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Background: Stimulants are used increasingly to enhance social (cocaine) or cognitive performance (stimulants normally prescribed, prescription stimulants [e.g., methylphenidate, amphetamines]). Chronic use, by contrast, has been associated with significant verbal memory and learning deficits. This study sought to determine whether subtle learning and memory problems characterize individuals who exhibit occasional but not chronic use of stimulants., Methods: One hundred fifty-four young (age 18-25), occasional, nondependent stimulant users and 48 stimulant-naive comparison subjects performed the California Verbal Learning Test II. Lifetime uses of stimulants and co-use of marijuana were considered in correlation and median split analyses., Results: Compared with stimulant-naive subjects, occasional stimulant users showed significant performance deficits, most pronounced in the verbal recall and recognition domains. Lifetime uses of stimulants and marijuana did not affect California Verbal Learning Test II performance. The type of stimulant used, however, was of major relevance: users of cocaine only were less impaired, whereas cumulative use of prescription stimulants was associated with impaired verbal learning and memory capacities., Conclusions: These results support the hypothesis of subtle and possibly pre-existing neurocognitive deficiencies in occasional users of stimulants, which might be related to the motivation for using these drugs. More importantly, despite beneficial short-term effects, cumulative use, particularly of prescription amphetamines and methylphenidate, intensifies these deficits., (Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Forty non-demented older adults who were divided into two groups on the basis of their cognitive status (MCI: n=20; normal control: n=20) underwent diffusion tensor imaging, and estimates of fractional anisotropy (FA) and mean diffusivity (MD) were obtained for the genu and splenium of the corpus callosum. Results demonstrated the following: (1) group comparisons revealed that splenium FA was significantly lower in MCI participants than in NC participants, despite no differences in gross morphometry or hippocampal volumes; (2) in the overall sample, higher stroke risk was associated with lower white matter integrity, particularly in the genu; (3) increased stroke risk was more strongly associated with poorer splenium FA in those with MCI than in normal elderly; (4) splenium FA significantly predicted performance on verbal memory (adjusting for the effects of age, education, and whole brain volume). Findings demonstrate a relationship between increased vascular burden and white matter changes, and they support the possibility that posterior white matter pathology may contribute to the development of MCI-related cognitive changes., ((c) 2008 Elsevier Inc. All rights reserved.)

We sought to investigate whether apolipoprotein E (APOE) genotype is associated with unique profiles of cognitive functioning during early-life. School-aged children (N=147) received standardized achievement tests, the Rey-Osterrieth Complex Figure Test (Copy Condition; RCFT-CC), assessment of hand dominance for writing, and buccal swab testing to determine their APOE genotype. Significant differences were found on the RCFT-CC, with epsilon 2-positive children performing worse on this measure relative to both epsilon 3/3 (p=0.032) and epsilon 4-positive children (p=0.018). Further, a higher prevalence of left-hand dominance for writing was observed among epsilon 2-positive children (29.2%) relative to epsilon 3/3 (8.9%) and epsilon 4-positive children (6.1%; p=0.012), although this finding did not account for the observed group differences on the RCFT-CC. Findings raise the possibility that in childhood, the epsilon 2 allele may be associated with: (a) decreased functioning in certain cognitive domains; (b) factors associated with atypical hemispheric dominance. Results may be consistent with the theory of antagonistic pleiotropy, which suggests that APOE may have different protective effects at different developmental stages., ((c) 2008 Elsevier Inc. All rights reserved.)

