S): Neuropsychological testing scores were compared between groups. RESULT(S): No statistically significant differences between the groups were found for general demographic, intellectual, and psychological measures. Scores from both the Weschler Memory Scale Visual Reproduction (delayed recall) and the Digit Vigilance Test (attention) showed statistically significant better performance and fewer errors in the group of women on HRT. CONCLUSION(S): Long-term postmenopausal HRT is associated with higher scores in tests of nonverbal memory and attention.

Cognitive function in euthymic bipolar I disorder.

Recent reports have suggested the presence of persistent cognitive impairments in patients diagnosed with Bipolar Disorder even after prolonged euthymic phases. In this work, various domains of cognitive function were examined in asymptomatic patients diagnosed with Bipolar I Disorder (BDI) in comparison with healthy subjects. Fifteen otherwise healthy BDI patients with a prior history of psychosis during mania completed a neuropsychological testing battery after a prolonged asymptomatic remission. Their scores were compared to those of individually matched healthy subjects with unpaired two-tailed t-tests at P<0.01. Relationships between cognitive performance measures and clinical variables related to illness severity were also examined with Pearson correlations, P<0.05. We detected poorer performance on measures of verbal learning, executive functioning and motor coordination in BDI patients compared to control volunteers. Scores on tests of executive functioning were negatively correlated with the number of episodes of mania and depression. Social and occupational scores were also associated with a poorer performance on measures of verbal learning and executive function. Euthymic BDI patients, therefore, demonstrate reductions in specific cognitive domains even after prolonged asymptomatic phases. Some of these deficits appear to be associated with a more severe course of illness and poorer social and occupational functioning.

Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer's disease.

We hypothesized that 20 patients with isolated memory impairment (IMI) would demonstrate [18F]-2-fluoro-2-deoxy-D-glucose utilization and a progression of neuropsychological symptoms consistent with Alzheimer's disease (AD). IMI subjects performed similarly to AD in recall and verbal fluency, but comparable to normal subjects in other areas of cognitive functioning. A positron emission tomography (PET) diagnostic index based on parietal Z-scores categorized IMI patients into normal and abnormal metabolic patterns. Ten of the original 20 IMI patients (50%) reflected PET AD abnormalities. Clinical information was available for IMI patients at three-year follow-up. Ten (50%) had converted to AD, three were found to have pseudodementia and the seven remained IMI. Of the 10 IMI patients with an originally normal PET index, three (30%) were diagnosed with AD at three years. Of the 10 with an abnormal index originally, seven (70%) converted to AD. The finding that memory deficit in IMI was as pronounced as that in AD patients is consistent with the notion that memory is an initial symptom of AD. A substantial number of the IMI patients reflected regional hypometabolism similar to AD, suggesting that IMI is likely an early stage in progressive dementia. A large percentage of IMI patients converted clinically to AD within three years of initial study, though we observed impaired memory functioning well before a clinical diagnosis of AD could be made. In addition to potential clinical utility, IMI and PET represent an opportunity to study dementia in relation to brain chemistry at a time when brain pathology is in the process of development.

Technology in the assessment of learning disability.

Recent neuroradiologic and brain imaging technologies, along with methods for displaying electrophysiologic data, have promulgated active exploration in the assessment of learning disability with attempts to improve diagnostic precision and elucidate the neurobiological substrates of learning disorders. The following article reviews these techniques and explores the research that has been conducted in this area over the past two decades. Initial investigations attempted to elucidate irregularities or abnormalities of brain morphology in individuals with learning disability utilizing computerized tomography (CT). The current standard for structural imaging of the brain is magnetic resonance (MR) imaging, which has allowed for greater specificity in identifying brain abnormalities. More recently, functional magnetic resonance imaging (fMRI) has been postulated as holding some promise in distinguishing anatomic/function differences in LD. Electrophysiological (EEG) and metabolic imaging techniques offer methods by which human brain activity can be studied during cognitive processes. Computerized EEG studies including evoked potentials (EP) or event-related potentials (ERP), spectral EEG analysis, and topographic EEG brain mapping have also identified a number of brain irregularities in individuals with learning disabilities, though no consistent exemplars have emerged. Studies with positron emission tomography (PET) and single photon emission computerized tomography (SPECT) have also demonstrated a number of abnormalities and inconsistencies in individuals with learning disabilities, but, again, no systematic research has demonstrated specific diagnostic abnormalities. Though inroads and some consistent patterns have begun to emerge in the assessment of learning disability with the preceding technologies, a number of challenges persist with neuroimaging and neurophysiological and metabolic imaging techniques. To date, no diagnostic conclusions have been drawn utilizing these methods in the assessment of the neurobiologic basis to LD.