Mesial temporal, diencephalic, and striatal contributions to deficits in single word reading, word priming, and recognition memory

Fifty-three volunteer participants were studied with the fade-in task (Ostergaard, 1998) to measure naming latency, word priming, and recognition-memory performance. and with morphometric magnetic resonance imaging (MRI) techniques to measure volumes of mesial temporal lobe, diencephalic, striatal, and neocortical structures. The relationship between measures of cerebral volume loss and performance deficits was modeled using simultaneous regression analyses in which the behavioral measures were dependent variables. The results suggested that damage in both hippocampal and amygdala/entorhinal areas as well as damage in the diencephalon and the nucleus accumbens all contributed independently to the severity of recognition-memory deficits. Both caudate nucleus damage and hippocampal damage contributed independently to increased naming latency (slowed single-word reading). Finally, only damage in the hippocampus appeared to result in decreased word priming. These results provide further evidence against the assertion that word priming represents a form of memory unaffected by damage to the mesial temporal lobes

Effects of traumatic brain injury on cognitive functioning and cerebral metabolites in HIV-infected individuals.

We explored the possible augmenting effect of traumatic brain injury (TBI) history on HIV (human immunodeficiency virus) associated neurocognitive complications. HIV-infected participants with self-reported history of definite TBI were compared to HIV patients without TBI history. Groups were equated for relevant demographic and HIV-associated characteristics. The TBI group evidenced significantly greater deficits in executive functioning and working memory. N-acetylaspartate, a putative marker of neuronal integrity, was significantly lower in the frontal gray matter and basal ganglia brain regions of the TBI group. Together, these results suggest an additional brain impact of TBI over that from HIV alone. One clinical implication is that HIV patients with TBI history may need to be monitored more closely for increased risk of HIV-associated neurocognitive disorder signs or symptoms

APOE interacts with age to modify rate of decline in cognitive and brain changes in Alzheimer's disease

Abstract Objective: To determine (1) whether age-standardized cognitive declines and brain morphometric change differ between Young-Old patients with Alzheimer's disease (YOAD) and Very-Old patients with Alzheimer's disease (VOAD), and (2) whether the apolipoprotein E (APOE) genotype modifies these neuropsychological and morphometric changes. Methods: Baseline and 12-month follow-up neuropsychological and morphometric measures were examined for healthy control subjects and patients with AD. The two AD groups were divided further into subgroups on the basis of the presence of at least one APOE ε4 allele. Results: The YOAD group showed more severe deficits and steeper declines in cognition than the VOAD group. Moreover, the presence of an APOE ε4 allele had a more deleterious effect on the YOAD group than the VOAD group on cognition and brain structure both cross-sectionally and longitudinally. Conclusions: Results underscore the importance of integrating an individual's age and genetic susceptibility-and their interaction-when examining neuropsychological and neuroimaging changes in the early stages of Alzheimer's disease

Genetic network properties of the human cortex based on regional thickness and surface area measures

We examined network properties of genetic covariance between average cortical thickness (CT) and surface area (SA) within genetically-identified cortical parcellations that we previously derived from human cortical genetic maps using vertex-wise fuzzy clustering analysis with high spatial resolution. There were 24 hierarchical parcellations based on vertex-wise CT and 24 based on vertex-wise SA expansion/contraction; in both cases the 12 parcellations per hemisphere were largely symmetrical. We utilized three techniques—biometrical genetic modeling, cluster analysis, and graph theory—to examine genetic relationships and network properties within and between the 48 parcellation measures. Biometrical modeling indicated significant shared genetic covariance between size of several of the genetic parcellations. Cluster analysis suggested small distinct groupings of genetic covariance; networks highlighted several significant negative and positive genetic correlations between bilateral parcellations. Graph theoretical analysis suggested that small world, but not rich club, network properties may characterize the genetic relationships between these regional size measures. These findings suggest that cortical genetic parcellations exhibit short characteristic path lengths across a broad network of connections. This property may be protective against network failure. In contrast, previous research with structural data has observed strong rich club properties with tightly interconnected hub networks. Future studies of these genetic networks might provide powerful phenotypes for genetic studies of normal and pathological brain development, aging, and function

Presence of ApoE ε4 Allele Associated with Thinner Frontal Cortex in Middle Age

Abstract. The presence of an ApoE ε4 allele (ε4+) increases the risk of developing Alzheimer's disease (AD). Previous studies support an adverse relationship between ε4+ status and brain structure and function in mild cognitive impairment and AD; in contrast, the presence of an ε2 allele may be protective. Whether these findings reflect disease-related effects or pre-existing endophenotypes, however, remains unclear. The present study examined the influence of ApoE allele status on brain structure solely during middle-age in a large, national sample. Participants were 482 men, ages 51-59, from the Vietnam Era Twin Study of Aging (VETSA). T1-weighted images were used in volumetric segmentation and cortical surface reconstruction methods to measure regional volume and thickness. Primary linear mixed effects models predicted structural measures with ApoE status (ε3/3, ε2/3, ε3/4) and control variables for effects of site, non-independence of twin data, age, and average cranial vault or cortical thickness. Relative to the ε3/3 group, the ε3/4 group demonstrated significantly thinner cortex in superior frontal and left rostral and right caudal midfrontal regions; there were no significant effects of ε4 status on any temporal lobe measures

Influence of young adult cognitive ability and additional education on later-life cognition

How and when education improves cognitive capacity is an issue of profound societal importance. Education and later-life education-related factors, such as occupational complexity and engagement in cognitive-intellectual activities, are frequently considered indices of cognitive reserve, but whether their effects are truly causal remains unclear. In this study, after accounting for general cognitive ability (GCA) at an average age of 20 y, additional education, occupational complexity, or engagement in cognitive-intellectual activities accounted for little variance in late midlife cognitive functioning in men age 56-66 (n = 1009). Age 20 GCA accounted for 40% of variance in the same measure in late midlife and approximately 10% of variance in each of seven cognitive domains. The other factors each accounted for <1% of the variance in cognitive outcomes. The impact of these other factors likely reflects reverse causation-namely, downstream effects of early adult GCA. Supporting that idea, age 20 GCA, but not education, was associated with late midlife cortical surface area (n = 367). In our view, the most parsimonious explanation of our results, a meta-analysis of the impact of education, and epidemiologic studies of the Flynn effect is that intellectual capacity gains due to education plateau in late adolescence/early adulthood. Longitudinal studies with multiple cognitive assessments before completion of education would be needed to confirm this speculation. If cognitive gains reach an asymptote by early adulthood, then strengthening cognitive reserve and reducing later-life cognitive decline and dementia risk may really begin with improving educational quality and access in childhood and adolescence.Peer reviewe

Genetic Influences on Cortical Regionalization in the Human Brain

SummaryAnimal data demonstrate that the development of distinct cortical areas is influenced by genes that exhibit highly regionalized expression patterns. In this paper, we show genetic patterning of cortical surface area derived from MRI data from 406 adult human twins. We mapped genetic correlations of areal expansion between selected seed regions and all other cortical locations, with the selection of seed points based on results from animal studies. “Marching seeds” and a data-driven, hypothesis-free, fuzzy-clustering approach provided convergent validation. The results reveal strong anterior-to-posterior graded, bilaterally symmetric patterns of regionalization, largely consistent with patterns previously reported in nonhuman mammalian models. Broad similarities in genetic patterning between rodents and humans might suggest a conservation of cortical patterning mechanisms, whereas dissimilarities might reflect the functionalities most essential to each species