Objectives: Operational definitions of cognitive impairment have varied widely in diagnosing mild cognitive impairment (MCI). Identifying clinical subtypes of MCI has further challenged diagnostic approaches because varying the components of the objective cognitive assessment can significantly impact diagnosis. Therefore, the authors investigated the applicability of diagnostic criteria for clinical subtypes of MCI in a naturalistic research sample of community elders and quantified the variability in diagnostic outcomes that results from modifying the neuropsychological definition of objective cognitive impairment., Design: Cross-sectional and longitudinal study., Setting: San Diego, CA, Veterans Administration Hospital., Participants: Ninety nondemented, neurologically normal, community-dwelling older adults were initially assessed and 73 were seen for follow-up approximately 17 months later., Measurements: Participants were classified via consensus diagnosis as either normally aging or having MCI via each of the five diagnostic strategies, which varied the cutoff for objective impairment and the number of neuropsychological tests considered in the diagnostic process., Results: A range of differences in the percentages identified as MCI versus cognitively normal were demonstrated, ranging from 10-74%, depending on the classification criteria used. A substantial minority of individuals demonstrated diagnostic instability over time and across diagnostic approaches. The single domain nonamnestic subtype diagnosis was particularly unstable (e.g., prone to reclassification as normal at follow up)., Conclusion: Our findings provide empirical support for a neuropsychologically derived operational definition of clinical subtypes of MCI and point to the importance of using comprehensive neuropsychological assessments. Diagnoses, particularly involving nonamnestic MCI, were variable over time. The applicability and utility of this particular MCI subtype warrants further investigation.

Background: The epsilon4 allele of the apolipoprotein E gene (APOE-epsilon4) and a family history (+FH) of Alzheimer's disease (AD) are both risk factors for the development of AD. Although studies to identify a preclinical phase of AD have led to evidence of APOE-epsilon4- and +FH-related differences in brain and cognitive functioning in healthy adults, the relative influence of these factors in children is unknown., Methods: To investigate this issue, school-age children (n = 109) received standardized achievement tests, the Rey-Osterrieth Complex Figure Test (Copy Condition; RCFT-CC), assessment of family medical history, and buccal swab testing to determine their APOE genotype., Results: Analyses revealed that, relative to children without these risk factors, children who possess both an APOE-epsilon4 allele and a +FH of AD and/or significant memory problems (MP) obtained lower scores on nearly every cognitive test administered., Conclusions: Findings suggest that when both AD risk factors are present, cognition may be adversely affected as early as childhood. Thus, risk factors for a disorder of pathological aging (i.e., AD) may have implications for the etiology of certain types of learning difficulties in children.

Objectives: Cognitive-discrepancy analysis has been shown to be a useful technique for detecting subtle cognitive deficits in normal-functioning elderly individuals who are genetically at-risk for Alzheimer disease (AD). However, studies that have used cognitive-discrepancy measures to date have used retrospective or cross-sectional designs, and the utility of this approach to predict cognitive decline has not been examined in a prospective investigation., Design: Longitudinal study., Setting: San Diego, CA, Veterans Administration Hospital., Participants: Twenty-four normal-functioning elderly individuals participated in the study, with 16 subjects exhibiting no change in their Dementia Rating Scale (DRS) scores over an 1-year period (Stable Group), and 8 subjects exhibiting a decline in DRS scores over the 1-year period (Decline group)., Measurements: A cognitive-discrepancy measure isolating cognitive switching was computed that contrasted performance on a new higher-level task of executive functioning (a Stroop/Switching measure) relative to a composite measure of lower-level Stroop conditions., Results: a) In the year before their cognitive changes, the Decline group exhibited a significantly larger cognitive-discrepancy (Stroop/Switching versus lower-level Stroop conditions) score compared with a control (Stable) group; and b) the cognitive-discrepancy measure was superior to APOE genotype in predicting DRS decline., Conclusion: Cognitive-discrepancy analysis isolating a component executive function ability not only seems to be a useful tool for identifying individuals at risk for cognitive deficits, but also shows promise in predicting individuals who may show subtle cognitive decline over time.

Profiles of verbal learning and memory performance were compared for typically developing children and for four developmental disorders characterized by different patterns of language functioning: specific language impairment, early focal brain damage, Williams Syndrome, and Down Syndrome. A list-learning task was used that allowed a detailed examination of the process of verbal learning, recall, and recognition (California Verbal Learning Test--Children's Version). Distinct patterns of performance characterized the four disorders. These patterns were consistent with the language deficits typically seen in the disorders, with the exception of a dissociation seen in Williams Syndrome.